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

Phase 4
Completed
Conditions
Infertility, Female
Interventions
Registration Number
NCT03177538
Lead Sponsor
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
32
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Follitropin alfa and lutropin alfaFollitropin alfa and lutropin alfaPergoveris 300 IU
Corifollitropin alfa and menotropinCorifollitropin alfa and menotropinElonva 150 mcg, Merional 150-300 IU
Primary Outcome Measures
NameTimeMethod
Number of cumulus-oocyte complexes (COCs)3-4 weeks after ET

Number of COCs, obtained during oocyte pick up (OPU), after controlled ovarian stimulation (COS) in two protocols

Secondary Outcome Measures
NameTimeMethod
Implantation rate3-4 weeks after ET

ratio of the number of intrauterine gestational sacs to the number of transferred embryos

Duration of stimulation2-4 weeks after randomization

total days of COS: from the first gonadotropins administration to ovulation triggering

Clinical pregnancy rate5-6 weeks after randomization

presence of intrauterine gestational sac at transvaginal ultrasound measured per embryo transfer

Number of mature (MII) oocytes2-4 weeks after randomization

assessment is done only for ICSI cycles at oocyte recovery day

Frequency of side reactions2-4 weeks after randomization

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

Cycle cancellation rate6-7 weeks after randomization

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)

Number of follicles at the end of stimulation2-4 weeks after randomization

measured for follicles ≥17 mm and ≥14 mm

Dose adjustment frequency2-4 weeks after randomization

number of participants with menopausal or recombinant human follicle stimulating hormone (FSH) dose increase

Number of participants with optimal or suboptimal response to COS2-4 weeks after randomization

≥ 5 COCs at at oocyte recovery day

Trial Locations

Locations (1)

D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology

🇷🇺

Saint Petersburg, Russian Federation

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