MENOPUR® in a Gonadotropin-Releasing Hormone (GnRH) Antagonist Cycle With Single-Blastocyst Transfer in a High Responder Subject Population

Study Overview
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Brief Summary
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The purpose of this trial is to demonstrate non-inferiority of MENOPUR® versus recombinant Follicle Stimulating Hormone (rFSH) (Gonal-f®) with respect to ongoing pregnancy rate in women undergoing controlled ovarian stimulation (COS) following GnRH treatment.

Official Title
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A Randomized, Assessor-blind Trial Comparing MENOPUR® (Menotropins for Injection) and Recombinant FSH (Follicle Stimulating Hormone) in a GnRH Antagonist Cycle With Single-Blastocyst Transfer in a High Responder Subject Population

Conditions
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Infertility

Intervention / Treatment
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* Drug: menotropin
* Drug: recombinant FSH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 21 to 35 years with regular ovulatory menstrual cycles of 21 to 45 days, with a Body Mass Index (BMI) between 18 and 30 kg/m2 who desire pregnancy. Subjects must be high responders, defined as subjects who have a serum anti-Müllerian hormone (AMH) ≥5 ng/mL at screening. Documented history of infertility (e.g., unable to conceive for at least 12 months or for at least 6 months if receiving donor sperm) with a Day 2 or Day 3 serum FSH level between 1 and 12 IU/L (inclusive), the results of which should be obtained within 6 months prior to randomization. Exclusion Criteria: Known stage III-IV endometriosis (American Society for Reproductive Medicine, 2012). History of recurrent miscarriage not followed by a live birth (recurrent is defined as two (2) or more consecutive miscarriages). Previous in vitro fertilization (IVF) or assisted reproductive technology (ART) failure due to a poor response to gonadotropins. Poor response is defined as development of ≤2 mature follicles or history of 2 previous failed cycle cancellations prior to oocytes retrieval due to poor response.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: menotropin<br>menotropins for injection | Drug: menotropin<br> <br> * Other names: Menopur®;|
| Active Comparator: recombinant FSH<br> | Drug: recombinant FSH<br> <br> * Other names: Gonal-f®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing Pregnancy Rate | Defined as the percentage of participants with the presence of at least 1 intrauterine pregnancy with a detectable fetal heartbeat at 10-11 weeks of gestation. | 8-9 weeks after blastocyst transfer in the fresh cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive β-human Chorionic Gonadotropin (hCG) Rate | Defined as the percentage of participants with 2 positive β-hCG tests within 2 days in serum. | First test approximately 10-14 days after blastocyst transfer in the fresh cycle, with a second test approximately 2 days later if first test was positive | 
| Clinical Pregnancy Rate | Defined as percentage of participants with transvaginal ultrasound (TVUS) showing at least 1 intrauterine gestational sac with fetal heart beat at 6-7 weeks of gestation. | 4-5 weeks after blastocyst transfer in the fresh cycle | 
| Early Pregnancy Loss | Defined as participants with 2 positive β-hCG tests but no ongoing pregnancy at 10-11 weeks of gestation in the fresh cycle. Percentage of participants with early pregnancy loss is presented. | At 10-11 weeks of gestation in the fresh cycle | 
| Follicular Development as Assessed by TVUS | Defined as average follicle size and average size of 3 largest follicles. | On stimulation Day 6 and last day of stimulation (a maximum of 20 stimulation days) | 
| Follicular Development as Assessed by TVUS | Defined as percentage of participants with follicles having a diameter of ≤9 mm, 10-11 mm, 12-14 mm, 15-16 mm, and ≥17 mm. | On stimulation Day 6 and last day of stimulation (a maximum of 20 stimulation days) | 
| Number of Oocytes Retrieved |  | At oocyte retrieval visit (approximately 36 hours after hCG administration) | 
| Number of Metaphase II Oocytes |  | At oocyte retrieval visit (approximately 36 hours after hCG administration) | 
| Fertilization Rate | Defined as 100 times the ratio of number of fertilized 2 pronuclei oocytes to the number of oocytes retrieved, for each participant. | On day 1 post-insemination | 
| Quality of Embryos | Assessed by blastomere uniformity, cell size, the degree of fragmentation, and visual signs of multinucleation. | 3 days after oocyte retrieval | 
| Quality of Embryos | Assessed by cleavage stage. | 3 days after oocyte retrieval | 
| Quality of Blastocysts | Assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cell). | 5 days after oocyte retrieval |