PPOS vs GnRH Antagonist in Ovarian Stimulation (ProGanOS Study)
- Conditions
- Progestins Primed Ovarian Stimulation
- Interventions
- Registration Number
- NCT06378268
- Lead Sponsor
- Mỹ Đức Hospital
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 626
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Progestins Primed Ovarian stimulation group Dydrogesterone 10 mg 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 Cetrorelix 0.25 mg 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.
- Primary Outcome Measures
Name Time Method Ongoing pregnancy At 10 weeks after embryo(s) placement defined as pregnancy with a detectable heart rate at 12 weeks gestation or beyond
- Secondary Outcome Measures
Name Time Method The incidence of premature LH surge On the day having indication of oocyte maturation LH level of ≥ 10 mIU/mL occurring before the criteria of oocyte maturation administration is met
Number of day 3 embryos At 62-66 hours after ICSI The number of day 3 embryos
Number of day 5 embryos At 112-116 hours after ICSI The number of day 5 embryos
Number of good quality day 3 embryos At 62-66 hours after ICSI Number of grade 1 and grade 2 day 3 embryos (acccording to Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011)
Number of good quality day 5 embryos At 112-116 hours after ICSI Number of grade 1 and grade 2 day 5 blastocysts (acccording to Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology, 2011)
Number of frozen embryos at 112-116 hours after ICSI the number of frozen embryos/blastocysts
Incidence of Ovarian hyperstimulation syndrome At 2 weeks after trigger Ovarian hyperstimulation syndrome (OHSS) is a potentially lethal iatrogenic complication of the early luteal phase or/and early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). OHSS was evaluated if symptoms were reported by the patient. OHSS was classified using the flow diagram developed by (Humaidan et al., 2016)
Positive ß-hCG test At 2 weeks after embryo(s) placement Serum human chorionic gonadotropin level greater than 25 mIU/mL
Clinical pregnancy at 6 weeks or more after the onset of last menstrual period diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy at 6 weeks or more after the onset of the last menstrual period. In addition to intra-uterine pregnancy, it includes a clinically documented ectopic pregnancy.
Ectopic pregnancy at 6 weeks after the onset of last menstrual period A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology
Early miscarriage <12 weeks At 12 weeks of gestation Spontaneous loss of intra-uterine pregnancy up to 12 weeks of gestation
Late miscariage 12-< 22 weeks between 12 to 22 completed weeks of gestational age The spontaneous loss of an intra-uterine pregnancy between 12 to 22 completed weeks of gestational age
Live birth rate At 22 weeks of gestation Defined as the complete expulsion or extraction from a woman of a product of fertilization, after 22 completed weeks of gestational age; which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached. A birth weight of 500 grams or more can be used if gestational age is unknown. Twins counted as one live birth.
Gestational age at birth At birth Calculated by gestational age of all live births
Mode of delivery At birth vaginal delivery, C-section (elective, suspected fetal distress, non-progressive labor)
Birth weight At birth Weight of the newborn measured right after delivery
Very low birth weight At birth Birth weight less than 1.500 g
Low birth weight At birth Birth weight less than 2.500 g
High birth weight At birth implies growth beyond an absolute birth weight, historically 4.000 g or 4.500 g, regardless of the gestational age
Very high birth weight At birth Birth weight over than 4.500 g for women with diabetes, and a threshold of 5000 g for women without diabetes
Preterm birth At birth defined as delivery at \<24, \<28, \<32, \<37 completed weeks. A birth that takes place after 22 weeks and before 37 completed weeks of gestational age.
Gestational diabetes mellitus At 24 to 28 weeks of gestation a 75-g OGTT, with plasma glucose measurement when patient is fasting and at 1 and 2 h, at 24-28 weeks of gestation in women not previously diagnosed with diabetes.
* Fasting: 92 mg/dL (5.1 mmol/L)
* 1 h: 180 mg/dL (10.0 mmol/L)
* 2 h: 153 mg/dL (8.5 mmol/L)Hypertensive disorders of pregnancy At 20 weeks of gestation or beyond Pregnancy-induced hypertension, pre-eclampsia, eclampsia and HELLP syndrome
Maternal mortality From randomization to within 42 days of termination of pregnancy female deaths from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy
Major congenital abnormalities From randomization to delivery Structural, functional, and genetic anomalies, that occur during pregnancy, and identified antenatally, at birth, or later in life, and require surgical repair of a defect, or are visually evident, or are life-threatening, or cause death. Any congenital anomaly will be included as followed definition of congenital abnormalities in Surveillance of Congenital Anomalies by Division of Birth Defects and Developmental Disabilities, NCBDDD, Centers for Disease Control and Prevention (2020)
NICU admission at birth The admittance of the newborn to NICU
Reason for NICU admission at birth Respiratory distress, Intraventricular Hemorrhage, Necrotizing enterocolitis, Sepsis
Neonatal mortality within 28 days of birth Death of a live-born baby within 28 days of birth. This can be divided into early neonatal mortality, if death occurs in the first seven days after birth, and late neonatal if death occurs between eight and 28 days after delivery.
The incidence of premature progesterone elevation On the day having indication of oocyte maturation A progesterone level of ≥1.0 ng/mL occurring before the criteria of oocyte maturation administration is met
Number of oocytes retrieved On the oocyte(s) retrieval day The number of oocyte retrieved
Number of mature oocytes On the oocyte(s) retrieval day The number of MII oocytes
Trial Locations
- Locations (1)
My Duc Hospital
🇻🇳Ho Chi Minh City, Vietnam