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

28 Participants Needed

Trial Summary

What is the purpose of this trial?

Pharmacokinetics of FSH and hCG after multiple subcutaneous injection of Gonadotropins-IBSA.

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.

What data supports the effectiveness of the drug Gonadotropins-IBSA, Menopur, Repronex, Humegon, Merional, Menogon, Metrodin, Pergonal, Gynogen HP, Humog, Menotropin, Human Menopausal Gonadotropin, hMG for infertility?

Research shows that human menopausal gonadotropin (hMG) can lead to better pregnancy rates in IVF cycles compared to recombinant FSH, and it helps produce more high-quality embryos in certain patients. Additionally, Menopur, a form of hMG, causes fewer injection site reactions than Repronex, indicating good tolerability. ^{1 2 3 4 5}

Is the use of gonadotropins for infertility generally safe in humans?

Gonadotropins, such as Menopur and Repronex, are generally safe for use in humans, but they can cause some side effects like injection site reactions and ovarian hyperstimulation syndrome (OHS), which occurred in 3.5% of cases in one study. Multiple pregnancies and gestational losses are also possible, so careful monitoring by healthcare professionals is important. ^{1 2 4 6 7}

How does the drug Gonadotropins-IBSA differ from other infertility treatments?

Gonadotropins-IBSA, which includes Menopur, is a highly purified human menopausal gonadotropin (hMG) that can be administered subcutaneously, causing fewer injection site reactions compared to other hMG preparations like Repronex. It is derived from human urine and is used for ovarian stimulation in infertility treatments, offering a different option compared to recombinant follicle stimulating hormone (rFSH), which is produced using recombinant DNA technology. ^{1 2 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 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]

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 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]

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]

References

1. England 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. [2022]

2. England 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. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

HMG improves IVF outcome in patients with high basal FSH/LH ratio: a preliminary study. [2022]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Is recombinant follicle-stimulating hormone more effective in IVF poor responders than human menopausal gonadotrophins? [2006]

6. Mexico pubmed.ncbi.nlm.nih.gov

[Ovulation induction with human menopausal gonadotropins in hypothalamic-hypophyseal disfunction]. [2006]

7. England pubmed.ncbi.nlm.nih.gov

Human menopausal gonadotropin versus highly purified-hMG in controlled ovarian hyperstimulation for in-vitro fertilisation: does purity improve outcome? [2010]

8. England 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. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Present and future of recombinant gonadotropins in reproductive medicine. [2019]