Secondary Logo

Share this article on:

Brief report on the advantages of ovulation monitoring using home urinary LH immunoassays in ovulation induction cycles with a gonadotropin-releasing hormone agonist trigger

Katler, Quinton S., MD, MSa,; Tricarico, Nicole M., BSb; Bishop, Lauren A., MDc

doi: 10.1097/GRH.0000000000000010
Brief Reports

Numerous medications are available to assist with follicular stimulation and ovulation induction in women with ovulatory dysfunction, including clomiphene citrate, aromatase inhibitors, and injectable gonadotropins. In patients that are at a higher risk for the development of ovarian hyperstimulation syndrome in an ovulation induction cycle, a gonadotropin-releasing hormone agonist trigger may be substituted for traditional hCG trigger at the expense of an increased potential for suboptimal response. When compared with serum luteinizing hormone (LH) evaluation, using a home urinary LH immunoassay for ovulation detection in gonadotropin-releasing hormone agonist agonist trigger cycles may serve multiple advantages. Accordingly, a home LH immunoassay may play a novel role as a safe, inexpensive and effective alternative to conventional phlebotomy, particularly in lower-resource settings.

aDepartment of Obstetrics and Gynecology, The George Washington University, Washington, DC

bDepartment of Medical Education, University of Central Florida College of Medicine, Orlando, FL

cDepartment of Reproductive Endocrinology and Infertility, National Institute of Child Health and Human Development, Bethesda, MD

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Published online 5 June 2018

Corresponding author. Address: Department of Obstetrics and Gynecology, The George Washington University, 2150 Pennsylvania Ave. NW, Washington, DC 20037. Tel: +954-258-6802; fax: +202-741-2550. E-mail address: qkatler@gwu.edu (Q.S. Katler).

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/

Received October 8, 2017

Accepted March 15, 2018

Back to Top | Article Outline

Background

One of the common indications for fertility treatment is ovulatory dysfunction, which accounts for ∼40% of infertility in women1. There are numerous medical approaches for overcoming ovulatory dysfunction that have been shown to improve reproductive outcomes within this population, most commonly with the aid of clomiphene citrate or aromatase inhibitors. The use of injectable gonadotropins may be indicated when these less invasive methods are unsuccessful2. The goal of ovulation induction in women with anovulatory infertility is to stimulate multifollicular development in order to achieve ovulation, subsequently increasing the likelihood for conception.

Serial pelvic ultrasounds are used to monitor the ovarian response to gonadotropin therapy during an ovulation induction cycle. Ovulation is induced using a “trigger” injection which is typically given when at least one follicle is >18 mm.

There are 2 medications that can be used to induce ovulation: hCG or a gonadotropin-releasing hormone agonist (GnRHa). While the use of a hCG trigger has been the standard of care in ovulation induction, the longer half-life of hCG compared with GnRHa creates a prolonged luteinizing hormone (LH) receptor stimulatory phase, which may put susceptible patients at a higher risk for ovarian hyperstimulation syndrome (OHSS) development3. Conversely, GnRHa triggers are being utilized as an alternative to hCG when patients are at a higher baseline risk for OHSS. As a result, the use of a GnRHa trigger has been shown to result in a significant reduction in OHSS development when compared with a hCG trigger4.

The patient’s risk of developing OHSS can help to determine the best trigger medication. Criteria that have been shown to increase a patient’s risk include the development of multiple intermediate-sized follicles, or elevated estradiol levels5–11. However, it is important to note that studies suggest that the overall pregnancy rate is lower in a GnRHa trigger cycle in comparison to a cycle with a hCG trigger12. Several mechanisms have been proposed for the decreased fecundity observed with the use of a GnRHa trigger. One possible explanation is likely due to the rapid postovulation drop in luteal LH compared with hCG trigger cycles13. In addition, certain cycle characteristics place patients at a higher risk for a suboptimal response to a GnRHa trigger, which has been defined as a serum LH level <15 mIU/mL on the morning after the trigger14. Such risk factors for suboptimal response to a GnRHa trigger include long-term hormonal contraception use, low serum LH level on the day of the trigger, lower body mass index, and higher total dosage of gonadotropins required for follicular stimulation (Table 1)14,15.

Table 1

Table 1

Because of the diminished ovulatory rate in suboptimal responders using GnRHa triggers, a serum LH level is drawn the day following trigger injection in order to determine that ovulation has occurred. If an LH surge is not detected, the cycle may either be abandoned, or a “dual trigger” using low-dose hCG may be employed in an attempt to achieve ovulation16. The use of a rescue dose of hCG when follicles are slow to mature or fail to ovulate despite GnRHa triggering has been shown to increase the implantation rate and clinical pregnancy rate compared with GnRHa trigger alone17.

Back to Top | Article Outline

Ovulation monitoring

Assessing ovulation status after GnRHa trigger is traditionally carried out by measuring the serum LH level, however, home ovulation predictor kits which measure urinary LH may be considered as an alternative method in an ovulation induction cycle. Home LH immunoassay kits function by measuring the LH surge through enzyme immunoassay to luteinizing hormone and are a quick, reliable, and inexpensive option for identifying the LH surge preceding ovulation18. In comparison to serum LH tests, most studies suggest that home LH immunoassay kits are as sensitive for detecting the LH surge and may be used as a reliable alternative for predicting ovulation within the ensuing 24 to 48 hours19–21. In patients who are undergoing ovulation induction, home ovulation predictor kits may be useful for timing intercourse after ovulation or for scheduling an intrauterine insemination. To our knowledge, the use of home LH immunoassay kits in ovulation induction cycles with GnRHa triggers has not been described in the literature.

Back to Top | Article Outline

Advantages

The use of home LH immunoassay kits to detect ovulation in a GnRHa trigger cycle have several advantages over traditional phlebotomy. Of primary concern is the socioeconomic reality of infertility treatment in the 21st century. Although we have witnessed tremendous advances in IVF over the past 40 years, patient access to assisted reproductive technologies is a challenge faced by many providers, particularly in resource-poor settings. Increasing research and focus is being directed toward developing safe and affordable techniques in low-resource settings22,23. In addition, the use of home ovulation kits may play a small but significant role in reducing the stress and cost on fertility programs24. The routine use of home ovulation predictor kits after a GnRHa trigger in an ovulation induction cycle may produce the cumulative effect of less clinic visits per patient per cycle. In a randomized prospective study comparing home LH detection using ovulation predictor kits compared with measuring serum LH levels in donor insemination cycles, there was a significant reduction in the number of clinic visits per cycle with ovulation kit use without a significant impact on monthly fecundity or cumulative conception rates25. Accordingly, the use of ovulation predictor kits in place of serum testing may reduce clinic staff burden on holidays, weekends, and during peak visit times such as morning monitoring. Furthermore, the absence of ovulation as demonstrated by home LH surge monitoring after a GnRHa trigger may also allow for the use of a low-dose hCG “rescue trigger” if ovulation has not occurred. Data comparing GnRHa trigger alone versus combined GnRHa/hCG triggers in controlled ovarian hyperstimulation cycles at risk for OHSS found that the dual approach improved oocyte yield with higher implantation and clinical pregnancy rates13.

Back to Top | Article Outline

Conclusions

The field of assisted reproductive technology has witnessed vast advancements in recent decades. However, access to fertility treatments worldwide has remained restricted, particularly in low-resource regions. Increased attention on developing low-cost, effective, and accessible treatment alternatives must be prioritized. The use of home LH immunoassays may be an inexpensive and readily available method for identifying failed trigger in ovulation induction cycles with GnRHa triggers. Future studies assessing the utility of this approach in a clinical setting are warranted.

Back to Top | Article Outline

Conflict of interest statement

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Back to Top | Article Outline

References

1. Mosher W, Pratt W. Fecundity and infertility in the United States: incidence and trends. Fert Steril 1991;56:192–3.
2. The Practice Committee of the American Society for Reproductive Medicine. Use of exogenous gonadotropins in anovulatory women: a technical bulletin. Fert Steril 2008;90:S7–12.
3. The Practice Committee of the American Society for Reproductive Medicine. Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. Fert Steril 2016;106:1634–47.
4. Engmann L, DiLuigi A, Schmidt D, et al. The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study. Fertil Steril 2008;89:84–91.
5. Kahnberg A, Enskog A, Brannstrom M, et al. Prediction of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization. Acta Obstet Gynecol Scand 2009;88:1373–81.
6. Papanikolaou E, Pozzobon C, Kolibianakis E, et al. Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles. Fertil Steril 2006;85:112–20.
7. Jayaprakasan K, Herbert M, Moody E, et al. Estimating the risks of ovarian hyperstimulation syndrome (OHSS): implications for egg donation for research. Hum Fertil (Camb) 2007;10:183–7.
8. Ashrafi M, Bahmanabadi A, Akhond M, et al. Predictive factors of early moderate/severe ovarian hyperstimulation syndrome in non-polycystic ovarian syndrome patients: a statistical model. Arch Gynecol Obstet 2015;292:1145–52.
9. Johnson M, Williams S, Seager C, et al. Relationship between human chorionic gonadotropin serum levels and the risk of ovarian hyperstimulation syndrome. Gynecol Endocrinol 2014;30:294–7.
10. Sousa M, Cunha M, Teixeira da Silva J, et al. Ovarian hyperstimulation syndrome: a clinical report on 4894 consecutive ART treatment cycles. Reprod Biol Endocrinol 2015;13:66.
11. Aramwit P, Pruksananonda K, Kasettratat K, et al. Risk factors for ovarian hyperstimulation syndrome in Thai patients using gonadotropins for in vitro fertilization. Am J Health Syst Pharm 2008;65:1148–53.
12. Kolibianakis E, Schultze-Mosgau A, Schroer A, et al. A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists. Hum Reprod 2005;20:2887–92.
13. Engmann L, Benadiva C. Agonist trigger: what is the best approach? Agonist trigger with aggressive luteal support. Fert Sterl 2012;97:531–3.
14. Meyer L, Murphy L, Gumer A, et al. Risk factors for suboptimal response to gonadotropin-releasing hormone agonist trigger during in vitro fertilization cycles. Fert Sterl 2015;104:637–42.
15. Chang F, Beall S, Cox J, et al. Assessing the adequacy of gonadotropin-releasing hormone agonist leuprolide to trigger oocyte maturation and management of inadequate response. Fertil Steril 2016;106:1093–1100.
16. Shapiro B, Daneshmand S, Garner F, et al. Gonadotropin-releasing hormone agonist combined with a reduced dose of human chorionic gonadotropin for final oocyte maturation in fresh autologous cycles of in vitro fertilization. Fertil Steril 2008;90:231–3.
17. Griffin D, Benadiva C, Kummer N, et al. Dual trigger of oocyte maturation with gonadotropin releasing hormone agonist (GnRHa) and low dose human chorionic gonadotropin (hCG) to optimize conception rates in high responders. Fertil Steril 2012;97:1316–20.
18. Corsan G, Ghazi D, Kemmann E. Home urinary luteinizing hormone immunoassays: clinical applications. Fert Steril 1990;53:591–601.
19. Miller P, Soules M. The usefulness of a urinary LH kit for ovulation prediction during menstrual cycles of normal women. Obstet Gyneol 1996;87:13–7.
20. Fedele L, Brioschi D, Dorta M, et al. Predication and self-prediction of ovulation in clomiphene citrate-treated patients. Eur J Obstet Gynec Rerod Biol 1988;28:297–303.
21. Critchley H, Hobson B, Flockhart J. Prediction of ovulation using a diptick sensitive to urinary luteinizing hormone. Cliic Exp Obstet Gynecol 1988;15:5–8.
22. Inhorn M, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update 2015;21:411–26.
23. Devlin N, Parkin D. Funding fertility: issues in the allocation and distribution of resources to assisted reproduction technologies. Hum Fertil (Camb) 2013;6:S2–S6.
24. Leader L, Russell T, Clifford K, et al. The clinical value of Clearplan home ovulation detection kits in infertility practice. Aust N Z J Obstet Gynaecol 1991;31:142–4.
25. Robinson J, Lockwood G, Dalton J, et al. A randomized prospective study to assess the effect of the use of home urinary luteinizing hormone detection on the efficiency of donor insemination. Hum Reprod 1992;7:63–5.
Keywords:

Home LH immunoassay; Ovulation monitoring; Suboptimal responder

Copyright © 2018 The Authors. Published by Wolters Kluwer on behalf of the International Federation of Fertility Societies. All rights reserved.