PPOS vs GnRH Antagonist in Ovarian Stimulation (ProGanOS Study)

Mỹ Đức Hospital

Status: Enrolling

Conditions: Progestins Primed Ovarian Stimulation

Treatments: Drug: Dydrogesterone 10 mg; Drug: Cetrorelix 0.25 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT06378268

05/24/DD-BVMD

Details and patient eligibility

About

This non-inferiority randomized controlled trial will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam.

This study compares the effectiveness of Progestin-Primed Ovarian stimulation versus GnRH protocol for ovarian stimulation in IVF treatment. Participants will be randomly assigned in a 1:1 ratio to receive Progestins or GnRH antagonists.

Full description

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.

Enrollment: 626 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Woman aged 18-40
• BMI ≤ 25kg/m2
• AMH > 1.2ng/mL or AFC >5
• Having indication for IVF treatment
• Agree to have frozen embryo(s) transfer
• Not participating in any other clinical trials
• Provision of written informed consent to participate

Exclusion criteria

• Undergoing IVF cycle with other protocols: Down-regulation, mild stimulation, Random start
• Oocyte donation cycles
• Undergoing vitrified oocyte accumulation
• Oocyte cryopreservation
• Cycle with PGT (Preimplatation genetic testing)
• Women with PCOS
• Women allergy to dydrogesterone, rFSH, GnRH antagonist

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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626 participants in 2 patient groups

Progestins Primed Ovarian stimulation group

Active Comparator group

Description:

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.

Treatment:

Drug: Dydrogesterone 10 mg

GnRH antagonist group

Active Comparator group

Description:

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.

Treatment:

Drug: Cetrorelix 0.25 mg