Gonadotropins for Infertility

Overseen By Claudia Scarsi Perler

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: Hepatitis, HIV, Pregnancy, Drug abuse, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new fertility treatment called Gonadotropins-IBSA to understand how the body processes it and how different doses affect this process. It focuses on women trying to conceive who are currently using a specific type of birth control. Healthy women who have been using oral contraceptives and do not smoke would be a good fit for this trial. As a Phase 1 trial, participants will be among the first to help researchers understand how this new treatment works in people.

Will I have to stop taking my current medications?

The trial requires participants to stop taking most medications, except for their prescribed oral contraceptive. 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 trial's treatments are likely to be safe?

Research shows that the hormones tested in this study are usually well-tolerated. Studies have found that serious safety issues are very rare with these treatments. Some women might experience mild side effects like breast tenderness, headaches, or mood swings, but these are uncommon. As a Phase 1 trial, the treatment is being tested in humans for the first time to assess its safety, so the researchers are still learning about its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Gonadotropins-IBSA for infertility because it offers a tailored approach with varying doses: 75 IU, 225 IU, and 450 IU. Unlike standard infertility treatments that often involve rigid dosing schedules and formulations, this treatment provides flexibility to match individual patient needs. Most treatments for infertility aim at stimulating ovulation, but Gonadotropins-IBSA could potentially optimize ovarian response by allowing for precise dose adjustments. This level of customization may enhance effectiveness and reduce side effects, offering a promising option for those seeking fertility solutions.

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

Studies have shown that gonadotropins, including hormones like FSH (follicle-stimulating hormone) and HCG (human chorionic gonadotropin), often treat infertility. Research indicates that about 15.8% of treatment cycles using these hormones result in pregnancy. In this trial, participants will receive different dosages of gonadotropins—specifically 75 IU, 225 IU, or 450 IU—to evaluate their effectiveness and safety. These newer hormone versions are safer and more effective than older ones, increasing success in assisted reproduction. While generally safe, some individuals might experience side effects such as injection site reactions or ovarian swelling and pain. Overall, gonadotropins effectively aid conception, especially in assisted reproductive technologies. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy, non-smoking women aged 18-45 with a BMI between 18.5 and 32, who are not currently experiencing significant illness or surgery recovery. Participants must use contraception if sexually active and be on a specific oral contraceptive for at least three months prior to the study.

Inclusion Criteria

I haven't had any major illnesses or surgeries in the last 4 weeks and don't have a history of significant diseases.

I understand the study and agree to participate.

I am a woman aged 18-45, don't smoke, have a BMI between 18.5 and 32, and weigh at least 45 kg.

Exclusion Criteria

Elevated FSH levels at admission in each period

I have a gynecological condition.

I don't have tattoos or skin conditions where the study drug would be injected.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single subcutaneous injection of Gonadotropins-IBSA at varying doses (450 IU, 75 IU, 225 IU) to evaluate pharmacokinetics and dose-proportionality of FSH and hCG

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pharmacokinetic endpoints and adverse events up to 240 hours post dose

10 days

Multiple visits (in-person and/or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Gonadotropins-IBSA

Trial Overview

The study tests how the body processes FSH and HCG hormones after a single subcutaneous injection of Gonadotropins-IBSA. It aims to understand the pharmacokinetics (PK) and dose-proportionality in healthy female participants.

How Is the Trial Designed?

Group I: Gonadotropins 75 IU Experimental Treatment 1 Intervention

Single dose 75 IU

Group II: Gonadotropins 450 IU Experimental Treatment 1 Intervention

Single dose 450 IU

Group III: Gonadotropins 225 IU Experimental Treatment 1 Intervention

Single dose 225 IU

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 double-blind, randomized, placebo-controlled trial involving 39 women with profound gonadotrophin deficiency, 75 IU of lutropin alfa combined with 150 IU of follitropin alfa led to successful follicular development in 65.4% of patients, compared to only 15.4% in the placebo group, demonstrating significant efficacy (P = 0.006).

The treatment was well tolerated, indicating that the subcutaneous administration of lutropin alfa alongside follitropin alfa is both safe and effective for inducing follicular development in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant LH (lutropin alfa) for the treatment of hypogonadotrophic women with profound LH deficiency: a randomized, double-blind, placebo-controlled, proof-of-efficacy study. Shoham, Z., Smith, H., Yeko, T., et al.[2013]

The development of recombinant human FSH (r-FSH) has led to more consistent and pure gonadotrophin preparations, improving the treatment of infertility since its introduction.

A new formula for determining the initial dosage of r-FSH based on individual clinical parameters (basal FSH, BMI, and mean ovarian volume) shows promise for standardizing induction therapy in infertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of consistent FSH delivery in infertility treatment. Levi Setti, PE.[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]

In a study of 365 IVF cycles, both follitropin beta and follitropin alfa showed similar efficacy in achieving pregnancy rates, regardless of the age of the women involved.

Pregnancy rates significantly decreased with advancing age, highlighting the impact of age on IVF success, but no significant differences were found between the two hormone treatments in terms of primary and secondary outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy rates in varying age groups after in vitro fertilization: a comparison of follitropin alfa (Gonal F) and follitropin beta (Follistim). Williams, RS., Vensel, T., Sistrom, CL., et al.[2019]

In a study involving over 28,000 women undergoing assisted reproductive technology, treatment with recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) resulted in significantly higher rates of live births, ongoing pregnancies, and clinical pregnancies compared to urinary highly purified human menopausal gonadotropin (hMG HP).

Patients treated with r-hFSH-alfa used 47% less medication per oocyte retrieved and experienced fewer cycle cancellations, indicating that r-hFSH-alfa may be a more efficient and effective option for fertility treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany. Bühler, KF., Fischer, R., Verpillat, P., et al.[2021]

Assisted reproduction techniques (ART) have significantly improved the chances of conception for infertile couples, but the use of pharmacological agents in ART can lead to various adverse effects, including ovarian hyperstimulation syndrome and potential congenital malformations.

While gonadotropins are effective in stimulating ovarian function, they may be associated with risks such as luteal phase deficiency and concerns about long-term cancer risks, although these have not been conclusively proven.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of drugs used in assisted reproduction techniques. Al-Shawaf, T., Zosmer, A., Dirnfeld, M., et al.[2018]

In a study of 832 infertile patients undergoing their first ICSI cycle, there was no significant difference in cumulative live birth rates (CLBR) between those using follitropin alpha (Ovaleap) and follitropin beta (Puregon), indicating both medications are equally effective for ovarian stimulation.

The study found comparable outcomes in terms of biochemical and clinical pregnancy rates, as well as live birth rates after fresh embryo transfer, suggesting that the choice of gonadotrophin does not impact the success of ICSI treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follitropin alpha versus beta in a first GnRH antagonist ICSI cycle: a retrospective cohort study. Van den Haute, L., Drakopoulos, P., Verheyen, G., et al.[2022]

Gonadotropin hormone analogs, like corifollitropin alfa, have been effective in fertility treatments but often require multiple injections and can vary in stability, prompting research into more efficient alternatives.

Recent developments in low-molecular-weight, orally active molecules targeting gonadotropin receptors show promise in reducing risks associated with traditional treatments and may have broader applications, including contraception and cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gonadotropins and Their Analogs: Current and Potential Clinical Applications. Anderson, RC., Newton, CL., Anderson, RA., et al.[2022]

Recent advancements in gonadotrophin pharmacology have made ovulation induction and superovulation for IVF safer and more effective, improving treatment options for anovular infertility.

The review discusses the benefits of both urinary and recombinant gonadotrophins, highlighting their roles in combination with gonadotrophin-releasing hormone agonists and antagonists to enhance assisted reproduction outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of gonadotrophin preparations. Ledger, W.[2019]

In a study involving 160 women undergoing IVF/ICSI cycles, the combined sequential hFSH/rFSH protocol (Group D) required fewer ampoules of FSH and resulted in higher serum estradiol levels compared to other gonadotropin protocols.

Despite these differences in stimulation duration and hormone levels, there were no significant differences in the number of oocytes, embryo quality, clinical pregnancy rates, or live birth rates among the four gonadotropin treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Four Different Gonadotropin Protocols on Oocyte and Embryo Quality and Pregnancy Outcomes in IVF/ICSI Cycles; A Randomized Controlled Trial. Parsanezhad, ME., Jahromi, BN., Rezaee, S., et al.[2020]

Gonadotropin therapy, traditionally used for infertility treatment, has been linked to high rates of multiple births and ovarian hyperstimulation syndrome, raising concerns about its safety and efficacy.

Recent randomized controlled trials suggest that the effectiveness of gonadotropins for superovulation and intrauterine insemination (SO/IUI) may be overstated, prompting a reevaluation of their use and consideration of lower doses for in vitro fertilization (IVF).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gonadotropin therapy: a 20th century relic. Reindollar, RH., Goldman, MB.[2021]

In a study of 164 stimulation cycles involving infertile patients, treatment with gonadotropin preparations containing LH (hMG) showed similar pregnancy rates (22.7%) compared to those treated with pure FSH (20.3%).

The rates of spontaneous abortion were also comparable between the two groups (8.0% for hMG and 9.1% for FSH), indicating that there is no significant advantage in using LH-free preparations, allowing patients to opt for more cost-effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar pregnancy and spontaneous abortion rates after treatment with low-dose human menopausal gonadotropin versus pure follicle stimulating hormone in women with luteal phase defects. Check, JH., Fine, W.[2020]

Recombinant gonadotrophin products are considered safer than urinary gonadotrophins, but urinary products may lead to better overall outcomes and lower costs for routine ovulation induction and IVF cycles.

Younger patients tend to benefit more from urinary gonadotrophins, while older women and those with ovarian resistance may have better results with recombinant pure FSH, suggesting that treatment effectiveness can vary based on age and ovarian function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bye-bye urinary gonadotrophins? Recombinant FSH: a real progress in ovulation induction and IVF? Gleicher, N., Vietzke, M., Vidali, A.[2019]

In a study involving 238 women undergoing in vitro fertilization, both highly purified human-derived follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta (Follistim) showed comparable efficacy in terms of oocyte retrieval and pregnancy rates.

Patients reported that Bravelle injections were significantly less painful than Follistim injections, indicating a potential advantage in terms of patient comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly purified human-derived follicle-stimulating hormone (Bravelle) has equivalent efficacy to follitropin-beta (Follistim) in infertile women undergoing in vitro fertilization. Dickey, RP., Nichols, JE., Steinkampf, MP., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9184418/

Effectiveness and safety of gonadotropins used in female ...

Overall, 15.8% of cycles successfully led to pregnancy. Compared to extractives, recombinant and combined treatments showed a stronger association with ...

2.

asrm.org

asrm.org/practice-guidance/practice-committee-documents/evidence-based-treatments-for-couples-with-unexplained-infertility-a-guideline-2020/

Evidence-based treatments for couples with unexplained ...

There is insufficient evidence that gonadotropins with timed intercourse is superior to expectant management in the treatment of unexplained infertility, and ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S1521693422001894

Comparative effectiveness of gonadotropins used for ...

This is the first study to assess the effectiveness of gonadotropins in France, in a nationwide claims database.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3971356/

Gonadotropin therapy in assisted reproduction

Undoubtedly, current gonadotropins have better quality and safety profiles as well as clinical efficacy than earlier ones.

5.

withpower.com

withpower.com/trial/gonadotropins-for-infertility-b0276

Gonadotropins for Infertility

Gonadotropins used in fertility treatments are generally safe, but they can have side effects like local injection site reactions and ovarian hyperstimulation ...

6.

asrm.org

asrm.org/practice-guidance/practice-committee-documents/use-of-exogenous-gonadotropins-for-ovulation-induction-in-anovulatory-women-a-committee-opinion-2020/

Use of exogenous gonadotropins for ovulation induction in ...

A systematic review of 13 studies evaluated ovulation induction with gonadotropins in anovulatory women and found pregnancy rates of 15% per cycle and 41% per ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35507074/

Effectiveness and safety of gonadotropins used in female ...

Outcomes related to maternal and infantile safety were generally very rare, and safety features were overlapping between gonadotropin ...

8.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2816889

Excessive Exogenous Gonadotropins and Genetic ...

Importance The safety of exogenous gonadotropin treatment, based on its effect on embryos and pregnancy outcomes, remains inconclusive.

9.

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)

Some women may experience breast tenderness, headaches, or mood swings from the gonadotropins. In Vitro Fertilization (IVF).