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IFFS Surveillance 2016

doi: 10.1097/GRH.0000000000000001
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The International Federation of Fertility Societies (IFFS) is a federation of national membership societies that have an interest in the clinical and research aspects of reproduction and fertility. IFFS is a non-governmental organization (NGO) in official relations with the World Health Organization (WHO).

Copyright 2016 by International Federation of Fertility Societies (IFFS). All rights reserved. No part of this publication may be reproduced by any means without the prior written consent of the IFFS.

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the IFFS concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The editorial board members and survey respondents are responsible for the views and comments, respectively, expressed in this publication and they do not necessarily represent the decisions, policy, or views of the IFFS.

The 2016 IFFS Surveillance was made possible, in part, through the funding of an MSD grant.

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FOREWORD

An estimated one in four couples worldwide are affected by infertility and the levels of primary and secondary infertility have changed little over the previous two decades. While infertility is rarely considered a national health priority by governments, its impact on the lives of individuals, couples and their families who experience problems having children are enormous. The development of Assisted Reproductive Technologies (ART) is gradually transforming the range of options available to couples and individuals, bringing hope to millions. As these technologies become more effective and affordable they become more accessible, thereby enabling more and more of those affected with fertility problems to have a genuine choice in achieving their fertility goals.

The World Health Organization’s (WHO) Department of Reproductive Health and Research, including the Special Programme of Research on Human Reproduction, wholeheartedly congratulates IFFS for producing Surveillance 2016. The information collected through its innovative rapid survey methodology provides extremely useful insights into the provision of ART globally, as well as nationally through the IFFS national members and respondents. Thoughtful selection of a wide range of topics on which data were collected affords a detailed understanding of the opportunities and challenges facing expansion of ART services. Of particular concern is the limited access to these services by those living in LMICs due to cost and other barriers. While some recent policy restrictions are noted, the overall situation is one of increasing access in most countries, and a better understanding of the complexity of the issues surrounding ART provision. WHO is delighted to have partnered with IFFS in preparing this document.

WHO is in the process of broadening its activities that address infertility and fertility care. We look forward to continuing and expanding our engagement with IFFS and other partners that are dedicated to improving the lives of those affected by infertility. The information in Surveillance 2016 provides a strong basis for guiding WHO’s work on ART and we thank IFFS for its leadership and partnership in producing this valuable resource.

Ian Askew

Director, Reproductive Health and Research

World Health Organization

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DEDICATION: HOWARD W. JONES, JR, MD, 1910 – 2015

Surveillance 2016 is dedicated to Dr. Howard W. Jones, Jr., in vitro fertilization (IVF) pioneer, surgeon, educator, visionary, and past editor of Surveillance. He was among the first to recognize the need to create a forum to record and compare ART practices around the world. He remained interested and engaged in this project until shortly before his death.

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CONTENTS

  1. Foreword
  2. Dedication
  3. Preface
    1. Number of centres
    2. Legislation and guidelines
    3. Insurance coverage
    4. Marital status
    5. Number of embryos for transfer in assisted reproductive technology (ART)
    6. Cryopreservation
    7. Posthumous insemination
    8. Donation
    9. Anonymity
    10. Micromanipulation
    11. Oocyte maturation
    12. Welfare of the child
    13. Fetal reduction
    14. Preimplantation genetic diagnosis
    15. IVF gestational carriers
    16. Experimentation with embryonic cells
    17. Cloning
    18. Status of the embryo
    19. Sex selection
    20. Fertility preservation
    21. Reporting mechanisms
    22. Same sex/ single parenting policy
    23. Cross border reproductive care
    24. Conclusions
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PREFACE

International Federation of Fertility Societies (IFFS) Surveillance 2016 represents several milestones. Surveillance 2016 serves as the first edition of the new online IFFS journal, Global Reproductive Health. Surveillance 2016 represents a broader joint effort of the IFFS and World Health Organization (WHO) in association with the IFFS status as a non-governmental organization (NGO) in official relations with WHO. WHO representatives participated in the reorganization and reformatting of the 2012 questionnaire and expansion of the database of contacts among global public health officials and experts in order to supplement the pre-existing Surveillance contact list. We anticipate, that as we fulfill our responsibilities in our relations with WHO, that our joint activities in subsequent editions will likely continue to expand.

An entirely new survey was developed and used for Surveillance 2016. The contract for conducting the online questionnaire, follow-up, data analysis an ultimate product development was awarded to Medtech For Solutions. The previous Excel spreadsheet was abandoned in favor of a streamlined, more focused web-based questionnaire that eliminated redundancies and sought more focused information in evolving areas of interest. A few sections were added addressing reporting mechanisms, policies regarding access for same sex and single parenting individuals, as well as policies governing cross-border reproductive care.

The questionnaire (2015 survey or questionnaire) consisted of 97 questions in English, and took the average respondent 2.5 hours to complete (cumulative onsite time). The online survey was launched on October 1, 2015 and requests to participate were submitted to over 600 individuals in 215 countries for preparation of the publication of Surveillance 2016. The survey officially ended on December 31, 2015, however responses were received as late as March 1, 2016 and were included in the report. Ultimately, responses were received from respondents in 75 countries with 70 providing data sufficient to be included in the overall analysis. Not all countries provided complete responses to all queries and the number of countries responding varied as noted within the chapter discussion and tabulation of topic responses.

Surveillance 2016 represents the culmination of the efforts of many. I am profoundly grateful to the respondents listed below who committed a great deal of time and effort to accurately compile and convey the information that was sought. A very talented editorial board was assembled and Drs. Sonia Allan, Basak Balaban, Manish Banker, Peter Brinsden, John Buster, Edgar Mocanu, Hrishikesh Pai, and Paul Le Roux all contributed substantially to the revision of the questionnaire, the selection of new content, the analysis of the data, and the individual organization and production of each section. Dr. Marcos Horton deserves special mention for doggedly and successfully pursuing countries that had not responded to the initial invitation to participate and assuming extra editorial duties. Kathleen Miller, from Medtech For Solutions, was a superb managing editor and was indispensable to the final product. She had essential roles throughout the process including oversight of the development of the new questionnaire, execution of the online survey, compilation and distribution of the data, facilitation of the online development of the manuscript, and production of the figures and tables. Dr. Sheryl van der Poel also made unique contributions. During her tenure at WHO, she served as a liaison between WHO and IFFS and made numerous suggestions pertaining to content, organization and language for both the development of the questionnaire and this final report. She played a key role in the revision of the 2009 International Committee Monitoring Assisted Reproductive Technologies (ICMART)-WHO Glossary on Assisted Reproductive Terminology and was invaluable in ensuring that our terminology was consistent with the new draft 2016 glossary on terminology for fertility care and infertility. I would also like to acknowledge the IFFS officers, Board of Directors, and administrative staff for their unflagging support and contributions.

Figure

Figure

Surveillance 2016 serves as a record and an overview of the practice, policies and activities associated with assisted reproductive technology (ART) as it existed globally, at the end of 2015. It also, provides an evaluation of specific national and global trends over time that concern specific, and sometimes controversial, topics and issues. However, there are significant limitations to this report. All aspects of ART are dynamic and continuing to change. The respondents for the 2016 edition represent the majority of countries with the most active ART services worldwide; however, the experiences of over 100 countries are not depicted in this report despite intensive efforts to find representative respondents to include them. The responses to the questionnaire were provided by one or two well-informed individuals in each country but these responses were not validated and may contain inherent accuracies. Caution should be taken when interpreting or re-presenting these data. There are limitations in the completeness and quality of the surveillance data reported, including the variability in respondents from countries who provided feedback to surveys in 2013 versus in 2016. Nevertheless, this report remains the only source of information that provides a global overview of ART practices. Potential partnerships with other global organizations and an increase in awareness of this IFFS data collection should improve the quality in years to come. Nevertheless, Surveillance 2016 attests to a robust and expanding scope of ART practices, policies, and activities among nations around the world while highlighting significant and important differences with a review of trends that have occurred the triennium.

Steven J Ory

Editor-in -Chief

Surveillance 2016

July 2016

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LIST OF PARTICIPANTS

Table

Table

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CHAPTER 1: NUMBER OF CENTRES

Compiling an accurate tabulation of the number of centres providing assisted reproductive technology (ART) services remains a formidable challenge. The number of countries where centres are licensed, registered, or where oversight is otherwise provided, continues to increase and reliable estimates may be made in these countries from that point forward. Significant global progress has been made in establishing ART registries and oversight over the intervening three years. The 2016 data for these countries may represent a more accurate and complete estimate than previous estimates with an ability to utilize the registries to determine ART centre numbers. However, many countries still lack national ART registries, clinic-specific information is collected sporadically (if at all), and there are no reliable estimates on clinic numbers. The 2016 data set offers a more comprehensive attempt to determine the total number of ART centres worldwide but over 100 countries contacted did not complete the 2015 questionnaire. While this poses a significant limitation to the study, many of the non-responding countries are known to not have ART programmes or are believed to have a small number of centres.

Overall, 74 countries had respondents who provided data about number and type of centres (Table 1). Of the estimated total number of centres reported, there is an increase from approximately 3800 in 2012 to 5353 in 2015. However, Surveillance 2016 includes 14 additional countries, which did not report in 2012. Most of the respondents that provided information for both years have reported a modest increase in the total number of clinics or no significant change. Comparing the 2013 to the 2016 publications, 49 countries reported by their respective respondents in both surveys, 25 were new to the 2016 edition and 10 that reported in 2013 did not report for 2016. Of countries whose representatives have provided reliable estimates for both years, Argentina, Bulgaria, Finland, India, Ireland, Kazakhstan, Peru, Saudi Arabia, Turkey and Venezuela appear to have had significant increases and only Brazil and the United States reported a decrease of 5 or more centres. Of the 10 countries that only had responses in 2013, only Egypt (58) and Vietnam (13) previously reported having greater than 10 centres. The apparent large increase in the total number of centres reported this year appears to reflect more complete capture of data from a greater number of country representatives and perhaps a modest overall increase in the number of centres in a few countries.

Chapter 1 Table 1 Number of Centres

Chapter 1 Table 1 Number of Centres

This year, respondents were queried regarding the types of centres included in their countries, including designations for public, private, hospital, university based and private practitioner models. The private physician clinic model appears to be the most prevalent type and the sole practitioner, the least.

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CHAPTER 2: LEGISLATION AND GUIDELINES

The practice of assisted reproductive technology (ART) is usually regulated by legislation promulgated in each country. Guidelines of professional societies, licensing bodies, and agency oversight also influence current ART practice. Of the 75 countries that responded to the questionnaire submitted in 2015, 70 provided sufficient information to be included in this analysis on legislation and guidelines.

In the previous 2013 International Federation of Fertility Societies (IFFS) Surveillance report, more than 90% of the country representatives reporting had legislation and/or guidelines regulating ART treatment. Legislation and guidelines are continually evolving and, for the most part, have established restrictions on various applications of the practice of ART. While some of these developments are intended to enhance the safety, access, and transparency of ART, other developments have limited or curtailed practices and techniques that are widely accepted and practiced in other countries. While the overall trend appears to be one of increasing uniformity and access, the local practices of ART vary significantly among regions and cultures and are ultimately determined by the local stakeholders. These stakeholders include patient advocacy groups, local healthcare providers, professional organizations, local and national government agencies, insurance and other organizations responsible for payment, legislative bodies, and religious organizations. As the practice of ART has become more pervasive within private and public health care services and a greater number of patients have been impacted, subsequent public awareness, scrutiny, and interest have been magnified.

Advances in the genetic assessment of embryos, trends in cross border reproductive care, ethical debates regarding the appropriateness of preserving anonymity for gamete donation, and proscriptions on gestational carriers are examples of topics that have received extensive attention over the past three years. Thus, many of these issues and related aspects of ART have been recently addressed in legislation and guidelines.

Surveillance 2016 offers a more detailed look at recently implemented legislation and guidelines compared to past efforts. The 2016 survey also highlights specific topics that received unique legislative attention. This more detailed questionnaire attempted to engage international respondents uniquely suited to provide the most reliable information. Specific queries to address the process for institution and monitoring of licenses for ART centres, affiliated labs, clinicians, lab directors, and staff were included in the 2016 questionnaire and provide a unique comparison of systems of governance among different countries (Table 1).

Chapter 2 Table 1 How is ART Regulated In Your Country?

Chapter 2 Table 1 How is ART Regulated In Your Country?

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Analysis of the Survey

Data was received from 93 respondents in 75 countries in this 2016 IFFS Surveillance Report survey. In this chapter, data deemed adequate for analysis was received from 70 countries. Of the 70 counties whose reports were deemed adequate for analysis, 40 (57.1%) had legislation promulgated in their country to regulate ART. Of these 40 countries, 41% had additional ART society guidelines in their country and 15.7% had legislation alone to regulate practice.

Out of all 70 countries, 24.3% of respondents had only national society guidelines without any formal legislation. In 18.6% of these countries, there were no regulatory structures in the form of legislation or guidelines (Table 1).

When queried regarding updates in legislation since the 2012 survey, 35% of the countries had new legislation and 48.5% had no updates. The remainder of respondents were unsure whether updates had occurred. Table 2 and Chart 1 list and illustrate the various aspects of ART addressed by legislation in the past three years in rank order, illustrating the most prevalent topics in new legislation.

Chapter 2 Table 2 Main Modification to Legislation in Last 3 Years

Chapter 2 Table 2 Main Modification to Legislation in Last 3 Years

Chart 1

Chart 1

In the countries in which updated legislation had occurred, the respondents noted that access to ART had not been restricted nor applications limited in 60% of countries. In 28% of countries, new legislation was perceived as having negatively affected access, and 12% replied that there had been a variable effect.

The relationship of media attention to allegations of violations of ART regulations was also assessed. In 23% of countries, respondents were aware of reports of violations, 57% responded that there had been no publicity related to ART violations, and in the remainder of countries it was unknown.

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The ART Centre Itself

The licensing criteria, monitoring of governance, and identification of the credentialing bodies pertaining to ART centres was assessed separately:

The Survey noted that 70% of countries had licensing criteria for ART centres as a whole unit. Of these, 73% relied on an examination or certification procedure, 57% utilized on-site inspection, and 63% used a period report. Some countries employed combined strategies.

Monitoring of ART centres was performed in 64% of countries. The principal mechanisms employed in the countries that had systems in place for monitoring included: on-site inspection (87%); a national registry, (73%); and a periodic report (64%). Twenty-two percent of the countries with monitoring also submitted their data to an international registry.

Government employees were responsible for monitoring ART centres in 58% of countries; independent agencies and medical officers were equally responsible for monitoring in 40% of countries. Two percent of countries utilized monitoring with unofficial agencies.

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Reproductive Medicine Physicians

In 50% of countries, licensing or credentialing criteria exist for reproductive medicine specialist physicians or endocrinologists who have undergone special training in ART medicine. This was accomplished in over 90% of countries by certification examination.

Thirty-seven percent of countries perform ongoing monitoring of reproductive medicine physicians.

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OB/GYN Practicing ART

In 41% of countries, there were licensing criteria for obstetrician gynecologist physicians practicing ART, accomplished by examination or certification in 91% of cases. It was not clear how many of these countries had separate sub-specialization fellowship programmes for reproductive medicine specialists, and overlap likely exists between the categories of obstetrician gynecologist with and without further fellowship qualifications.

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The ART Laboratory

In 59% of countries, there were licensing requirements specific to the ART laboratory rather than the whole centre. The majority of countries relied on a certification system in 89% of cases. An onsite inspection system was performed in 61% of countries, and a periodic report was performed in 44% of countries’ laboratories.

Fifty-one percent of countries had ongoing monitoring criteria for the ART labs, and the majority (61%) used onsite inspection for this process. Government employees performed the monitoring in 43% of countries, medical officials in 18%, independent agencies in 14%, and unofficial agencies in 2% of countries.

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Lab Director and Lab Staff

In 51% of countries, there were licensing criteria for the lab director and 36% had licensing criteria for the lab staff. In more than 80% of cases this was accomplished by examination and certification.

Ongoing monitoring was performed in 30% of countries for the lab director and 19% for lab staff, using similar mechanisms to the original licensing criteria.

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Monitoring of ART Outcomes

The respondents were queried regarding mechanisms for monitoring ART outcomes. In 34% of countries a national registry was used. Fourteen percent reported that they presented data to an international registry and 31% had periodic reports submitted from ART units on their ART outcomes. Verification was accomplished by on-site inspections in 16% of countries. This was performed in 34% of countries by government employees, 18% by medical officials, 12% by independent agencies, and 3% by unofficial agencies.

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Penalties for Violation of Governance, Licensure or Credentialing

In 57% of 70 countries responding, penalties were in place for violations of governance, licensure, or credentialing. In 27% of countries responding there were no penalties in place, and it was unknown whether penalties existed in 16%.

A variety of penalties existed across the different countries. In 19%, a fine could be imposed, in 33% the IVF unit could lose its registration or be closed, criminal prosecution or imprisonment was possible in 23% of countries, and one country reported that publication of the details of an IVF unit’s infraction was a potential penalty.

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Discussion

In more than 80% of countries, ART was regulated by legislation, guidelines, or a combination of both. Over the last 3 years, legislation was updated in 35% of countries and the changes were perceived as positive in the majority of cases.

The perception of acceptable and best practice in reproductive medicine is continuing to evolve. New initiatives are underway in licensing and legislation, and professional societies’ guidelines often reflect these changes. The respondents viewed the changes implemented as a positive development, in that they did not restrict access or limit the application of ART in 60% of cases.

This survey accurately surveyed 70 countries, which was an improvement compared with the 2013 survey published where only 60 countries had complete data for analysis. In addition, there was more meaningful data obtained about the topics updated in recently introduced legislation. There was also an in-depth analysis of how the different facets of an ART centre are licensed and monitored over time.

The issues that received the most attention in legislation were insurance coverage for ART, limits on the numbers of embryos for transfer, role of marital status in determining access, cross-border reproduction, gamete donation, sex selection, preimplantation genetic testing (PGT), and same sex parenting policies.

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Summary

The chapter on Legislation and Guidelines in this Surveillance 2016 included complete data from 70 countries, which was more extensive than previous IFFS reports. The 2015 questionnaire was intended to elicit more specific data for each topic, and provide more detailed information about international ART practices. More than 80% of countries used legislation, guidelines, or a combination of both to regulate ART practice. New legislation had been introduced in 35% of countries since 2012, and 60% of these updates were perceived to be positive by the respondents. The focus of new legislation over the past three years included insurance coverage, access to ART services based on marital and relationship status, cross-border reproduction, performance of gamete donation, and limits on the number of embryos for transfer. More countries are adopting measures to promote safety, efficacy, and standardization, but a variety of mechanisms has been employed to accomplish this.

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CHAPTER 3: INSURANCE COVERAGE

Introduction

The provision of assisted reproductive technology (ART) therapy has seen a constant growth in recent years due to a better understanding of the causes of infertility and an increased opportunity to avail of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments in a larger number of countries worldwide. In a recent publication, the International Committee Monitoring Assisted Reproductive Technologies (ICMART) world report detailed results from years 2008, 2009, and 2010 and showed an annual increase to each preceding year of 9.0%, 6.4%, and 13.1%, respectively [1]. The reported ART utilization rates (number of initiated cycles per million population) varied widely from 4775 in Israel, 2337 in Australia/New Zealand, to the lowest rates in Latin America (152) and sub-Saharan Africa (87). Such variations are likely due to treatment availability and the possibility that access to care may be limited by lack of financial support for couples in need. The previous (2013) IFFS Surveillance report analyzed data from 60 countries and showed the number of countries providing cover for ART to be decreasing (60% in 2010 and 52% in 2013), possibly due to respondent profile variability [2]. The importance of this chapter lies in detailing the global ART insurance coverage and in particular, revealing the gap between service need and financial support from states and private insurers.

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Analysis of the Survey

The present survey is comprised of data from 70 countries with respondents providing data on this topic (a 17% increase compared to 2013). We acknowledge limitations in the completeness and quality of data associated with the issue of insurance coverage, as in previous reports. For example, only one question was answered by all respondents from 70 countries, and one had as few as 35 country respondents, making data difficult to compare with previous years in order to observe trends.

Only 37 countries (53%) reported providing coverage for infertility treatments. Among the 35 out of 67 countries (52%) where reimbursement was regulated (Table 1), 26 reported regulations on the national level. Furthermore, a large proportion of government funding was reported to be provided on the national level in 32/47 (68%) of responding countries with the remaining at local or regional level. However, the extent of number of cycles, and the limitations on public health support and access to ART care can vary greatly from country to country and in some cases, within regions or states of a country. The extent of insurance coverage for ART was measured as either complete or partial. Of the 52 respondents, 15 countries provide national complete coverage (29%) though a national health plan, whereas nine countries offer state/ provincial/ regional complete coverage (17.3%). Six countries (11.6%) reported full coverage by private insurance. A partial national health plan coverage is offered in 22 countries (42%); partial state/ provincial/ regional in seven countries (13%), and partial private insurance in eight countries (15%).

Chapter 3 Table 1 Are There Regulations that Address Reimbursement of ART Procedures in Your Country?

Chapter 3 Table 1 Are There Regulations that Address Reimbursement of ART Procedures in Your Country?

Twenty-four countries (36%) of 66 respondents provide no ART insurance coverage compared to 40% reported in a different cohort of countries represented in the 2013 report. Large countries from the Western Pacific and Southeast Asian regions (India, China, the Philippines, Hong Kong [China {Reporting separately for this report.{]) and some from Central and Latin American region (Mexico, Columbia, Venezuela) are not financially supporting any ART activity (Chart 1). Of the 46 countries that reported providing some level of government funding, 34 have a national plan (74%), nine (19%) have regional plans, and 4 (7%) have local plans. With regard to changes from the previous 2013 report, of those 56 countries with respondents, 32 (57%) reported no insurance modifications, five recorded a reduction in access to coverage or reimbursement, and 16 an increase in coverage. Specifically, for example, Slovakia reported initiation of cross-border reproductive care coverage for ART, and Japan reported the introduction of an age limit for insurance coverage of less than 43 years for women.

Chart 1

Chart 1

Specific limitations in funding of ART were reported for 62 countries. Half of these countries (31/62) reported offering funding based on fertility status (Table 2 and Chart 2), however in 20 (32%) countries, both primary and secondary infertility were reported to be covered by insurance. Similarly, 18% reported to have ART reimbursement tied to a policy of elective single embryo transfer (eSET), while only five of 37 countries reported basing their funding upon duration of infertility (Table 3 and Chart 3) (Turkey, Finland, UK, USA: three years; Romania: two years). The age profile of patients covered by ART health plans varies widely, with 31 out of 39 countries imposing an age limit (range of 39 to 50 y old for the woman). For example, Italy and Greece reported 50 as the upper limit, while 24 countries reported limits between 40-45 years of age for the woman.

Chapter 3 Table 2 Is Insurance Coverage or Government Funding Based on Fertility Status?

Chapter 3 Table 2 Is Insurance Coverage or Government Funding Based on Fertility Status?

Chart 2

Chart 2

Chapter 3 Table 3 What is Coverage Based On?

Chapter 3 Table 3 What is Coverage Based On?

Chart 3

Chart 3

Interestingly, only three countries (Chile, Japan, and Switzerland) out of 35 reported that their ART reimbursement is tied to income. Of the 37 countries that had respondents who answered this question, 29 have a limit on the number of cycles covered by insurance. For example, respondents from Australia, Russia, Israel, Estonia, Greece, Panama, and Switzerland reported that their countries do not limit the number of cycles reimbursed. Romania, Canada and Chile reimburse one cycle only, while Belgium, Japan, Singapore, and the USA (USA is individual state specific) reported that they offer up to six reimbursed treatments.

Details of fertility treatments that are covered by insurance (as reported by country respondents) are present in Tables 4–6 and Charts 4–7. Interestingly, coverage for pre-implantation genetic testing (PGT) for diseases (previously defined as PGD) is exclusively present in Israel and European countries, while in four European countries (Spain, Portugal, Finland, and Czech Republic) PGT for screening (previously defined as PGS) is also covered. It is noteworthy that no country representative reported reimbursements for either oocyte or ovarian tissue cryopreservation for non-medical reasons.

Chapter 3 Table 4 Does Insurance Coverage or Government Funding Typically Cover the Following ART Services?

Chapter 3 Table 4 Does Insurance Coverage or Government Funding Typically Cover the Following ART Services?

Chapter 3 Table 5 Does Insurance Coverage or Government Funding Typically Cover the Following ART Third Party Reproduction Services?

Chapter 3 Table 5 Does Insurance Coverage or Government Funding Typically Cover the Following ART Third Party Reproduction Services?

Chapter 3 Table 6 Does Insurance Coverage or Government Funding Typically Cover the Following ART Cryopreservation Services?

Chapter 3 Table 6 Does Insurance Coverage or Government Funding Typically Cover the Following ART Cryopreservation Services?

Chart 4

Chart 4

Chart 5

Chart 5

Chart 6

Chart 6

Chart 7

Chart 7

Chart 8

Chart 8

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Discussion

The percentage of countries whose respondents reported providing ART coverage has modestly increased since the last report and now stands at 64% of reporting countries. In 29% of countries, the reimbursement coverage has increased from the previous report, offering reassurance that policy makers realize the societal importance of supporting fertility therapy. Respondents from some countries with large populations (e.g., India, China) report not providing funding for ART treatments. Considering the significant shift toward eSET worldwide, it is noteworthy that only 18% of countries tie their ART reimbursement programmes to an eSET policy. eSET in ART has the potential for significant cost-effectiveness when considering the care for multiple newborns born through ART who often present with medical complications and prematurity. The cost savings for an eSET policy linked to national ART reimbursement policies perhaps requires greater research and assessment at the country level. Similarly, PGT for disease detection, a procedure with clear medical indications, is covered only in Israel and a few European countries. Cross-border reproductive care is a world phenomenon and the Slovakian initiative to reimburse cross-border ART therapy is unique; however, no details on the eligibility criteria were provided.

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Summary

Insurance coverage for ART remains an area of great disparity as reported among the world’s countries. This report notes a modest increase in coverage, with 74% of countries providing a reported coverage at various levels through a national, regional/provincial, or state plan. Eligibility criteria for funding and expanded equity of access are areas that require greater exploration.

References

[1] Dyer S, Chambers GM, De Mouzon J, et al. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010. Hum Reprod 2016;31(7):1588-1609.

[2] Ory SJ (Ed.). IFFS Surveillance 2013. Available at: https://c.ymcdn.com/sites/iffs.site-ym.com/resource/resmgr/iffs_surveillance_09-19-13.pdf. Accessed August 9, 2016.

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CHAPTER 4: MARITAL STATUS

Introduction

A stable, legal heterosexual relationship (marriage) is reported to be a requirement for assisted reproductive technology (ART) services in most countries offering treatment. The concept of marriage has been expanded to include couples or individuals in a stable same sex relationship. This current survey also addresses provisions for care for single individuals and patients in same sex relationships, including their acceptance as legal parents, and the type of treatments offered to them.

In Surveillance 2013, only marital status and relevant laws pertaining to access to ART were addressed. In this survey, access to ART based on relationship status was explored in the following categories:

  • Which countries require a stable relationship as a basis for ART treatment;
  • Whether laws or guidelines exist to regulate this;
  • What type of treatment may be offered to patients who are not a part of this category; and,
  • If a same sex partner has legal rights to parenthood.
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Analysis of the Survey

Of 68 countries that had respondents who provided responses to this topic, 31 countries reported that a patient is required to be in a recognized or stable heterosexual relationship to avail of ART treatment (Table 1 and Chart 1). Of these, 17 countries reported federal laws or statutes governing these regulatory processes. Ten countries, including several Southeast Asian countries, have professional organizations or guidelines that address access to care based on relationship status. In six countries, primarily in Islamic nations, the requirement for a stable relationship was reported by the respondents to be chiefly based upon the religious and cultural preferences of that country, although no official laws may exist.

Chapter 4 Table 1 To Access IVF or ART Services, are a Couple or an Individual Required to be in a Recognized or Stable Heterosexual Relationship?

Chapter 4 Table 1 To Access IVF or ART Services, are a Couple or an Individual Required to be in a Recognized or Stable Heterosexual Relationship?

Chart 1

Chart 1

In the 2015 survey, this topic was further explored in three additional categories. Those countries that did not cite existence of a stable relationship as a requirement were surveyed to find out whether access to treatment was available to the following groups: single women, single men, males in same sex relationships, females in same sex relationships, transgender individuals, and intersex individuals (Table 2).

Chapter 4 Table 2 If there is No Requirement for an Official or Stable Heterosexual Union, is IVF or ART Services Accessible to?

Chapter 4 Table 2 If there is No Requirement for an Official or Stable Heterosexual Union, is IVF or ART Services Accessible to?

Of the 36 countries included in this category, all respondents (with the exception of Columbia) reported that their countries offer treatment to single women. Sixteen of these countries reportedly offered ART services to single males. Twenty-eight countries offered treatment to same sex female couples, whereas only 13 allowed treatment for same sex male couples. In addition, 14 of these countries had respondents who reported that their country allows treatment of transgender and intersex individuals. Based upon respondent responses, those countries with the greatest access for all infertile populations (e.g., those that allow treatment to all patients, regardless of their relationship status) included Australia, Belgium, Brazil, Canada, Mexico, Paraguay, Peru, South Africa, UK, and USA (individual state specific).

The next query determined whether a country has laws that recognize the same-sex partner of a person who has used ART as a legal parent of the resulting child (Table 3 and Chart 2). A total of 70 countries had respondents who answered this question. Eighteen of these countries were reported to regard the same sex partner of a woman as a legal parent, and 11 of these countries were reported to also regard a man with a male partner as a legal parent.

Chapter 4 Table 3 Does Your Country have Laws that Recognize the Same-sex Partner of a Person who has used Assisted Reproduction as a Legal Parent of the Resulting Child?

Chapter 4 Table 3 Does Your Country have Laws that Recognize the Same-sex Partner of a Person who has used Assisted Reproduction as a Legal Parent of the Resulting Child?

Chart 2

Chart 2

A slight discrepancy in the responses from surveyed countries showed that Argentina and Denmark recognized a man with a male partner as a legal parent. However, respondents from these two countries did not report that same sex male couples were allowed to undergo ART treatment. Similarly, Israel is reported to recognize a woman’s same sex partner as a legal parent, but also was reported to not allow treatment for same sex female couples.

This year’s survey also included a new section, which listed the types of treatments available to unmarried couples. Respondents from 60 countries answered this section, and reported that basic infertility evaluations were available for single women. Of these 60 countries, 13 were reported to permit the use of traditional gestational carriers and 15 countries were reported to allow embryo donation with gestational carriers for single women desiring pregnancies. Forty of the 54 responding country respondents reported that diagnostic evaluation of single men was permitted but only 14 of these countries were reported to permit advanced treatments, including in vitro fertilization (IVF). Respondents from 30 countries reported to offer treatment to male same sex partners, female same sex partners, and transgender couples.

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Summary

Most countries reportedly offered infertility treatment to women regardless of their relationship status. Laws and guidelines in some countries often limit access to services to specific population groups or to specific treatments such as IVF, pre-implantation genetic testing (PGT) for disease, and the use of gestational carriers.

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CHAPTER 5: NUMBER OF EMBRYOS FOR TRANSFER IN ART

Introduction

The World’s first in vitro fertilization (IVF) baby, born in 1978, resulted from the recovery of a single oocyte from a “natural cycle” followed by fertilization with sperm in a culture dish, and transfer of the resulting single embryo to the uterus of the woman. However, shortly thereafter, it became apparent that IVF production and subsequent transfer of multiple embryos was associated with a greater success rate, and that controlled ovarian hyperstimulation or multiple follicular stimulation was performed in order to produce more oocytes and respectively more embryos. It became common practice to transfer three, four, or more embryos to achieve a better chance of a pregnancy. However, it soon became apparent that large numbers of twins and higher order multiple (HOMs; triplets and greater) births resulted in an unacceptably high fetal and maternal complication rate. Multiple pregnancies remain the single greatest risk of assisted reproductive technology (ART) despite great concern and efforts to reduce this risk over the past two decades.

The incidence of twin and HOM births quadrupled after 1980 – the beginning of the ART era – and peaked in many countries in the 1990s. Many countries addressed this alarming public health problem with a variety of initiatives intended to reduce the number of embryos transferred [2]. A dramatic reduction in multiple pregnancies, particularly HOMs, followed in most countries but considerable variation continues to exist in the strategies employed and their efficacy in reducing multiple rates. Limitations on the number of embryos permitted for transfer has had a profound effect on multiple rates; however, the continued practice of controlled ovarian hyperstimulation (COH) that results in high numbers of oocyte maturation (with or without intra-uterine insemination [IUI; procedure within which the number of embryos generated cannot be controlled]) remains an important contributor to multiple pregnancies, especially HOMs.

The risk of fetal, neonatal, and infant death is considerably increased for twins, triplets, and quadruplets. For example, the perinatal mortality and infant mortality rates for singleton versus multiple births in England and Wales for the year 2013 [1] were as follows: - Neonatal deaths: 2.4 versus 13.8 per 1000 live births; Infant deaths: 3.6 versus 17.7 per 1000 live births, and post-neonatal deaths: 1.1 versus 3.9 per 1000 live births. For quadruplets, the mortality rate was 40 to 50% higher than for triplets. This increase in perinatal mortality is primarily due to premature delivery, but also to utero-placental compromise and an increased rate of congenital anomalies amongst these infants. Maternal complications of triplet and HOM births include pregnancy-induced hypertension, ante-partum and post-partum haemorrhage, and severe anemia.

An intensive effort to inform patients of the extensive and severe risks of multiple pregnancies has served to inform the debate and promote broader patient acceptance of more restrictive embryo transfer policies. However, some patients are still insistent on the transfer of an inappropriate number of embryos for a variety of reasons and some clinicians advocate and practice transfer of an excessive number of embryos. The methods by which this problem is addressed (or not addressed) vary enormously among countries and remains one of the most contentious issues in ART.

During the past 10 years in Europe, especially within the last five years, a variety of measures have been employed to greatly limit the number of embryos that can be transferred. Most recently, studies from Sweden, Denmark, the Netherlands, and Belgium have shown that single embryo transfer (SET), especially when combined with frozen/thawed embryo transfer (FET) in a subsequent cycle, achieves pregnancy and live birth rates equivalent to the transfer of two and even three or more embryos, without the complications of twin and HOM pregnancies and births. Several countries now have firm guidelines or regulations allowing only SET for certain categories of patients. The United Kingdom regulatory body has put in place measures to ensure that national and clinic specific multiple pregnancy rates must be maintained at below 10% of all IVF births. Thus, increasingly, practitioners are advocating the transfer of a single embryo.

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Some Recommended Indications for SET

The American Society of Reproductive Medicine (ASRM) in their recent Practice Committee Report on SET [3,4] recommended the following as guidelines for considering SET:

  • Female age <35
  • More than one “top quality embryo” available for transfer
  • First or second treatment cycle
  • Previous successful IVF cycle
  • Recipient of embryos created from donor oocytes.

Some European countries are recommending a tighter criterion for SET, setting the age for SET at <37 or 38. The British Fertility Society (BFS) in 2015 recommended that at least 50% of embryo transfers should be SET and never more than two embryos [5]. The effect of this policy would be to bring the multiple pregnancy rate down to <10%. They recommend that practitioners consider the following factors:

  • Female partner’s age
  • Previous pregnancies
  • Cause of infertility
  • Number of previous IVF failures
  • Response to follicular stimulation
  • Number of oocytes
  • Number of good quality embryos
  • Number cultured to blastocyst.
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Analysis of the Survey

Three separate questions were included in the 2015 survey to assess current practices regarding this issue.

In response to the question: “Are the number of embryos transferred regulated in your country; if so, by what means”, 41 (59%) confirmed the existence of guidelines or laws governing the number of embryos permitted for transfer, while 24 did not, and five gave no or non-valid replies (Table 1 and Chart 1). Of the 41 countries having regulations/guidelines, 14 were reported to be enforced by federal or national laws, and 27 by guidelines or professional organizations.

Chapter 5 Table 1 Are the Number of Embryos Transferred Regulated in Your Country by?

Chapter 5 Table 1 Are the Number of Embryos Transferred Regulated in Your Country by?

Chart 1

Chart 1

To the query: “If the number of embryos transferred is under governance in your country, is there a penalty for violation? (Table 2). If “yes”, what is the violation and is it variable”; 17 countries (24%) had responses that affirmed that there was indeed a penalty, 36 (51%) noted that no penalty exists, and 17 (24%) of the country respondents did not answer the question. Nine of the 17 that reported penalties responded with details of the penalty for violation. These penalties included (1) revocation of the ART license in four countries; (2) up to six months in jail or a 50,000 Euro fine; (3) a warning letter to the physician in charge; (4) 10 years in jail for the director; (5) a fine of 1000-10,000 Euros if >3 embryos are transferred; and (6) a requirement that the centre to pay all the expenses of the pregnancy, delivery, and neonatal care of multiple pregnancies.

Chapter 5 Table 2 If the Number of Embryos Transferred is Under Governance in Your Country, is there a Penalty for Violation?

Chapter 5 Table 2 If the Number of Embryos Transferred is Under Governance in Your Country, is there a Penalty for Violation?

In response to the question: “What is the maximum number of embryos allowed to be transferred” (Table 3), the 23 countries that had respondents who provided complete answers noted:

Chapter 5 Table 3 Maximum Number of Embryos Allowed to be Transferred?

Chapter 5 Table 3 Maximum Number of Embryos Allowed to be Transferred?

  • Oocyte age <35: 1 country=1 embryo only, 8 countries=2 embryos, 8 countries=3 embryos, 2 countries=4 embryos, and 4 countries with no response.
  • Oocyte age 35-39: No countries limited to 1 embryo, 7 countries=2 embryos, 9 countries=3 embryos, 2 countries=4 embryos, and 5 countries with no response.
  • Oocytes age ≥40: No countries limited to 1 embryo, 3 countries=2 embryos, 11 countries=3 embryos, 4 countries=4 embryos, and 5 countries with no response.

Of note is that only one country (USA, individual state specific) established new guidelines to reduce the recommended number of embryos for transfer from 2 to 1 for women <35 years of age, based on blastocyst stage.

In response to the question about criteria for the number of embryos to be transferred (Table 4), 26 countries had respondents who provided responses regarding the age of the donor oocyte recipient: 11 countries answered “yes”, 5 answered “no”, and 10 answered “not addressed”. When considering the age of the donor: 7 countries answered “yes”. 8 “no”. and 11 answered “not addressed”. Regarding the quality of the embryos as a determinant: 11 countries answered “yes”, 8 “no”, and 7 answered “not addressed”. Regarding the stage of the embryo (cleavage or blastocyst stage): 7 countries answered “yes”, 10 “no”, and 9 “not addressed”. The tables below list the individual policies of the countries’ respondent responses regarding the number of embryos allowed for transfer, which also in some cases included qualifying or detailed comments provided by some respondents.

Chapter 5 Table 4 Is the Number of Embryos to be Transferred Based on?

Chapter 5 Table 4 Is the Number of Embryos to be Transferred Based on?

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Discussion

There is clear evidence that a major effort has been made in most countries to reduce the number of embryos transferred in an IVF cycle, but there is still room for considerable improvement. There are clinics in a few countries that reportedly continue to condone the transfer of an excessive number of embryos. However, the data presented in Surveillance 2016 do show an overall reduction in the number of embryos transferred and a significant trend to increasing the proportion of single embryo transfers.

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Summary

The evidence from this 2016 International Federation of Fertility Societies (IFFS) Survey supports the notion that there has been an increase in the proportion of countries with legislation or clinical guidelines restricting the number of embryos permissible for transfer to women undergoing IVF/ART cycles (59% vs. 38% in 2013). Respondents reported a variety of sanctions that have been imposed by the 17 countries that noted that penalties exist for non-compliance, ranging from revocation of a clinic's license to practice ART, to substantial fines, to prison terms for responsible individuals.

Progress in the actual reduction of the number of embryos transferred has been more gradual but improvements in culture systems, embryo selection methods, and cryopreservation technology have led to improved embryo implantation rates and live birth rates. As these advances become evidence-based and are more consistently applied, further reductions in multiple embryo transfers and multiple pregnancy rates should become evident.

References

[1] Office for National Statistics. Statistical bulletin: Childhood, Infant and Perinatal Mortality in England and Wales: 2013; March 2015.

[2] Maheshwari A, Griffiths S, Bhattacharya S Global variations in the uptake of single embryo transfer. Hum Reprod Update 2011;17(1):107–120.

[3] Practice Committee of the Society for Assisted Reproductive Technology, Practice Committee of the American Society for Reproductive Medicine. Elective single-embryo transfer. Fertil Steril 2012;97:835–842.

[4] Practice Committee of the American Society for Reproductive Medicine, Practice Committee of the Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: A Committee Opinion. Fertil Steril 2013;99:44-46.

[5] Harbottle S, Hughes C, Cutting R, et al; Association Of Clinical Embryologists (ACE) & The British Fertility Society (BFS). Elective single embryo transfer: an update to UK Best Practice Guidelines. Hum Fertil 2015;18(3):165-183.

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CHAPTER 6: CRYOPRESERVATION

There has been considerable interest in the field of cryopreservation of human tissue for over 200 years. Recent advances in freezing reproductive tissues have potentiated several new clinical applications. Initial development of slow freezing techniques and subsequent vitrification technology coupled with newer cryoprotectants in various combinations have advanced the field considerably. Sperm, oocytes, and embryos can now be frozen at various stages of development, allowing for safer and more efficacious assisted reproductive technology (ART) treatments as well as allowing for the cryopreservation of gametes and embryos for fertility preservation [1].

Human ART today, routinely in a majority of in vitro fertilization (IVF) laboratories, utilizes both sperm and embryo cryopreservation. Sperm banking is indicated for cancer patients facing gonadotoxic therapy. Preservation of testicular tissue obtained from prepubertal boys undergoing gonadotoxic treatment and those with cryptorchidism has been performed but is still experimental. Techniques to induce in vitro spermatogenesis are being developed with the aim of preserving fertility in patients affected by diseases such as Klinefelter Syndrome and Sertoli cell only syndrome [2]. Embryo cryopreservation offers the opportunity to avoid repeated ovarian stimulation, optimizes achieving embryo-endometrial synchrony, and facilitates performing single embryo transfer (SET). The improved results of embryo cryopreservation have been an essential component for preimplantation genetic testing, especially when trophectoderm biopsy is performed [3] Oocyte cryopreservation for fertility preservation is now being widely used in the majority of clinical ART centres. It is indicated for fertility preservation in patients of reproductive age facing treatment of malignancies or chronic illnesses in which the underlying disease or its treatment would likely result in loss of fertility potential. It is also commonly performed for donor oocyte banking and elective postponement of childbirth. Cited advantages are that it eliminates certain ethical, moral, and in some jurisdictions, legal obstacles to embryo freezing. The limited available studies suggest that the technique of vitrification of oocytes has higher pregnancy rates as compared to slow-freezing [4]. The advent of donor egg cryobanks with cryopreserved oocytes allows larger supplies of potential donor oocytes to be produced and avoids the need for cycle synchronization with the recipient [5]. Oocyte cryopreservation also allows for the quarantining of human immunodeficiency virus (HIV) affected oocytes [6,7]. A more controversial but increasingly prevalent application involves offering oocyte vitrification to healthy women with good reproductive potential with the intent of extending their reproductive lifespan [8].

Potential concerns regarding the effects of cryopreservation on the embryo genome have been addressed in various studies. The limited numbers of long-term follow-up human studies provide reassurance but they are mostly derived from retrospective studies with some methodological weaknesses [9].

Ovarian tissue cryopreservation is still considered an experimental procedure. It is indicated for patients who require immediate gonadotoxic treatment without the opportunity for oocyte or embryo freezing and is the only option available for prepubertal girls. Vitrification of ovarian tissue was found to be similar to slow freezing, and both preserved the morphologic integrity of the ovarian tissue [10]. Orthotopic transplantation of the cortical strips from the tissue has been successful, and live births have been reported. However, it could not be ascertained whether ovulation from a remaining, untreated ovary produced the pregnancy [11].In vitro activated ovarian tissue cryopreservation and transplantation is a new method requiring more clinical research. This procedure involves stimulation of dormant follicles within the cryopreserved tissue graft prior to transplantation, in order to generate mature oocytes shortly after transplantation [12].

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Analysis of Survey ( Tables 1 and 2)

Of the 68 respondents that provided information on this topic, the results show that 27 countries are regulated by cryopreservation laws or statutes; 15 have only guidelines and nine have both statutes and guidelines to follow. However, 17 of these countries were reported to have no regulations or guidelines, follow individual practice policies, or are guided by cultural or religious decrees.

Chapter 6 Table 1 How is Cryopreservation Governed?

Chapter 6 Table 1 How is Cryopreservation Governed?

Chapter 6 Table 2 The Duration of Storage of Cryopreserved Fertilized Eggs, and Country Specific Comments

Chapter 6 Table 2 The Duration of Storage of Cryopreserved Fertilized Eggs, and Country Specific Comments

Cryopreservation of fertilized oocytes and embryos was permitted at all stages through blastocyst development in all the participating countries except Italy, which permits oocyte cryopreservation but not embryo freezing. Prior to 2008, the law in Italy banned embryo freezing and permitted that a maximum of three oocytes per cycle be inseminated. Transfer of all embryos produced was required, prohibiting surplus embryo production and freezing. In May 2009, the Constitutional Court declared this law to be unconstitutional, removing most of its limitations. The changes allowed embryo selection and cryopreservation in specific cases [13]. Venezuela now permits embryo cryopreservation, which was not allowed at the time of publication of Surveillance 2013; cryopreservation of oocytes, ovarian, testicular tissue has been and remains acceptable. In the Netherlands, though permitted, fertilized egg freezing is not practiced, yet oocyte cryopreservation is commonly used. In Ireland, the issue of personhood with regard to the embryo has raised ethical questions and led to the passage of legislation restricting the creation of excess embryos with the intent of avoiding cryopreservation and the need to discard unused embryos. However, after the Supreme Court of Ireland judgment of 2009 stated that embryos in storage are not guaranteed a right to life, the Irish Medical Council altered its guidelines to no longer specifically require that embryos “must be used for normal implantation and must not be deliberately destroyed” [14].

The permissible duration for embryo cryopreservation varies between countries. There is no limit reported for the duration of storage in most of the countries. There is however a reported limit of five years in Belgium, China, Denmark, Norway, Romania, South Korea, Sweden, Switzerland, Turkey, Australia, Greece, Barbados, Mali, and Chile. An extension of five years is permitted in Belgium and in South Korea as well. The limit on embryo cryopreservation is seven years in Estonia and 10 years in Austria, Hungary, Singapore, South Africa, Taiwan [China (Reporting separately for this report.)], UK, Ecuador and Hong Kong [China (Reporting separately for this report.)]. In the UK, the cryopreserved embryos should be transferred before the age 50 of the female partner, and until such time embryo storage can be extended beyond 10 years. The issue of time limit for cryopreservation of gametes and embryos has not been specifically addressed in the Czech Republic, Uruguay, Cameroon, India, Jordan, Germany, Mexico, Paraguay, or Sri Lanka. Survey participants from Ireland, the Philippines, Portugal, and Kenya did not provide an answer to the question, and the answer is unknown to those from France, Slovak Republic, Netherlands, and Malaysia. In Japan, embryos can remain cryopreserved for as long as the couple is married and the female partner is within reproductive age. Spain permits embryo storage until the age of 59 years for the female partner. The American Society for Reproductive Medicine (ASRM) guidelines in the USA recommend storage for an unlimited time, but unclaimed embryos should be discarded after five years of unsuccessful attempts to contact the individual or couple and if there are no written instructions from the couple concerning disposal [15].

All countries with respondents, except Uruguay, permit oocyte cryopreservation. Senegal and Bangladesh have no developed programmes and oocyte cryopreservation has never been performed. Oocyte preservation is reported to be permitted for medical indications such as cases of ovarian hyperstimulation syndrome, failure to obtain a sperm sample, and for fertility preservation for cancer patients only, and specifically not for non-medical (social) indications in Austria, Denmark, France, Hungary, Norway, Singapore, Turkey, Cameroon, Jordan, and Saudi Arabia.

Ovarian and testicular tissue preservation is reported to not be permitted in Bulgaria, Taiwan [China (Reporting separately for this report.)], Nigeria, El Salvador, and Bangladesh. In the countries where it is reported to be permitted, fertility preservation in anticipation of cancer treatment is the main indication for its practice. A few countries including Uruguay, Cameroon, Ecuador, and Barbados report acceptance of testicular tissue cryopreservation, but not for ovarian tissue.

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Summary

Cryopreservation of human gametes and embryos has found broad application in the practice of assisted reproduction and has contributed to its overall safety and efficacy. A successful cryopreservation programme for both gametes and embryos is an important component for any ART programme. It can promote optimal success rates, reduce the risk of multiple pregnancy, and effectively address unique patient needs, such as those that require genetic testing or screening, cancer treatment, and special measures to reduce risk of the IVF process (e.g., those at risk for ovarian hyperstimulation). The responses in the current questionnaire indicate broader acceptance of cryopreservation technologies but considerable variation around the world in their regulation and implementation reflecting individual cultural concerns. In addition, various service providers have self-imposed ethnic, societal, or religion based policies guiding these practices. The long-term follow-up of the children born following an IVF cycle from frozen embryos has been reassuring thus far, but there is limited long-term data regarding children who are born following a cycle from frozen oocytes. It is recommended that circumstances governing the duration of storage and disposal of frozen gametes and embryos be addressed in writing prior to the start of a treatment cycle of such use.

References

[1] Griveau JF, Lopes M, Jouve G, et al. Vitrification: principles and results. J Gynecol Obstet Biol Reprod (Paris) 2015;44(6):485-495. French.

[2] Goossens E, Tournaye H. Male fertility preservation, where are we in 2014? Ann Endocrinol (Paris) 2014;75(2):115-117.

[3] Konc J, Kanyo K, Kriston R, et al. Cryopreservation of embryos and oocytes in human assisted reproduction. Biomed Res Int 2014:307268.

[4] Glujovsky D, Riestra B, Sueldo C, et al. Vitrification versus slow freezing for women undergoing oocyte cryopreservation. Cochrane Database Syst Rev 2014;9:CD010047.

[5] Cobo A, Remohi J, Chang CC, et al. Oocyte cryopreservation for donor egg banking. Reprod Biomed Online 2011;23(3):341-346.

[6] Vajta G, Rienzi L, Ubaldi FM Open versus closed systems for vitrification of human oocytes and embryos. Reprod Biomed Online 2015;30(4):325-333.

[7] Bielanski A A review of the risk of contamination of semen and embryos during cryopreservation and measures to limit cross-contamination during banking to prevent disease transmission in ET practices. Theriogenology 2012;77(3):467-482.

[8] Cobo A, Garcia-Velasco JA. Why all women should freeze their eggs. Curr Opin Obstet Gynecol 2016;28(3):206-210.

[9] Kopeika J, Thornhill A, Khalaf Y The effect of cryopreservation on the genome of gametes and embryos: principles of cryobiology and critical appraisal of the evidence. Hum Reprod Update 2015;21(2):209-227.

[10] Sanfilippo S, Canis M, Smitz J, et al. Vitrification of human ovarian tissue: a practical and relevant alternative to slow freezing. Reprod Biol Endocrinol 2015;13:67.

[11] Practice Committee of American Society for Reproductive Medicine. Ovarian tissue cryopreservation: a committee opinion. Fertil Steril 2014;101(5):1237-1243.

[12] Meirow D, Roness H, Kristensen SG, et al. Optimizing outcomes from ovarian tissue cryopreservation and transplantation; activation versus preservation. Hum Reprod 2015;30(11):2453-2456.

[13] Levi Setti PE, Albani E, Cesana A, et al. Italian Constitutional Court modifications of a restrictive assisted reproduction technology law significantly improve pregnancy rate. Hum Reprod 2011;26(2):376-381.

[14] Sills ES, Murphy SE. Determining the status of non-transferred embryos in Ireland: a conceptus of case law and implications for clinical IVF practice. Philos Ethics Humanit Med 2009;4:8.

[15] Ethics Committee of the American Society for Reproductive Medicine. Disposition of abandoned embryos: a committee opinion. Fertil Steril 2013;99(7):1848-1849.

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CHAPTER 7: POSTHUMOUS REPRODUCTION

The assessment of applications of posthumous reproduction was expanded in the 2015 questionnaire to support the Surveillance 2016 report. The 2013 report noted that 25% of countries allowed posthumous insemination, but did not specify the circumstances, including the permissibility of immediate postmortem extraction of gametes and specific limitations pertaining to recovery of sperm, ova, and embryos.

Posthumous reproduction can occur at two different stages. Firstly, it may include the immediate extraction of sperm, ova, or excision of reproductive tissue from a comatose person who is usually brain dead. Immediate testicular sperm extraction has also been performed on males following complete cessation of cardiac activity. Immediate extraction is often not addressed by existing legislation and is usually performed following an urgent court order. Recent updates in legislation are now targeting this controversial topic in many countries.

Posthumous reproduction can also occur through the utilization of products (gametes, reproductive tissue, or embryos) that had been cryopreserved before the individual died. New cryopreservation techniques (slow freezing or vitrification) allow stored sperm, ova, and embryos to be used many years after freezing, and thus with the potential to be used long after the demise of the person whose reproductive products had been stored. Increasingly, patients are freezing gametes or embryos for fertility preservation after they have been diagnosed with cancer and before they receive gonadotoxic therapy in the hope that they may preserve their reproductive potential to be used at a later date. This reproductive option usually arises at an inopportune time, when the patients are forced to confront several difficult issues simultaneously relating to their cancer treatment, including decisions regarding the disposition of their gametes, reproductive tissue, or embryos in the event of their death. Other complicated cases include occasions in which a person may die unexpectedly and their partner may wish to proceed with fertility treatment using their cryopreserved biological material with or without previously obtained express written permission. These cases may be further complicated when the decreased individual may have verbally expressed their wish to have children together, but not formally made an agreement or given written consent.

Actual utilization of cryopreserved gametes, reproductive tissue, or embryos after the death of a person depend on existing legislation, prior written legal agreements or consent documentation, and family input about the wishes of the decreased person. The onus often falls on the courts to determine whether the person may have truly wished to procreate after their death. Although the courts have generally tended to err on the side of caution and deny most of these requests, recent international media attention in some of these cases has led some governments to update legislation in this area.

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Analysis of Survey ( Tables 1–4)

There were respondents from 63 countries who had responded to the questionnaire that addressed questions about whether posthumous reproduction procedures were allowed in their countries. Frozen sperm insemination was reported to be permitted in 27% of countries, insemination of frozen ova from a decreased woman was reported to be allowed in 24% of countries, and in 30% of countries transfer of frozen embryos from a deceased person was reported to be allowed. Immediate posthumous procedures in brain dead or just deceased patients were reported to be allowed in 14% of countries.

Chapter 7 Table 1 Immediate Posthumous Collection of Sperm or Oocytes

Chapter 7 Table 1 Immediate Posthumous Collection of Sperm or Oocytes

Chapter 7 Table 2 Posthumous Sperm Insemination

Chapter 7 Table 2 Posthumous Sperm Insemination

Chapter 7 Table 3 Posthumous Insemination of Frozen Ova

Chapter 7 Table 3 Posthumous Insemination of Frozen Ova

Chapter 7 Table 4 Posthumous Transfer of Frozen Embryos

Chapter 7 Table 4 Posthumous Transfer of Frozen Embryos

Legislation to allow immediate posthumous reproduction was reported to be present in 34% of these countries, whereas 42% of countries reportedly allowed posthumous sperm insemination. Thirty-four percent of countries allowed insemination of frozen ova, 45% countries had legislation allowing posthumous transfer of frozen embryos.

Although legislation may exist in some countries allowing the procedures, the data from the respondents addressing actual application of these procedures indicate that they are performed infrequently. Respondents from 65 countries reported in response to whether posthumous reproduction procedures were actually performed in their countries. Frozen sperm insemination was done in 25% of countries, insemination of frozen ova from a decreased woman was done in 15% of countries, and in 25% of countries, transfer of frozen embryos from a deceased person was performed. Immediate posthumous procedures in brain dead or recently deceased patients was infrequently performed (11% of countries).

The use of immediate posthumous extraction of gametes was reported to be infrequent (11% of countries), and the usage of frozen ova was reported to be practiced in 15% of these countries. The non-immediate posthumous use of sperm for insemination was reportedly used more often in 25% of countries, and the transfer of frozen embryos was reported to be performed in 25% of these countries.

Where legislation existed about posthumous reproduction, the procedures were reported to be mostly covered by federal law (immediate posthumous 57%, insemination with frozen sperm 67%, insemination of frozen ova 67%, implantation of frozen embryos 70%). In less than 10% of countries, the legislation was addressed via state laws or agency oversight. In approximately 10% of countries the topic was covered by professional society guidelines, and in 10% of countries, respondents reported that religious decree affected practice.

Tables 1–4 show whether respondents stated that legislation exists, if procedures are allowed, or if procedures are actually done in their country, for the following categories: immediate posthumous reproduction, posthumous insemination with sperm, insemination of frozen ova, and posthumous embryo transfer respect. The most recent questionnaire provided respondents the opportunity to provide additional details regarding the practice of posthumous reproduction with specific information about unique applications, oversight, and actual prevalence of practices.

In more than a third of countries with respondents providing feedback, there was legislation in place to govern posthumous reproduction. These data show that there is a definite trend internationally to include this topic in national legislation, and most countries were reported to do so through federal legislation.

Fertility clinics and courts are often confronted with difficult decisions regarding disposition of cryopreserved gametes, reproductive tissue, and embryos following the death or demise of a donor when his or her clear preferences and instructions are not available. It is beneficial to have legislation in place to assist medical practitioners and legal practitioners with such decisions.

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Summary

Based upon this Surveillance report, posthumous reproduction is increasing on a global scale and being addressed by national-level legislation (usually by federal statute). Controversies in this area, as highlighted by the respondents, include the circumstances in which posthumous gametes, or reproductive tissue may be obtained and conditions in which gametes, reproductive tissue, and embryos may be utilized after death.

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CHAPTER 8: DONATION

Gamete and embryo donation are well-established assisted reproduction procedures that are increasingly used around the world. Egg donation is performed either with fresh oocytes, or, since the advent and clinical application of vitrification [1], with vitrified-warmed oocytes. The widespread use of egg vitrification has significantly altered the practice of assisted reproduction and more clinics are banking oocytes for future donation, as the clinical pregnancy results in egg donation cycles have been found to be similar between fresh and frozen eggs [2]. However, additional clinical evidence is needed to address the comparison of obstetric, neonatal, and long term child outcomes. Recently, both the American Society for Reproductive Medicine and European Society of Human Reproduction and Embryology (ESHRE) have described oocyte vitrification as a safe and efficient procedure [3,4], rendering it no longer an experimental procedure.

There are significant differences in the use and regulations applied to gamete donation between different countries, even in the same continent or in countries with similar cultural and religious background. This situation is clearly reflected in Europe, where periodic reporting to the European IVF (in vitro fertilization) Monitoring Consortium (EIM)/ ESHRE registry has shown the imbalance of IVF/ intracytoplasmic sperm injection (ICSI) to egg donation cycles in some countries [5]. Also, countries regulate differently the allowance of male and female gamete donation; consequently, there has been a surge of cross-border reproductive care for patients to access care to obtain specific sex gamete donation procedures in order to avoid restrictions in their home countries. This is raising new, challenging ethical questions [6].

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Analysis of Survey

Countries whose representatives have responded to the questions on donation for both the previous 2013 report and this current report, do report changes since the last publication. For example, in Italy, sperm donation for assisted reproductive technology (ART), previously banned, is currently allowed following a 2014 court ruling. Out of these countries, 13% completely ban all gamete and embryo donation, as reported to include the following: Bangladesh, El Salvador, Jordan, the Philippines, Saudi Arabia, Senegal, Tunisia, and Turkey. (Table 1) When gamete donation is reported to be allowed, most of those surveyed stated that the country allows both male and female gamete donations (Table 1 and Chart 1).

Chapter 8 Table 1 Is Third Party Reproduction Allowed/Permitted in Your Country?

Chapter 8 Table 1 Is Third Party Reproduction Allowed/Permitted in Your Country?

Chart 1

Chart 1

However, in some countries, gamete donation is differentially regulated depending on sex (Tables 2 and 3, Charts 2 and 3). Germany, Japan, Norway, and Switzerland are reported to only allow sperm donation, but do not permit egg donation. Interestingly, only Israel reflects the opposite position, i.e. Israel is reported to allow egg donation but has some restrictions regarding sperm donation. None of these countries are reported to allow embryo donation from a previous IVF cycle with the exception of Germany that allows this type of embryo donation. A number of the countries’ respondents reported that they permit both sperm and egg donation, but do not allow embryo donation, including Belarus, Bulgaria, Cameroon, Denmark, Israel, Italy, Malaysia, Sweden, and Taiwan [China (Reporting separately for this report.)].

Chapter 8 Table 2 Are There Regulations That Govern Third Party Reproduction in Your Country?

Chapter 8 Table 2 Are There Regulations That Govern Third Party Reproduction in Your Country?

Chapter 8 Table 3 If Donation is Regulated in Your Country, How is it Done?

Chapter 8 Table 3 If Donation is Regulated in Your Country, How is it Done?

Chart 2

Chart 2

Chart 3

Chart 3

Chart 4

Chart 4

Almost 57% (37/65 respondents) described sperm and oocyte donation as “commonly used” in their countries, in contrast with embryo donation, with 23% eliciting “commonly used” responses (Table 4). Some country respondents reported that both sperm and egg donation were “infrequently used”, for example in Cameroon, China, France, Iran, Italy, Japan, Kazakhstan, Malaysia, Romania, Singapore, South Korea, and Sri Lanka. The respondents reported that local regulations and restrictions on donors account for some of these differences, because the social, political, and cultural backgrounds of these countries vary.

Chapter 8 Table 4 How Often is Third Party Reproduction Performed in Programmes Within Your Country?

Chapter 8 Table 4 How Often is Third Party Reproduction Performed in Programmes Within Your Country?

The majority of countries who had respondents who were surveyed (almost 55%) reported that their countries do not allow the de-novo generation of embryos with donor gametes for purposes of donation, encompassing the countries that ban embryo donation noted above with the exception of Belarus. An additional group of countries including Brazil, Chile, Ecuador, Estonia, Finland, Greece, Iran, Netherlands, Nigeria, Portugal, Romania, Singapore, Spain, and Uruguay were reported by respondents to specifically forbid this form of embryo donation. Twenty-three (37%) countries were reported to permit this form of embryo donation, and two of which (Italy and Belarus) were reported to not allow conventional embryo donation from previous IVF cycles. Seven (8%) countries had respondents leave this question unanswered, or had answered that the situation was unclear or unknown. Finally, the following countries reportedly permit both forms of embryo donation: Australia, Austria, Barbados, Canada, Czech Republic, France, Guatemala, Hungary, India, Kazakhstan, Panama, Paraguay, Russia, Slovak Republic, South Africa, Sri Lanka, Trinidad & Tobago, UK, USA, and Venezuela.

A new technique called cytoplasmic transfer (see Chapter 10, Micromanipulation).has been developed with the principal intention of avoiding mitochondrial disorders. This requires an oocyte or fertilized embryo cytoplasmic donation from a non-affected female donor in order to replace the cytoplasm of an affected female recipient. This process of cytoplasmic transfer is reported to be allowed in Canada, Chile, Guatemala, India, Kazakhstan, Mexico, Russia, Slovak Republic, and Uruguay. However, 14 respondents (around 23%) acknowledge that the status of potential legislation or regulation of cytoplasmic donation is unknown or unclear, and that it is possible that cytoplasmic donation could be used in an experimental environment. Thirty-nine countries (63%) were reported to not allow the procedure. This is an active research and clinical field, with several recent, significant advances reported by UK researchers. It is not surprising that the UK representative responded negatively to these questions, although the UK Human Fertilisation and Embryology Authority (HFEA) recently (October 2015, during the official completion dates of this survey) approved cytoplasmic transfer as a procedure for mothers at risk to pass on serious mitochondrial diseases to their children, but not for other fertility treatments [7].

Respondents reported that ovarian tissue donation is allowed in countries including Australia, Belgium, Canada, Chile, Finland, Guatemala, India, Kazakhstan, Mexico, Russia, Slovak Republic, UK, and the USA, representing 21% of those surveyed. A majority of the respondents (35 countries; 55%) reported that this procedure was not permissible and 15 respondents (24%) answered that the status was “unknown.”

Similarly, testicular tissue donation followed the same pattern of response as ovarian tissue donation, with the exception of the UK, where the respondent stated that it is unknown if this procedure is allowed, although the respondent noted that the HFEA does provide a flow diagram for testicular tissue donation, under strict guidelines that requires prior authorization [8].

Regulation of third party reproduction was reported to affect 63% (39 of the 62 countries). Most of the European countries were reported to be highly regulated for sperm and egg donation by federal/national laws or statutes, except for Ireland and Belgium that have no regulation on this issue. Canada, Australia, and the USA have either national or state/provincial laws governing third party reproduction. (Table 3) On the contrary, in most of Latin America, respondents reported no regulation regarding third party reproduction, and the same situation was reported for several Caribbean countries including Barbados and Trinidad & Tobago. This was also the case in several southeast Asian countries (Sri Lanka, Malaysia, Mali, and Bangladesh). Some countries in Latin America were, however, reported to be regulated by third party reproduction (namely government agencies), including Brazil and Mexico. In the case of Colombia and Uruguay, there is regulation by law that was reported, but only concerning sperm donation.

Compensation for donors is reported to be permitted in most countries, although the amount of compensation varies widely. As noted in Table 5, donors are reported to often be reimbursed for their time and expenses, but in some countries, for example in the USA, Spain, Portugal, Russia, Belarus, India, Iran, Cameroon, Nigeria, Venezuela, and Chile, compensation goes beyond simple reimbursement (in the USA this varies per state law). In Canada, France, Italy, and Japan, the respondents reported that compensation to donors is illegal; and in other countries, it was reported that minimum and maximum fees could be payed to donors. (Table 6)

Chapter 8 Table 5 If Third Party Reproduction is Allowed/Permitted in Your Country, are Donors Compensated?

Chapter 8 Table 5 If Third Party Reproduction is Allowed/Permitted in Your Country, are Donors Compensated?

Chapter 8 Table 6 What is Donor Compensation?

Chapter 8 Table 6 What is Donor Compensation?

Most countries (53/62, 85.5%) had respondents who reported that qualifications had been established for individuals to become a sperm or egg donor, although this issue was less clear for embryo donors, where 19 countries had respondents who reported that this issue was either “not addressed” or “unknown (Table 7).”

Chapter 8 Table 7 If Third Party Reproduction is Allowed/Permitted in Your Country, are the Qualifications to be a Donor Based Upon Medical, Mental Health and/or any Lifestyle (Age and Occupational) Criteria?

Chapter 8 Table 7 If Third Party Reproduction is Allowed/Permitted in Your Country, are the Qualifications to be a Donor Based Upon Medical, Mental Health and/or any Lifestyle (Age and Occupational) Criteria?

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Summary

According to this report, the practice of gamete and embryo donation continues to be increasing worldwide; despite this, social acceptance and use is reported to be restricted in some countries. Respondents often perceived this to be due to ethical, legal, or religious constraints. Restrictive policies can pose additional emotional stress, financial burdens, and may result in forms of discrimination for access to care for couples and individuals obliged to travel abroad to receive desired treatments. Most of the European countries that had respondents who were surveyed are highly regulated by laws, statutes, or government regulatory authorities. Although a minority of countries are reported to completely ban any form of donation, some countries are reported to have regulations restricting some types of donation (for example, embryo donation from either a previous IVF cycle or the de-novo generation of IVF embryos for donation). Other countries are reported to have discordant views toward sperm versus egg donation. In North, Central, and South America, it is reported that gamete and embryo donation is more homogeneously utilized. Cytoplasmic donation is reported to be used primarily within experimental environments, and most of the countries surveyed reported to infrequently use either ovarian or testicular tissue donation.

References

[1] Kuwayama M, Vajta G, Kato O, et al. Highly effective vitrification method for cryopreservation of human oocytes. Reprod Biomed Online 2005;11(3):300-308.

[2] Cobo A, Meseguer M, Remohí J, et al. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. Hum Reprod 2010;25:2239–2246.

[3] Dondorp W, de Wert G, Pennings G, et al; ESHRE Task Force on Ethics and Law. Oocyte cryopreservation for age-related fertility loss. Hum Reprod 2012;27(5):1231-1237.

[4] Practice Committees of American Society for Reproductive Medicine; Society for Assisted Reproductive Technology. Mature oocyte cryopreservation: a guideline. Fertil Steril 2013;99(1):37-43.

[5] Kupka MS, D’Hooghe T, Ferraretti AP, et al; European IVF-Monitoring Consortium (EIM); Europeann Society of Human Reproduction and Embryology (ESHERE). Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE. Hum Rep 2016;31(2):233-248.

[6] Pennings G, de Wert G, Shenfield F, et al. ESHRE task force on ethics and law 15: cross-border reproductive care. Hum Rep 2008;23(10):2182-2184.

[7] Human Fertilisation & Embryology Authority. Mitochondrial donation. Available at: http://www.hfea.gov.uk/9933.html. Accessed August 9, 2016.

[8] Human Fertilization & Embryology Authority; Human Tissue Authority. Regulation of ovarian and testicular tissue. Available at: http://www.hfea.gov.uk/docs/Regulation_of_ovarian_and_testicular_tissue_-_flow_diagram.pdf. Accessed August 9, 2016.

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CHAPTER 9: ANONYMITY

Anonymous gamete donation is still reported to be the most prevalent practice for sperm and oocyte donation around the world. However, there has been a gradual trend in some countries toward a more open approach in obtaining information from donors, with the intent of sharing with prospective parents and for potential disclosure to future offspring [1]. In some cases, donors may also obtain some limited information from the offspring but this practice remains more controversial and has had a much more limited application. There are inevitable conflicts of interests involving ethical and legal considerations, and these include the rights of autonomy and privacy of the prospective parents, the right of privacy of the donor, and the right of the child to know his/her genetic origins [2].

The ability for a donor to remain anonymous can no longer be ensured. Recently, current technologies include affordable massive gene sequencing, commercial direct-to-consumer genetic testing, and the creation of human DNA databases have made assurances of anonymity increasingly problematic and difficult, if not impossible to ensure. This lack of an ability to ensure donor anonymity profoundly impacts the practice of anonymous gamete and embryo donation, and currently results in additional debates and considerations that address ethical, legal, and medical implications of this practice [3].

In the vast majority of countries, the respondents surveyed (45/56, 80%), reported no modifications in regulations that address anonymity since 2012 (the time of the previous International Federation of Fertility Societies [IFFS] questionnaire), and 12.5% reported the issue as unknown (Table 1).

Chapter 9 Table 1 If You Responded to the Surveillance Survey 2012, have there Been any Modifications to Legislation or Guidelines on Anonymity of Donors?

Chapter 9 Table 1 If You Responded to the Surveillance Survey 2012, have there Been any Modifications to Legislation or Guidelines on Anonymity of Donors?

A few countries had respondents who reported modifications in their regulations within the triennium. One example is Australia, where more information is currently required from the donor and offspring. This information includes identifying and non-identifying data from the donor to be provided to the offspring and non-identifying data from the offspring to be provided to the donor. These modifications have been reported to be implemented within both state/provincial laws and by professional organization guidelines.

In Argentina, it was reported that an extensive reform of the Civil Code to include assisted reproductive technology (ART) filiation took place in 2013, and has led to a registry of newborns from ART procedures, leaving open the possibility that offspring from a donor ART cycle can request non-identifying data from the donor (when they reach the age of 18, and only after obtaining a court order). The respondent from Hong Kong [China (Reporting separately for this report.)] also reports new policies from regulatory agencies allowing the ability to request information from the donor to be provided to the offspring. In Uruguay, the respondent reported that modifications to national laws have implied that information can be provided to offspring under certain circumstances.

In total, 13 countries had respondents who reported having no regulations regarding information addressing anonymity, including Barbados, Bangladesh, Canada, Chile, Ecuador, Guatemala, Honduras, Kenya, Malaysia, Mexico, Nigeria, Panama, Paraguay, Peru, Sri Lanka, Trinidad & Tobago, and Tunisia (Table 2).

Chapter 9 Table 2 Are there Practices or Regulations that Address Anonymity in Your Country?

Chapter 9 Table 2 Are there Practices or Regulations that Address Anonymity in Your Country?

Every European country which had a respondent who was surveyed, with the exception of Ireland, have national laws requiring potential disclosure of information regarding donors or offspring, although the situation is not homogeneous among all European countries with regard to the type of information disclosed and how it is implemented. Table 3 shows the type of disclosure in some countries with laws in place, reflecting the wide variety of practices in each country assessed. Nonetheless, Australia, Belgium, and the UK are the countries that are reported to currently be more open to full disclosure of donor and offspring information to both parties (identifying and non-identifying data). When asked if it is customary to disclose this information, regardless of the existence of laws or regulations, most of the respondents in these countries reported having laws that require disclosure as customary (Table 4).

Chapter 9 Table 3 What Type of Information can be Provided?

Chapter 9 Table 3 What Type of Information can be Provided?

Chapter 9 Table 4 What Information is Customary to Provide?

Chapter 9 Table 4 What Information is Customary to Provide?

Cameroon, Bangladesh, Jordan, and Nigeria respondents report that this issue is addressed through cultural practice and religious decree. In the case of Ireland, this issue is reported to be addressed by standards and guidelines from professional organizations, and the same situation was reported to apply to the USA, Canada, Colombia, Japan, and Mali, where no federal laws exist regarding this issue. In Iran, it was reported that government agencies and national laws regulate anonymity, and identifying data from donors can be provided to offspring in certain circumstances. A similar situation exists was reported to exist in Brazil, where identifying data from donors to offspring, and from offspring to donors, can be disclosed under certain conditions, and is overseen by a government agency. Table 3 allo shows the multiple approaches that are reported to be used by different countries to address the issue of donor anonymity.

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Summary

In brief, based upon this report, donor and offspring anonymity remains the most commonly practiced form of donor gamete treatment in the majority of countries with respondents who were surveyed. Recently, regulatory agencies and professional organizations have promoted changes that have gradually established a trend toward disclosing more information from donors to prospective parents and future offspring, or from offspring to donors. This data is provided freely and openly in some countries (e.g., UK, Australia, and Belgium), or released only under certain circumstances or court orders in other countries. Anonymity and issues revolving around disclosure in gamete donation remains a matter of scientific and ethical debate worldwide.

References

[1] van den Akker O. A review of family donor constructs: current research and future directions. Hum Reprod Update 2006;12(2):91-101.

[2] ESHRE Task Force on Ethics and Law. III. Gamete and embryo donation. Hum Reprod 2002;17(5):1407-1408.

[3] Harper JC, Kennett D, Reisel D. The end of donor anonymity: how genetic testing is likely to drive anonymous gamete donation out of business. Hum Reprod 2016;31(6):1135-1140.

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CHAPTER 10: MICROMANIPULATION

Introduction

Micromanipulation techniques in the context of this Surveillance report are interventions performed on the oocyte or embryo with the specific intention of improving assisted reproductive treatment outcomes. These micromanipulation assisted reproductive technology (ART) procedures include intracytoplasmic sperm injection (ICSI), assisted hatching (AH), and various types of embryo biopsy. All of these particular procedures have been employed for some time but their value and specific indications are still debated.

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Microinsemination or Intracytoplasmic Sperm Injection (ICSI)

Since its introduction to clinical practice in 1992, ICSI has been used effectively for couples with significant male factor infertility. In patients undergoing ART with surgically retrieved spermatozoa for obstructive or non-obstructive azoospermia and in those patients with significant quantitative and qualitative sperm abnormalities, ICSI is usually obligatory to achieve an effective oocyte fertilization rate. Although commonly employed for other milder, male factor parameters, benefit is less clearly established. ICSI is recommended in the setting of mild male factor (as defined by a minimum of one semen parameter abnormality per World Health Organization [WHO]). In addition, it has been empirically used for cases of previous fertilization failure, poor-quality oocytes, cryopreserved oocytes, in vitro maturation oocytes and diminished ovarian reserve [1]. The American Society for Reproductive Medicine (ASRM) Practice Committee opines that the routine use of ICSI in non-male factor infertility is not supported by adequate data [2].

With the widespread application of in vitro fertilization (IVF) and ICSI in infertility management, the health of offspring produced has been an ongoing concern. The interventions involved, parental age, and factors underlying infertility have all been suggested to be associated with adverse epigenetic effects on the offspring. Cases of severely impaired spermatogenesis are associated with specific chromosomal anomalies, especially a high frequency of Y-chromosomal micro deletions. ICSI is a more invasive intervention than conventional fertilization and confers heightened potential concerns regarding risk of congenital anomalies in children conceived with ICSI [3]. A systematic literature review from 1985 to May 2014 suggested that there was a slightly higher risk of genitourinary congenital malformation such as hypospadias and cryptorchidism in children conceived with ICSI compared to IVF offspring. However, a subsequent analysis of selective, higher quality studies did not find an increased risk [4]. Frequency of imprinting disorders, metabolic syndromes, and various malignancies have also been assessed among IVF and IVF/ICSI children. A direct link between IVF/ICSI and the studied disorders has not been established [5].

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Assisted Hatching (AH)

AH is a technique used to improve ART success rates by facilitating the emergence of the embryo from the zona pellucida. It involves the artificial thinning or breaching of the zona pellucida, using either acidified Tyrode’s solution, a glass microneedle, laser photo ablation, or a piezo micromanipulator. It has been utilized for “poor prognosis” embryos based on factors including zona thickness, blastomere number, fragmentation rates, and maternal age. The ASRM Practice Committee in 2014 recommended against the routine use of AH for all patients undergoing IVF. Although there is good evidence that the clinical pregnancy rates are slightly improved in poor prognosis patients, the evidence that it improves live birth rates remains insufficient [6].

Assisted hatching has been associated with a higher risk of monozygotic twin pregnancy in patients with a maternal age less than 35 years. However, a Cochrane database review in 2012 did not find an association between monozygotic twinning and assisted hatching in either fresh or frozen transfer cycles [7].

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Embryo Biopsy

The procurement of embryonic DNA for pre-implantation genetic testing (PGT) may utilize PGT for aneuploidies (PGT-A), PGT for monogenic/single gene defects (PGT-M), and PGT for chromosomal structural rearrangements (PGT-SR). Overall assessment of the safety of the biopsy on the embryo, and determination of the optimal stage of development for biopsy for safety and efficacy are ongoing.

Recent studies have concluded that trophectoderm biopsy of a blastocyst rather than cleavage stage biopsy may be preferable. The cleavage stage embryos are believed to be more vulnerable to injury with resultant slower development and a higher chance of embryonic death. Also, the higher level of mosaicism at this stage increases the embryonic misdiagnosis rate even when cellular diagnosis is correct. Some experts believe that the removal of a euploid cell from a mosaic cleavage stage embryo may result in a higher aneuploid cellular load, which could have further deleterious effects. Moreover, pregnancy rates are higher when trophectoderm biopsy for preimplantation genetic screening is performed at the blastocyst stage, although recent reports of a high frequency of mosaicism in trophectoderm biopsies have now cast doubt on the specificity of the use of PGT for identifying euploidy, i.e., normal embryos that are diploid [8].

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Cytoplasmic and Mitochondrial Transfer

Cytoplasmic transfer was a technique initially attempted to prevent serious mitochondrial disease. It involves the transfer of a small amount of ooplasm from a healthy donor oocyte to a recipient oocyte, creating a heteroplasmic oocyte. The presumed mutated mitochondrial DNA (mtDNA) of the recipient oocyte is not removed, but healthy donor mitochondrial DNA is added to it. However, there are three modifications of the cytoplasmic approach that are currently being actively researched and applied in experimental clinical trials. In the pronuclear transfer technique, the pronuclei from the zygote of the affected woman are inserted into the enucleated donor zygote containing nonpathogenic mtDNA. The second is the spindle transfer technique, in which the metaphase II spindle of chromosomes from the unfertilized oocyte of an affected woman is transferred to an enucleated donor oocyte. The most recent is the polar body transfer technique. In these methods, the nuclear chromosomes are from the two parent gametes, but the mtDNA is primarily inherited from the donor oocyte. The risk of epigenetic abnormalities is unknown and further clinical research and long term child outcome data are needed before direct clinical application [9].

In the USA, the Food and Drug Administration (FDA) has oversight of technology pertaining to techniques for mtDNA transfer. These procedures may be undertaken as clinical trials, after appropriate approvals are awarded. The Human Fertilisation and Embryology Authority (HFEA) in the UK has permitted mitochondrial replacement techniques as a clinical procedure since the end of 2015, proposing that these techniques be restricted to clinics licensed specifically to perform them and monitor outcomes [10].

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Analysis of Survey ( Table 1)

Of the 63 respondents that addressed this topic, ART legislation or guidelines were reported to be applicable to micromanipulation procedures in 40 countries. Eighteen countries were reported to be governed by statute. Activities were reported to be conducted within published guidelines within a further 16 countries, and activities were also reported to be covered under both statutes and guidelines in six countries. There are neither laws nor guidelines for the main micromanipulation techniques of ICSI and AH reported by respondents from 23 countries.

Chapter 10 Table 1 How Is Micromanipulation Governed?

Chapter 10 Table 1 How Is Micromanipulation Governed?

ICSI was reported to be allowed by statute or guidelines, and commonly practiced in all countries that are represented in this report. ICSI with surgically retrieved sperm is reported to be infrequently used in Belarus, Denmark, Germany, Jordan, Kenya, Malaysia, Mali, Senegal, and Sri Lanka.

Assisted hatching is also a generally accepted procedure in all countries represented in this report except for Bangladesh and Mali, where it is reportedly never performed. In Tunisia, the frequency of its use was unknown to the respondent.

Embryo or oocyte biopsy is reported to never be performed in Bangladesh, Mali, Norway, and the Philippines. Blastomere biopsy on cleavage stage embryos was reportedly not allowed to be performed in Austria and Germany but polar body and trophectoderm biopsy were reported to be allowed. Countries whose respondents stated that embryo biopsy could be performed but not polar body biopsy include Colombia, Denmark, Ecuador, Guatemala, Hong Kong [China (Reporting separately for this report.)], Iran, Mexico, the Netherlands, Paraguay, and Sweden. Trinidad and Tobago infrequently do blastomere biopsy, but do not perform polar body or trophectoderm biopsy.

Cytoplasmic transfer is reported to be used infrequently throughout the world. As noted and presented in greater detail in Chapter 8, cytoplasmic transfer is reported to be “commonly used” in only four countries: Kazakhstan, Cameroon, Slovak Republic, and Uruguay. It is reported to be used infrequently in India, Israel, and Mexico. Mitochondrial transfer is reported to be used infrequently in the UK, Cameroon, Israel, Slovak Republic, and Mexico. The other countries that had respondents fill out the questionnaire stated that their countries do not perform cytoplasmic or mitochondrial transfer.

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Summary

ICSI remains the primary method of achieving fertilization for severe or mild male factor infertility and is utilized by all countries with respondents reporting for this Surveillance 2016. It is also commonly used for other instances of non-male factor infertility but these other applications are not currently recommended by large regional and some national professional societies. AH is reported to be utilized in all but two countries sampled. Embryo biopsy for PGT is reported to be performed in a large majority of countries and is reported to be usually preferentially performed on trophectoderm from blastocysts.

Cytoplasmic and mitochondrial transfer, which may ultimately be used to prevent serious mitochondrial disease, remain experimental with very limited clinical application worldwide with few respondents reporting their country to be utilizing these techniques. Pronuclear and spindle transfer are the newer research refinements but have even more limited use reported by the countries represented in this 2016 Surveillance report.

References

[1] Babayev SN, Park CW, Bukulmez O. Intracytoplasmic sperm injection indications: how rigorous? Semin Reprod Med 2014;32(4):283-290.

[2] Practice Committees of the American Society for Reproductive Medicine and Society for Assisted Reproductive Technology. Intracytoplasmic sperm injection (ICSI) for non-male factor infertility: a committee opinion. Fertil Steril 2012;98(6):1395-1399.

[3] Pinborg A, Henningsen AK, Malchau SS, et al. Congenital anomalies after assisted reproductive technology. Fertil Steril 2013;99(2):327-332.

[4] Massaro PA, MacLellan DL, Anderson PA, et al. Does intracytoplasmic sperm injection pose an increased risk of genitourinary congenital malformations in offspring compared to in vitro fertilization? A systematic review and meta-analysis. J Urol 2015;193(Suppl 5):1837-1842.

[5] Fauser BC, Devroey P, Diedrich K, et al. Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature. Reprod Biomed Online 2014;28(2):162-182.

[6] Practice Committee of the American Society for Reproductive Medicine; Practice Committee of the Society for Assisted Reproductive Technology. Role of assisted hatching in in vitro fertilization: a guideline. Fertil Steril 2014;102(2):348-351.

[7] Carney SK, Das S, Blake D, et al. Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). Cochrane Database Syst Rev 2012;12:CD001894.

[8] Brezina PR, Kutteh WH. Clinical applications of preimplantation genetic testing. BMJ 2015;350:g7611.

[9] Amato P, Tachibana M, Sparman M, et al. Three-parent in vitro fertilization: gene replacement for the prevention of inherited mitochondrial diseases. Fertil Steril 2014;101(1):31-35.

[10] Board on Health Sciences Policy, Institute of Medicine. Ethical and social policy considerations of novel techniques for prevention of maternal transmission of mitochondrial DNA diseases. In: Claiborne A, English R, Kahn J, eds. Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations. Washington (DC): National Academies Press (USA); 2016.

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CHAPTER 11: OOCYTE MATURATION

Introduction

In-vitro maturation (IVM) following the recovery of immature oocytes was first suggested in the early 1990s as an option for improving potential fertilization rates of women undergoing in vitro fertilization (IVF). Currently, the major difference between this technique as it is typically performed, and conventional IVF treatment, is that oocyte retrieval is performed without prior controlled ovarian hyperstimulation (COH), and the immature oocytes recovered are subsequently cultured in vitro in enhanced culture environments until they complete maturation at the metaphase II (MII) stage. Several potential advantages of IVM have been cited, including improved safety by eliminating risk of ovarian hyperstimulation syndrome (OHSS), particularly for patients with polycystic ovarian syndrome (PCOS) and reduced cost and greater convenience with less stress to the patient by eliminating COH. However, clinical adaptation has been slow because of concerns pertaining to a lower overall clinical success, need for development of competency to perform the laboratory technique, limited follow-up data regarding the health of the resulting offspring, and the possible inducement of permanent changes in the expression of imprinted genes when compared to conventional IVF treatment [1].

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Analysis of the Survey ( Tables 1 and 2, Charts 1 and 2)

Oocyte Maturation

This survey topic included analyzable data from feedback from respondents from 64 countries. The procedure is reported to be permitted in 57 of these countries, whereas in two countries (Bangladesh and Belarus) it is reported to not be allowed. The situation was not reported by respondents in five countries (Australia, Mali, Paraguay, Sri Lanka, and Tunisia). In the majority of the countries, oocyte maturation is reported not to be overseen by an authority whereas in 14 countries application is reported to be primarily regulated by federal/ national rules or voluntarily by professional organization standards and guidelines. Oocyte maturation was reported to be commonly used in only in nine countries.

Chapter 11 Table 1 Parameters for Oocyte Maturation

Chapter 11 Table 1 Parameters for Oocyte Maturation

Chapter 11 Table 2 If Oocyte Maturation is Regulated in Your Country, how is it Done?

Chapter 11 Table 2 If Oocyte Maturation is Regulated in Your Country, how is it Done?

Chart 1

Chart 1

Chart 2

Chart 2

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Discussion

Despite evidence of a modest increase in the utilization of IVM as noted from the IFFS Surveillance 2010 until 2013, the current survey results in 2016 provide very similar information when compared with 2013. Since current data have not shown the clinical efficiency of the technique to offer superior results to conventional IVF treatment, new clinical evidence will be needed to promote wider application of IVM.

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Summary

IVM offers significant hypothetical advantages over conventional IVF but the extant reported clinical experience does not yet support broader application, which has limited its adoption. This situation has not significantly changed over the past three years.

References

[1] Paulson RJ, Fauser BC, Vuong LT, et al. Can we modify assisted reproductive technology practice to broaden reproductive care access? Fertil Steril 2016;105(5):1138-1143.

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CHAPTER 12: WELFARE OF THE CHILD

The ultimate goal of all infertility treatments is the birth of a single healthy baby. Initial early observational studies of neonates provided reassurance that assisted reproductive technology (ART) interventions were not associated with adverse outcomes. More recently, larger population-based studies with longer and more thorough follow-up have raised concerns regarding an increased frequency of abnormalities. Early reports published after intracytoplasmic sperm injection (ICSI) was established as a new method of fertilization reported an expected incidence of birth defects, comparable to the general population. However, de-novo sex chromosome anomalies and structural autonomic anomalies were increased in newborns after ICSI but not after in vitro fertilization (IVF), presumed to be inherited through the paternal pathway and thus not due to the ICSI treatment itself [1]. Other studies described a higher incidence of birth defects [2,3] in newborns after ICSI compared to IVF. It is not clear whether this effect, if significant, is a result of the intervention or if it instead represents an increase in the baseline anomaly rate in an infertile population (as reported in a systematic review in 2014) [4]. There is evidence to support both hypotheses. Considering the widespread use of ART in general, and ICSI in particular (which is increasingly being used for non-male factor indications), follow-up of children born following ART is essential.

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Analysis of the Survey

Of the 68 countries that had respondents providing answers for the current survey concerning this topic, 31 (45.6%) report having legislation addressing the welfare of the child (Table 1 and Chart 1). Most of these countries were in Europe and included Belgium, Bulgaria, the Czech Republic, Estonia, Finland, France, Germany, Greece, Norway, Romania, Russia, Slovak Republic, Spain, Sweden, Switzerland, and the UK. Other countries reported to have pertinent legislation were Australia, Barbados, Canada, China, Iran, Israel, Jordan, Philippines, Singapore, South Korea, Tunisia, Turkey. Latin American countries included Brazil, Colombia, Panama, and Uruguay. Some countries have addressed this with multiple mechanisms, such as national, state, and municipal laws, and include Australia, the Philippines, Russia and Sweden. This topic was reported to not be addressed by 26 countries (38.2%), all of which have no reported legislation. Five countries were reported to have an unknown status on these issues (Cameroon, Denmark, India, the Netherlands, and Saudi Arabia). Six countries had respondents who gave no response (Table 1). Hong Kong [China (Reporting separately for this report.)] has reported to have oversight by a government agency, and Australia, Brazil, Germany, Iran, and the Philippines have been reported to have an agency oversight as well as legislation. Jordan and India have been reported to address the welfare of the child by religious decree and cultural practice. The latter was also reported by respondents from Cameroon, the Philippines, Russia, Slovak Republic, and the USA. Nineteen countries were reported to have professional organizations that address the welfare of the child, including Argentina, Australia, Belarus, Brazil, Cameroon, El Salvador, Finland, Germany, India, Ireland, Japan, Mali, Nigeria, the Philippines, Russia, Senegal, Slovak Republic, Sweden, and the USA.

Chapter 12 Table 1 Are There Practices or Regulations that Address the Welfare of the Child in Your Country?

Chapter 12 Table 1 Are There Practices or Regulations that Address the Welfare of the Child in Your Country?

Chart 1

Chart 1

However, when the questionnaire asked the respondents if formal assessment of welfare of the child was an obligatory part of the initial evaluation of prospective parents in fertility clinics, 40 respondents (61%) answered negatively (Tables 2 and 3, Chart 2). The following countries were reported to include the welfare of the child as part of a routine infertility evaluation: Australia, Ecuador, Finland, Guatemala, Hong Kong [China (Reporting separately for this report.)], India, Ireland, Israel, Norway, Paraguay, the Philippines, Romania, Senegal, Slovak Republic, Sweden, Trinidad & Tobago, Turkey, and the UK (18/65 or 28%).

Chapter 12 Table 2 Assessment or Concerns Regarding the Welfare of the Child

Chapter 12 Table 2 Assessment or Concerns Regarding the Welfare of the Child

Chapter 12 Table 3 Are Prospective Parents Asked About the Following Information?

Chapter 12 Table 3 Are Prospective Parents Asked About the Following Information?

Chart 2

Chart 2

Chart 3

Chart 3

As part of the future welfare of the child evaluation and its familial and social environment, additional questions were posed to the respondents to determine whether prospective parents are asked about their background, including any previous clinical, psychiatric, or criminal history. Results are depicted in Tables 2 and 3. Twenty-seven countries (41%) had respondents report that topics such as history of family violence, harming a child, or prior history of contacting social services regarding care of other children were not being addressed prior to initiation of fertility treatment. Eleven countries (18%), had respondents note that a history of alcohol or drug abuse was not sought prior to fertility treatment, including Austria, Barbados, France, India, Japan, Jordan, Mexico, Panama, South Africa, South Korea, Tunisia, and the USA. Forty-four countries (70%) were reported to inquire about serious mental or physical illness that could potentially impact child care, and 43 (66.1%) reported that counseling about the risk of the child for a serious medical condition was included prior to initiation of fertility treatment. Furthermore, Austria, India, Japan, Mexico, Panama, South Korea, Tunisia, and the USA had respondents report that prospective parents are not routinely evaluated for any of these issues. Forty-four countries (44/65 respondents, 67.7%) were reported to have the ability to deny fertility services when a potential significant risk of affecting the future welfare of a child was determined to exist. (Tables 2 and 3).

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Discussion

The results of the survey reflect a heterogeneous approach to the assessment of the welfare of the child. The current survey does show a clear trend towards more extensive and consistent assessment prior to initiating treatment. For example, the UK’s Human Fertilisation and Embryology Authority (HEFA)’s code of practice refers to guidance notes about the assessment process, mechanisms for obtaining further information, and circumstances for refusing treatment [5]. The survey also reveals insufficient information and resources for the assessment and management of these issues. This is reflected by a significant percentage of respondents responding to several questions with “unknown” or “no response” (data not fully shown in tables).

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Summary

The assessment of the welfare of the child is assuming increasing importance among countries that perform ART and is being addressed with many different models. This 2016 Surveillance report does show a clear trend in comparison to the 2013 report toward more extensive and consistent assessment prior to initiating therapy. Welfare of the child is reported to be primarily addressed by federal or local laws/statutes, and, in countries reported to be without legislation, professional organizations usually provide guidelines and standards to properly assess prospective parents.

References

[1] Bonduelle M, Liebaers I, Deketelaere V, et al. Neonatal data on a cohort of 2889 infants born after ICSI (1991-1999) and of 2995 infants born after IVF (1983- 1999). Hum Reprod 2002;17:671-694.

[2] Hansen M, Kurinczuk JJ, Bower C, et al. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346:725-730.

[3] Wen J, Jiang J, Ding C, et al. Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril 2012;97(6):1331-1337.

[4] Simpson JL Birth defects and assisted reproductive technologies. Semin Fetal Neonatal Med 2014;19(3):177-182.

[5] Human Fertilisation & Embryology Authority. HFEA Code of Practice 8. Welfare of the Child Available at: http://www.hfea.gov.uk/5473.html. Accessed August 10, 2016.

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CHAPTER 13: FETAL REDUCTION

Introduction

Multiple pregnancy remains the primary risk of all infertility treatment involving ovulation induction agents and has been the focus of intense public health scrutiny for two decades. Multiple pregnancy and high order multiple pregnancy (HOM), in particular, confer substantial fetal, neonatal, and maternal risk (see Chapter 5). In essence, two approaches have been adopted to reduce this risk. Many countries have adopted strict measures to limit the number of embryos transferred and have confirmed the efficacy of this approach with subsequent substantial reductions in multiple rates, particularly HOMs. Countries that have not developed legislation or guidelines to reduce the number of embryos transferred continue to see high HOM rates. In addition, countries in which significant numbers of ovulation induction cycles with gonadotropins (controlled ovarian hyperstimulation or super-ovulation with or without intra-uterine insemination) are performed experience significant numbers of multiple pregnancies, especially HOMs. Fetal or selective reduction (FR) has most often been employed in these circumstances to mitigate this risk. While highly controversial and unacceptable to many, fetal reduction has been shown to significantly reduce risk to the mother and surviving progeny [1].

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Analysis of the Survey

Respondents from 66 countries provided analyzable data for this topic. The respondents could select one of four answers regarding the status of FR: allowed (21 countries); allowed with permission (21 countries); not allowed (13 countries); and not addressed or status unknown (11 countries) (Table 1 and Chart 1).

Chapter 13 Table 1 Is Selective Reduction Allowed?

Chapter 13 Table 1 Is Selective Reduction Allowed?

Chart 1

Chart 1

FR is reported to be frequently used in four countries: Belarus, Bulgaria, Czech Republic, and Greece. It is reported to be infrequently used in 39 countries, and not practiced at all in 14 countries (Table 2 and Chart 2).

Chapter 13 Table 2 Is Fetal Selective Reduction Performed in Your Country?

Chapter 13 Table 2 Is Fetal Selective Reduction Performed in Your Country?

Chart 2

Chart 2

The survey results show that the practice of FR was reported to be mandated: by federal law in 21 countries; by state laws or statutes in four countries; by agency regulations in four countries; by professional organizational standards or guidelines in nine countries; and by cultural practices or religious decrees in two countries (Table 3).

Chapter 13 Table 3 If Allowed/Permitted in Your Country, are There Regulations that Address Selective Fetal Reduction?

Chapter 13 Table 3 If Allowed/Permitted in Your Country, are There Regulations that Address Selective Fetal Reduction?

A new category was added to this year’s questionnaire, which queried respondents on their country’s regulation or monitoring of FR practices. Nineteen countries were reported to monitor regularly, 11 countries were reported to partially or inconsistently monitor, and 19 countries were reported to have no provisions (Table 4 and Chart 3).

Chapter 13 Table 4 Are Outcomes of Selective Reduction Monitored And/or Documented?

Chapter 13 Table 4 Are Outcomes of Selective Reduction Monitored And/or Documented?

Chart 3

Chart 3

As noted in Surveillance 2013, most South American countries are reported to not allow the FR procedure. Many European countries were reported to have in existence some legislation regulating reduction but the respondents noted that they are inconsistently monitored. Venezuela is the only country in which fetal reduction is reported to be infrequently performed although it is not legally permissible.

In 2013, respondents from Brazil and Latvia reported the practice of FR even though it was not allowed by statute or approved by guidelines. In 2016, the respondent from Brazil noted that FR is allowed with certain conditions, although it was reported to be infrequently performed. The respondent from Latvia did not submit a response to this issue for the 2016 survey.

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Summary

Most of the countries represented in this 2016 Surveillance were reported to permit FR but the respondents noted that it is infrequently performed. Most respondents report some form of ongoing regular monitoring but 19 countries were reported to not have strict regulations for monitoring. As noted in 2013, the majority of the respondents who report outright prohibition of FR in their country are in South America, and according to the respondents, this appears to reflect their country’s religious and cultural preferences.

Reference

[1] Evans MI, Andriole S, Britt DW Fetal reduction: 25 years’ experience. Fetal Diagn Ther 2014;35:69-82.

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CHAPTER 14: PREIMPLANTATION GENETIC DIAGNOSIS (PGD) AND PREIMPLANTATION GENETIC SCREENING (PGS)

Introduction

Preimplantation genetic testing (PGT) is a test performed to analyze the DNA from oocytes (polar bodies) or embryos (cleavage stage or blastocyst) for human leukocyte antigen (HLA)-typing or for determining genetic abnormalities. These include: PGT for aneuploidy (PGT-A), PGT for monogenic/single gene defects (PGT-M), and PGT for chromosomal structural rearrangements (PGT-SR). This terminology now supplants the terminology preimplantation genetic diagnosis (PGD) and screening (PGS). Since the field and the 2015 questionnaire used the terminology PGD and PGS, the tables of responses reflect the older terms. However, this chapter will adopt the new terminology.

PGT-M for monogenic/single gene defects (PGT-M) has been used for detection of molecular defects linked with specific inherited diseases in embryos prior to uterine transfer. Non-affected embryos are selected and transferred to the patient with the expectation of producing a child free of that disease. Additional PGT-M applications include generation of embryos followed by selection by HLA haplotype to produce a “savior sibling” for a family member afflicted with a potentially lethal disease that may be treated with hematopoietic stem cell transplantation or other cell or organ transplantation.

PGT-M was initially performed on cleavage stage (8-cell) and involved removal of 1 or 2 blastomeres [1]. Currently PGT-M is most often performed with trophectoderm biopsy at the blastocyst stage and involves removal of a greater number of cells than typically performed with cleavage stage embryos. Biopsied blastocysts are usually cryopreserved for subsequent transfer following completion of the molecular analysis. Molecular diagnosis may be done using fluorescent in situ hybridization (FISH), polymerase chain reaction (PCR) whole genome amplification (WGA), microarrays, or next generation sequencing (NGS) technology [2-10]. Unaffected blastocysts are transferred back after thaw. Since embryos with genetic abnormalities are discarded, the decision to utilize PGT-M implies that patients are making a moral distinction between termination of an implanted pregnancy and discarding an affected embryo [1-11].

There are nine general categories for which PGT is currently used:

  1. Autosomal single gene disorders [5-7]
  2. Some chromosomal rearrangements [5-7]
  3. X-linked diseases [5-7]
  4. HLA typing [5-7]
  5. Cancer predisposition genes [8]
  6. Mitochondrial DNA disorders [9]
  7. PGT-A for embryonic aneuploidy [5-7,12-16]
  8. Adult onset disorders [10]
  9. Non-medical sex selection [5,6]

PGT-A and PGT-SR were previously defined as preimplantation genetic screening (PGS). PGT-SR and PGT-A are used increasingly to identify structural or numerical chromosomal abnormalities, respectively, as an adjunct to IVF [12-16]. PGT identifies euploid blastocysts for transfer to increase implantation and live birth rates. When optimally performed, PGT-A and PGT-SR augments strategies to perform successful elective single embryo transfer (eSET) and avoid multiple pregnancies. Current diagnostics focus on analysis of 24 chromosome numbers for evaluation and transfer of only euploid embryos. Different molecular techniques used for this propose include FISH, comparative genome hybridization (CGH), array CGH (aCGH), digital polymerase chain reaction (dPCR), single-nucleotide polymorphism (SNP) array, real-time quantitative PCR (qPCR), and NGS [12-16]. Earlier versions of PGS utilized FISH, which was only able to evaluate smaller subsets of chromosomes (usually only 5-10), instead of the 24 chromosomes performed with newer molecular technology [12-16]. Randomized controlled trials (RCT) assessing PGS performed with FISH showed no significant improvement in pregnancy and live birth rates [12]. Evidence with the newer technologies offer more encouraging results. Since 24 chromosome technology has emerged, there have been three level one RCTs using either qPCR based comprehensive chromosomal screening (CCS) or rapid aCGH showing significant improvements in ongoing pregnancy rates, birth rates, and single pregnancy rates from SET with PGT [13-15]. The two most commonly used molecular techniques, qPCR and aCGH, appear to produce similar results [16]. SNP microarray and NGS are increasingly reported in recent studies. Despite this progress, recent reports of a high frequency of mosaicism in trophectoderm biopsies have now cast doubt on the specificity of PGT for identifying euploid embryos [17].

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Analysis of the Survey ( Tables 1-7 and Charts 1–4)

Respondents from 66 countries addressed this topic of PGT-M for single gene disorder. It was reported that PGT-M is permitted in 57 countries by statutes, laws, or guidelines (Table 1). It is reported to not be addressed in one country and not allowed in eight countries. PGT-M is regulated by guidelines that govern its use in 26 of the 63 countries in which it is reported to be condoned. It is not regulated in 36 countries, and its status is unknown by the respondent of one country (Table 2). PGT-M for single gene disorders is reported to be commonly performed as a clinical service in 23 of 67 countries, infrequently performed in 33 countries, never performed in nine countries, and not reported by the respondents for two countries (Table 4). PGT-M for single gene disorders is reported by the respondents as being acceptable to prevent or allow disease in the child to be born from the embryo in 58 out of 64 of these countries (Table 5). Respondents also reported that it was acceptable for producing an offspring to serve as a cell donor (savior sibling) for a diseased family member in 31 of 64 countries; PGT-M is permissible for the assistance of creating a child for an immunologically matched donor in 19 of 64 countries. It is acceptable for generating an embryo with a selected disease (e.g., genetic congenital deafness) to be used for procreation in 19 of 64 countries, and for generating a diseased embryo for research or experimentation in 3 of 64 countries.

Chapter 14 Table 1 Is Pre-implantation Genetics Allowed/Permitted in Your Country?

Chapter 14 Table 1 Is Pre-implantation Genetics Allowed/Permitted in Your Country?

Chapter 14 Table 2 If Allowed/Permitted, are there Regulations that Govern these Techniques in Your Country?

Chapter 14 Table 2 If Allowed/Permitted, are there Regulations that Govern these Techniques in Your Country?

Chapter 14 Table 3 If these Techniques are Regulated in Your Country, How is it Done?

Chapter 14 Table 3 If these Techniques are Regulated in Your Country, How is it Done?

Chapter 14 Table 4 Are these Techniques Performed in Your Country?

Chapter 14 Table 4 Are these Techniques Performed in Your Country?

Chapter 14 Table 5 Is Pre-implantation Genetic Diagnosis (Single Gene) Accepted for Use to Prevent or Allow Disease?

Chapter 14 Table 5 Is Pre-implantation Genetic Diagnosis (Single Gene) Accepted for Use to Prevent or Allow Disease?

Chapter 14 Table 6 Are there Specific Centres or Institutions where these Techniques are Only Allowed/Permitted to be Performed?

Chapter 14 Table 6 Are there Specific Centres or Institutions where these Techniques are Only Allowed/Permitted to be Performed?

Chapter 14 Table 7 Are these Techniques Considered Experimental or Part of Established Medical Practice?

Chapter 14 Table 7 Are these Techniques Considered Experimental or Part of Established Medical Practice?

Chart 1

Chart 1

Chart 2

Chart 2

Chart 3

Chart 3

Chart 4

Chart 4

PGT-A for aneuploidy was reported by the respondents to be permitted in 57 of 66 countries by statutes, laws, and guidelines, not addressed by eight countries, and not allowed in seven countries (Table 1). When allowed for screening for aneuploidy, it was reported to be regulated by guidelines that govern its use in 27 of 63 countries, not regulated in 30, and respondents did not report for six countries (Table 2). PGT-A for genetic sex selection was reported to be allowed in 21 of the 66 countries, not addressed by five countries, and reported by respondents to not be allowed in 41 countries. When reported to be allowed for sex selection, PGT-A is regulated by guidelines that govern its use in 16 of 63 countries, not regulated in 39, and respondents did not report for eight countries. PGT-A for aneuploidy was reported by the respondents to be commonly performed as a clinical service in 28 of 67 countries, infrequently performed in 24 countries, never performed in 13 countries, and not reported by two countries (Table 4). PGT-A for aneuploidy performed in tandem with PGT-M for single gene disorders was reported by the respondents to be commonly performed as a clinical service in 17 of 67 countries, infrequently performed in 28 countries, never performed in 12 countries, and respondents for 10 countries did not report.

Regulatory bodies reported by respondents to be governing PGT in their countries range from none to various combinations of federal, provincial, municipal, various agencies, and professional organizations (Table 3). Thus 27 of 61 countries with respondents providing feedback have reported no regulations governing PGT. Respondents representing 29 countries reported governances by federal authorities, one by provinces, five by regulatory agencies, and 13 by professional organizations. Centres providing PGT services include sole practitioners in private clinics in 12 of 56 countries, large multiple practitioner clinics in 26 countries, hospital based clinics in 20 countries, university clinics in 23 countries, and public hospitals in 15 countries (more than one response was permitted) (Table 6).

PGT-M for single gene disorders is reported to be considered an established (not experimental) medical practice in 55 of 62 countries. PGT-A and PGT-SR are considered established (not experimental) techniques in 32 of 62 countries. PGT-M for single gene disorders performed in tandem with PGT-A for aneuploidy is now considered an established medical practice in 29 of 62 countries (Table 7).

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Discussion

Compared to Survey 2013, PGT-M now comprises an increasing percentage of assisted reproductive technology (ART) services throughout the world. Its application, however, is often reported as being restricted by statute or local clinical tradition. It is reported by the respondents to be prohibited in only eight countries. PGT-M for single gene disorders is reported to be commonly performed as a clinical service in 23 of 67 countries, infrequently performed in 33 of 67 countries, never performed in nine of 67 countries, and respondents did not respond on this issue for two of 67 countries. Now a well-established and reliable procedure, PGT-M has a low error rate when performed in experienced centres. A number of drawbacks remain. These include the high cost and inefficiency of IVF as a platform, requirements for development to blastocyst stage, and compromised birth rates (even in fertile women), because PGT-A eliminates some embryos for transfer. (Table 1)

Although not considered to be experimental, PGT-M was reported to be frequently denied insurance reimbursement in the USA and is usually not covered except for some single gene disorders and selected chromosomal defects. However, with the advent of new genetic screening tests, utilization of PGT-M by fertile couples in the USA, European Union, and the Middle Eastern region is reported by respondents to be expanding with the detection of carriers who are at risk for transmission of genetic disorders to their progeny and who are otherwise reluctant to have children. In addition, identification of common but devastating genetic mutations, such as BRCA, are now possible by PGT-M. The availability of new molecular genetic tests, public initiatives surrounding specific genetic diseases, and increasing Internet marketing of tests and identification of carriers should increase demand for PGT-M worldwide [2-5,7]. (Table 1)

Compared to Survey 2013, PGT-A and PGT-SG are reported to constitute an increasing proportion of ART service effort throughout the world (Table 2). These two types of PGT are reported by the survey respondents to be allowed in 57 of the 66 countries by statutes, laws, and guidelines, however the respondents did not report on this technology in eight of the 63 countries. However, they did report that they were not allowed in seven of the 46 countries. When reported to be allowed for aneuploidy, they are reported to be regulated by guidelines that govern their use in 27 of the 63 countries and not regulated in 30 countries. Six respondents of the 63 respondent countries did not answer the query.

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Summary

PGT is reported to be increasingly available and more commonly performed worldwide when compared to results from Surveillance 2013. PGT offers benefits, is generally considered safe, and has an acceptably low frequency of errors. PGT-M clearly prevents women from delivering offspring with serious genetic disorders, avoids terminations, and brings peace of mind to many couples that are fearful of, or would not otherwise attempt to have children. The newer technologies for performing PGT-A for aneuploidy are superior to FISH and may play a major role in the reduction of multiple pregnancies by virtue of improved embryo selection for eSET. PGT-A and PGT-SR are reported to be more commonly performed but recent concerns about their reliability may limit universal application.

References

[1] Simpson JL Preimplantation genetic diagnosis at 20 years. Prenat Diagn 2010;30(7):682-695.

[2] Simpson JL, Rechitsky S, Kuliev A Next generation sequencing for preimplantation genetic diagnosis. Fertil Steril 2013;99(5):1203-1204.

[3] Treff NR, Fedick A, Tao X, et al. Evaluation of targeted next-generation sequencing-based preimplantation genetic diagnosis of monogenic disease. Fertil Steril 2013;99(5):1377-1384.

[4] Martín J, Cervero A, Mir P, et al. The impact of next-generation sequencing technology on preimplantation genetic diagnosis and screening. Fertil Steril 2013;99(4):1054-1061.

[5] Collins SC Preimplantation genetic diagnosis: technical advances and expanding applications. Curr Opin Obstet Gynecol 2013;25(3):201-206.

[6] SenGupta SB, Delhanty JD Preimplantation genetic diagnosis: recent triumphs and remaining challenges. Expert Rev Mol Diagn 2012;12(6):585-592.

[7] Tur-Kaspa I Clinical management of in vitro fertilization with preimplantation genetic diagnosis. Semin Reprod Med 2012;30(4):309-322.

[8] SenGupta SB, Vadaparampil ST, Menon U Preimplantation genetic diagnosis for hereditary cancers. Adv Exp Med Biol 2012;732:103-113.

[9] Treff NR, Campos J, Tao X, et al. Blastocyst preimplantation genetic diagnosis (PGD) of a mitochondrial DNA disorder. Fertil Steril 2012;98(5):1236-1240.

[10] Roos RA Huntington's disease: a clinical review. Orphanet J Rare Dis 2010;5(1):40.

[11] Harper JC, Wilton L, Traeger-Synodinos J, et al. The ESHRE PGD Consortium: 10 years of data collection. Hum Reprod Update 2012;18(3):234-247.

[12] Mastenbroek S, Twisk M, van der Veen F, et al. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update 2011;17:454-466.

[13] Forman EJ, Hong KH, Ferry KM, et al. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril 2013;100:100-107.

[14] Scott RT, Upham KM, Forman EJ, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril 2013;100:697-703.

[15] Yang Z, Liu J, Collins GS, et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 2012;5:24-31.

[16] Capalbo A, Treff N, Cimadomo D, et al. Comparison of array comparative genomic hybridization and quantitative real-time PCR-based aneuploidy screening of blastocyst biopsies. Eur J Hum Genet 2015;23(7):901-906.

[17] Greco E, Minasi MG, Fiorentino F Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med 2015;373:2089-2090.

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CHAPTER 15: IVF GESTATIONAL CARRIERS

Introduction

Considerable confusion persists regarding definitions of the different forms of gestational carriers. The terms “surrogate host”, “surrogate mother” or “surrogate” were commonly applied when referring to a woman that carries and delivers a baby for another couple, however the term “gestational carrier” is currently the preferred term. “Need for a gestational carrier in assisted reproduction” refers to treatments where the gametes of a genetic couple, the “intended parent or parents” in a gestational carrier arrangement or relationship are used to produce embryos, which are subsequently transferred to a woman who agrees to carry the pregnancy and deliver a child (or children) for the intended parent or parents. The gestational carrier is therefore genetically unrelated to the offspring that may be born as a result of this arrangement or relationship. Surveillance 2016 primarily addresses this form of gestational carrier relationship. “Genetic parent or parents” is the term used in this survey for the couple or individual who initiate the arrangement and whose gametes are used; the woman who subsequently carries the child is the “gestational carrier”.

“Traditional surrogacy (TS)”, “natural surrogacy”, or “partial surrogacy” were terms that were commonly used refer to circumstances in which the intended gestational carrier is inseminated with the semen of the partner of the “intended couple”, and does not involve IVF. It is not a treatment associated with assisted reproductive technology (ART), but is considered to be medically assisted reproduction (MAR). This particular process is currently defined as a “traditional gestational carrier” arrangement. This process results in progeny who are genetically related to the gestational carrier since her oocytes have been utilized.

The laws that govern IVF/ART gestational carrier relationships are complex and vary greatly among jurisdictions. Determining the local legal status of the child or children born is usually a first step. Full and informed legal advice from an adviser experienced in the laws of the country in which the treatment is to be performed, and, if different, in the country of domicile of the couple or individual, is mandatory. Careful medical assessment and complete counseling of all parties involved in any IVF/ART gestational carrier relationship are essential.

The principal indications for treatment through an “IVF/ART gestational carrier relationship” are:

  • Women without a uterus, but with one or both ovaries functioning:
    • Women with congenital absence of the uterus [LINE SEPARATOR]
    • Women who have had a hysterectomy for carcinoma or other reasons.
  • Women who suffer repeated miscarriages and for whom the prospect of carrying a baby to term is very remote. In this group, women who have repeatedly failed to become pregnant following IVF treatment may also be considered.
  • Women with certain medical conditions that may make pregnancy life-threatening, but for whom the long-term prospects for health are good.
  • Requests for non-medical or social reasons are currently not considered to be reasonable indications.
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Analysis of the Survey

For the 2016 survey, complete responses pertaining to the issue of gestational carrier arrangements and relationships were received from respondents representing 65 countries, compared to 62 countries in 2013. In some countries, multiple mechanisms for regulation and oversight exist and multiple responses were received from respondents from these 65 countries and are included in this 2016 report.

Respondents from 65 countries responded to the question, “is gestational carrier arrangements permitted in your country? (Table 1 and Chart 2)” Those representing 24 (38%) countries noted that gestational carrier arrangements are allowed by statute or guidelines, compared with 19 (31%) in 2013. Respondents from 36 (56%) countries reported that it was not allowed, compared with 24 (39%) in 2013. Respondents from seven countries were not able to answer the question. Eight countries that allow gestational carrier arrangements noted that traditional gestational carrier arrangements were not allowed.

Chapter 15 Table 1 Are Gestational Carriers Allowed/Permitted in Your Country?

Chapter 15 Table 1 Are Gestational Carriers Allowed/Permitted in Your Country?

Chart 1

Chart 1

Chart 2

Chart 2

Responding to the query, “are there regulations that govern IVF gestational carrier arrangements in your country (Table 2 and Chart 2)”, respondents from 26 of the 65 countries (40%) reported that gestational carrier arrangements are practiced (compared to 37% in 2013). Respondents from six countries were unable to answer the question. With regard to traditional gestational carrier arrangements, respondents from 29 countries reported that there are regulations, however respondents from 29 countries reported to have no regulations and respondents representing seven countries did not respond to the question. Of interest, respondents from three countries reported to have regulations pertaining to gestational carrier arrangements (Czech Republic, Greece, Japan) but not for traditional carriers.

Chapter 15 Table 2 Are there Regulations that Govern Gestational Carriers in Your Country?

Chapter 15 Table 2 Are there Regulations that Govern Gestational Carriers in Your Country?

In response to the question, “if gestational carrier arrangements are regulated in your country (Table 3), how is it done”, respondents from 17 countries reported to have no regulations regarding any form of gestational carrier arrangements, those from three countries report to have regulations addressing gestational carrier arrangements only and one on traditional carriers only. As far as the nature of regulation, federal or national laws or statutes governing all both types of gestational carrier arrangements are reported by respondents to exist in 17 countries. Respondents from seven countries reported gestational carrier arrangements only and one country reported traditional carriers only. State, provincial, or regional laws regulate both types of arrangements as reported by respondents from two countries (Australia and Austria) and respondents from one country (USA) reported that they have state laws pertaining to gestational carrier arrangements only. Respondents from only one country (Mexico) reported that gestational carrier arrangements are regulated by municipal laws.

Chapter 15 Table 3 If Gestational Carriers are Regulated in Your Country, How is it Done?

Chapter 15 Table 3 If Gestational Carriers are Regulated in Your Country, How is it Done?

Regulation or oversight of gestational carrier arrangements by agencies were reported by respondents to exist in three countries (Greece, Hong Kong [China (Reporting separately for this report.)] and USA) and that both types of arrangements exist in one country (Brazil). Professional organization standards or guidelines prescribe practice for gestational carrier arrangements in five countries and for both types of arrangements in seven countries.

Respondents from one country (Bangladesh) cited religious reasons for a prohibition of both forms of gestational arrangements. This was the only respondent from a country offering a potential basis for the ban, but it is likely that other countries also do not perform these arrangements for religious reasons.

In response to the query, “how often is third party reproduction performed in programmes in your country”, respondents from 62 countries reported (Table 4 and Chart 3). Of these 62, respondents from 26 countries noted that gestational carrier arrangements are “never practiced”, 21 responded “infrequently”, nine replied “commonly”, and respondents from six countries responded that this was “not known”. Regarding traditional gestational arrangements, the respondents reported “never” from 34 countries, “infrequently” from 15, “commonly” from one, and reported “not known” from 13 countries.

Chapter 15 Table 4 How Often is Gestational Carrier Arrangements Performed in Programmes within Your Country?

Chapter 15 Table 4 How Often is Gestational Carrier Arrangements Performed in Programmes within Your Country?

Chart 3

Chart 3

In response to the question, “if gestational carrier arrangements are allowed in your country, are these women compensated”, responses from respondents representing 61 countries were received (Table 5). The responses indicated that 16 countries are reported to not allow any compensation, seven permit payment for time and expenses only, and eight allow payment in addition to reimbursement for expenses. However, respondents from 30 countries did not report or used the “unknown” response. With regard to the respondents representing the 61 countries, 21 countries were reported not to permit any payment; 4 allow compensation for time and expenses; 4 for payment in addition to expenses; and, respondents from 32 countries did not answer this question or responded with “unknown” (Table 6).

Chapter 15 Table 5 If Gestational Carriers are Allowed/Permitted in Your Country, are Gestational Carriers Compensated?

Chapter 15 Table 5 If Gestational Carriers are Allowed/Permitted in Your Country, are Gestational Carriers Compensated?

Chapter 15 Table 6 What is Gestational Carrier Compensation?

Chapter 15 Table 6 What is Gestational Carrier Compensation?

This year the new questionnaire attempted to determine the range of compensation. Respondents from 36 countries answered this question regarding the amount of compensation permitted, therefore limited data was received and specific currencies were inconsistently provided. Respondents from three countries listed actual values for compensation for gestational carrier arrangements, but without a denomination. Respondents from seven countries stated there is no stipulated minimum or maximum fee (also for traditional carrier arrangements in three countries), and respondents from 16 countries answered with “unknown” or “not addressed”.

Regarding the topic, “if third party reproduction is permitted in your country, are the qualifications to be a gestational carrier based upon medical, mental health and/or any lifestyle (age and occupational) criteria”, respondents from 61 countries answered but details regarding the relevant criteria were not sought (Table 7). For gestational carrier arrangements, respondents from 23 countries reported that there are medical or other criteria required, five had no criteria, and respondents from seven countries answered with “not known”. Thirteen stated that the issue is “not addressed”. Respondents from 13 countries provided no response to this question. For traditional carrier arrangements the responses were as follows: “yes” from14 countries, “no” from seven; “not known” from seven, “not addressed” by 14, and 17 countries did not complete the question.

Chapter 15 Table 7 If Gestational Carrier Arrangements are Allowed/Permitted in Your Country, are the Qualifications to be a Gestational Carrier Based Upon Medical, Mental Health and/or any Lifestyle (Age and Occupational) Criteria

Chapter 15 Table 7 If Gestational Carrier Arrangements are Allowed/Permitted in Your Country, are the Qualifications to be a Gestational Carrier Based Upon Medical, Mental Health and/or any Lifestyle (Age and Occupational) Criteria

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Discussion

Gestational carrier arrangements remain a contentious practice worldwide. Respondents from the 65 countries that answered questions on this issue for the current surveillance report that 24 (37%) of these countries allow and perform gestational carrier arrangements, and that they are practiced in an additional nine countries without guidelines or legislation. In those countries where respondents reported gestational carrier arrangements were being conducted and from which statistics were available, gestational carrier arrangements appear to account for 0.05-0.2% of IVF/ART treatment cycles. However, several countries are reported to practice gestational carrier arrangements for couples or individuals from other countries (Cross-Border Reproduction, see Chapter 23) because it is unavailable or more expensive in their own country. Both types of gestational carrier arrangements are fraught with multiple potential conflicts when the interests of the various stakeholders clash, and these issues are further exacerbated when conducted in an international arena, as several highly publicized cases have demonstrated.

Payment of gestational carriers continues to be an issue that provokes much debate. Many countries are reported to prohibit any form of compensation, which likely serves to significantly reduce the number of potential carriers. In countries where payment is reportedly not allowed, gestational carriers are usually relatives or personal friends of the intended couple or individual who likely receive only “reasonable expenses”. Eight of 61 countries are reported to allow payment of gestational carriers, which consistently provides a larger potential group of women willing to become a gestational carrier but has been claimed to promote the commercialization of these gestational carrier arrangements. This is particularly a concern in less developed countries or lower resource settings with greater potential for exploitation.

Recent, limited studies have offered reassurance regarding the psychological and physical well-being of children produced through gestational carrier arrangements as well as their gestational carriers and the intended couples or individuals [1,2]. In most countries, the “birth mother” has been recognized as the legal mother of a child. This issue has been resolved in many countries or states by legislation enabling the genetic parent(s) to become a legal parent(s) at the birth of the child. The majority of gestational carrier arrangements proceed without problems and provide a positive and successful treatment option for a small group of women or individuals who otherwise would be unable to have their or their partner’s own genetic children.

Both the European Society of Human Reproduction and Embryology (ESHRE) [3] and the American Society for Reproductive Medicine (ASRM) have published ethical and clinical guidelines pertaining to gestational carrier relationships [4,5], advocating thorough evaluation and provisions for managing the small group of women or individuals who require this specialized treatment to have a genetically related child or children.

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Summary

Gestational carrier arrangements represent a useful and effective treatment option allowing the intended parent or parents to have their own children. These arrangements are important options especially for women who have no uterus, or are otherwise unable to bear children for other medical reasons. It is also an option for individuals who are not in a partnership or are in a same sex relationship (see Chapter 23). Gestational carrier arrangements remain controversial and are permitted in a relatively few countries, usually with significant limitations particularly regarding compensation. The topic engenders considerable international debate regarding indications for its application and potential for exploitation of its participants.

References

[1] Golombok S, MacCallum F, Murray C, et al. Surrogacy families: parental functioning, parent-child relationships and children’s psychological development at age 2. J Child Psychol Psychiatry 2006;47(2):213-222.

[2] MacCallum F, Lycett E, Murray C, et al. Surrogacy: the experience of commissioning couples. Hum Reprod 2003;18(6):1334-1342.

[3] Shenfield F, Pennings G, Cohen J, et al; ESHRE Task Force on Ethics and Law. ESHRE Task Force on Ethics and Law 10: Surrogacy. Hum Reprod 2005;20:2705-2707.

[4] Practice Committee of the American Society for Reproductive Medicine; Practice Committee of the Society for Assisted Reproductive Technology. Fertil Steril 2015;103(1):e1-8.

[5] Ethics Committee of the American Society for Reproductive Medicine. Using family members as gamete donors or surrogates. Fertil Steril 2012;98(4):797-803.

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CHAPTER 16: EXPERIMENTATION WITH EMBRYONIC CELLS

Introduction

The topic “experimentation on the embryo” spans a range of applications including technical refinements of assisted reproductive technology (ART), such as assessment of media conditions to whole alterations of the genome with a consequent range of potential beneficial and harmful results. As such, there are inherent ethical conflicts that emerge as the intent to prevent or alleviate human suffering may diverge from the obligation to respect the value of human life. The issue of the status of the embryo is discussed in Chapter 18. On the other hand, the topic of working with embryonic cells taken from embryos generated in vitro has been reviewed in the literature and parameters for the conduct of embryonic cell research have been developed, with regulations and guidelines that differ worldwide [1-3]. Although many ethical, legal, political, and social arguments for and against embryonic cells have been written, they have helped frame the debate but have not mitigated many of the concerns that such research has raised. The literature reflects a broad range of approaches that various countries have undertaken to address these issues and whether or not embryonic stem cell research is permitted.

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Analysis of the Survey ( Tables 1 and 2 and Charts 1–4)

Respondents from 64 countries answered the questions concerning the topic of experimental research on cells from the pre-implantation embryo and their responses are included in the survey. Human embryonic research on donated unused preimplantation embryos was reportedly allowable in seven countries, not allowed in 21 countries, and permissible with some restrictions in 21 countries. The respondents from nine countries reported that the status was “unknown”. Although respondents from 23 countries reported that embryos were used for stem cell research with or without restrictions, generating embryos for embryonic stem cell research was reported to be forbidden in 27 countries. For a larger proportion of countries in which experimentation was permissible on donated or un-used pre-implantation embryos, specific approval for the research on either stem cells or embryonic stem cells was reported to be required. Research involving stem cells (including embryonic stem cells) were reported to be regulated by either national ethics/oversight panels, local or national Institutional Review Boards, or local ethics panels. Respondents reported a considerable range that was permitted for the stage of development for embryos able to be used for experimentation but respondents from the majority of countries reported that experimentation using a non-implanted embryo can be performed up to 14 days of development. None of the respondents from 64 countries acknowledged performing reproductive cloning (see Chapter 17), with respondents from 54 countries reporting that cloning was never performed; the situation was unknown in 10 countries. Stem cell research and embryonic stem cell research with embryos were both reported to be infrequently conducted in the majority of countries in which experimentation is permitted.

Chapter 16 Table1a Is Experimentation on Preimplantation Embryo Allowed?

Chapter 16 Table1a Is Experimentation on Preimplantation Embryo Allowed?

Chapter 16 Table 1b Is Experimentation on Preimplantation Embryo Performed?

Chapter 16 Table 1b Is Experimentation on Preimplantation Embryo Performed?

Chapter 16 Table 1c Is Experimentation on the Pre-implantation Embryo Being Performed by Clinical or Research Programmes?

Chapter 16 Table 1c Is Experimentation on the Pre-implantation Embryo Being Performed by Clinical or Research Programmes?

Chapter 16 Table 2a Are there Regulations that Address Experimentation on the Pre-implantation Embryo?

Chapter 16 Table 2a Are there Regulations that Address Experimentation on the Pre-implantation Embryo?

Chapter 16 Table 2b Regulations that Govern Experimentation on Preimplantation Embryo

Chapter 16 Table 2b Regulations that Govern Experimentation on Preimplantation Embryo

Chapter 16 Table2c What Body/Agency Approves Experimentation/Research?

Chapter 16 Table2c What Body/Agency Approves Experimentation/Research?

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Chart 4

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Summary

Embryonic stem cell research remains controversial and is performed in very few countries. Experimentation on human embryonic cells remains a contentious and complex issue based upon the outcome from this 2016 Surveillance. Despite this, an increase in the amount of research performed when compared to the Surveillance 2013 is depicted for countries in which stem cell research has been reported to be permissible.

References

[1] National Institutes of Health. Report of the Human Embryo Research Panel: Final Draft. September 27, 1994. Bethesda, MD: National Institutes of Health; 1994.

[2] Council on Human Reproductive Technology. For embryo researchers. Available at: http://www.chrt.org.hk/english/embryo/embryo.html. Accessed August 10, 2016.

[3] Cattapan A, Snow D Of research and reproduction: defining embryo “research” in Canada. Monash Bioeth Rev 2015;33(4):379-395.

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CHAPTER 17: CLONING

Reproductive cloning is a process in which an animal with the nuclear somatic cell DNA of another animal is generated. The technique, called somatic cell nuclear transfer (SCNT), produces an almost identical twin that differs from being a true identical twin in that the clone has the mitochondrial DNA of the recipient (usually genetically unrelated) egg. The historical first mammalian prototype, a sheep named Dolly, was a product of reproductive cloning. Reproductive cloning has been, thus far, extremely inefficient. The number of oocytes undergoing SCNT that subsequently develop to a live birth is approximately 1-2%. These observations and pervasive ethical concerns preclude its application to clinical practice [1-3].

Therapeutic cloning is a process in which stem cells are harvested from the inner cell mass of blastocysts from embryonic clones generated for this purpose. These embryonic stem cells may be expanded in vitro with the intent of allowing them to undergo controlled differentiation to various developmental cell types for therapeutic purposes. Therefore, embryonic stem cell lines that could be of therapeutic value can be created by SCNT using a nucleus from a particular person or animal. This procedure offers the advantage of avoiding rejection since these generated therapeutic cells, tissues, or organs may be transplanted back into the same person or animal as they would be immunologically homologous [1,3].

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Analysis of the Survey ( Tables 1–5 and Charts 1 and 2)

Reproductive Cloning

Human reproductive cloning is not allowed (often with formal statues, laws, and guidelines), or its status is unstated, as reported by respondents from 65 out of the 66 countries. A respondent reported that reproductive cloning is allowed in one country (Uruguay) however with restrictions. (Table 1) Laws, regulations, statutes, or guidelines prohibit the use reproductive human cloning as reported by the respondents of the 2016 Surveillance. None of the respondents representing 66 countries report current practice or research in reproductive cloning.

Chapter 17 Table 1 Is Cloning Allowed/permitted in Your Country?

Chapter 17 Table 1 Is Cloning Allowed/permitted in Your Country?

Chapter 17 Table 2 What Body and/or Agency Approves Cloning?

Chapter 17 Table 2 What Body and/or Agency Approves Cloning?

Chapter 17 Table 3 Is Cloning Performed in Your Country?

Chapter 17 Table 3 Is Cloning Performed in Your Country?

Chapter 17 Table 4 Are there Regulations that Address Cloning in Your Country?

Chapter 17 Table 4 Are there Regulations that Address Cloning in Your Country?

Chapter 17 Table 5 Is Cloning Being Performed by Clinical or Research Programmes in Your Country?

Chapter 17 Table 5 Is Cloning Being Performed by Clinical or Research Programmes in Your Country?

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Therapeutic Cloning

Therapeutic cloning is reported by respondents to be allowed in five of the 66 countries via formal statutes, laws, or guidelines. Specific approval involving national ethics committees are reported to be required and involve oversight by various local and national bodies. Therapeutic cloning is reported to be prohibited, or its status was left unstated, in 61 of the 66 countries. (Table 2) Laws, regulations, statutes or guidelines in virtually all countries where it was reported to be officially allowed, restrict the use of therapeutic cloning to stem cell research and not transplantation back into the same person as a form of therapy or treatment. Respondents from six of the 66 countries reported that active research in therapeutic stem cell cloning exists.

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Discussion

Reproductive cloning, despite early reported success in experimental animals and well-publicized initiatives with humans, has not produced a verified human birth. As reflected in Surveillance 2016, reproductive cloning was reported to be prohibited in all but one country (Uruguay). However, there are no reports of attempted reproductive cloning in Uruguay. Therapeutic cloning, in which a human in vitro fertilization (IVF) somatic cell nuclear transfer (SNCT) generated blastocyst serves as a source of human stem cells, was reported by the respondents to be permitted in five of 66 countries.

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Summary

Human reproductive cloning is almost uniformly prohibited by countries whose respondents reported on this issue. The United Nations Declaration on Human Cloning, which prohibits all forms of human cloning, passed in 2005 during its 82[nd] General Assembly with 84 member nations voting in favor, 34 against, and with 37 abstentions. Therefore, there was no global consensus on this issue through the Declaration as there were concerns by some member nations that there could be misconceptions concerning the wording in the Declaration about prohibitions that would be applied to all forms of cloning. This 2016 Surveillance does show that therapeutic cloning, with significant potential clinical therapeutic benefits, is practiced where allowed under restriction in a limited number of the countries surveyed.

References

[1] Ogura A, Inoue K, Wakayama T Recent advancements in cloning by somatic cell nuclear transfer. Philos Trans R Soc Lond B Biol Sci 2013;5;368(1609):20110329.

[2] Trounson AO Future and applications of cloning. Methods Mol Biol 2006;348:319-332.

[3] Hill JR Incidence of abnormal offspring from cloning and other assisted reproductive technologies. Ann Rev Anim Biosci 2014;2:307-321.

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CHAPTER 18: STATUS OF THE EMBRYO

Ultimately, the practice of assisted reproductive technology (ART) in all countries in which it is offered is governed by the status conferred on the embryo. There are significant differences among countries’ approaches to this issue, which are determined by their individual interpretation of guidelines and statutes unique to their locale [1-3]. Practices are also influenced by religious doctrines and universal moral and ethical principles. In essence, these policies focus on two issues: the point at which an embryo, fetus or child becomes a potential entity with personhood, and the legal status afforded before and after that point is reached. Clinical interventions resulting in pregnancy pose unique challenges as decision making is governed by classical ethical concerns for autonomy, beneficence, and non-maleficence for both mother and the ultimate live born child. Resolution of potential conflicts when each may be differentially affected pose unique challenges. While universally accepted ethical principles exist, there are very significant international differences in the way these considerations are approached and resolved. It is worth noting that many countries do have points at which the fetus is legally protected (often the point of viability if outside of the mother), and this distinction was not addressed by the respondents in this context, presumably because the surveillance questions pertained to ART only.

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Analysis of the Survey

Two questions were posed for the 2015 survey questionnaire: “For your country, is there a recognized point in time during human development at which a human person is considered to exist and thus provided human rights?” (Table 1) and “For your country, is there a recognized point in time during human development before which a human person is considered not to exist and thus not provided human rights?” (Table 2) Respondents were then asked if such a determination were made for each circumstance, the recognized time that the status of personhood was conferred, and the governing body or agency making the determination. (Tables 3 and 4) The second question was a new addition to the 2015 questionnaire. Respondents from a total of 64 countries recorded responses to both questions, but the respondent from Israel responded to the first question but not the second, and the respondent from Paraguay responded only to the second. For each of the two questions, respondents from 19 and 21 countries, respectively, replied that the answers to the first and second questions were “unknown”. Respondents from 27 countries reported that no recognized point in human development existed in which a human person existed and rights were conferred. However, respondents representing 18 countries did report that such a point had been defined and it ranged from the first day post fertilization (Brazil, Ecuador, Guatemala, Italy, and the UK) to 280 days (the Russian Federation). Where personhood status was conferred, it was most often reported to be achieved through federal or national laws and statutes (24 countries).

Chapter 18 Table 1 Is there a Recognized Point in Time During Human Development at which a Human Person is Considered to Exist and thus Provided Human Rights?

Chapter 18 Table 1 Is there a Recognized Point in Time During Human Development at which a Human Person is Considered to Exist and thus Provided Human Rights?

Chapter 18 Table 2 Is there a Recognized Point in Time During Human Development before which a Human Person is Considered Not to Exist, and thus Not Provided Human Rights?

Chapter 18 Table 2 Is there a Recognized Point in Time During Human Development before which a Human Person is Considered Not to Exist, and thus Not Provided Human Rights?

Chapter 18 Table 3 Through which Governing Bodies or Agencies, is this Time of Human Existence Determined?

Chapter 18 Table 3 Through which Governing Bodies or Agencies, is this Time of Human Existence Determined?

Chapter 18 Table 4 If Yes, through Which Governing Bodies or Agencies is this Time Frame Determined?

Chapter 18 Table 4 If Yes, through Which Governing Bodies or Agencies is this Time Frame Determined?

Regarding the converse question, pertaining to a point before which personhood is not considered to exist, of the respondents for 44 countries who had entered a yes or no answer, 32 had responded “no” that such a point had not been defined. Of the affirmative responses representing 12 countries, only seven of these had noted a specific time ranging from day 0, the moment of fertilization (Greece, Ireland, and the UK) to 125 days (Jordan).

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Discussion

Although a greater number of responses were received for the current survey when compared to the previous one, there were participants and thus countries represented in 2013 that did not provide responses this time. Overall, there did not appear to be many significant changes noted by the respondents over the ensuing three years. Nevertheless, there have been pertinent, noteworthy events that have occurred.

In Surveillance 2013, we noted that the Inter-American Court of Human Rights (IACHR), based in San Jose, Costa Rica had reversed the Cost Rica Constitutional Chamber of the Supreme Court’s (Sala IV) 2000 ruling declaring that in vitro fertilization (IVF) was unconstitutional on the basis that it violated the constitutional guarantee to the embryo of the right to life. By July 2013, no action had been taken to make IVF available and compensate the 18 plaintiffs in the original suit as ordered by IACHR. Subsequently, in September 2015, President Luis Guillermo Solis issued an executive decree legalizing IVF and a subsequent government report outlined a process for reinstating IVF services. The executive decree went into effect October 11, 2015 but was subsequently challenged by legislators and the decree was reversed by Sala a month later. The original decree was upheld by IACHR in a report issued February 26, 2016 and currently there are no legal impediments to IVF in Cost Rica. However, it is not clear whether IVF cycles have been performed yet. Costa Rica did not participate in either the 2012 or 2015 Surveillance questionnaires. There have been reports of a high incidence of high order multiple pregnancies attributed to gonadotropin therapy occurring in Costa Rica during the 15 year period in which the ban was in place.

In the USA, several states have attempted to enact “personhood amendments” that seek to confer legal rights and protection to the embryo from the moment of fertilization. The primary intent of these proposed laws has been to restrict access to abortion but they also effectively ban several forms of contraception and have potential profound implications for the practice of IVF, including holding patients and clinicians legally liable for the fate of all in vitro generated embryos. Over the past four years, two federal proposals and over 70 bills from 25 states have been generated with the intent of enacting personhood legislation. To date only two states, Kansas and Missouri, have passed bills with personhood language. Both have evaded being declared unconstitutional by including provisions that make them subject to the USA Constitution and Supreme Court, which has previously upheld the legitimacy of abortion. In addition to the legislative efforts, there have been 13 attempts at ballot initiatives to pass state constitutional amendments. Only Colorado and Mississippi had actual referendums and both measures failed.

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Summary

Although IVF appears to be almost universally available and there are no longer extant legal obstacles to its application, there are significant differences among countries in terms of the status and protection that they confer to the embryo. These differences have been responsible for regional variations in practice patterns (e.g. oocyte vs. embryo cryopreservation) but the current survey does not note significant changes related to status conferred to the embryo by respondents representing their countries. Nevertheless, controversies within many countries regarding the point at which the embryo or fetus should be given legal protection continue unabated.

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References

[1] Arias L Human rights court backs Costa Rica’s decree on legalizing IVF. Available at: http://www.ticotimes.net/2016/03/01/human-rights-court-validates-executive-decree-reinstate-ivf-costa-rica. Accessed August 10, 2016.

[2] Morgan LM IVF ban lifted in Costa Rica: a success for reproductive rights? Available at: http://blogs.plos.org/globalhealth/2016/03/ivf-ban-lifted-in-costa-rica-a-success-for-reproductive-rights/. Accessed August 10, 2016.

[3] “Personhood”. Available at: https://rewire.news/legislative-tracker/law-topic/personhood/. Accessed August 10, 2016.

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CHAPTER 19: SEX SELECTION

Introduction

Sex selection is used frequently for social reasons, mostly to balance families. It is less often used to prevent transmission of sex-linked inherited genetic disorders [1,2]. Reliable technologies for pre-implantation sex selection did not exist prior to the advent of the assisted reproductive technologies (ART).

In the most recent 2015 questionnaire, four different strategies were surveyed:

  • Preimplantation genetic testing (PGT)-A and PGT-SR (previously PGS): PGT-A with sex chromosome identification on in vitro fertilization (IVF) embryos is performed and embryos of the desired sex are selected for transfer. IVF with PGT is more precise than other sex selection methods, being successful for the desired sex in up to 99% of cases [2]. Some clinics combine sorting with IVF and PGT to enrich sperm toward X or Y to then obtain larger numbers of embryos of the desired sex [3].
  • PGT-M/ PGT-A and PGT-SR (previously PGD/PGS): PGT-M for single gene disorders and PGT-A for embryo/sex selection are frequently combined in tandem [3].
  • Intrauterine Insemination (IUI) with sperm sorting: Sperm cells are separated by flow cytometry, an automated in vitro process that separates sperm into X- or Y-enriched semen for insemination [4].
  • Selective fetal reduction: Reduction is performed to select embryos of the desired sex.
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Analysis of the Survey

Respondents representing 66 countries submitted replies in response to this topic (Tables 1–4 and Charts 1–3).

Chapter 19 Table 1 Is Sex Selection and Sex-selective Fetal Reduction Allowed/permitted in your Country?

Chapter 19 Table 1 Is Sex Selection and Sex-selective Fetal Reduction Allowed/permitted in your Country?

Chapter 19 Table 2 If Allowed/Permitted, are there Regulations that Govern these Techniques in your Country?

Chapter 19 Table 2 If Allowed/Permitted, are there Regulations that Govern these Techniques in your Country?

Chapter 19 Table 3 If These Techniques are Regulated in your Country, how is it Done?

Chapter 19 Table 3 If These Techniques are Regulated in your Country, how is it Done?

Chapter 19 Table 4 Are These Techniques Performed in your Country?

Chapter 19 Table 4 Are These Techniques Performed in your Country?

Chapter 19 Table 5 Are there Specific Centres or Institutions where these Techniques are Only Allowed/Permitted to be Performed?

Chapter 19 Table 5 Are there Specific Centres or Institutions where these Techniques are Only Allowed/Permitted to be Performed?

Chapter 19 Table 6 Are these Techniques Considered Experimental or Part of Established Medical Practice?

Chapter 19 Table 6 Are these Techniques Considered Experimental or Part of Established Medical Practice?

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PGT-A/PGT-SR (Previously PGS)

Sex selection by PGT-A (aneuploidy screening and sex chromosome selection) was reported by respondents to be allowed and performed in 38 countries per statutes, laws, or guidelines. It was reported not to be allowed in 23 countries and its status was reported to not be mentioned in statutes four countries. PGT-A for sex selection in various combinations was reported to be performed in 20 countries. Sex selection by PGT-A was reported to be most often performed in larger university hospital centres and large clinics where the technology is available.

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PGT-M/ PGT-A and PGT-SR (Previously PGD/PGS)

PGT-M for single gene disorders with PGT-A for aneuploidy, embryo selection, and sex chromosome selection are reported to be commonly performed in tandem. PGT-M/PGT-A was reported to be allowed and performed in 38 of the 66 countries with statutes, laws, and guidelines. However, this procedure was reported to not be allowed in 24 countries. The procedure was reported to not be addressed in the statutes of four of these countries. PGT-MA/PGT-A for sex selection in various combinations were reported by respondents to be performed in 20 countries. Sex selection by PGT-M/PGT-A was most often reported to be performed in larger university hospital centres.

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IUI with Sperm Sorting

Sex selection by IUI with sperm sorting was reported to be allowed in 19 countries with statutes, laws, or guidelines, and reported to not be allowed in 32 countries. According to the respondents IUI with sperm sorting was not addressed in statutes of 15 countries. Sex selection by IUI with sperm sorting was reported to be performed in 11 countries. Sex selection by IUI with sperm sorting was most often reported to be performed in larger university hospital centres, large clinics, and smaller clinics.

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Selective Fetal Reduction

Sex selection by selective fetal reduction was reported to be allowed in 18 of the 66 countries with statutes, laws, and guidelines. However, respondents reported that this procedure was not allowed in 26 countries and was not mentioned in the statutes of 12 countries. Sex selection by selective fetal reduction was reported to be performed in 25 countries. Selective reductions were reported to be performed in all clinical environments ranging from sole practitioner clinics to large university hospital centres.

Sex selection involving these methods was reported by respondents to be governed in 37 of the 66 countries by regulations originating from combinations of federal authorities, provincial authorities, mandated agencies, and professional organizations.

In 24 countries, sex selection was reported to not be governed by specific regulations. Sex selection by PGT was reported to be considered as an established medical practice in 12 of 66 countries, experimental in four of 66 countries, and was not reported as either for 50 of 66 countries. Sex selection by IUI with sperm sorting was reported to be considered an established medical practice in eight countries and experimental in five countries. Its status was not reported for 53 countries. Sex selection by selective fetal reduction was reported to be considered as an established medical practice in eight of 66 countries, experimental in five of 66 countries, and not reported for 27 of 66 countries. Sex selection by PGT was reported to be the favored method in most countries.

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Discussion

A long-standing debate has surrounded the legitimacy of the sex selection methods evaluated in this survey [1,2]. Historically, it has been customary not to disclose sex selection as a practice. PGT-A appears to be changing this practice and use of this sex selection technology has increased. In Surveillance 2013, sex selection was reported to be permitted by statute in only nine countries and not allowed in 29 others. In Surveillance 2016, sex selection by PGS alone is allowed in 38 of 66 countries.

IVF with PGT-A is the most accurate and reliable method for sex selection because it allows chromosomal identification of preimplantation embryo selection of the desired sex before embryo transfer but it is a relatively expensive procedure.

IUI with sperm sorting with insemination of X- or Y-enriched semen has reported success rates of 75% for boys and 85% for girls [1]. Sperm sorting thus carries considerable risk of having not having a child of the desired sex. Although available by license internationally, sperm sorting was reported to be allowed in 19 of 66 countries but was reported to be performed in only 11 countries. Sex selection by IVF with PGT-A, combined with sorted insemination has been reported as more efficient than PGT-A or sorting alone.

Selective fetal reduction was reported to be openly practiced and performed in 26 of 66 countries even though it was reported to be only officially approved 18 of 66 countries.

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Summary

While still controversial, use of sex selection technology has become more widely available and prevalent. Increased demand for sex selection technology is likely to be reflected in future surveys. Sex selection and gender-biased sex selection for non-medical reasons remains highly controversial. Normal sex ratio at birth should range from 102 to 106 males per 100 females, yet rates in some regions have been reported to be as high as 130. The bias to have a boy can be rooted in social, economic, and cultural values, with a concurrent lower bias against having a girl. Therefore, the Office of the United Nations High Commissioner for Human Rights (OHCHR), the United Nations Population Fund (UNFPA), the United Nations Children’s Emergency Fund (UNICEF), United Nations Women, and the World Health Organization (WHO) have generated a UN interagency statement titled Preventing gender-biased sex selection. [5]. This joint interagency statement was generated to “reaffirm the commitment of United Nations agencies to encourage and support efforts by States, international and national organizations, civil society and communities to uphold the rights of girls and women and to address the multiple manifestations of gender discrimination including the problem of imbalanced sex ratios caused by sex selection. It thus seeks to highlight the public health and human rights dimensions and implications of the problem and to provide recommendations on how best to take effective action” [5] In a consensus statement, the American Society for Reproductive Medicine (ASRM) Ethics Committee wrote: “Recognizing reasoned differences of opinion, the ASRM Ethics Committee has not reached consensus on whether it is ethical for providers to offer ART for sex selection for nonmedical purposes. Arguments regarding patient autonomy and reproductive liberty have been offered in support of the practice. Risks and burdens of the procedure, gender bias, sex stereotyping and no acceptance of offspring, efforts to guard against coercion, and issues of justice all raise concerns about the practice. Practitioners must take care to ensure that parents are fully informed” [6]

References

[1] Dondorp W, De Wert G, Pennings G, et al. ESHRE Task Force on ethics and Law 20: sex selection for non-medical reasons. Hum Reprod 2013;28(6):1448-1454.

[2] Macklin R The ethics of sex selection and family balancing. Semin Reprod Med 2010;28(4):315-321.

[3] Harper JC, Sengupta SB Preimplantation genetic diagnosis: state of the art 2011. Hum Genet 2012;131(2):175-186.

[4] Garner DL, Evans KM, Seidel GE Sex-sorting sperm using flow cytometry/cell sorting. Methods Mol Biol 2013;927:279-295.

[5] World Health Organization. Preventing gender-biased sex selection: an interagency statement OHCHR, UNFPA, UNICEF, UN Women and WHO. Available at: http://apps.who.int/iris/bitstream/10665/44577/1/9789241501460_eng.pdf. Accessed August 10, 2016.

[6] Ethics Committee of the American Society for Reproductive Medicine. Use of reproductive technology for sex selection for nonmedical reasons. Fert Steril 2015;103:1418-1422.

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CHAPTER 20: FERTILITY PRESERVATION

Utilization of assisted reproductive technology (ART) for fertility preservation in patients facing loss of fertility potential as a result of a malignancy, chronic inflammatory disease, or their treatment is a relatively new application. Increased public awareness of the adverse impact of malignant disease on reproductive potential and the development of new preservation technology has increased demand for fertility preservation services [1]. This need is further enhanced by increased cancer survival rates in reproductive age women hoping to reproduce. The Oncofertility Consortium, a large USA initiative, reported that over 40,000 reproductive age women face loss of fertility from cancer treatment each year [2].

The 2016 survey collected information regarding five principal technologies, which make fertility preservation feasible: oocyte cryopreservation, embryo cryopreservation, ovarian tissue cryopreservation, testicular tissue cryopreservation, and semen cryopreservation [3-6].

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Analysis of the Survey (Chapters 1-5)

Oocyte Cryopreservation

Oocyte cryopreservation is allowed in 49 of 66 countries for medical reasons with formal statutes, laws, and guidelines and in 55 of 66 countries for medical reasons. It is not mentioned or is unstated in the statutes of seven of these 66 countries for non-medical reasons and in two of the 66 for medical reasons. It is prohibited in 11 of the 66 countries for nonmedical reasons and in two of the 66 countries (Uruguay and Bangladesh) for medical reasons. Frozen thawed oocytes are used commonly or infrequently in 50 of the 66 countries for non-medical reasons and in 61 of the 66 countries for medical reasons. Storage limits for cryopreserved oocytes regardless of indication range from no limit to 10 years depending on the country [5] (Table 1).

Chapter 20 Table 1 Is Fertility Preservation of Reproductive Tissues Allowed/Permitted in Your Country?

Chapter 20 Table 1 Is Fertility Preservation of Reproductive Tissues Allowed/Permitted in Your Country?

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Embryo Cryopreservation

Embryo cryopreservation is allowed for nonmedical reasons in 40 of the 66 countries with formal statutes, laws, and guidelines and in 56 of 66 for medical indications. It is not mentioned or is not known in the statutes of five of these 66 countries for nonmedical reasons and in two of the 66 for medical reasons. It is not permitted in 21 of the 66 countries for non-medical reasons and in eight of the 66 countries for medical indications. Frozen thawed preimplantation embryos are used commonly or infrequently in 49 of the 66 countries for non-medical reasons and in 59 of the 66 countries for medical reasons. Storage limits for preimplantation embryos regardless of indication range from no limit to 10 years depending on the country (Table 2).

Chapter 20 Table 2 Is Fertility Preservation Performed in Your Country?

Chapter 20 Table 2 Is Fertility Preservation Performed in Your Country?

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Ovarian Tissue Cryopreservation

Ovarian cryopreservation is allowed in 35 of the 66 countries with statutes for non-medical reasons and in 55 of the 66 countries for medical reasons. It is not mentioned in the statutes of 10 of these 66 countries for non-medical reasons and in two of the 66 for medical reasons. Ovarian cryopreservation is prohibited in 21 of the 66 countries for non-medical reasons and in nine of the 66 countries for medical reasons. Frozen ovarian tissue is used commonly or infrequently in 22 of the 66 countries for non-medical reasons and in 54 of the 66 countries for medical reasons. Storage limits for ovarian tissue regardless of indication range from no limit to 10 years depending on the country [3,4] (Table 3).

Chapter 20 Table 3 If Cryopreservation is Permitted in Your Country, how is Fertility Preservation for the Following Cells and Tissues, for Non-medical Indications, e

Chapter 20 Table 3 If Cryopreservation is Permitted in Your Country, how is Fertility Preservation for the Following Cells and Tissues, for Non-medical Indications, e

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Testicular Tissue Cryopreservation

Testicular tissue cryopreservation is allowed in 39 of the 66 countries with statutes for non-medical reasons and in 59 of the 66 countries for medical reasons. It is not mentioned in the statutes of 10 of these 66 countries for non-medical reasons and in two of the 66 for medical reasons. Testicular tissue cryopreservation is prohibited in 17 of the 66 countries for non-medical reasons and in five of the 66 countries for medical reasons. Frozen testicular tissue is used commonly or infrequently in 32 of the 66 countries for non-medical reasons and in 39 of the 66 countries for medical reasons. Storage limits for testicular tissue regardless of indication range from no limit to 10 years depending on the country [6]. (Table 4)

Chapter 20 Table 4 If Cryopreservation is Allowed in Your Country, how is Fertility Preservation for Medical Indications, (e

Chapter 20 Table 4 If Cryopreservation is Allowed in Your Country, how is Fertility Preservation for Medical Indications, (e

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Semen Cryopreservation

Semen cryopreservation is allowed in 56 of the 66 countries for non-medical indications and in 65 of the 66 for medical indications. It is not mentioned in the statutes of five of these 66 countries for non-medical indications and in one of 66 for medical indications. It is prohibited in Turkey and Uruguay for non-medical indications and in 0 of 66 for medical indications. Frozen thawed sperm is used commonly or infrequently in 55 of the 66 countries for non-medical reasons and in 62 of the 66 countries for medical reasons. Storage limits for cryopreserved sperm regardless of indication ranges from no limit to 10 years depending on the country. (Table 5)

Chapter 20 Table 5 Maximum Duration of Storage Allowed?

Chapter 20 Table 5 Maximum Duration of Storage Allowed?

In countries where cryopreservation of oocytes, ovarian tissue, sperm, testicular tissue, and embryos is permitted for personal reasons, there is governance by federal ordinances in 21, provincial in two, mandated agencies in five, professional organizations in 15, and cultural religious practices in four. In countries where cryopreservation of oocytes, ovarian tissue, sperm, testicular tissue, and embryos is permitted for medical reasons, there is governance by federal ordinances in 39, provincial in one, mandated agencies in seven, professional organizations in 21, and cultural religious practices in four.

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Discussion

Currently, in vitro fertilization (IVF) technology combined with embryo or oocyte cryopreservation is the best option for preserving fertility in women. This survey tabulated five technology paradigms commonly embodied into fertility preservation programmes [3,4].

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Oocyte Cryopreservation

Oocyte cryopreservation has become an increasingly viable option over the past three years. Its major advantage is that a potential male partner is not needed at the time of oocyte collection. Except for unresolved concerns about future birth rates and insurance coverage, oocyte cryopreservation, as reflected in survey statistics, is a less controversial method of fertility preservation. Oocyte cryopreservation is allowed in all of countries surveyed, but laws, regulations, statutes, or guidelines in virtually all countries where it is officially permitted limit its use.

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Embryo Cryopreservation

Embryo cryopreservation has been a viable method of fertility preservation for over 25 years. Its major disadvantage is that it requires sperm from a specific male partner to be used at the time of oocyte retrieval for fertilization. Embryo cryopreservation is allowed in all but one country with time limits for storage specified in many of the countries surveyed.

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Ovarian Tissue Cryopreservation

Ovarian tissue cryopreservation is an option that has emerged over the past 10 years. Reproductive tissues (ovarian or testicular) can be cryopreserved, as can other tissues such as bone marrow, but there is considerable uncertainty about revitalization after thaw. Successful re-implantation and revascularization of ovarian tissue has been described in a limited number of case reports and many failures have also been reported [5]. Methods of restoring oocyte viability by in vitro maturation of primordial oocytes have been successful in laboratory animals but not for human subjects. Despite these unresolved concerns, ovarian or testicular cryopreservation is practiced as a clinical service in 38 of the 43 countries with statutes, laws, and guidelines where it may be offered as a method of fertility preservation for patients diagnosed with malignant disease.

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Testicular Tissue Cryopreservation

Testicular tissue cryopreservation, given the routine use of intracytoplasmic sperm injection (ICSI) with sperm dissected from testicular tissue, is a logical application and is now available as a fertility-sparing paradigm [6].

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Semen Cryopreservation

Semen cryopreservation is the traditional and best-established fertility-sparing paradigm now established throughout the world except in a limited number of cultures, which ban this practice.

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Summary

Continued increased survival rates of reproductive age cancer patients and increasing expectations of survival in these individuals is likely to fuel expanding international demand for fertility preservations that will be reflected in the next 3-year survey. Fertility preservation for these applications was first assessed in Surveillance 2016 and there are no prior data available for historical comparison.

Chart 1

Chart 1

Chart 2

Chart 2

References

[1] McLaren JF, Bates GW Fertility preservation in women of reproductive age with cancer. Am J Obstet Gynecol 2012;207(6):455-462.

[2] Woodruff TK Oncofertillity: a grand collaboration between reproductive medicine and oncology. Reproduction 2015;150(3):S1-10.

[3] MACROBUTTON HTMLDirect Meirow D, Roness H, Kristensen SG, et al. Optimizing outcomes from ovarian tissue cryopreservation and transplantation; activation versus preservation. Hum Reprod 2015;30(11):2453-2456.

[4] Rosendahl M, Greve T, Andersen C The safety of transplanting cryopreserved ovarian tissue in cancer patients: a review of the literature. J Assist Reprod Genet 2013;30(1):11-24.

[5] Argyle CE, Harper JC, Davies MC Oocyte cryopreservation: where are we now? Hum Reprod Update 2016;22(4):440-449.

[6] Picton HM, Wyns C, Anderson RA, et al; ESHRE Task Force On Fertility Preservation In Severe Diseases. A European perspective on testicular tissue cryopreservation for fertility preservation in prepubertal and adolescent boys. Hum Reprod 2015;30(11):2463-2475.

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CHAPTER 21: REPORTING MECHANISMS

Assisted reproductive technology (ART) monitoring, reporting, and follow-up are paramount for the delivery of safe and efficient medically assisted reproductive (MAR) care. Reporting mechanisms measure performance but also register trends in time and changes in practice. The impact on overall safety may be noted while collecting important epidemiologic information [1]. Monitoring mechanisms are also utilized for governing, licensing and credentialing individual professionals and clinics and are an integral part of quality control and quality assurance programmes [2]. Finally, reporting and monitoring are essential for long-term follow up of children born via different ART techniques [3]

The respondents from different countries who completed the International Federation of Fertility Societies (IFFS) questionnaire have presented diverse means for reporting mechanisms including obligatory, legally sanctioned reporting and voluntary reporting to governments, non-governmental organizations, or scientific/clinical societies. Several countries have no regulation whatsoever.

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Analysis of the Survey

The respondents from a majority of countries who completed the IFFS questionnaire (49/70, 70%) reported that some form of reporting requirement is in place, especially in Europe, Australia, Canada, Israel, South Africa, and some Middle Eastern and Asian countries, where the practice of ART was reported to be controlled by laws. In 10 countries (Australia, Austria, Bulgaria, Canada, Germany, Indonesia, Italy, Russian Federation, Sweden and Switzerland), there is even more than one law (e.g.: national and provincial and/or municipal) addressing the matter. In the USA there are multiple statutes (e.g., national, state, and municipal) that have been reported to be addressing ART. Respondents from 20 countries reported that they have no regulations regarding reporting mechanisms, including some in Latin America (Chile, Colombia, Ecuador, El Salvador, Honduras, Mexico, Paraguay, and Venezuela), the Caribbean (Barbados, Trinidad & Tobago), Africa (Cameroon, Nigeria, Kenya, Senegal), India, and Asia (Myanmar, Philippines, Sri Lanka, and Japan). The respondent from Ireland reported there were no reporting mechanisms. Argentina was reported to have a new, expanded, more detailed ART bill including provisions for reporting mechanisms pending in Parliament after an insurance coverage law was reported to have been passed in 2013 (Table 1 and Chart 1).

Chapter 21 Table 1 Are there Monitoring Mechanisms for Governance, Licensure or Credentialing in Your Country?

Chapter 21 Table 1 Are there Monitoring Mechanisms for Governance, Licensure or Credentialing in Your Country?

Chart 1

Chart 1

Respondents from 16 countries (Australia, Brazil, Bulgaria, China, Denmark, Estonia, Finland, France, Germany, Greece, Guatemala, Indonesia, Iran, Portugal, Romania, USA) reported that ART clinics must report to a governmental agency, and respondents from 31 countries a indicated that reports must be made to a licensing body (in some cases with simultaneous reporting to a governmental agency). Finally, respondents from 46 countries (65.7%) reported that ART clinics must report to a professional organization or scientific society, which represents the most prevalent reporting mechanism in place globally (Table 2 and Chart 2).

Chapter 21 Table 2 How is ART Monitored in Your Country

Chapter 21 Table 2 How is ART Monitored in Your Country

Chart 2

Chart 2

The questionnaire also asked respondents about monitoring mechanisms for governance, licensure, or credentialing for centres and for individual professionals (physicians and embryologists). Respondents from a majority of countries (64.2%) reported to have monitoring mechanisms for governance or credentialing of ART centres; respondents from 26 countries (37.1%) reported having monitoring mechanisms applied to individual professionals, including respondents from three countries who reported that monitoring of ART centres does not take place (Canada, Mali and the Netherlands). Respondents from several countries, including Turkey, Austria, and Belgium, reported that there is no monitoring of reproductive endocrinologists, but those countries do have monitoring for Obstetrics and Gynecology (OBGYN) physicians dedicated to reproductive care. Respondents from 36 countries reported monitoring of ART laboratory facilities and procedures, including respondents from 35 of the 45 countries (77.8%) reporting as having ART centre monitoring. The respondent from the Netherlands reported that ART centres are not monitored. Finally, respondents from 22 countries reported having monitoring mechanisms for the ART laboratory director, eight of which do not monitor the rest of laboratory personnel (Austria, Colombia, France, Germany, Israel, the Netherlands, Taiwan [China (Reporting separately for this report.)] and Turkey). Table 3a and b show the distribution and use of these monitoring mechanisms around the world.

Chapter 21 Table 3a How is Monitoring of Governance, Licensure or Credentialing Carried Out?

Chapter 21 Table 3a How is Monitoring of Governance, Licensure or Credentialing Carried Out?

Chapter 21 Table 3b How is Monitoring of Governance, Licensure or Credentialing Carried Out?

Chapter 21 Table 3b How is Monitoring of Governance, Licensure or Credentialing Carried Out?

Table 4a and b show who monitors the adherence to governance, licensure, or credentialing around the world. Adherence to monitoring mechanisms by ART centres was reported to be usually controlled by government officials, or a combination of government officials and agencies (38 of 70 countries, 54.2%). Respondents from nine countries (12.8%) (Austria, France, Greece, Iraq, Ireland, Myanmar, Portugal, South Africa, UK) indicated that the control of this activity was charged to independent agencies, and in Denmark and Japan, by medical officials. Respondents from 11 countries (15.7%) (Bangladesh, Barbados, Cameroon, El Salvador, Guatemala, Malaysia, Nigeria, Senegal, Sri Lanka, Trinidad & Tobago, and Venezuela) reported that there are no mechanisms in place to monitor adherence.

Chapter 21 Table 4a Who Monitors the Adherence of Governance, Licensure or Credentialing in Your Country?

Chapter 21 Table 4a Who Monitors the Adherence of Governance, Licensure or Credentialing in Your Country?

Chapter 21 Table 4b Who Monitors the Adherence of Governance, Licensure or Credentialing in Your Country?

Chapter 21 Table 4b Who Monitors the Adherence of Governance, Licensure or Credentialing in Your Country?

Adherence control in the ART laboratory was similarly distributed, with respondents from 29 countries (41.4%) using government officials or a combination of government officials and agencies. Seven countries (10%) utilized independent agencies, and 13 (18.6%) reported that no mechanisms were in place for checking adherence.

The same trend was observed in the monitoring of adherence control of clinicians, as reported from respondents. Nineteen countries (27.1%) were reported to use governmental officials, independent agencies, or a combination thereof to monitor adherence to regulation. Six countries (8%) were reported to control adherence through independent agencies, 6 (8%) via medical officials, and 16 countries (22.8%) were reported to have no monitoring of adherence.

Regarding laboratory personnel, respondents from 17 countries (24.3%) reported the regulation of issues surrounding activities through governmental officials, independent agencies, or a combination thereof Six (8%) use just independent agencies, four rely on medical officials, and 16 countries (22.8%) were reported to have no regulation.

ART outcome monitoring was also addressed in the questionnaire. The majority of countries were reported to rely on governmental officials and independent agencies (28/70, 40%) for outcome assessments. Four countries were reported to utilize medical officials for monitoring outcomes, and 14 (20%) were reported to have no requirement for follow-up. In many countries, outcomes were reported to also be monitored by professional organizations or scientific societies (including most Latin American countries, which report to the Redlara Society, and specially created licensing and/or regulatory agencies in the UK and Australia). Monitoring of ART centres was carried out with a variety of mechanisms. Respondents from five countries (7.1%; Colombia, Estonia, Guatemala, Ireland and Venezuela) claimed that they reported to an international registry, and respondents from 18 countries (25.7%) claimed that they reported sending results to national registries. Respondents from 11 countries (Argentina, Austria, Belgium, Denmark, Germany, Indonesia, Italy, South Africa, Spain, UK, and the US) reported also having onsite inspections to validate their reports or had periodic reporting. Respondents from six countries (Australia, Bulgaria, Kazakhstan, Singapore, Slovak Republic, and South Korea) noted that monitoring was carried out through periodic reporting and on-site inspection only, and respondents from two countries (Philippines and Senegal) reported use of only periodic reporting. Bangladesh, Belarus, Ecuador, India, Iran, the Netherlands, and The Russian Federation reportedly have only on-site inspection. The respondent from Canada reported that voluntary reporting to a national database was taking place, and the respondent from Greece reported that they were in the process of instituting new regulatory measures.

Monitoring of reproductive endocrinologists and other physicians practicing ART was reported to be performed through national registries in 11 countries (11/70, 15.7%), in 12 countries (17.1%) through on-site inspection or periodic reporting (in some cases jointly with an accreditation process), and in seven cases (10%) through a recertification process. Nine respondents (12.8%) did not know how physicians were monitored.

Monitoring of the ART laboratory followed the same trend as ART centres as a whole, with respondents from 13 countries (18.6%) reporting to a national registry and undergoing on-site inspections and periodic reporting. Five (7.1%) report to international registries and 22 (31.4%) utilize only on-site inspections, periodic reporting, or both.

Respondents from 16 countries (16/70, 22.8%) reported the occurrence of previous violations of national policies pertaining to the practice of ART. These countries include Australia, Belgium, Brazil, Canada, China, Czech Republic, Germany, Greece, Iran, Israel, Japan, Kazakhstan, Panama, Romania, Russian Federation, and the US. Furthermore, respondents from 40 countries (57.1%) reported that there had been no violations and the violation history was reported by respondents from 11 countries (15.7%) as unknown (Table 5).

Chapter 21 Table 5 Violations of ART Policies

Chapter 21 Table 5 Violations of ART Policies

Respondents from 40 countries (57.1%) reported that specific penalties exist for such violations, and a variety of punishments were reported including financial penalties, loss of accreditation or license to practice, closure of the centre, and criminal charges including fines and imprisonment.

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Summary

In brief, monitoring and reporting mechanisms are reported to be in place in most of Europe, Australia, the USA, Southeast Asia, and Latin America. A wide array of mechanisms was reported to be in place to accomplish monitoring and ensure enforcement. These mechanisms include utilization of government officials and independent agencies, but primarily professional organizations and scientific societies. The latter also were reported to play a prominent role in auditing clinical and laboratory outcomes, as well as licensing and certifying ART procedures.

References

[1] European IVF-Monitoring Consortium (EIM); for the European Society of Human Reproduction and Embryology (ESHRE). Kupka MS, D’Hooghe T, Ferraretti AP, et al. Assisted reproductive technology in Europe, 2011: results generated from European registers by ESHRE. Hum Reprod 2016;31(2):233-248.

[2] McTavish A, Akande V, Cutting R, et al. Quality Manual. Incorporating HFEA Standard Licence Conditions. Available at: http://http://www.hfea.gov.uk/docs/Quality_Manual_June_2011.pdf Accessed August 11, 2016.

[3] Belva F, Roelants M, Painter R, et al. Pubertal development in ICSI children. Hum Reprod 2012;27(4):1156-1161.

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CHAPTER 22: SAME SEX AND SINGLE PARENTING POLICIES

Requirement for Recognized or Stable Heterosexual Relationship

Participants were asked whether a couple or an individual was required to be in a recognized or stable heterosexual relationship in order to access in vitro fertilization (IVF) or assisted reproductive technology (ART) services in their country (Table 1). Of the 70 respondents, 36 (51%) responded that there was no such requirement in their country. Thirty-one (44%) responded that there was a requirement for a recognized or stable heterosexual relationship. Three respondents did not know.

Chapter 22 Table 1 Access to IVF or ART Services

Chapter 22 Table 1 Access to IVF or ART Services

Where there did exist a requirement, countries differed on whether such a requirement was found in law, ordinances, guidelines, cultural practice, and/or religious decree. Eighteen of the countries that required a recognized or stable heterosexual relationship reported that this requirement was found in federal or state laws or ordinances. Of these, the Slovak Republic and Jordan also mentioned cultural practice, and Jordan also religious decree. Hong Kong [China (Reporting separately for this report.)] reported the requirement was governed by agency regulation and oversight. Nine countries reported the requirement as stemming from professional organization standards and guidelines, noting that of these, Senegal and Bangladesh also mentioned cultural standards, and Bangladesh and Saudi Arabia also mentioned religious decree. Indonesia and Iran reported their requirement as being found only in religious decree. The Philippines did not report where the requirement came from.

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Single, Transgender, and Intersex People, and Same Sex Couple Policies

Introduction

This is the first time data on access to ART by single males or females, transgender, or intersex people, and people in same sex male or female couples, has been comprehensively considered in Surveillance (Table 2).

Chapter 22 Table 2 If there is no Requirement for an Official or Stable Heterosexual Union, is IVF or ART Services Accessible to?

Chapter 22 Table 2 If there is no Requirement for an Official or Stable Heterosexual Union, is IVF or ART Services Accessible to?

While Chapter 4 considered the marital status question, this Chapter considers first questions directed at countries that do not have a specified requirement for a stable heterosexual relationship for access to ART or IVF. Thus, 36 countries were asked if single women, single men, same sex female couples, same sex male couples, transgender, and/or intersex people could access ART or IVF services. Questions were also asked of these respondents regarding whether their respective countries recognize the same sex partner of someone who has accessed treatment as the legal parent of any child born as a result.

Following this, analysis of the types of treatments and practices available to single males or females, transgender, or intersex people, and people in same sex male and/or female couples, in all responding countries is undertaken. This includes consideration of whether diagnostic evaluation was available, intra-uterine insemination, IVF, pre-implantation genetic diagnosis, pre-implantation genetic screening, donor sperm, eggs and embryos, and consideration of traditional and gestational forms of surrogacy.

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Access to ART and IVF in Countries that do Not have a Specified Heterosexual Relationship Requirement

Of the 70 respondents, there were 36 countries that had no requirement for a recognized or stable heterosexual relationship to access IVF or ART. Respondents from these 36 countries were asked if single women, single men, same sex female couples, same sex male couples, transgender, and/or intersex people could access services.

Columbia answered negative to all services, suggesting that while there was no official law, guidance, or religious decree governing such practices in that jurisdiction, single people, people in same sex relationships, transgender and intersex people could not be provided access IVF or ART services.

The other 35 countries all reported that single women would be able to access services. They then varied regarding single men, people in same sex relationships, and transgender or intersex people. Access to IVF or ART services by (Chart 1):

Chart 1

Chart 1

  • Single men were reported as possible by 16 respondents, with the Netherlands stating it was unknown, and 18 reporting it was not possible;
  • Same sex female couples were reported as possible by 28 respondents, with three unknown, and four reporting it was not possible;
  • Same sex male couples were reported as possible by 13 respondents, with three unknown, and 19 reporting it was not possible;
  • Transgender people was reported as possible by 14 respondents, with nine unknowns, and 12 reporting it was not possible; and
  • Intersex people was reported as possible by 14 respondents, with nine unknowns, and 12 reporting it was not possible.
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Same Sex Couples: Recognition of Same Sex Partner as Parent of Resulting Child

Participants were also asked whether their country has laws that recognize the same sex partner of a person who has used assisted reproduction as a legal parent of the resulting child (Table 3).

Chapter 22 Table 3 Does Your Country have Laws that Recognize the Same Sex Partner of a Person Who has Used Assisted Reproduction as a Legal Parent of the Resulting Child?

Chapter 22 Table 3 Does Your Country have Laws that Recognize the Same Sex Partner of a Person Who has Used Assisted Reproduction as a Legal Parent of the Resulting Child?

Eighteen countries (52%) recognized the same sex partner of a woman as a legal parent of the resulting child, while 12 (34%) recognized the same sex partner of a man as a legal parent of the resulting child.

Interestingly, this may indicate that although same sex coupled women are permitted to access treatment in a greater number of countries than men in same sex couples, the recognition of legal parentage of the resulting child for both people in the couple did not necessarily follow for women. For men, countries that allow same sex coupled males to access treatment also generally recognize both members of the couple as legal parents.

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Types of ART Accessible by Single, Transgender or Intersex People, and Same Sex Female or Male Couples

All respondent countries were also asked questions about access by single, transgender, intersex people, and people in same sex relationships, to certain ART techniques; procedures; egg, sperm and embryo donation practices; and surrogacy (Table 4 and Charts 2–4).

Chapter 22 Table 4 To Whom are Treatments Allowed/Permitted?

Chapter 22 Table 4 To Whom are Treatments Allowed/Permitted?

Chart 2

Chart 2

Chart 3

Chart 3

Chart 4

Chart 4

It was reported that none of the above ART treatments or practices are available to single, transgender, or intersex people, or same sex couples in Bangladesh, Colombia, Hong Kong [China (Reporting separately for this report.)], Indonesia, Iraq, Japan, Jordan, Kenya, Mali, Myanmar, Portugal, Sri Lanka, Taiwan [China (Reporting separately for this report.)], or Tunisia. Other procedures varied across countries. It is noteworthy that in many countries some practices are not available to anyone, and it may not just be a matter of relationship status, sex, or gender identity that determines the availability of services. For example, egg donation, embryo donation, and/or surrogacy are prohibited in many countries.

The following is nevertheless useful in considering which services are available and to whom in relation to non-heterosexual relationship status, sex, and/or gender identity.

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Diagnostic Evaluation

Twenty four (34%) of the 70 respondent countries reported that diagnostic evaluation was available to all people regardless of relationship status, sex, or gender identity. Many others reported limited and varied availability of diagnostic evaluation to single, transgender or intersex people, and/or same sex female or male couples.

Respondents from Saudi Arabia and Senegal specified diagnostic evaluation being available only for intersex people. In France, it was only reported to be available for transgender people.

Other respondent countries included only single women (Barbados, Greece, Nigeria, and Uruguay); same sex female married couples (Austria and Sweden); single women and same sex women in married relationships (Chile, Ecuador, Estonia, Finland); single women, same sex women in married relationships, and intersex people (the Netherlands); and single women, same sex women in married relationships, intersex, and transgender people (Denmark).

Cameroon, China, Honduras, Hungary, India, Iran, Israel, Italy, Kazakhstan, Malaysia, and Peru reported diagnostic evaluation as available for single women and single men. El Salvador added to that women in same sex married relationships. The Philippines and Venezuela added to that again by including men in same sex married relationships.

The Russian Federation, Slovak Republic, and Turkey reported that diagnostic evaluation was available in their respective countries to single women, single men, transgender, and intersex people.

Access to diagnostic evaluation by single women was mentioned by 51 (73%) of the respondents; women in same sex relationships by 34 (49%) of the respondents; intersex people by 31 (44%) of the respondents; single men by 30 (43%) of the respondents; transgender people by 29 (41%) of the respondents; and men in same sex relationships by 26 (37%) of the respondents.

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Intra-Uterine Insemination (IUI)

Twenty four respondent countries did not report on any availability of IUI for non-heterosexual coupled people. Australia, Belgium, Brazil, Canada, Ireland, Romania, and the UK reported that IUI is available to all people regardless of relationship status, sex, or gender identity. The USA was similar, although did not select same sex male married couples in this section.

Saudi Arabia and Senegal reported its availability for intersex people, whereas France reported for transgender people.

Barbados, Greece, Nigeria, Uruguay, Hungary, India, Israel, Peru, Belarus, and the Russian Federation for single women. Austria, Sweden, and Norway for same sex female married couples. Chile, Ecuador, Estonia, Finland, the Netherlands, El Salvador, Argentina, Bulgaria, Germany, Guatemala, and Paraguay for both single women and women in same sex married couples.

Denmark, Mexico, South Africa, South Korea, Spain, and Trinidad and Tobago reported IUI for single women and women in same sex married couples, and transgender and intersex people.

Honduras and Kazakhstan reported IUI for single women and single men. Venezuela and Panama adding to single women and men, same sex female and same sex male couples.

Access to IUI by single women was therefore mentioned by thirty nine of the respondents (56%); women in same sex relationships by thirty two of the respondents (46%); intersex people by sixteen of the respondents (23%); transgender people by fifteen of the respondents (21%); single men by twelve of the respondents (17%); and men in same sex relationships by nine of the respondents (13%). Presumably the countries that responded that men may access IUI must be alluding to circumstances in which that male seeks the treatment of a female (e.g., a gestational carrier mother).

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In-Vitro Fertilization (IVF)

Twenty five countries (36%) did not select IVF as being available to single people, people in same sex relationships, or transgender or intersex people. In contrast, Mexico, Australia, Belgium, Canada, Ireland, Romania, the UK, and the USA all report the availability of IVF to all such people. The respondent from Brazil also selected all such people, except intersex.

Other respondents selected varied availability of IVF as follows:

  • Saudi Arabia and Senegal reported its availability for intersex people. France reported for transgender people.
  • Barbados, Greece, Nigeria, Uruguay, Hungary, Israel, Belarus, the Russian Federation, and Kazakhstan report IVF is available for single women. Austria, Sweden, and Norway for same sex female married couples. Chile, Ecuador, Estonia, Finland, the Netherlands, El Salvador, Argentina, Bulgaria, Germany, Guatemala, and Paraguay for both single women and women in same sex married couples.
  • Denmark, South Africa, South Korea, Spain, and Trinidad and Tobago reported the availability of IVF for single women and women in same sex married couples, and transgender and intersex people.
  • India, Peru, and Honduras report the availability of IVF for single women, and single men. Venezuela and Panama report the available of IVF for single women, single men, same sex female married couples, and same sex male married couple.
  • Access to IVF by single women was therefore mentioned by 39 (56%) of the respondents; women in same sex relationships by 30 (43%) of the respondents; intersex people by 16 (23%) of the respondents; transgender people by 16 (23%) of the respondents; single men by 14 (20%) of the respondents; and men in same sex relationships by 11 (16%). Presumably, the availability of IVF to men would entail them having to enter an arrangement for a woman to carry the pregnancy.
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Pre-Implantation Genetic Diagnosis (PGD)

Thirty two (46%) of the 70 respondents did not select PGD as being available to single people, people in same sex relationships, or to transgender or intersex people. Again, it is noteworthy that PGD may also not be available to heterosexual people in some cases as it may not be practiced or may be against the law.

Where availability was selected, it again varied as to whom may access PGD. Respondents from South Africa, South Korea, Brazil, Mexico, Australia, Belgium, Canada, Ireland, Romania, UK, and USA reported its availability to all people regardless of sex, gender identity, or relationship status.

Saudi Arabia reported its availability for intersex individuals. France, for transgender people. Barbados, Greece, Nigeria, Israel, Belarus, the Russian Federation, Kazakhstan, Peru, and Panama reported its availability for single women. Austria, Sweden, and Norway reported PGD is available for same sex women married couples. Chile, Estonia, Finland, the Netherlands, Bulgaria, Guatemala, Paraguay, and Spain reported PGD as available to both single women, and same sex female married couples.

Denmark, and Trinidad and Tobago, reported PGD as available for single women, women in same sex married couples, transgender, and intersex individuals. India reported IVF availability for single women and single men. Venezuela reported availability for single women, single men, same sex female married couples, and same sex male married couples.

Access to PGD by single women was therefore mentioned by 32 (46%) of the respondents; women in same sex relationships by 25 (36%) of the respondents; intersex people by 14 (20%) of the respondents; transgender people by 14 (20%) of the respondents; single men by 13 (19%) of the respondents; and men in same sex relationships by 12 (17%) of the respondents. It should be stated that the circumstances in which PGD is available were not made explicit here, and there may be further conditions, such as risk of passing on a genetic disease, that must be met in some locations.

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Pre-Implantation Genetic Screening (PGS)

Thirty nine of seventy respondents (56%) reported that PGS was not available to single, transgender, intersex people, or to people in same sex couples. Again, PGS may or may not be available to heterosexual couples, or permitted at all in these countries.

PGS was reported to be available to all people regardless of relationship status, sex, or gender identity in South Africa, South Korea, Brazil, Mexico, Australia, Belgium, Canada, Romania, and the USA. In Saudi Arabia, PGS was reported to be available to intersex people. In Barbados, Greece, Nigeria, Belarus, the Russian Federation, Kazakhstan, and Panama, it was reported to be available for single women. In Austria, it is available to women in same sex married couples. In Chile, Ecuador, Estonia, Finland, Bulgaria, Guatemala, Paraguay, and Spain it was reported that PGS as available to both single women and women in same sex married couples.

The respondent from Trinidad and Tobago reported PGS as available for single women, women in same sex married couples, transgender individuals, and intersex individuals. In Israel, PGS was reported to be available to single men. It is available to both single women and single men in India and Peru. In Venezuela, PGS was reported as available to single women, single men, women in same sex married couples, and men in same sex married couples.

Access to PGS by single women was therefore mentioned by 28 (40%) of the respondents; women in same sex relationships by 20 (29%) of the respondents; single men by 13 (19%) of the respondents; intersex people by 11 (16%) of the respondents; transgender people by 10 (14%) of the respondents; and men in same sex relationships by 10 (14%) of the respondents. It is important to note that the circumstances in which PGS is available were not made explicit here, and there may be conditions - such as risk of passing on a genetic disease - that must be met in some locations.

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Donor Sperm

Twenty seven (39%) of 70 respondents reported that donor sperm was not available to single, transgender, intersex people, or to people in same sex couples. Again, donor sperm may or may not be available to heterosexual couples, or permitted at all in these countries.

Donor sperm was reported to be available to all people regardless of relationship status, sex, or gender identity in South Africa, South Korea, Brazil, Mexico, Australia, Belgium, Canada, Romania, Ireland, the UK, and the USA.

In France, donor sperm was reported as being available for transgender people. In Israel, Barbados, Greece, Nigeria, Belarus, the Russian Federation, Kazakhstan, Panama, India, Uruguay, and Hungary it was reported to be available for single women. In Austria, Sweden, and Norway donor sperm is available to women in same sex married couples. In Chile, Ecuador, Estonia, Finland, Bulgaria, Guatemala, Paraguay, Spain, the Netherlands, El Salvador, Argentina, and Germany it was reported that donor sperm was available to both single women and women in same sex married couples. Respondents from Denmark and Trinidad and Tobago reported donor sperm as available for single women, women in same sex married couples, transgender individuals, and intersex individuals. Peru and Honduras reported availability for single women and single men. In Venezuela, donor sperm was available for single women, single men, women in same sex married couples, and men in same sex married couples.

Access to donor sperm by single women was therefore mentioned by 39 (56%) of the respondents; women in same sex relationships by 29 (41%) of the respondents; single men by 14 (20%) of the respondents; transgender people by 14 (20%) of the respondents; intersex people by 13 (19%) of the respondents; and men in same sex relationships by 12 (17%) of the respondents.

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Donor Egg

Thirty three (47%) of 70 respondents reported that donor eggs were not available to single, transgender, intersex people, or to people in same sex couples. Again, donor eggs may or may not be available to heterosexual couples, or permitted at all in these countries.

Donor eggs were reported as being available to all people regardless of relationship status, sex, or gender identity in South Africa, South Korea, Brazil, Mexico, Australia, Belgium, Canada, Romania, Ireland, the United Kingdom, and the USA. In France, donor eggs were reported as being available for transgender people.

Respondents from Barbados, Greece, Nigeria, Belarus, the Russian Federation, Kazakhstan, Panama, Uruguay, and Hungary reported that donor eggs were available for single women. In Chile, Estonia, Finland, Bulgaria, Guatemala, Paraguay, Spain, the Netherlands, and Argentina, it was reported that donor eggs are available to both single women, and women in same sex married couples. Trinidad and Tobago reported donor eggs as available for single women, women in same sex married couples, transgender, and intersex individuals. Israel, India, Peru and Honduras report that donor eggs are available for single women and single men.

In Venezuela, donor eggs were reported as available for single women, single men, women in same sex married couples, and men in same sex married couples.

Access to donor eggs by single women was therefore mentioned by 35 (50%) of the respondents; women in same sex relationships by 22 (31%) of the respondents; single men by 16 (23%) of the respondents; transgender people by 13 (19%) of the respondents; intersex people by 12 (17%) of the respondents; and men in same sex relationships by 12 (17%) of the respondents (17%).

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Donor Embryos

Thirty five (50%) of 70 respondents reported that donor embryos were not available to single, transgender, intersex people, or to people in same sex couples. Again, donor embryos may or may not be available to heterosexual couples, or permitted at all in these countries. Donor embryos were reported as being available to all people regardless of relationship status, sex, or gender identity in South Africa, South Korea, Brazil, Australia, Belgium, Canada, Romania, Ireland, the United Kingdom, and the USA. In France, donor embryos were reported as being available for transgender people. In Israel, donor embryos were reported as being available to single men.

In Barbados, Greece, Nigeria, Belarus, the Russian Federation, Kazakhstan, Panama, Uruguay, India, and Hungary, donor embryos were reported to be available for single women. In Chile, Estonia, Finland, Bulgaria, Guatemala, Paraguay, Spain, the Netherlands, and Argentina, it was reported that donor embryos are available to both single women, and women in same sex married couples. Trinidad and Tobago reported donor embryos as available for single women, women in same sex married couples, transgender individuals, and intersex individuals. Peru and Honduras report that donor embryos are available for single women and single men. In Venezuela donor embryos were reported as available for single women, single men, women in same sex married couples, and men in same sex married couples.

Access to donor eggs by single women was therefore mentioned by 24 (34%) of the respondents; women in same sex married couples by 21 (30%) of the respondents; single men by 14 (20%) of the respondents; transgender people by 12 (17%) of the respondents; intersex people by 11 (16%) of the respondents; and men in same sex relationships by 11 (16%) of the respondents.

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Gestational Carrier Arrangements

Traditional gestational carrier - i.e. in which the gestational carrier (mother’s) ova are inseminated with a prospective parent’s sperm. Fifty five (79%) of the 70 responding countries did not report permitting traditional gestational carrier (TGC) arrangements.

Seven countries (Brazil, Australia, Belgium, Canada, Romania, USA, and Mexico) reported allowing traditional gestational carriers regardless of relationship status, sex, or gender identity. Israel reported allowing single men to access traditional gestational carriers, while Nigeria, the Russian Federation, Kazakhstan, and Peru reported allowing single women to access traditional gestational carriers. The Netherlands reported allowing access by single women and women in same sex relationships. Honduras reported allowing access to traditional gestational carriers by single women and single men.

It is important to note that within these countries, the circumstances, in which; such arrangements were permitted (i.e. altruistic vs. commercial; any criteria to be met—such as infertility, age, screening, etc.), were not further detailed.

Gestational Carrier Arrangements Using Donated Ova and Commissioning Person’s Sperm.Fifty two (74%) of the 70 responding countries did not report permitting gestational carrier arrangements GC) using donated ova and the commissioning person’s sperm.

Seven countries (Brazil, Australia, Belgium, Canada, Mexico, South Africa, and South Korea) reported allowing gestational carriers in such circumstances regardless of relationship status, sex, or gender identity. The USA reported allowing all such people other than intersex individuals.

The respondent from India reported allowing single men to access gestational carriers using donated ova and the commissioning person’s sperm. Nigeria, the Russian Federation, Kazakhstan, Greece, Belarus, Uruguay, and Peru reported allowing single women to access gestational carriers using donated ova and the commissioning person’s sperm.

The Netherlands reported allowing access by single women and women in same sex relationships. Honduras reported allowing access to gestational carriers using a donated ova and the commissioning person’s sperm by single women and single men.

Again, it is important to note that within these countries the circumstances in which such arrangements were permitted (i.e. altruistic vs. commercial; any criteria to be met—such as infertility, age, screening, etc.) were not further detailed.

Gestational Carrier Arrangements Using Donated Ova and Donated Sperm.Fifty three (76%) of the 70 responding countries did not report permitting gestational carriers using donated ova and donated sperm.

Seven countries (Brazil, Australia, Belgium, Canada, Mexico, Romania, and the USA) reported allowing gestational carriers in such circumstances regardless of relationship status, sex, or gender identity. The respondent from Israel reported allowing single men to access gestational carriers using donated ova and donated sperm. Respondents from Nigeria, the Russian Federation, Kazakhstan, Greece, Belarus, and Peru reported allowing single women to access gestational carriers using donated ova and donated sperm. Honduras respondents reported allowing access to gestational carriers using a donated ova and donated sperm by single women and single men.

The Netherlands and Bulgaria reported allowing its use by women in same sex married couples. Bulgaria also allowed its use by single women.

Note again, within these countries the circumstances in which such arrangements were permitted (i.e. altruistic vs. commercial; any criteria to be met—such as infertility, age, screening, etc.) were not further detailed.

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Discussion

Thirty six of the 70 respondents that participated in Surveillance reported that they had no formal laws, ordinances, guidelines, or religious decrees that required a recognized stable heterosexual relationship to access ART or IVF. These respondents were then asked if single women, single men, same sex female couples, same sex male couples, transgender individuals, and/or intersex people could access ART or IVF services. Thirty five of the respondents answered in the positive, with access by identified group then varying. Single women were reported to have access in all 35 (100%) countries, women in same sex couples were reported to have access in 80% of the countries, single men had access in 46% of the countries, transgender and intersex people in 40% of the countries, and men in same sex couples, access in 37% of the respondent countries.

Questions were also asked regarding whether the respective countries recognize the same sex partner of someone who has accessed treatment as the legal parent of any child born as a result. Interestingly, while the above had reported allowing rates of 80% for access to ART or IVF for women in same sex couples, the recognition of same sex female partners as parents of the resulting child was only 52%. For men in same sex couples, the recognition of the partner as a legal parent of any resulting child also low (34%), and much closer to the actual permitted access rate.

Further scrutiny of all 70 responding countries was undertaken to examine access to a variety of treatments and practices by single males or females, transgender individuals, intersex people, and people in same sex male or female couples. This included consideration of whether diagnostic evaluation was available; intra-uterine insemination; IVF; pre-implantation genetic diagnosis; pre-implantation genetic screening; and access to donor sperm, eggs and embryos.

When access was available, single women generally had the most access, but also the greatest variability of access across treatments. Single women’s reported access ranged from 34% for donor embryos to 73% for diagnostic evaluation across the 70 respondent countries. This was followed by women in same sex couples, whose rates of access ranged from 29% for donor embryos to 49% for diagnostic evaluation. Single men, transgender individuals, and intersex people, as well as men in same sex couples, often had similar rates of access (within 1-3% of each other) with countries showing only slight differences at times in relation to the service or practice available to them. The reported range of access for single males was 17% (access to IUI) to 43% (access to diagnostic evaluation). For same sex male couples, reported access rates ranged from 13% (access to IUI) to 44% (access to diagnostic evaluation). For transgender people, reported rates of access ranged from 14% (access to PGS) to 41% (access to diagnostic evaluation). For intersex people, access rates ranged from 16% (access to PGS and to donor embryos) to 44% (access to diagnostic evaluation).

Overall the results indicate that single men, men in same sex couples, and transgender and intersex people had less access than single women to treatments and ART practices such as diagnostic evaluation; intra-uterine insemination; IVF; pre-implantation genetic diagnosis; pre-implantation genetic screening; and access to donor sperm, eggs and embryos. Women in same sex couples had only slightly higher access than men, transgender and intersex people, and had less access than single women. The reasons for such differences were not explored, however it is noted that some of the included treatment types may have been less suitable for application in men (e.g., IUI). There may also have been some differences in interpretation of questions by respondents. For example, it is difficult to know why people selected access to IUI for single men or men in same sex relationships, unless they had assumed a female’s presence.

Finally, access to surrogacy by the above mentioned groups was also explored. Many countries reported not permitting access to surrogacy at all (79% traditional; 74% gestational with donated ova and commissioning person’s sperm; 76% gestational with donated ova and donated sperm). It is likely, given the extensive prohibitions of such practices across the globe, that these countries’ positions most often would apply to all people, and are not based on relationship status, sex, or gender identity, although there may be some countries that only permit surrogacy for stable heterosexual couples. In the countries that did report permitting some form of surrogacy, access was generally available to people regardless of relationship status, sex, or gender identity, while there were some countries that specified single male, single female, or same sex female couple. There were slight variations also among whether countries permitted traditional gestational carriers (using the birth mother’s own ova), gestational carriers using donated ova and commissioning person’s sperm, and/or gestational carriers using donated ova and donated sperm. Note, however, that data collected in relation to surrogacy for this chapter only gives some indication regarding access by the respective groups of people examined. The circumstances in which such arrangements were permitted (i.e. altruistic vs. commercial; criteria to be met—such as infertility, age, screening, counseling, approvals, etc.), was not further explored or detailed.

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CHAPTER 23: CROSS-BORDER REPRODUCTION

Respondents from 64 countries replied to some or all of the questions concerning cross-border reproduction.

Of particular interest was whether or not people travel to or from the respondent’s country to engage in assisted reproductive technology (ART), including whether they do so to seek lower cost services, higher quality services, or services not available in their home country, as well as whether people seek egg, embryo, or sperm donations, and/or gestational carrier arrangements.

In addition, information was gathered about whether there exists regulation of inbound and outbound people wishing to engage in cross-border reproduction, and regarding the import and export of tissue.

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Do People Visit Your Country to Seek Cross-border Reproduction? ( Table 1 and Charts 1–3)

Incoming for Lower Cost Services

Charts 1–3 Respondents from 47 countries (73%) reported people traveling to their country to seek lower cost ART services. Respondents from Chile, France, Italy, Japan, Norway, Singapore, and Switzerland (11%) reported that people do not travel to their country for lower cost services. In Australia, Greece, Ireland, the Netherlands, Portugal, Sweden, and the United Kingdom (11%) the respondents reported that this information was unknown. Respondents from 3 (5%) of the 64 countries that reported on questions concerning cross-border reproduction did not address this question.

Chapter 23 Table 1 Do People Visit your Country to Seek Assisted Reproduction?

Chapter 23 Table 1 Do People Visit your Country to Seek Assisted Reproduction?

Chart 1

Chart 1

Chart 2

Chart 2

Chart 3

Chart 3

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Incoming for Higher Quality ART Services

Respondents from 51 countries (80%) reported that people travel to their country for higher quality services. Respondents from Norway, Bangladesh, and Estonia (5%) reported that people do not travel to their country for higher quality services. In Australia, Greece, Ireland, the Netherlands, Portugal, the United Kingdom, Kenya, and Trinidad and Tobago (13%) such actions were reported by the respondents as unknown. Respondents from 2 (2%) of the 64 countries that answered the cross-border reproduction questions did not answer this question.

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Incoming for ART Services Unavailable in their Home Country

Respondents from 52 countries (82%) reported that people travel to their country to access services that are not available in their home country. Respondents from Norway, Japan, China, Romania, and Tunisia (8%) reported that people do not visit their country for cross-border reproduction. Respondents from Bangladesh, Australia, and the Netherlands (5%) replied that this was unknown. Respondents from four (5%) of the countries that responded to questions on cross-border reproduction did not address this query.

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Incoming for Egg Donation

Respondents from 33 countries (52%) reported that people travel to their country to access egg donation. Seventeen respondents (27%) reported that people from other countries do not travel to their country to engage in egg donation. Respondents from Australia, the Netherlands, Ireland, the United Kingdom, Kenya, and Argentina (9%) reported that this was unknown. Respondents from eight of the 64 countries that responded to questions on cross-border reproduction did not address this issue.

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Incoming for Embryo Donation

Respondents from 21 countries (33%) reported that people travel to their country to access embryo donation. Twenty-one respondents (33%) reported that people from other countries do not travel to their country to engage in embryo donation. Respondents from Hungary, Australia, the Netherlands, Ireland, the United Kingdom, Kenya, Argentina, Estonia, Portugal, Malaysia, Mexico, and Brazil (19%) reported that this information was unknown. Respondents from 10 of the 64 countries (15%) that responded to questions on cross-border reproduction did not address this issue.

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Incoming for Sperm Donation

Respondents from 29 countries (45%) reported that people travel to their country to access sperm donation. Eighteen respondents (28%) reported that people from other countries do not travel to their country to engage in sperm donation. Respondents from Switzerland, Germany, Australia, the Netherlands, Ireland, the United Kingdom, Kenya, Argentina, and Brazil (14%) reported that this was unknown. Respondents from eight of the 64 countries that responded to questions on cross-border reproduction did not address this issue.

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Incoming for Gestational Carrier Arrangements

Respondents were asked if people travelled to their countries to engage in gestational carrier arrangements, defined as “the gestational carrier is implanted with an embryo(s) created using the gametes of both prospective parents; or donated ova and commissioning male’s sperm; or a donated embryo”. Fourteen respondents (22%) answered in the affirmative, 29 (45%) answered “no”, nine respondents (14%) said that this was unknown, and 12 respondents (19%) did not address the question.

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Incoming for Traditional Gestational Carrier Arrangements

Respondents were asked if people travelled to their countries to engage in traditional gestational carrier arrangements, defined as being a procedure “in which the gestational carrier’s ova are inseminated with a prospective parent’s sperm”. Six respondents (9%) answered in the affirmative, 32 (50%) answered “no”, 11 respondents (17%) said that this was unknown, and 15 respondents did not address the question.

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Do People Travel from Your Country to Another Country to Seek Cross-border Reproduction? ( Table 2 and Charts 4–6)

Outgoing for Lower Cost Services

Respondents from 26 countries (41%) reported people traveling from their country to other countries to seek lower cost ART services. Twenty respondents (31%) said that people from their country do not travel to other countries for lower cost services. Respondents from Argentina, Greece, Kenya, Mali, the Slovak Republic, South Korea, Sri Lanka, and Taiwan [China (Reporting separately for this report.)], (12.5%) reported that this information was unknown. Respondents from 10 of the 64 countries that responded to questions on cross-border reproduction did not address this question.

Chapter 23 Table 2 Do People Travel From your Country to Seek Assisted Reproduction?

Chapter 23 Table 2 Do People Travel From your Country to Seek Assisted Reproduction?

Chart 4

Chart 4

Chart 5

Chart 5

Chart 6

Chart 6

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Outgoing for Higher Quality ART Services

Respondents from 33 countries (52%) reported that people travel from their country to another country to access higher quality services. Respondents from 13 countries (Austria, Belgium, Chile, Czech Republic, Finland, France, Hungary, Ireland, Peru, South Africa, Switzerland, the United Kingdom, and the USA) (20%) reported that people do not travel from their country to other countries for higher quality services. Respondents from 10 countries (15.5%) reported such actions as unknown. Respondents from eight (12.5%) of the 64 countries that answered the cross-border reproduction questions did not answer this question.

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Outgoing for ART Services Unavailable in their Home Country

Respondents from 33 countries (52%) reported that people travel from their country to other countries to access services not available in their home country. Respondents from 17 countries (26.5%; including Austria, Chile, Peru, South Africa, USA, Canada, Slovak Republic, Sri Lanka, Trinidad and Tobago, China, Greece, Panama, Romania, Russian Federation, Saudi Arabia, Senegal, and Turkey) reported that people do not travel to other countries for these purposes. Respondents from Argentina, Mali, Bangladesh, South Korea, and Kenya (8%) replied that this was unknown. Respondents from nine of the 64 countries (14%) that responded to questions on cross-border reproduction did not address this issue.

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Outgoing for Egg Donation

Respondents from 35 countries (55%) reported that people travel from their country to another country to access egg donation. Thirteen respondents from 13 countries (20%; Chile, Peru, South Africa, USA, China, Greece, Panama, Russian Federation, the Philippines, Czech Republic, Finland, Portugal, and Guatemala) reported that people from their countries do not travel to other countries to seek egg donation. Respondents from Paraguay, Argentina, Mali, South Korea, Bangladesh, Kenya, and Estonia (11%) reported that this information was unknown. Respondents from nine of the 64 countries that responded to questions on cross-border reproduction did not address this issue.

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Outgoing for Embryo Donation

Respondents from 25 countries (39%) reported that people travel from their country to another country to access embryo donation. Sixteen respondents (25%) reported that people from their country do not travel to other countries for embryo donation. Respondents from Paraguay, Mali, South Korea, Bangladesh, Kenya, Switzerland, Estonia, Malaysia, Singapore, Taiwan [China (Reporting separately for this report.)], Tunisia, (18%) reported that this information was unknown. Respondents from 12 of the 64 countries that responded to questions on cross-border reproduction did not address this issue.

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Outgoing for Sperm Donation

Respondents from 22 countries (34%) reported that people travel from their country to another country to access sperm donation. Twenty respondents (31%) reported that people from other countries do not travel to their country to engage with sperm donation. Respondents from 13 countries (20%) reported that this information was unknown. Respondents from nine of the 64 countries that responded to questions on cross-border reproduction did not address this issue.

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Outgoing for Gestational Carrier Arrangements

Respondents were asked if people travelled from their countries to other countries to engage in gestational carrier arrangements, defined as “the gestational carrier is implanted with an embryo(s) created using the gametes of both prospective parents; or donated ova and commissioning male's sperm; or a donated embryo”. Respondents from 31 countries (48%) answered “yes”; respondents from 10 countries (16%; South Africa, USA, China, Greece, Russian Federation, Czech Republic, Romania, the Netherlands, Senegal, and Bulgaria) answered “no”; respondents from 13 countries (20%; Brazil, Switzerland, Hungary, Paraguay, South Korea, Bangladesh, Kenya, Tunisia, Belgium, Slovak Republic, Ireland, United Kingdom, and Colombia) said that this information was unknown; and respondents from 10 countries (16%) did not address the question.

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Outgoing for Traditional Gestational Carrier Arrangements

Respondents were asked if people travelled to their countries to engage in traditional gestational carrier arrangements, defined as being a process “in which the gestational carrier’s ova are inseminated with a prospective parent’s sperm”. Respondents from 19 countries (30%) answered in the affirmative (“yes”). Respondents from 10 countries (16%; South Africa, USA, China, Russian Federation, Czech Republic, Romania, the Netherlands, Senegal, Bulgaria, and Norway) answered “no”. Respondents from 22 countries (34%) said that this information was unknown, and respondents from 13 countries (20%) did not address the question.

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Regulation of Cross-Border Reproduction ( Table 3)

Respondents were also asked if their country had regulations that governed cross-border gestational carrier arrangements. Specifically, they were asked about regulations governing citizens that visit other countries seeking treatment, and people visiting their home country seeking treatment.

Chapter 23 Table 3 Are there Regulations that Govern Cross Border Reproduction in Your Country?

Chapter 23 Table 3 Are there Regulations that Govern Cross Border Reproduction in Your Country?

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No Regulation of Certain Practices

Respondents from 64 countries answered the queries within the cross-border reproductive care section. Respondents from 4 countries (6%) (Belgium, Greece, Norway, and the United Kingdom) said that they do not have regulations governing their citizens that visit other countries seeking treatment. Respondents from 12 countries (19%; Denmark, Germany, Bangladesh, Chile, El Salvador, Hong Kong [China (Reporting separately for this report.)], Israel, Philippines, Saudi Arabia, South Korea, Spain, and Uruguay) reported not having regulations regarding patients visiting their country seeking treatment. Respondents from 37 countries (58%) reported having neither regulations governing people going to other countries nor people coming to their own country to seek treatment.

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Regulation of Outbound People Visiting other Countries to Seek Treatment

Respondents from two countries, Denmark and Germany, reported having federal laws. Respondents from Australia indicated that state laws are in effect. Respondents from Sweden reported that professional organization standards/guidelines govern their citizens who travel from their country to visit other countries for treatment.

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Regulation of Inbound People Seeking Treatment

Respondents from Belarus, Belgium, Greece, Norway, the United Kingdom, Bangladesh, and Singapore reported having federal laws. People who travel to Saudi Arabia must adhere to cultural practice and religious decrees that govern treatment in that country.

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Regulation of Both Outbound and Inbound Cross-border Reproduction

Respondents from Finland, Slovak Republic, and Taiwan (China (Reporting separately for this report.)), reported having federal laws that govern people going to other countries, and people who travel to their own country, seeking treatment. Respondents from Turkey reported having state laws that governed both, and respondents from Belarus and India reported having professional organization standards/guidelines governing both travel to and from their respective countries for treatment.

Note that respondents from some countries reported that they had/did not have one particular type of regulation, but did not make reference elsewhere to the other type of regulation. For example, a respondent from one country may have noted the existence of regulation of people travelling from their country to seek treatment, but did not answer (or did not select “no regulation”) regarding people traveling to their country.

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Regulation of the Import and Export of Tissue ( Tables 4 and 5)

Import

Ova: Respondents from 34 countries (53%) reported that there was regulation of the import of ova into their countries, while respondents from 15 countries (23%) reported no regulations. Respondents from nine countries (14%) reported that the information was “unknown” and respondents from six countries (9%) did not answer the query.

Chapter 23 Table 4 Are there Regulations Regarding the Import of Reproductive Tissue Into Your Country?

Chapter 23 Table 4 Are there Regulations Regarding the Import of Reproductive Tissue Into Your Country?

Chapter 23 Table 5 Are there Regulations Regarding the Export of Reproductive Tissue into Your Country?

Chapter 23 Table 5 Are there Regulations Regarding the Export of Reproductive Tissue into Your Country?

Spermatozoa: Respondents from 37 countries (58%) reported that there was regulation of the import of spermatozoa into their countries, while respondents from 12 countries (19%) reported no regulations. Respondents from nine countries (14%) reported that the information was “unknown” and respondents from six countries (9%) did not answer the query.

Zygotes: Respondents from 32 countries (50%) reported that there was regulation of the import of zygotes into their countries, while respondents from 14 countries (22%) reported no regulations. Respondents from 10 countries (15.5%) reported that the information was “unknown” and respondents from eight countries (12.5%) did not answer the query.

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Export

Ova: Respondents from 32 countries (50%) said that there was regulation of the import of ova into their countries, while respondents from 18 countries (28%) reported no regulations. Respondents from eight countries (12.5%) reported that the information was “unknown” and respondents from six countries (9%) did not answer the query.

Spermatozoa: Respondents from 32 countries (50%) reported that there was regulation of the import of spermatozoa into their countries, while respondents from 18 countries (28%) reported no regulations. Respondents from eight countries (12.5%) reported that the information was “unknown” and respondents from six countries (9%) did not answer the query.

Zygotes: Respondents from 32 countries (50%) reported that there was regulation of the import of ova into their countries, while respondents from 18 countries (28%) reported no regulations. Respondents from seven countries (11%) reported that the information was “unknown” and respondents from seven countries (11%) did not answer the query.

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Discussion: Cross-Border Reproduction

Movement

Overall, a high proportion of respondents reported people travelling to their home country to seek treatments that were lower cost, higher quality, and/or not available in the country from which the person was travelling (73%, 80%, and 83%, respectively). Fewer respondents reported people travelling to their country for egg, embryo, or sperm donation (52%, 43%, and 45%, respectively), and even fewer again for gestational or traditional gestational carrier arrangements (22% and 9%, respectively). One might draw from this that the people travelling to a majority of countries seek more standard services (such as intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), intrauterine insemination (IUI), etc.), and are not primarily engaging in cross-border reproduction to seek donor egg, embryo, or sperm, or to engage in gestational carrier arrangements. When people seek the latter services, they may travel to particular destinations.

A lower proportion of respondents reported people travelling from their home country to seek treatment elsewhere for lower cost, higher quality, or services not available at home (41%, 52%, and 52%, respectively). Similar figures to inbound people (those travelling to the country on which the respondent reported) were found for outbound people (people travelling from the country on which the respondent reported) seeking egg, embryo, and sperm donation (55%, 39%, and 34%, respectively). Rates for outbound people seeking gestational carrier arrangements were higher than inbound figures, with 40% of respondents reporting people travelling out of the country for gestational carrier arrangements, and 30% reporting people travelling out of the country for traditional gestational carrier arrangements. This again intuitively makes sense, as many countries prohibit some or all of the examined practices, and so if people wanted to access them, they might travel elsewhere.

Of course it is imperative to note that such figures and percentages give no indication as to how many people actually travel; these data simply indicate the perception that if people seek certain services they may travel to or from another country to engage with them due to cost, quality, and/or type of service required.

The other factor perhaps of note is that there were less responses of “unknown” in relation to inbound people than for outbound people, presumably because the practicing clinicians (respondents) who filled in the questionnaire have more direct knowledge of the type of treatments people seek in their own clinics and countries, but not of what people do externally.

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Regulation

Concerning regulation, despite a significantly high level of perceived movement across borders, the responses indicated that there was very little regulation of people travelling to or from other countries to seek ART treatment. Regulation of the import and export of tissue appeared more prevalent; however, a number of respondents reported no regulation, did not know if regulation existed, or did not answer the question.

The lack of regulation, or lack of knowledge about regulation, may be of particular relevance in areas of egg, embryo, and sperm donation, as well as gestational carrier arrangements, in which children born as a result may seek information about their donors and/or gestational carriers in the future (an increasing occurrence all over the world).

Tracking and reporting of treatments and treatment outcomes may also become difficult. Patient follow-up may not occur across borders.

It should be noted that the data gathered in this section on regulation related only to whether or not regulations existed in relation to cross-border gestational carrier arrangements and/or the import and export of tissues. It did not ascertain whether there were other types of regulations. Other laws or regulations relevant to ART generally, and/or general laws governing professional practice, laws regarding civil liability, contract laws, human rights law, and more, would likely be relevant in cross-border situation.

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CHAPTER 24: CONCLUSIONS

Surveillance 2016 captured more data from a larger proportion of countries actively providing assisted reproductive technology (ART) services than previous surveys. The data confirms that respondents from most countries have experienced a modest growth in the number of ART centres in their respective nations, reflecting further maturation of ART as a clinical service. The responses from the 74 countries suggest that collectively they contain over 5300 ART centres.

Over 80% of countries were reported to rely on legislation, guidelines, or a combination of both to promote the safety, efficacy, standardization, and access to ART. Monitoring and reporting mechanisms were reported to be in place in most of Europe, Australia, the USA, Southeast Asia, and Latin America. Over a third of respondents have noted the passage of new legislation since the last questionnaire, most often perceived as salutary by the respondents; and, with a majority of countries now implementing legislation or guidelines restricting the number of embryos permissible for transfer to women undergoing in vitro fertilization (IVF)/ART cycles.

Preimplantation genetic testing (PGT) was reported to constitute a greater proportion of IVF cycles than previously. A variety of techniques was reported to be available in almost all countries represented in this 2016 Surveillance report for fertility preservation, including gamete and embryo cryopreservation, and are reported to be widely performed. Historical comparisons could not be obtained for this topic since it was not previously queried. Practices such as cryopreservation, posthumous reproduction, and gamete donation have been reported to receive more attention from stakeholders over the past three years and are overall reported to be more widely performed; however, there are significant regional differences in practice, access, and frequency of application. Intracytoplasmic sperm injection (ICSI) was reported to be almost universally available and performed. Access to and utilization of donor gametes and embryos and gestational carriers, while reported to be greater than previously noted, was reported to remain restricted in many countries due to legal, ethical, and religious constraints. Significant differences in available options and restrictions were reported to exist even among countries in close proximity and this phenomenon has contributed greatly to a reported increased demand for cross-border reproductive services raising a new set of ethical concerns. There have been some highly publicized adverse outcomes involving some of these activities and several measures have been reported to have been enacted to address perceived abuses.

Social aspects of ART including the pre-treatment assessment for the potential welfare of the child, addressing the issues of anonymity and disclosure for families utilizing donor gametes, and the status accorded the embryo were all reported to have received more intensive scrutiny over the last three years. A wide variety of new measures were reported to have been proposed and undertaken to address all of these issues, but the topics remain highly contentious and no universal recommendations have been reported to have been endorsed. There are reported incremental increases in utilization of ART techniques (e.g., oocyte maturation, assisted hatching) but no new significant trends were identified.

Experimentation on the embryonic cells was reported to be permitted to a limited extent. Stem cell research on embryonic cells was reported to be allowed, however with rigid guidelines in less than half of countries featured in this report. The amount of research actually performed has been reported to have increased. Therapeutic cloning research has been reported to be performed in very few countries, and respondents from one country (Uruguay) indicated that reproductive cloning is not expressly prohibited.

Overall, the Surveillance 2016 report depicts that worldwide, ART services have been made more accessible to a larger number of individuals. Barriers to utilization of ART services based on location, marital status, and gender are reported to still exist. There are also reports of ongoing efforts to curtail the practice of ART in some locales. However, the expanding application of ART and participation of all stakeholders acknowledges ART’s great clinical value. Much of the legislative and other initiatives over the past three years have sought to promote safety, efficacy, and availability. Surveillance 2016 attests to an expanding scope of ART practices, policies, and activities among nations around the world while highlighting significant and important differences. Several encouraging trends were identified over the triennium and it is hoped that they will promote safety, efficacy, and availability of needed fertility services.

© 2016 by Lippincott Williams & Wilkins, Inc.