IVM Versus IVF in High Antral Follicle Count Patients
Condition: PCOS; IVF; IVM
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): IVM; IVF
Intervention type(s): Procedure; Procedure
Intervention description(s): Patients in IVM group will receive FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and the ultrasound scan will be performed subsequently. Oocytes retrieval will be performed 42 hours after the last injection. Pre-maturation will last for 24-30 hours. ICSI will be used for insemination. Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred.; Patients in IVF arm will undergo controlled ovarian hyperstimulation with recombinant FSH (Menopur, Ferring) in GnRH antagonist protocol, treatment monitoring using ultrasound scans and blood tests. GnRH agonist will be used for final oocytes maturation. ICSI will be used for insemination. Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment