Dual Trigger IVF for OHSS

Overseen By Ellen Greenblatt, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Mount Sinai Hospital, Canada

Must be taking: GnRH antagonist

Must not be taking: GnRH agonist

Disqualifiers: Low ovarian reserve, Hypogonadotropic hypogonadism, Recurrent implantation failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3-5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a "dual trigger" approach can improve IVF outcomes for individuals at high risk of developing Ovarian Hyperstimulation Syndrome (OHSS). The researchers aim to determine if combining two medications, including Pregnyl (a hormone injection), can enhance egg quality and embryo potential compared to using a single medication. Suitable participants are those undergoing IVF with specific risk factors, such as having 13 or more follicles or high estradiol levels. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is the safety track record for these treatments?

Research has shown that using Pregnyl, a type of human chorionic gonadotropin (hCG), in fertility treatments can be safe but carries some risks. One study examined a dose of 2,500 IU of hCG in women at high risk for ovarian hyperstimulation syndrome (OHSS). It found that none of these women experienced moderate or severe OHSS, suggesting that Pregnyl is generally well-tolerated at certain doses.

However, injectable fertility drugs can have side effects. These include OHSS, which occurs when the ovaries react too strongly to the hormones. Other possible side effects are multiple pregnancies, such as twins or more, and ectopic pregnancies, where the baby grows outside the womb.

This study is in Phase 4, meaning researchers are assessing the treatment's safety and effectiveness in a larger group of people. By this stage, the treatment is usually considered safe, but researchers continue to gather more information on any side effects. Always consult a doctor about any concerns or questions regarding joining a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the dual trigger IVF approach for preventing ovarian hyperstimulation syndrome (OHSS) because it combines a GnRH agonist with hCG (Pregnyl), potentially reducing the risk of OHSS while maintaining high success rates for egg maturation. Unlike standard IVF treatments that typically use only hCG to trigger ovulation, this method uses both a GnRH agonist and a lower dose of hCG, which could result in fewer side effects and a safer treatment process for patients. This dual trigger approach aims to balance efficacy and safety, offering a promising alternative for those at risk of OHSS.

What evidence suggests that this trial's treatments could be effective for improving IVF outcomes in patients at high risk of OHSS?

Research has shown that using a "dual trigger" method with Pregnyl (hCG), which participants in this trial may receive, can improve IVF outcomes by enhancing egg quality and embryo development. Studies have found that different doses of hCG, as used in dual triggers, result in similar numbers of mature eggs and successful fertilizations. This suggests that adding hCG to the GnRH agonist could be beneficial. Additionally, using hCG has been linked to managing the risk of ovarian hyperstimulation syndrome (OHSS) without significantly increasing severe cases. This makes it a promising option for those at high risk of OHSS during IVF. ^{3 6 7 8 9}

Who Is on the Research Team?

Miguel Russo, MD

Principal Investigator

Mount Sinai Hospital, Canada

Are You a Good Fit for This Trial?

This trial is for women aged 18-40 undergoing IVF with a risk of Ovarian Hyperstimulation Syndrome (OHSS). They must have at least 13 follicles or high estradiol levels on the day of trigger. Women who've had poor outcomes with dual triggers, low ovarian reserve, are preserving fertility due to cancer, have recurrent implantation failure, or certain medical conditions can't participate.

Inclusion Criteria

You are between 18 and 40 years old.

You are currently receiving a specific type of treatment for infertility.

You have a high risk for Ovarian Hyperstimulation Syndrome (OHSS) because you have a lot of large follicles in your ovaries.

Exclusion Criteria

They plan to use a "dual trigger" because a previous IVF cycle using a GnRH agonist trigger had poor results.

You have a low number of eggs in your ovaries.

You are currently getting treatment to save your ability to have children in the future.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 'dual trigger' or placebo comparator followed by oocyte retrieval and embryo transfer

3-5 days

Multiple visits for injections and monitoring

Follow-up

Participants are monitored for safety and effectiveness after embryo transfer, including assessment of pregnancy and live birth rates

10 months

Regular follow-up visits

Outcome Assessment

Assessment of live birth rate, OHSS incidence, and other secondary outcomes

Up to 20 weeks post-pregnancy confirmation

What Are the Treatments Tested in This Trial?

Interventions

• Normal Saline
• Pregnyl

Trial Overview The study tests if a 'dual trigger' (Pregnyl and saline) improves IVF outcomes compared to just GnRH agonist in patients at high OHSS risk. It focuses on oocyte quality and embryo potential by looking only at freeze-all cycles followed by frozen embryo transfers.

How Is the Trial Designed?

Group I: Treatment Arm- Group A Experimental Treatment 1 Intervention

A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of hCG (Pregnyl 1,500 IU).

Group II: Control Arm- Group B Placebo Group 1 Intervention

A subcutaneous injection of a GnRH agonist (Suprefact 0.5 mg) and a separate intramuscular injection of normal saline (1.5 mL) (sham-placebo).

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Recruited

70,700+

Published Research Related to This Trial

The study aims to evaluate the safety and efficacy of using low dose hCG alongside GnRH agonist for oocyte maturation in 82 women undergoing IVF, focusing on preventing ovarian hyperstimulation syndrome (OHSS) and improving pregnancy rates.

By comparing two groups—one receiving low dose hCG at the trigger and placebo at retrieval, and the other receiving placebo at trigger and higher hCG at retrieval—the study will assess live birth rates and OHSS incidence, providing insights into optimal IVF protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dual trigger study: Rationale and study design of a prospective double-blind randomized clinical trial comparing pregnancy rates after co-administration of low dose hCG at the time of GnRH agonist trigger or 35 h later for the prevention of OHSS. Griffin, D., Benadiva, C., Budinetz, T., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15482757/

Reducing the Dose of Human Chorionic Gonadotropin in ... A reduced hCG dose of 3300 IU results in a similar proportion of mature eggs, similar fertilization rates, and similar PRs compared to 5000 IU.

2. asrm.org asrm.org/practice-guidance/practice-committee-documents/prevention-and-treatment-of-moderate-and-severe-ovarian-hyperstimulation-syndrome-a-guideline/

Prevention of moderate and severe ovarian ... This systematic review aims to identify who is at high risk for developing ovarian hyperstimulation syndrome, along with evidence-based strategies to prevent ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0015028205005716

In vitro fertilization Effects of the ovulatory serum ... These results suggest little or no loss of efficacy as serum concentrations varied within the range seen in this study, that is, 55 to 530 IU/L. However, of the ...

4. fertstert.org fertstert.org/article/S0015-0282(04)02223-X/fulltext

Reducing the dose of human chorionic gonadotropin in ... The 5,000 IU hCG group had one case of moderate OHSS and no cases of severe OHSS. The 3,300 IU hCG group had five cases of moderate OHSS and two cases of severe ...

5. jmrh.mums.ac.ir jmrh.mums.ac.ir/article_7979.htmlhttp:/jmrh.mums.ac.ir/article_11519.html

Effect of Low-dose Human Chorionic Gonadotropin on the ... There was no significant difference in the rate of OHSS incidence and cancellation of embryo transfer between the two groups (1600 and 5000 units). Conclusion: ...

6. mayoclinic.org mayoclinic.org/diseases-conditions/ovarian-hyperstimulation-syndrome-ohss/symptoms-causes/syc-20354697

Ovarian hyperstimulation syndrome - Symptoms & causes Ovarian hyperstimulation syndrome is an exaggerated response to excess hormones. It usually occurs in women taking injectable hormone medications to stimulate ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2842872/

Ovarian hyperstimulation syndrome: pathophysiology and ... More recently, a pilot study evaluated the safety and efficacy of hCG dosages of 2,500 IU in 21 high risk women [41]. No moderate or severe OHSS was observed, ...

8. reproductivefacts.org reproductivefacts.org/news-and-publications/fact-sheets-and-infographics/side-effects-of-injectable-fertility-drugs-gonadotropins/

Side effects of injectable fertility drugs (gonadotropins) What are some of the potential side effects of gonadotropins? · Ovarian Hyperstimulation Syndrome (OHSS) · Multiple Gestation · Ectopic (Tubal) Pregnancies.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02715336

Efficacy and Safety of Medication Used to Stimulate Ovulation Individuals undergoing In Vitro Fertilization must undergo controlled ovarian hyperstimulation (COH) to produce enough quality eggs for fertility treatment.