Gonadotropins for Infertility

Overseen By Barbara PS Cometti, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: IBSA Institut Biochimique SA

Must be taking: Oral contraceptives

Must not be taking: Prescription medications, Vaccines

Disqualifiers: Pregnancy, Drug abuse, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, Gonadotropins-IBSA (a type of hormone therapy), to observe how the body absorbs and processes two hormones, FSH and hCG, which are crucial for fertility. The trial includes two groups: one receives a daily dose of 300 IU, and the other 150 IU, both for a week. Women who have used certain birth control pills for at least three months and are healthy with no major medical conditions may be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires participants to stop taking most medications, except for their prescribed oral contraceptive pills. Prescription medications must be stopped 14 days before the study drug is given, and over-the-counter products and natural health products must be stopped 7 days before.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that treatments using hormones like Gonadotropins-IBSA are generally safe for fertility treatments. Studies have found that similar treatments, such as Menopur, are well-tolerated and do not present major safety issues. These treatments typically do not raise significant concerns about side effects and are commonly used without problems.

It is important to note that this trial is in its early stages. While promising safety data exists from similar treatments, the specific safety of Gonadotropins-IBSA is still under investigation. Participants in the trial assist researchers in confirming the safety and effectiveness of this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about gonadotropins-IBSA for treating infertility because it offers a potentially more customizable approach compared to standard treatments like Clomid or Letrozole. Unlike these oral medications, gonadotropins are administered via injections, which allows for precise dosing and control over ovarian stimulation. The trial explores two different dosages, 150 IU and 300 IU daily, providing insights into tailoring treatment intensity to individual needs. This precision could lead to improved outcomes and reduced side effects, making it a promising option for those struggling with infertility.

What evidence suggests that Gonadotropins-IBSA might be an effective treatment for infertility?

Studies have shown that medications called gonadotropins, like those used in this trial, can help treat infertility. This trial will compare different dosages of Gonadotropins-IBSA, specifically 150 IU and 300 IU daily for 7 days. Research indicates that human menopausal gonadotropins (hMG) often lead to higher pregnancy rates compared to other treatments like recombinant FSH. For example, one study found that the chance of ongoing pregnancy exceeded 25% per cycle with hMG. Another study demonstrated that the rate of healthy embryos was much higher with these treatments than with some other methods. These findings suggest that Gonadotropins-IBSA could be promising for improving fertility outcomes. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for non-smoking women aged 18-45, with a BMI between 18.5 and 32, who are healthy and not currently pregnant or lactating. Participants must be on certain birth control pills for at least three months prior to the study and agree to continue them until the end of the trial. They should have no significant medical conditions or history of drug/alcohol abuse.

Inclusion Criteria

I am a woman aged 18-45, don't smoke, have a healthy weight, and can have children.

I have not been sick or had surgery in the last 4 weeks and do not have a history of significant illness.

I have been on a birth control pill with at least 20 µg of ethinyl estradiol for 3 months and will continue it.

Exclusion Criteria

Any clinically significant abnormal finding at physical examination at screening

Positive pregnancy test or lactating subject

Any reason that, in the opinion of the Investigator, would prevent the subject from participating in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous injections of Gonadotropins-IBSA at either 300 IU or 150 IU for 7 days

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including analysis of Inhibin B and Estradiol (E2) levels

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Gonadotropins-IBSA

Trial Overview The trial studies how FSH (follicle-stimulating hormone) and hCG (human chorionic gonadotropin) levels change after multiple doses of Gonadotropins-IBSA given through under-the-skin injections in women undergoing ovarian stimulation for infertility treatment.

How Is the Trial Designed?

Group I: Gonadotropins 300 IU Experimental Treatment 1 Intervention

300 IU daily for 7 days

Group II: Gonadotropins 150 IU Experimental Treatment 1 Intervention

150 IU daily for 7 days.

Gonadotropins-IBSA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Menopur for:

• Female Infertility
• Follicle Stimulation
• Ovulation Induction

Approved in United States as Repronex for:

• Female Infertility
• Follicle Stimulation
• Ovulation Induction

Approved in European Union as Menopur for:

• Female Infertility
• Follicle Stimulation
• Ovulation Induction

Approved in European Union as Merional for:

• Female Infertility
• Follicle Stimulation
• Ovulation Induction

Approved in Canada as Menogon for:

• Female Infertility
• Follicle Stimulation
• Ovulation Induction

Who Is Running the Clinical Trial?

IBSA Institut Biochimique SA

Lead Sponsor

Trials

42

Recruited

10,300+

Published Research Related to This Trial

In a study involving 125 women undergoing IVF, Menopur, a new urine-derived hMG preparation, resulted in significantly fewer injection site reactions compared to the currently available Repronex (P < 0.001).

Overall, while both treatments had similar rates of adverse events, Menopur demonstrated a better safety and tolerability profile, making it a potentially preferable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneously administered Menopur, a new highly purified human menopausal gonadotropin, causes significantly fewer injection site reactions than Repronex in subjects undergoing in vitro fertilization. Keye, WR., Webster, B., Dickey, R., et al.[2018]

In a study of 43 normoovulatory patients with suboptimal responses to recombinant FSH (rFSH), adding human menopausal gonadotrophin (HMG) significantly improved serum oestradiol levels and the number of oocytes retrieved compared to simply increasing the rFSH dose.

The addition of LH through HMG resulted in a pregnancy rate of 50% in the treatment group, which is comparable to the control group, suggesting that LH supplementation can enhance ovarian response in patients not initially responding well to rFSH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young women characterized by a poor initial response to recombinant FSH. De Placido, G., Mollo, A., Alviggi, C., et al.[2022]

A systematic review of six trials involving 2371 participants found that highly purified human menopausal gonadotropin (HP-hMG) showed a higher probability of clinical pregnancy compared to recombinant FSH (rFSH), with an odds ratio of 1.21, indicating a potential advantage for HP-hMG.

In women undergoing in vitro fertilization (IVF), HP-hMG significantly improved ongoing pregnancy/live-birth rates compared to rFSH, with an odds ratio of 1.31, suggesting it may be the preferred choice for assisted reproduction in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly purified hMG achieves better pregnancy rates in IVF cycles but not ICSI cycles compared with recombinant FSH: a meta-analysis. Al-Inany, HG., Abou-Setta, AM., Aboulghar, MA., et al.[2022]

Gonadotropins, particularly recombinant FSH and LH, are crucial for ovarian stimulation in reproductive medicine, effectively aiding in treatments for female infertility and conditions like hypogonadotropic hypogonadism.

Recent advancements in recombinant DNA technology have improved the production of gonadotropins, enhancing their efficacy and expanding their use in treating male infertility, such as oligozoospermia, by potentially increasing sperm count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present and future of recombinant gonadotropins in reproductive medicine. De Leo, V., Musacchio, MC., Di Sabatino, A., et al.[2019]

In patients with a high basal FSH/LH ratio undergoing IVF, administration of human menopausal gonadotrophin (HMG) resulted in a significantly higher number of top-quality embryos (3.9 vs. 2.5) compared to recombinant FSH (rFSH).

HMG treatment also led to higher implantation rates (27.9% vs. 5.3%) and clinical pregnancy rates (44.4% vs. 11.1%) compared to rFSH, indicating its greater efficacy in this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HMG improves IVF outcome in patients with high basal FSH/LH ratio: a preliminary study. Orvieto, R., Homburg, R., Meltcer, S., et al.[2022]

In a study of 36 patients undergoing IVF, those treated with highly purified human menopausal gonadotropin (HP-hMG) had significantly higher implantation rates (20.0% vs. 8.1%) and pregnancy rates (47.2% vs. 19.4%) compared to those treated with traditional human menopausal gonadotropin (hMG).

While the total number of top-quality embryos was similar between the two groups, the proportion of top-quality embryos generated was significantly higher in the HP-hMG group, indicating better overall embryo quality with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human menopausal gonadotropin versus highly purified-hMG in controlled ovarian hyperstimulation for in-vitro fertilisation: does purity improve outcome? Orvieto, R., Meltcer, S., Liberty, G., et al.[2010]

In a study involving 150 patients with poor response to previous IVF treatments, recombinant human follicle-stimulating hormone (rFSH) showed no significant advantage over human menopausal gonadotrophin (hMG) in terms of ovarian response, as measured by the number of follicles and oocytes retrieved.

Both treatments resulted in similar pregnancy rates and cycle characteristics, indicating that rFSH does not provide a better outcome for poor responders in IVF cycles compared to hMG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is recombinant follicle-stimulating hormone more effective in IVF poor responders than human menopausal gonadotrophins? Eskandar, M., Jaroudi, K., Jambi, A., et al.[2006]

In a randomized clinical trial involving 89 infertile women undergoing in-vitro fertilization, recombinant follicle stimulating hormone (rFSH) showed a higher mean number of oocytes retrieved (11.2) compared to human menopausal gonadotrophin (HMG) (8.3), suggesting better efficacy in ovarian response.

Ongoing pregnancy rates were also higher in the rFSH group (22.2%) compared to the HMG group (17.1%), indicating that rFSH is at least as effective as HMG for achieving pregnancy without the need for a gonadotrophin-releasing hormone (GnRH) agonist.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective randomized clinical trial comparing recombinant follicle stimulating hormone (Puregon) and human menopausal gonadotrophins (Humegon) in non-down-regulated in-vitro fertilization patients. Jansen, CA., van Os, HC., Out, HJ., et al.[2019]

In a study of 180 anovulatory women with hypothalamic-hypophysial dysfunction who previously failed clomiphene citrate therapy, Human Menopausal Gonadotropins (HMG) successfully induced ovulation in 81% of treatment cycles (340 out of 420 cycles).

The treatment resulted in a pregnancy rate of 33.8% among ovulatory cycles, with a manageable incidence of ovarian hyperstimulation syndrome (3.5%) and multiple pregnancies (10.4%), indicating that HMG is an effective option for these patients when monitored properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ovulation induction with human menopausal gonadotropins in hypothalamic-hypophyseal disfunction]. Ibarra Chavarria, V., Mota Gonzalez, M., Carballar Lopez, G., et al.[2006]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12152847/

Clinical efficacy and safety of two highly purified human ... Notably, both products' viable embryo rates (Gynogen HP: 83.6%; Menopur: 80.0%) significantly exceeded the 54% reported in a recent Chinese ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0015028203021873

Effectiveness of human menopausal gonadotropin versus ... Use of hMG resulted in higher clinical pregnancy rates than did use of recombinant FSH in IVF/ICSI cycles after GnRH agonist down-regulation in a long protocol.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07216742

Human Menopausal Gonadotropin Research in Infertility ... A Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of a Human Menopausal Gonadotropin in the ...

4. fertstert.org fertstert.org/article/S0015-0282(07)01207-1/fulltext

Effectiveness of highly purified human menopausal ... The ongoing pregnancy rates per started cycle were 26.3% and 25.2% for highly purified hMG and rFSH, respectively (no statistically significant difference).

5. rbej.biomedcentral.com rbej.biomedcentral.com/articles/10.1186/s12958-021-00768-3

Comparative effectiveness of recombinant human follicle ... This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly ...

6. reference.medscape.com reference.medscape.com/drug/menopur-repronex-menotropins-342877

Menopur, Repronex (menotropins) dosing, indications, ... A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S102845592100139X

Supplementation with human menopausal gonadotropin in ... The aim of this study was to investigate whether patients with high AMH had better pregnancy outcomes with the combination of r-FSH and HMG than with r-FSH ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/1999/21047lbl.pdf

repronex - accessdata.fda.gov Repronex is not indicated in women who are pregnant. There are limited human data on the effects of menotropins when administered during pregnancy.