How fertility preservation guidelines have progressed worldwide: Potential implications and inspiration : Reproductive and Developmental Medicine

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Review Article

How fertility preservation guidelines have progressed worldwide: Potential implications and inspiration

Chen, Min-Xin1; Zhang, Ying2; Cai, Qing-Qing3; Zhang, Shuo4; Xu, Ran5; Chen, Hua6; Kang, Yu7; Wu, Yue1; Chian, Ri-Cheng8,*; Xu, Cong-Jian1,*

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Reproductive and Developmental Medicine 6(1):p 34-41, March 2022. | DOI: 10.1097/RD9.0000000000000010
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In recent years, there has been an increased interest in age-related infertility and improvement in the quality of life of cancer survivors[1-2]. Survival has improved in patients with most common cancers since the mid-1970s, with a major and longterm decline in mortality associated with the 4 leading cancers. As of 2017, the mortality rate has decreased by 25% and 40% in women with lung and breast cancers, respectively. Breast cancer accounts for 30% of all new diagnoses in female patients, with an estimated 42,170 deaths reported in the US alone every year[3].

Cancer has been a major problem in China, with 4,285,033 new cases and 2,865,174 deaths recorded in 2018. This high cancer burden highlights the demand for further clinical improvement and efforts to improve patients' quality of life[4]. Cancer treatment can negatively affect female fertility. Thus, a steep decline in the death rate will translate into many women who may need fertility preservation (FP) before treatment. However, the American Society of Clinical Oncology guidelines concluded that patients with cancer do not have access to sufficient information on FP options[5]. Moreover, given the mortality risk, patients may have deficient FP, depending on the cancer stage and individual condition, as cancer treatment must be prioritized. According to the International Breast Cancer Study Group, the risk of amenorrhea is 33% and 10% to 20% in patients <40 years[6] and <30 years of age[7], respectively. For these patients, FP options should be offered as soon as possible.

Apart from medical reasons, there has been an increase in the social trend of women post-poning pregnancy until they are financially independent and emotionally confident. As an emerging field with established techniques, FP can offer the opportunity to preserve the reproductive health of women with gonadotoxic impairment or who wish to delay pregnancy[8-9]. Furthermore, fertility remarkably declines in women as they age. At 40 years of age, a notable proportion of women experience unsuccessful conceptions. The pregnancy rate per in vitro fertilization cycle has been shown to reach only 13.9% and <4% at 40 years and over 42 years of age, respectively[10]. Equal access to FP should also be available for women with normal fertility considering the growing trend of delaying conception. However, stagnant progress in guidelines for FP in certain regions of the world reflects a lack of satisfactory answers for women in need.

This review aims to provide an overview of the evolution of FP worldwide from the perspective of governmental legislation and guidance provided by professional facilities. Furthermore, we aim to highlight future developments in this field and help policymakers and healthcare professionals treat different groups of women with diverse fertility intentions better.


Search strategy

This study adhered to the Cochrane handbook for systematic reviews of interventions, and the quality of reporting of Metaanalyses of randomized controlled trials flow diagram outlines the search process (Fig. 1). Two independent reviewers developed the search strategy for the following 5 reference databases (PubMed, Embase, CMB, ClinicalKey, Wanfang Data, and China Knowledge Resource Integrated) and 7 guideline databases (Guideline International Network, National Collaborating Centre for Women's and Children's Health, National Guideline Clearinghouse, The National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network, New Zealand Guideline Group, and Canadian Medical Association infobase). The definitive search strategy was refined after several pilot searches, choosing studies published in English and Chinese. In addition, the official websites of various societies and other Chinese websites were searched to find relevant guidelines and consensus.

Figure 1.:
QUOROM flow diagram outlining the results of the literature search and selection of studies for inclusion in the review. ACOG: American College of Obstetricians and Gynecologists; ASRM: American Society for Reproductive Medicine; CKNI: China Knowledge Resource Integrated Database; CMB: China BioMedical Literature Database; ESHRE: European society of human reproduction & embryology; FIGO: International Federation of Gynecology and Obstetrics; GIN: Guideline International Network; ICER: Institute for Clinical and Economic Review; IFFS: International Federation of Fertility Societies; ISFP: International Society for Fertility Preservation; NZGG: New Zealand Guideline Group; NCC-WCH: National Collaborating Centre for Women's and Children's Health; NFOG: Nordic Federation of Societies of Obstetrics and Gynecology; NGC: National Guideline Clearinghouse; NICE: The National Institute for Health and Care Excellence; RCOG: Royal College of Obstetricians and Gynaecologists; SIGN: Scottish Intercollegiate Guidelines Network; SOGC: Society of Obstetricians and Gynecologists of Canada; QUOROM: quality of reporting of Meta-analyses of randomized controlled trials.

Selection of eligible studies

Two groups of reviewers independently assessed the abstracts for eligibility. Reviewers completed the calibration exercise before reviewing and reported the search strategy and results in the literature review phase, addressing uncertainties and discrepancies with the help of the corresponding author. A selective literature search was performed using the following keywords: guidelines, consensus, guidance, FP, and China. Searches were carried out for reviews, guidelines, and consensus provided or conducted by professional bodies. The search strategy retrieved 304 records with the following keyword setting in the literature search: limiting a PubMed search with MeSH terms; keywords containing “fertility preservation,” “cryopreservation,” “oocyte freezing,” “egg freezing,” “oocyte banking,” “fertility decline,” or “oncofertility”; Title containing “contraception,” “guideline,” “standards,” “practice,” “statement,” “guides,” “consensus,” “opinion,” “guidance,” or “recommendations”; and authors or abstract containing “society,” “committee,” “association,” “commission,” “group,” or “council.” No language or date limits were included in the search. Other databases or websites were searched similarly. The criteria for selection were as follows: articles written by writing committees instead of individuals or a single organization; such committees were not influenced by any issue that could lead to bias, and the articles provided recommendations based on the strongest available scientific evidence, generally encompassing grading and staging. Any study that could be of value for the understanding of FP progress was pre-selected.

Data extraction

Two reviewers independently screened the data after calibration and selection using a data extraction sheet. The reviewers were not blinded to the information of the authors, journals, and institutions.


The review showed that access to FP for women varies significantly worldwide. A total of 305 records (including 4 in Chinese) of existing guidelines were retrieved for full-text review, and 55 guidelines were identified after manual selection (Table 1), which demonstrated that FP guidance and options are unevenly distributed worldwide (Fig. 2).

Figure 2.:
Professional and governmental guidance of each country in Table 1.

The US plays a leading role in formulating professional guidelines and governmental directives, which also contributes to progress in academic research on FP. In recent years, 4 state bills regarding FP and 9 professional guidelines have been launched by United States and academic organizations (Table 1). Embryo research and laboratory practices are carried out under federal law and in compliance with the American Society for Reproductive Medicine guidelines. Therefore, FP is mainly performed under professional guidance and governmental legislation.

China seems much more prudent in easing FP, especially for women, considering the pressure of safety assurance for such a large population. As shown in Table 1, only 1 guideline and 2 governmental directives launched by China's National Health and Family Planning Commission (now called the National Health Commission) are available.

Patients in EU member states have the freedom to access treatment in other countries under the 2008 European Commission Directive. Legislation for artificial reproductive technology covers all EU member states (except Ireland). Almost all European countries, such as the UK, Spain, and France, have developed professional guidelines to supplement their national legislation. In Asia, Japan founded the Japan Society for FP (JSFP) in 2012 to appropriately implement oncofertility treatment and published widely recognized guidelines on FP. The Republic of Korea and China also established an FP society in 2013 and 2017, respectively, and the Korean Society for FP (KSFP) has published 4 guidelines targeting patients with hematological malignancies, gynecological malignancies, and breast cancer. Together with JSFP, KSFP has played an integral role in the Oncofertility Consortium.


Nowadays, ovarian tissue cryopreservation (OTC) is still considered experimental. Cryopreservation of embryos or oocytes has been considered as the standard method of FP. Other techniques, like ovarian suppression and ovarian transposition also used, but were not as confident as formers[11]. Various studies on fertility techniques have reported the evolution and improvement of FP techniques over the past years, especially with respect to recent advances in OTC and transplantation[12] and oocyte in vitro maturation (IVM).

Oocyte vitrification

The first oocyte cryopreservation baby was born in 1986[13], and the first vitrified oocyte baby was born in 1999[14]. Cryopreservation technology has developed from slow programmed freezing to rapid vitrification freezing. At present, vitrification technology has been widely recognized, and in many European and American countries, single women of childbearing age have been allowed to preserve fertility via this technology. Technically, mature oocytes require 1 to 2 weeks of ovulation induction before freezing, which is not suitable for infants, pre-pubertal children, and patients who are supposed to be treated as soon as possible. In addition, the effects of delayed treatment and ovulation induction drugs on tumor cells require further study. In contrast, live births obtained from oocyte cryopreservation decreased with increasing age. On average, for women <35 years, every 15 oocytes cryopreserved can obtain a live birth. Correspondingly, women aged between 35 and 40 years would have to freeze 16 to 25 oocytes to have a likelihood of having 1 live birth, whereas for women aged ≥41 years, the number is expected to be at least 40[15].

Table 1 - Currently available guidance on fertility preservation



Legislation and regulation






Fertility preservation in children newly diagnosed with cancer: existing standards of practice in Australia and New Zealand

Medical Journal of Australia (2006)



Fertility preservation for AYAs diagnosed with cancer. Guidance for health professionals

Clinical Oncology Society of Australia (2014)



Processing and cryopreservation of male and female gonadal tissue and gametes prior to or after gonadotoxic treatment to preserve fertility for the future

Medical Service Advisory Committee (2018)



Rheumatology fertility preservation guidelines

Australian Rheumatology Association (2018)



Fertility preservation in reproductive age women facing gonadotoxic treatments


CFAS (2014)



Fertility preservation in post-pubescent female cancer patients: a practical guideline for clinicians

Molecular and Clinical Oncology (2018)



Egg freezing for age-related fertility decline

Society of Obstetricians and Gynaecologists of Canada

Journal of Obstetrics and Gynecology Canada (2018)



Managerial Directive for Human Assisted Reproduction

National Health Commission (2001)



Managerial Directive for Human Sperm Bank

National Health Commission (2001)



Technical Directive for Human Assisted Reproduction

National Health Commission

Journal of Reproductive Medicine (2003)



Technical Directive for Human Sperm Bank

National Health Commission

Journal of Reproductive Medicine (2003)



Chinese guideline on ovarian tissue cryopreservation and transplantation

Beijing Obstetrics and Gynecology Hospital

Gynecological Endocrinology (2018)



Chinese expert consensus on fertility-preserving for women

China Maternal and Child Health Association Society of fertility preservation

Chinese Journal of Reproduction and Contraception (2021)



The European Union Tissue & Cells Directive (2004/23/EC)

European Parliament and Council (2004)



The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer

European Society of Breast Cancer Specialists

European Journal of Cancer (2012)



Cancer, pregnancy and fertility: ESMO clinical practice guidelines for diagnosis, treatment and follow-up


Annals of Oncology (2013)



EMAS position statement: Fertility preservation


The European Menopause Journal (2014)



Guide to the quality and safety of tissues and cells for human application

European Committee on Organ Transplantation

file:///Users/apple/Downloads/pub_PUBSD-122.pdf (2019)


Germany, Austria, Switzerland

FertiPROTEKT guidelines: fertility preservation in women- a practical guide to preservation techniques and therapeutic strategies in breast cancer


Archives Gynaecology Obstetrics (2011)


Germany, Austria, Switzerland

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part II: fertility preservation techniques


Archives Gynaecology Obstetrics (2018)


Germany, Austria, Switzerland

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part I: fertility preservation techniques


Archives Gynaecology Obstetrics (2018)



Oncofertility Consortium clinical pocket guides

The Oncofertility Consortium (2006)



Fertility preservation in young women with haematological malignancies


Journal of Assisted Reproduction and Genetics (2012)



Recommendations for fertility preservation in patients with lymphoma, leukaemia and breast cancer


Journal of Assisted Reproduction and Genetics (2012)



Fertility preservation in young women with breast cancer


Journal of Assisted Reproduction and Genetics (2012)



Recommendations for fertility preservation in patients with lymphoma


Journal of Assisted Reproduction and Genetics (2012)



Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications.

Children's Oncology Group

Journal of Clinical Oncology (2013)



Perspectives on harvesting, freezing and storage of gametes and ovarian tissue based on medical indication

Japan Society of Obstetrics and Gynecology (JSOG)

Fertility preservations should be provided JSPG Perspectives were updated in (2016)



Clinical guidelines for fertility preservation in children, adolescents and young adults with cancer

Japan Society of Clinical Oncology (JSCO)

International Journal of Clinical Oncology (2019)


New Zealand

Fertility preservation for people with cancer: a New Zealand guideline

National Child Cancer Network (2014)


Republic of Korea

Fertility preservation for patients with hematologic malignancies: the Korean Society for fertility preservation clinical guidelines


Clinical and Experimental Reproductive Medicine (2017)


Republic of Korea

Fertility preservation for patients with gynecologic malignancies: the Korean society for fertility preservation clinical guidelines


Clinical and Experimental Reproductive Medicine (2017)


Republic of Korea

Fertility preservation for patients with breast cancer: the Korean society for fertility preservation clinical guidelines


Clinical and Experimental Reproductive Medicine (2017)


Republic of Korea

Fertility preservation for patients with during cancer treatment: the Korean society for fertility preservation clinical guidelines


Clinical and Experimental Reproductive Medicine (2017)



Cancer and fertility preservation: Barcelona consensus meeting


Gynaecological Endocrinology (2013)



SEOM clinical guideline of fertility preservation and reproduction in cancer patients

Society of Spanish Oncology Medicine

Clinical Translational Oncology (2016)



Fertility problems: assessment and treatment

NICE** (2013)



Long-term follow up of survivors of childhood cancer

Scottish Intercollegiate Guidelines Network (2013)



Guidelines for the first line management of classical Hodgkin lymphoma

British Fertility Society

British Journal of Haematology (2014)



Fertility preservation for medical reasons in girls and women: British Fertility Society policy and practice guideline

British Fertility Society

Human Fertility (2018)



Commissioning guidance for fertility treatment

HFEA†† (2019)



American Society of clinical oncology recommendations on fertility preservation in cancer patients


Journal of Clinical Oncology (2006)



Position statement: health insurance coverage for iatrogenic infertility

Livestrong and the Cancer Legal Resource Center (2011)



Fertility preservation in women

Fertility preservation for patients with cancer: American society of clinical oncology clinical practice guideline update


Journal of Clinical Oncology (2013)



Fertility preservation in patients undergoing gonadectomy: a committee opinion


Fertility and Sterility (2013)



Mature oocyte cryopreservation: a guideline


Fertility and Sterility (2013)



Preliminary report of action

American Medical Association House of Delegates (2014)



Ovarian tissue cryopreservation: a committee opinion


Fertility and Sterility (2014)



ACOG committee opinion on oocyte cryopreservation for fertility preservation in women facing medically-induced infertility


The American College of Obstetricians and Gynecologists Committee Opinion (2016)



ASCO Gguideline: fertility preservation in patients with cancer


Journal of Clinical Oncology (2018)



National Comprehensive Cancer Network guidelines for patients: adolescent and young adult (AYA) with cancer

NCCN¶¶ (2018)


US (California)

Senate Bill No.600 Chapter 853

Senate of State of California

State of California Authenticated Electronic Legal Material (2019)


US (Massachusetts)

Senate Bill No.560

Senate and House of Representative of the Commonwealth of Massachusetts

Senate Docket of Commonwealth of Massachusetts (2019)



State of New York Act No. 719

Senate of State of New York

State of New York 2019-2020 regular sessions (2019)


US (New Jersey)

A3150 and S2133

Senate of New Jersey

Assembly Committee Substitute for Assembly, No. 3150 of Senate of New Jersey (2019)

* CFAS: Canadian Fertility and Andrology Society.
ESMO: European Society for Medical Society.
EMAS: European Menopause and Andropause Society.
§ ISPF: International Society of Fertility Preservation.
JSOG: Japan Society of Obstetrics and Gynecology.
JSCO: Japan Society of Clinical Oncology.
# KSFP: Korean Society for Fertility Preservation.
** NICE: National Institute for Health and Clinical Excellence.
†† HFEA: the Human Fertilisation and Embryology Authority.
‡‡ ASRM: American Society for Reproductive Medicine.
§§ ACOG: American College of Obstetricians and Gynecologists.
‖‖ ASCO: American Society of Clinical Oncology.
¶¶ NCCN: National Comprehensive Cancer Network.

Ovarian tissue cryopreservation

Since the first report of successful pregnancy after human ovarian tissue transplantation in 2004, its application and success rates have reached promising levels. As early as 2017, >130 live births have been reported worldwide, and the number has steadily increased over the past several years[16]. According to statistics, the cumulative pregnancy rate of OTC has reached 37%[17]. OTC mainly includes the steps of ovarian tissue excision, transfer, freezing, resuscitation, and transplantation. The advantages of ovarian tissue freezing are as follows: it does not delay the timing of tumor treatment, it is not affected by the menstrual cycle, it is essential for hormone-sensitive tumor patients, fertility can be preserved in pre-pubertal girls, and it helps maintain endocrine function[18].

OTC has made significant progress in achieving FP, but there remains a pragmatic challenge - tumor recurrence - especially in patients with hematological malignancies, such as leukemia, neuroblastoma, and lymphoma. To date, tissue metastasis has been excluded by polymerase chain reaction analysis, histopathological analysis, and ovarian skin grafts transplanted into combined immunodeficiency mice for tumor formation experiments.

Many factors may influence the efficiency of OTC. Although ovarian reserve before cryopreservation is the most important one, the methods of freezing and transplanting, the patients' age, the patients' disease, treatments after OTC all may affect the results. But there are several reasons to be optimistic about future improvements to deal with potential problems. For example, artificial uterus, artificial ovary, stent transplantation of single follicles, and in vitro culture of primordial follicles may be the future directions in the FP community.

Oocyte in vitro maturation

Oocyte IVM is defined as the maturation of immature cumulus oocyte complexes collected in vitro from small antral follicles. By establishing a biphasic IVM system, the efficiency of IVM has been improved significantly. In the clinic, IVM can be used for PCOS patients to avoid the occurrence of ovarian hyperstimulation syndrome. It can be easily combined with other FP strategies like OTC to improve the efficiency of FP. IVM may applied widely in the near future[19].

Fertility preservation guidance worldwide

According to the World Marriage Data 2019, approximately 1 in 5 women aged between 25 and 29 years remained unmarried in 2016, and the percentage of single women has steadily increased since 1990, from 5.0% to 27.8%[20]. The fertility trends of having a small number of children and delaying conception have been evident as early as almost 10 years ago[21], and the problem of involuntary childlessness has also been exacerbated due to the impact of older age on reproductive capacity[22]. It remains a daunting task to fulfill all social demands from women who are physically and psychologically handicapped due to the adverse effects of medical treatments or age-related infertility. An up-todate cohort study in China, including 158 women with polycystic ovary syndrome, verified the feasibility and safety of oocyte retrieval followed by IVM, enhancing the scope of FP[23]. Human ovarian cortex biobanking using oocytes derived in vitro from ovarian stem cells is a fascinating resource for cancer patients to preserve their fertility[24]. According to Rienzi et al.[25], the pregnancy rate following oocyte vitrification is not inferior to that using freshly transferred oocytes based on a randomized sibling-oocyte study involving 224 oocytes. This finding was later confirmed in a meta-analysis published in 2017[26]. Advancements in FP strategies provide hope to those with limited fertility, whereas lack of guidance from professional communities and governmental bodies has caused confusion among patients. The conflict between technical advancements and weak regulatory infrastructure is increasingly visible in certain regions such as China.


With the population pyramid shifting with changing fertility intentions across the world, clarified and well-informed decisions should be made by regulators to ensure universal access to FP services. Therefore, professional bodies should identify standardized and established techniques based on strong evidence from randomized clinical trials, and large prospective cohort studies[27-28]. Thus, evidence-based protocols and options can be provided to address patient demands to enable women to make fertility decisions not only in a life-threatening context but also in a life-changing context. This way, authorities can consider licensing practitioners and facilities offering FP services to address social needs.



Author contributions

C.X., R.C. and M.C. designed the review, S.Z., Y.Z., Q.C. and R. X. collected the guidelines. M.C. wrote the manuscript. H.C., Y. W., Y.K. revised the manuscript and provided edits. All authors contributed to the final manuscript and approved the submitted version.



Conflicts of interest

All authors declare no conflict of interest.


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Fertility preservation; Cancer patient; Aging; Guidance

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