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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: (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.

Received October 8, 2017

Accepted March 15, 2018

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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.

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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.

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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.

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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.

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Conflict of interest statement

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

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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.