Progestins Primed Ovarian Stimulation
Conditions
Keywords
Progestins Primed Ovarian Stimulation, GnRH antagonist, ongoing pregnancy
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.
Interventions
Dydrogesterone 10mg orally 2 times daily, starting on the day of gonadotropin injection to the oocyte maturation trigger night.
DRUGCetrorelix 0.25 mg
Cetrorelix 0.25mg is injected subcutaneously once a day. It is given from day 5 or day 6 of stimulation by the oocyte maturation trigger day.
Sponsors
Mỹ Đức Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing pregnancy | At 10 weeks after embryo(s) placement | defined as pregnancy with a detectable heart rate at 12 weeks gestation or beyond |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
Countries
Vietnam
Contacts
PRINCIPAL_INVESTIGATORLan N Vuong, MD, PhD
University of Medicine and Pharmacy at Ho Chi Minh City
Outcome results
None listed