GnRH Agonist for Infertility

Overseen By Peter G McGovern, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University Reproductive Associates

Disqualifiers: Day 3 transfers

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a GnRH agonist, a type of hormone treatment, can boost pregnancy success during IVF (in vitro fertilization) treatments. Researchers aim to determine if adding this hormone treatment around the time of embryo transfer can improve embryo implantation and live birth rates. The trial includes two groups: one receiving the GnRH agonist and the other receiving a placebo, a harmless substance with no treatment effect. Women undergoing IVF or frozen embryo transfers who have experienced implantation issues might be suitable candidates. As a Phase 4 trial, this study involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What is the safety track record for GnRH agonist?

Research has shown that GnRH agonists, studied for use in IVF treatments, are generally safe. These medications are already used for conditions like infertility and early puberty, indicating their safety.

In some cases, GnRH agonists have been linked to risks such as ectopic pregnancy and miscarriage, though these are not common for all users.

Overall, while some risks exist, research indicates that GnRH agonists are a safe and effective treatment for many. Prospective trial participants should discuss health concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for infertility typically involve hormone therapies or procedures like in vitro fertilization (IVF). However, the GnRH agonist is unique because it works by modulating the release of hormones from the brain, specifically targeting the hypothalamic-pituitary-gonadal axis to enhance fertility. This mechanism may offer a more direct way to address hormonal imbalances that contribute to infertility. Researchers are particularly excited about the potential for improved outcomes and fewer side effects compared to conventional hormone treatments.

What evidence suggests that this treatment might be an effective treatment for infertility?

Studies have shown that using a GnRH agonist, which participants in this trial may receive, can improve pregnancy rates during IVF treatments. One study found that patients who received a GnRH agonist had a higher ongoing pregnancy rate of 80% compared to 53.85% in those who did not. Another report showed that women who used this drug had better overall pregnancy outcomes, with a significantly higher live birth rate. These improved outcomes suggest that the GnRH agonist can enhance IVF effectiveness by aiding successful embryo implantation and growth. ^{1 2 6 7 8}

Who Is on the Research Team?

Peter G McGovern, MD

Principal Investigator

Rutgers University

Are You a Good Fit for This Trial?

This trial is for women under 40 years old undergoing IVF, ICSI, or frozen embryo transfers to help with infertility. It's not for those having an embryo transfer on day 3 of the process.

Inclusion Criteria

I am a woman under 40 planning to undergo IVF/ICSI or FET.

Exclusion Criteria

Day 3 transfers

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a GnRH agonist or placebo around the time of embryo transfer to support endometrial development

1 week

Follow-up

Participants are monitored for implantation success and pregnancy outcomes

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GnRH

Trial Overview The study tests if a single dose of GnRH agonist given around the time of embryo transfer improves implantation and live birth rates in IVF cycles compared to a placebo.

How Is the Trial Designed?

Group I: GnRH agonist Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University Reproductive Associates

Lead Sponsor

Trials

6

Recruited

460+

Published Research Related to This Trial

Gonadotropin-releasing hormone (GnRH) agonists are promising new therapeutic agents with potential applications in various medical fields, including endocrinology, gynecology, pediatrics, and oncology.

The review highlights the physiological and neuroendocrine effects of GnRH, emphasizing the clinical relevance of both the native hormone and its analogs in treating various conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of gonadotropin-releasing hormones in reproductive disorders. Moghissi, KS.[2006]

In a study involving 100 women undergoing assisted reproductive technology (ART) cycles, no significant differences were found in IVF outcomes such as oocyte retrieval, fertilization, implantation, or pregnancy rates between short-acting and long-acting GnRH agonist formulations.

Both formulations of GnRH agonists (1.87 mg Triptorelin and 0.1 mg Decapeptyl) showed similar efficacy, indicating that there may not be a clear advantage of one over the other in ART protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of pregnancy outcome in half-dose Triptorelin and short-acting Decapeptyl in long protocol in ART cycles: A randomized clinical trial. Eftekhar, M., Rahmani, E., Mohammadian, F.[2021]

GnRH analogues are established as safe and effective treatments for hormone-dependent advanced prostate cancer, but their unique mechanism of action complicates the entry of generic versions into the market.

Regulatory requirements for GnRH analogues are stringent due to their comparison with surgical castration, which has a 100% success rate, and they face competition from antagonistic treatments that do not cause flare-up effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and regulatory consequences of GnRH analogues in prostate cancer. Eckstein, N., Haas, B.[2022]

GnRH and its agonists play a crucial role in regulating reproductive functions and are used to treat various conditions like prostate cancer, endometriosis, and infertility, highlighting their therapeutic efficacy.

Recent developments in small molecule GnRH antagonists present a promising alternative to peptidic forms, potentially allowing for oral administration and expanding treatment options for conditions currently managed with injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-peptidic GnRH receptor antagonists. Armer, RE., Smelt, KH.[2019]

GnRH agonists effectively induce reversible hypogonadotropic hypogonadism by desensitizing the pituitary gland, leading to reduced gonadotropin and estradiol levels, which can successfully treat estrogen-dependent conditions like endometriosis and metastatic breast cancer.

These synthetic peptides not only have therapeutic applications but also exhibit contraceptive properties and can be used in combination with other treatments to induce ovulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[GnRH analogs in gynecology. Possibilities for therapeutic use]. Niesert, S.[2006]

In a study of 40 women with previous IVF or ICSI failures, using the GnRH antagonist cetrorelix led to a significantly higher number of patients developing at least one expanded blastocyst compared to the GnRH agonist protocol (25 vs. 9).

The cetrorelix protocol resulted in a pregnancy rate of 42.1%, with 16 women becoming pregnant, indicating that this approach may enhance pregnancy outcomes by improving blastocyst quality in patients with a history of unsuccessful treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GnRH antagonist improved blastocyst quality and pregnancy outcome after multiple failures of IVF/ICSI-ET with a GnRH agonist protocol. Takahashi, K., Mukaida, T., Tomiyama, T., et al.[2019]

GnRH antagonists, such as cetrorelix and ganirelix, provide a promising alternative to traditional GnRH agonists for preventing premature LH surges during ovarian stimulation, with comparable clinical outcomes and reduced treatment times.

These antagonists are associated with a lower risk of ovarian hyperstimulation syndrome (OHSS) and are preferred by patients over agonist treatments, indicating their potential to become the preferred choice in assisted reproductive techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The place of gonadotrophin-releasing hormone antagonists in reproductive medicine. Howles, CM.[2019]

LHRH agonists, when used in the long protocol before gonadotrophins in IVF, have been associated with higher pregnancy and live birth rates in women with PCOS, indicating their efficacy in enhancing reproductive outcomes.

The timing of LHRH agonist administration is important; starting in the early follicular phase, possibly after pre-treatment with contraceptives, can help prevent risks associated with early pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of luteinizing hormone releasing hormone agonists in polycystic ovary syndrome. Buckett, WM., Tan, SL.[2019]

GnRH antagonists are safe and effective for preventing premature LH surges during in vitro fertilization, allowing for flexible treatment options across various patient groups, including those with polycystic ovary syndrome.

Compared to long agonists, GnRH antagonists require a shorter treatment duration and fewer injections, leading to lower gonadotropin use and potentially better patient compliance without negatively impacting reproductive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal usage of the GnRH antagonists: a review of the literature. Copperman, AB., Benadiva, C.[2022]

GnRH agonists are essential for enhancing the effectiveness of gonadotrophins in ovulation induction during assisted reproduction, indicating their critical role in fertility treatments.

Long regimens of GnRH agonists are particularly effective, as they help optimize patient scheduling and improve clinical outcomes in assisted reproductive technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of different GnRH agonist regimens in pituitary suppression and the outcome of controlled ovarian hyperstimulation. Filicori, M., Cognigni, GE., Arnone, R., et al.[2019]

The GnRH analogue [(imBz1)-D-His6,Pro9-NEt]GnRH is 200 times more potent than the natural hormone in vitro, leading to significantly increased levels of LH and FSH in single-dose studies in humans.

This analogue not only shows a prolonged duration of activity but also appears to be safe, suggesting potential clinical applications for treating conditions related to hormone regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose responses to the gonadotropin-releasing hormone agonist analogue [(imBz 1)-D-His6,Pro9-NEt]GnRH. Doelle, GC., Evans, RM., Alexander, AN., et al.[2013]

Men with advanced nonmetastatic prostate cancer on gonadotropin-releasing hormone (GnRH) agonists experienced a significantly higher increase in comorbidity rates compared to those on antiandrogens (AAs), with a 5.6% greater excess rate of change per year after starting treatment.

The risk of developing new comorbidities was 32% higher for men on GnRH agonists compared to those on AA monotherapy, indicating that GnRH agonists may pose a greater risk of adverse health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer. Beckmann, K., Garmo, H., Adolfsson, J., et al.[2019]

In a study of 333 patients treated with the GnRH antagonist ganirelix during IVF or ICSI, the pregnancy outcomes were generally positive, with 68 vital pregnancies leading to 46 singletons, 12 twins, and one triplet, indicating the treatment's efficacy.

The rate of miscarriages was 9%, and the overall incidence of adverse obstetrical and neonatal outcomes was comparable to standard IVF pregnancies, suggesting that ganirelix is safe for use in human fertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perinatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF or ICSI: a preliminary report. Olivennes, F., Mannaerts, B., Struijs, M., et al.[2019]

In a study of 45,059 men with prostate cancer receiving androgen deprivation therapy, the risk of major adverse cardiovascular events (MACE) was found to be significantly higher for those treated with GnRH antagonists compared to LHRH agonists, with a hazard ratio of 1.62.

Additionally, the risk of all-cause mortality was also greater for patients on GnRH antagonists versus LHRH agonists, indicating that LHRH agonists may be a safer option in terms of cardiovascular health following ADT initiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist. Crawford, ED., Hafron, JM., Debruyne, F., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12068405/

Effects of Different Gonadotropin-Releasing Hormone ... In this study, we retrospectively collected four-year data of different GnRH-a formulations, in order to provide real-world evidence of the ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0015028202033733

Clinical article Effect of prolonged gonadotropin-releasing ... Patients who received the long-acting GnRH regimen had significantly higher ongoing pregnancy rates (80% vs. 53.85%) and a trend toward higher implantation ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/07853890.2022.2071458

Effectiveness of gonadotrophin-releasing hormone agonist ... The cumulative pregnancy rates were all higher in patients administered with GnRH-a than those without GnRH-a treatment in different cycles (one cycle: 17.07% ...

4. cureus.com cureus.com/articles/255926-gonadotropin-releasing-hormone-gnrh-agonist-protocol-improves-pregnancy-outcomes-during-in-vitro-fertilization-ivf-and-intracytoplasmic-sperm-injection-icsi-treatment-in-young-infertile-women-a-retrospective-study

Gonadotropin-Releasing Hormone (GnRH) Agonist ... Comparison of pregnancy outcomes between two groups ; Clinical pregnancy rate (%), 61.54 (216/351), 47.30 (70/148), 0.037, 4.327 ; Live birth rate ...

5. link.springer.com link.springer.com/article/10.1007/s00404-024-07914-3

Exposure to gonadotropin-releasing hormone agonist in ... Exposure to GnRH-a during the luteal phase of down-regulation can adversely affect pregnancy outcomes. Therefore, we recommend contraception ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK547863/

Gonadotropin Releasing Hormone (GnRH) Analogues - NCBI They are used off-label for precocious puberty, gender dysphoria and infertility. Common side effects of the GnRH agonists and antagonists ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666334123000077

Pulsatile gonadotropin-releasing hormone: clinical ... In summary, pulsatile GnRH administration was found to be an extremely safe and effective tool to treat hypogonadotropic men and women and correct anovulation.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.78.0858

Gonadotropin-Releasing Hormone Agonists During ... To date, temporary ovarian suppression obtained by administering gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy is the only ...