Clinical trial NCT03177538: Corifollitropin Alfa Combined With Menotropin Versus Follitropin and Lutropin Alfa in Expected Suboptimal Responders
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility, Female
Keywords: suboptimal response
Corifollitropin alfa
IVF
Ovarian stimulation
Lead sponsor: D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Sponsor class: OTHER
First posted: 2017-06-06
Enrollment: 32
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 41
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of cumulus-oocyte complexes (COCs)
timeFrame: 3-4 weeks after ET
Secondary outcomes:
measure: Duration of stimulation
timeFrame: 2-4 weeks after randomization
measure: Number of follicles at the end of stimulation
timeFrame: 2-4 weeks after randomization
measure: Dose adjustment frequency
timeFrame: 2-4 weeks after randomization
measure: Number of participants with optimal or suboptimal response to COS
timeFrame: 2-4 weeks after randomization
measure: Number of mature (MII) oocytes
timeFrame: 2-4 weeks after randomization
measure: Cycle cancellation rate
timeFrame: 6-7 weeks after randomization
measure: Frequency of side reactions
timeFrame: 2-4 weeks after randomization
measure: Implantation rate
timeFrame: 3-4 weeks after ET
measure: Clinical pregnancy rate
timeFrame: 5-6 weeks after randomization
Other outcomes:
measure: Biochemical pregnancy rate
timeFrame: 3-4 weeks after ET
measure: Fertilization rate
timeFrame: 1 day after OPU
measure: Embryo quality
timeFrame: 3-5 days after oocyte recovery
measure: Cost-effectiveness of COS
timeFrame: 6-7 weeks after randomization
Locations:
city: Saint Petersburg
country: Russian Federation
facility: D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
Study officials:
affiliation: D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
name: Alexdandr Gzgzyan, Prof, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ob'edkova KV, Kogan IY, Muller VC, Tapilskaya NI, Krikhely IO, Dzhemlikhanova LK, Abdulkadirova ZK, Mekina ID, Lesik EA, Komarova EA, Ishchuk MA, Gzgzian AM. IVF protocol efficacy in women with expected suboptimal response depending on ovary stimulation mode. Gynecol Endocrinol. 2021;37(sup1):44-48. doi: 10.1080/09513590.2021.2006526.