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: 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

Trial Summary

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.

What evidence supports the effectiveness of the drug Gonadotropins-IBSA for infertility?

Research shows that gonadotropins, including those derived from human urine and recombinant versions, are effective in stimulating the ovaries for assisted reproductive techniques (ART) and treating certain infertility conditions. They have been used successfully in both female and male infertility treatments, such as increasing sperm count in men with specific hormonal deficiencies. ^{1 2 3 4 5}

Is the use of gonadotropins for infertility treatment generally safe?

Gonadotropins used in fertility treatments are generally safe, but they can have side effects like local injection site reactions and ovarian hyperstimulation syndrome (a condition where the ovaries swell and become painful). There is also a potential, but unproven, risk of ovarian and breast cancer, and concerns about congenital malformations, though these may be more related to the underlying infertility issues rather than the treatment itself. ^{6 7 8 9 10}

How is the drug Gonadotropins-IBSA different from other infertility treatments?

Gonadotropins-IBSA is unique because it involves the use of gonadotropins, which are hormones that stimulate the ovaries to produce eggs, and it may offer a more stable and uniform treatment compared to traditional hormone preparations. Additionally, advancements in gonadotropin analogs aim to reduce the need for multiple injections and minimize risks like ovarian hyperstimulation syndrome. ^{5 11 12 13 14}

What is the purpose of this trial?

The objectives of this study is to evaluate the PK and the dose-proportionality of FSH and HCG following a single dose of Gonadotropins-IBSA, administered subcutaneously.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

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

Gonadotropin therapy: a 20th century relic. [2021]

3. Singapore 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. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Bye-bye urinary gonadotrophins? Recombinant FSH: a real progress in ovulation induction and IVF? [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2022]

7. England 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. [2013]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Safety of drugs used in assisted reproduction techniques. [2018]

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

The importance of consistent FSH delivery in infertility treatment. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Follitropin alpha versus beta in a first GnRH antagonist ICSI cycle: a retrospective cohort study. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of gonadotrophin preparations. [2019]

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

Gonadotropins and Their Analogs: Current and Potential Clinical Applications. [2022]

13. Iran 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. [2020]

14. United States 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). [2019]