Study Procedures
Participants will be randomized into two arms:
PPOS group: Recombinant FSH 150-300 IU/day will start from day 2 to day 4 of
menstruation. The initial FSH dose will be chosen based on age, anti-Müllerian hormone
(AMH) level, antral follicle count (AFC), and body mass index (BMI). The FSH dosage will
be fixed during ovarian stimulation. Dydrogesterone (Duphaston, Abbott, USA) 20mg/day
will start on the day of gonadotropin injection to the oocyte maturation trigger night.
GnRH antagonist group: Recombinant FSH 150-300 IU/day will be given from day 2 to day 4
of menstruation. The initial FSH dose will be chosen based on age, anti-Müllerian
hormone (AMH) level, antral follicle count (AFC), and body mass index (BMI). The FSH
dosage will be fixed during ovarian stimulation. Cetrorelix (Cetrotide, Merck, Germany)
0.25mg/day will be given from day 5 of stimulation by the oocyte maturation trigger day.
Follicular monitoring will start on the fifth or sixth day of ovarian stimulation and was
performed every 3-5 days thereafter using transvaginal ultrasound to record the number of
developing follicles. Measuring LH, estradiol, and progesterone serum levels will be
performed on the fifth or sixth day of ovarian stimulation and oocyte maturation day (before
the trigger injection). The FSH dosage will be fixed during ovarian stimulation. When more
than two dominant follicles reach a diameter of at least 17mm, >= 50% diameter of remaining
follicles cohort >=12 mm, the final stage of oocyte maturation will trigger using human
chorionic gonadotropin (hCG; IVF-C 10.000 IU, LG Chem, Ltd., Korea or Ovitrelle Pen 250µg,
Merck Serono S.p.A., Italy). In individuals who are at high risk for OHSS, GnRH agonist
trigger 0.2mg (Diphereline 0.2mg, Ipsen Pharma, France) will given subcutaneously.
Transvaginal ultrasound-guided oocyte retrieval will be performed 34-36 hours after trigger,
with the retrieval of all follicles exceeding 10mm in diameter. Oocyte fertilization will be
carried out in vitro using ICSI. On the third day after fertilization, embryos will be
evaluated for the degree of embryonic fragmentation, regularity, and number of blastomeres in
accordance with the Istanbul consensus (Alpha Scientists in Reproductive Medicine and ESHRE
Special Interest Group of Embryology, 2011). Day 3 embryos will be cryopreserved or cultured
until the blastocyst stage based on physician recommendation or patient references; viable
blastocysts will then be cryopreserved on day 5 or day 6.
Endometrial preparation for frozen embryo transfer (FET) will be given using an exogenous
steroid regimen from day 2 to day 4 of the menstrual cycle. Oral estradiol valerate
(Progynova, Bayer Schering Pharma, Germany) 8mg/day will be given for 10-12 days. When
endometrial thickness reaches ≥ 7mm, along with a triple-line pattern, micronized
progesterone 800mg will be administered. FET will be performed three to five days after
progesterone administration. There will be no more than 2 embryo(s) transfers each FET cycle.
After FET, estradiol and progesterone supplementation will be continued for all participants
until the day of taking the pregnancy test. Participants with a positive pregnancy test
continued to receive oral estradiol valerate 8mg/day and micronized progesterone 800mg/day
until the fetal heart appeared, and then only micronized progesterone 800mg will be used
until 12 weeks of gestation.
All participants will be followed up per local protocol until outcomes are achieved.
