Comparison of Progestin Primed Ovarian Stimulation (PPOS) vs.GnRH Antagonist Methods on IVF Outcomes

The goal of this randomized clinical trial is to compare the effects of two different ovarian stimulation methods: Progestin Primed Ovarian Stimulation (PPOS) vs. GnRH Antagonist in embryologic outcomes of IVF Patients.

Ovarian stimulation will be conducted according to the assigned arm protocol.

Both artificially prepared and modified natural cycles will be eligible to be included and the choice will be done according to the doctor's preference and the patient's menstrual cycle regularity.

* For artificially prepared transfers, Estradiol Hemihydrate (Estrofem©, 2mg, Novo Nordisk, Malov/Denmark) 3x1 PO will be started on the day 2 of the menstrual cycle. After 12-14 days of usage, in order not to cancel the cycle, endometrial thickness needs measured at least 7mm and serum progesterone level < 1.5 ng/mL.
* For luteal support in addition to Progesterone (Progestan Dex©, 25mg, Kocak Farma İlaç ve Kimya Sanayi A.Ş., Istanbul, Turkiye) 2x1 SC once, with a 12-hour interval at day 14 of the menstrual cycle; Progesterone (Progestan©, 200mg, Kocak Farma İlaç ve Kimya Sanayi A.Ş., Istanbul, Turkiye) 2x1 PV will be started and continued for 5 days. Embryo transfer will be performed at 6th day. Estradiol Hemihydrate will be stopped on week 2 and progesterone support will be continued until the 8th week of gestation.

• Progestin (Drug), also known as Progestin Primed Ovarian Stimulation Protocol: In this regimen, Dydrogesterone (Duphaston©; 10mg; Deva Holding, Tekirdag/Turkiye) 3x1 PO will be started on day 2 of menstrual cycle and will be continued until the trigger day. The patient's dosage will be tailored based on their BMI, AMH value, and the number of follicles observed during the ultrasound examination on the 2nd day of the menstrual cycle. For triggering, Choriogonadotropin-α (Ovitrelle©, 250 mcg/0.5 mL, Merck Serono S.p.A., Bari/Italy) 1 amp SC + Triptorelin Acetate (Gonapeptyl©, 0.1mg/mL, Ferring GmbH, Kiel/Germany) 2 amp SC will be used. All oocytes picked-up will be frozen.
• GnRH antagonist (Drug), also known as GnRH Antagonist Ovarian Stimulation Protocol: In this regimen, Cetrorelix (Cetrotide©, 250 mcg/mL, Pierre Fabre Medicament Production, Idron, France) 1x1 SC will be started on day 7 of menstrual cycle and will be continued until the trigger day. For triggering, Choriogonadotropin-α (Ovitrelle©, 250 mcg/0.5 mL, Merck Serono S.p.A., Bari/Italy) 1 amp SC + Triptorelin Acetate (Gonapeptyl©, 0.1mg/mL, Ferring GmbH, Kiel/Germany) 2 amp SC will be used. All oocytes picked-up will be frozen.

Primary outcomes

• Blastulation Rate [Day 5 or 6 after fertilization]: number of blastocysts up to day 6 / the number of fertilized 2PN embryos

Secondary outcomes

• PGT Results [14 days after blastocyte culture sampling]: Euploidy and aneuploidy rates
• Ongoing pregnancy [on gestational week 12]: Fetal heart rate examination via USG
• Live Birth Rate [9 months]: For pregnancies resulted within the study period, live birth/embryo transfer count
• Chemical Pregnancy [on day 11 after transfer]: Serum ß-hcg level

Sex: Female, ages: 18 Years to 45 Years, accepts healthy volunteers

Inclusion Criteria:

* BMI > 18 kg/m2 ve <35 kg/m2
* Couples that accept being included in the study
* Couple accepting thawed embryo transfer

Exclusion Criteria:

* Known chromosomal abnormality in either member of the couple
* Couples with unexplained infertility
* BMI > 30 kg/m2
* Mullerian malformations
* Undergoing oocyte cryopreservation for medical reasons (such as malignancies)
* Couple insists on fresh embryo transfer

• Ercan Bastu, M.D., Study director, Owner