Corifollitropin Alfa Combined With Menotropin Versus Follitropin and Lutropin Alfa in Expected Suboptimal Responders

Study Overview
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Brief Summary
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In an opened randomized study of women undergoing in vitro fertilization with expected suboptimal response to controlled ovarian stimulation (Poseidon Group 2b) investigators will examine clinical efficacy and safety of two stimulation protocols: Corifollitropin alfa (Elonva) in combination with menotropin (Merional) versus Follitropin alfa and lutropin alfa (Pergoveris).

Detailed Description
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Patients, found eligible for the study, will be randomized (envelope method) into two arms in 1:1 ratio at the start of stimulation (menstrual cycle day 2-3, randomization day): Arm A - ovarian stimulation with Corifollitropin alfa in combination with menotropin; Arm B - ovarian stimulation with Follitropin alfa and lutropin alfa. At the first day of controlled ovarian stimulation (COS) participants in the first group will receive a single injection of Corifollitropin alfa 150 mcg followed by daily menotropin administration at the dose of 150 international unit (IU) from stimulation day 1 to day 7 and at the dose of 300 IU from day 8 up to the end of stimulation. Ovarian stimulation in group B will be performed with daily 300 IU of Follitropin alfa and lutropin alfa starting on menstrual cycle day 2-3. For all subjects, a fixed dose of gonadotropin-releasing hormone (GnRH) antagonist will be injected daily as soon as one of the follicles reaches the ≥14 mm diameter and stopped one day before oocyte pick up (OPU); ovulatory dose of human chorionic gonadotropin (hCG) could be administered when at least one follicle reaches 16.5 mm in diameter. Retrieved oocytes following fertilization (conventional IVF or ICSI) will be cultured to morula or blastocyst stage followed by ultrasound guided single or double embryo transfer (ET day, performed 4-5 days after OPU).

Official Title
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Open Randomized Study Comparing Clinical Efficacy of Corifollitropin Alfa (Elonva) in Combination With Menotropin (Merional) With Follitropin and Lutropin Alfa (Pergoveris) for Ovarian Stimulation in Expected Suboptimal Responders

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: Corifollitropin alfa and menotropin
* Drug: Follitropin alfa and lutropin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female age between 35-41 years; BMI 17,5-30 kg/m2; Expected suboptimal responders (according to Poseidon classification, 2016, Group 2b): patients with suboptimal ovarian reserve prestimulation parameters in terms of antimüllerian hormone (AMH) and antral follicle count (AFC): AFC 5-9, AMH ≥0.8 ng/mL; Early follicular phase follicle stimulating hormone (FSH) ≤15 IU/L; Presence of viable spermatozoa in partner's sperm; Signed informed consent. Exclusion Criteria: Pre-existing medical condition preventing or interfering with IVF treatment: any clinically significant systemic disease; inherited or acquires thrombophilia and thromboembolism; endocrine or metabolic abnormalities; moderate or severe impairment of renal or hepatic function; any oncological diseases in anamnesis; known history of recurrent miscarriage, abnormal karyotype of both partners; currently active pelvic inflammatory disease; Abnormal IVF screening tests: Papanicolaou test, Syphilis, HIV 1&2, Hepatitis B, Hepatitis C, Chlamydia, and Gonorrhea; Presence of uterine pathology: Asherman's Syndrome, endometrial polyps, nodus form of adenomyosis or uterine fibroids ≥3 mm in diameter; Visualization of ovarian cysts ≥25 mm, endometriomas or hydrosalpinx; One or more follicles ≥8 mm on randomization day.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 41 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Corifollitropin alfa and menotropin<br>Elonva 150 mcg, Merional 150-300 IU | Drug: Corifollitropin alfa and menotropin<br>* Procedure: Ovarian stimulation is performed by the combination of a single Corifollitropin alfa 150 mcg injection on menstrual cycle day 2-3 and daily menotropin administration at the dose of 150 IU from stimulation day 1-7 and at the dose of 300 IU from day 8 to the end of stimulation (maximal dose adjustment to 450 IU). Other interventions: conventional GnRH antagonist protocol and in vitro fertilization (IVF/ICSI) cycle<br>* Other names: Elonva, Merional;|
| Active Comparator: Follitropin alfa and lutropin alfa<br>Pergoveris 300 IU | Drug: Follitropin alfa and lutropin alfa<br>* Procedure: Ovarian stimulation is performed with daily 300 IU of Follitropin alfa and lutropin alfa starting on menstrual cycle day 2-3. Maximal allowed dose adjustment is 450 IU daily. Other interventions: conventional GnRH antagonist protocol and in vitro fertilization (IVF/ICSI) cycle.<br>* Other names: Pergoveris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of cumulus-oocyte complexes (COCs) | Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols | 3-4 weeks after ET | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of stimulation | total days of COS: from the first gonadotropins administration to ovulation triggering | 2-4 weeks after randomization | 
| Number of follicles at the end of stimulation | measured for follicles ≥17 mm and ≥14 mm | 2-4 weeks after randomization | 
| Dose adjustment frequency | number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase | 2-4 weeks after randomization | 
| Number of participants with optimal or suboptimal response to COS | ≥ 5 COCs at at oocyte recovery day | 2-4 weeks after randomization | 
| Number of mature (MII) oocytes | assessment is done only for ICSI cycles at oocyte recovery day | 2-4 weeks after randomization | 
| Cycle cancellation rate | number of cancelled cycles during COS (no response), at OPU (premature ovulation, absence or degradation of COCs), during in vitro cultivation (fertilization failure, inadequate embryo quality) or due to other reasons (adverse events, ovarian hyperstimulation syndrome (OHSS), withdrawal) | 6-7 weeks after randomization | 
| Frequency of side reactions | number of patients with local reactions (redness, itching, swelling or pain) or abdominal discomfort evaluated using visual analogue scale at the end of COS and at ET day | 2-4 weeks after randomization | 
| Implantation rate | ratio of the number of intrauterine gestational sacs to the number of transferred embryos | 3-4 weeks after ET | 
| Clinical pregnancy rate | presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer | 5-6 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, suboptimal response, Corifollitropin alfa, Ovarian stimulation