IVM Versus IVF in High Antral Follicle Count Patients

IVF, IVM, PCOS

In vitro maturation (IVM) is postulated to be an alternative to conventional in vitro fertilization (IVF) to avoid ovarian hyperstimulation syndrome. This has particular potential in women with Polycystic Ovarian Syndrome (PCOS), who are at increased risk for the ovarian hyperstimulation syndrome. However, no randomized controlled trials on the comparison of IVM and conventional IVF in women with PCOS have been reported with respect to pregnancy rate and hyper-stimulation. Investigators aim to compare the effectiveness and safety of IVM with controlled ovarian hyperstimulation/IVF in women with high antral follicle count.

Women with PCOS and PCOM or high AFC: ≥24 Antral Follicles in Both Ovaries will be given the information about the study during the first consultation which is at least 2 weeks before having periods. On the second day of periods, women will be screened for eligibility by the treating clinicians. Women who met the inclusion criteria will be invited to participate in the study. Women will be randomized (1:1) to IVM or IVF- GnRH agonist triggering cycle using block randomization by an independent study coordinator via telephone, using a computer-generated random list (block size 2, 4, 6 or 8). Group 1: IVM Patients with a normal cycle length (\>/=35 days) will receive injected highly purified human menopausal gonadotropin (hp-hMG; Menopur, Ferring) 150 IU/day starting on day two or three of the spontaneous menstrual cycle. Oocyte retrieval will be performed 42 hours after the last hp-hMG injection. Women who do not have a normal cycle length (\>35 days; 4-9 menstrual cycles in a year or amenorrhea) will take an oral contraceptive for 2 weeks, then receive hp-hMG 150 IU/day (hp-hMG; Menopur, Ferring injection for 2 days starting 5 days later. In all patients, ultrasound will be performed on the second day of gonadotrophin injection and OPU is scheduled for 42 hours after the last gonadotrophin injection. After oocyte pick-up, all oocytes will be placed in pre-maturation medium (CAPA Pre-maturation in Medicult IVM medium, Origio, Denmark) for 24 hours, then transferred to maturation culture (Medicult IVM system with phenol red, Origio, Denmark) for 30 hours. Group 2: IVF All women in this group will undergo COH using a hp-hMG/GnRH antagonist protocol, with an hp-hMG dose of 150-225 IU/day (Menopur, Ferring), depending on age and body mass index. Follicular development will be monitored using ultrasound scanning, and estradiol and progesterone levels. When at least two leading follicles reach 17 mm in diameter, GnRH agonist (GnRHa) triggering with triptorelin 0.2 mg (Diphereline, Ipsen Beaufour) will be administered, and oocyte retrieval performed 36 hours later. Laboratory procedures For both groups, insemination will be performed using intra-cytoplasmic sperm injection (3-4 hours after oocyte retrieval or maturation check); only matured oocytes will be inseminated. Fertilization check will be performed under an inverted microscope at 16-18 hours after insemination. Embryo evaluation will be performed at 68 ±1 hours after fertilization using the Istanbul consensus. Freeze-all and Frozen embryo transfer In both groups, all embryos will be frozen on day 3. Frozen transfer of a maximum of 2 embryos will be performed in a subsequent cycle using HRT for endometrial preparation. In the following cycle, the endometrium will be prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day starting from the second or third day of the menstrual cycle. Endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Cyclogest®; Actavis) 800 mg/day will be started when endometrial thickness reached 8 mm or more. A maximum of 2 embryos will be thawed on the day of embryo transfer, three days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance. When women had more than two embryos frozen, the procedure will be repeated in subsequent cycles if they fail the first transfer.

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