- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03405701
IVM Versus IVF in High Antral Follicle Count Patients
The Effectiveness and Safety of in Vitro Maturation of Oocytes Versus in Vitro Fertilization in Women With High Antral Follicle Count (AFC): a Randomised Controlled Trial
Study Overview
Detailed Description
Women with PCOS and PCOM or high AFC: ≥24 Antral Follicles in Both Ovaries will be given the information about the study during the first consultation which is at least 2 weeks before having periods. On the second day of periods, women will be screened for eligibility by the treating clinicians. Women who met the inclusion criteria will be invited to participate in the study. Women will be randomized (1:1) to IVM or IVF- GnRH agonist triggering cycle using block randomization by an independent study coordinator via telephone, using a computer-generated random list (block size 2, 4, 6 or 8).
Group 1: IVM Patients with a normal cycle length (>/=35 days) will receive injected highly purified human menopausal gonadotropin (hp-hMG; Menopur, Ferring) 150 IU/day starting on day two or three of the spontaneous menstrual cycle. Oocyte retrieval will be performed 42 hours after the last hp-hMG injection. Women who do not have a normal cycle length (>35 days; 4-9 menstrual cycles in a year or amenorrhea) will take an oral contraceptive for 2 weeks, then receive hp-hMG 150 IU/day (hp-hMG; Menopur, Ferring injection for 2 days starting 5 days later.
In all patients, ultrasound will be performed on the second day of gonadotrophin injection and OPU is scheduled for 42 hours after the last gonadotrophin injection. After oocyte pick-up, all oocytes will be placed in pre-maturation medium (CAPA Pre-maturation in Medicult IVM medium, Origio, Denmark) for 24 hours, then transferred to maturation culture (Medicult IVM system with phenol red, Origio, Denmark) for 30 hours.
Group 2: IVF All women in this group will undergo COH using a hp-hMG/GnRH antagonist protocol, with an hp-hMG dose of 150-225 IU/day (Menopur, Ferring), depending on age and body mass index. Follicular development will be monitored using ultrasound scanning, and estradiol and progesterone levels. When at least two leading follicles reach 17 mm in diameter, GnRH agonist (GnRHa) triggering with triptorelin 0.2 mg (Diphereline, Ipsen Beaufour) will be administered, and oocyte retrieval performed 36 hours later.
Laboratory procedures For both groups, insemination will be performed using intra-cytoplasmic sperm injection (3-4 hours after oocyte retrieval or maturation check); only matured oocytes will be inseminated. Fertilization check will be performed under an inverted microscope at 16-18 hours after insemination. Embryo evaluation will be performed at 68 ±1 hours after fertilization using the Istanbul consensus.
Freeze-all and Frozen embryo transfer In both groups, all embryos will be frozen on day 3. Frozen transfer of a maximum of 2 embryos will be performed in a subsequent cycle using HRT for endometrial preparation.
In the following cycle, the endometrium will be prepared using oral estradiol valerate (Valiera®; Laboratories Recalcine) 8 mg/day starting from the second or third day of the menstrual cycle. Endometrial thickness will be monitored from day six onwards, and vaginal progesterone (Cyclogest®; Actavis) 800 mg/day will be started when endometrial thickness reached 8 mm or more. A maximum of 2 embryos will be thawed on the day of embryo transfer, three days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance. When women had more than two embryos frozen, the procedure will be repeated in subsequent cycles if they fail the first transfer.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
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Tan Binh
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Ho Chi Minh City, Tan Binh, Vietnam
- Mỹ Đức Hospital
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women with high AFC (≥24 Antral Follicles in Both Ovaries), including PCOS plus PCO or high AFC
- Having indications for ART
- Having ≤ 2 IVM/IVF attempts
- Permanent resident in Vietnam
- Agree to have all embryos frozen on day 3
- Agree to have ≤ 2 embryos transferred in a subsequent frozen transfer
- Not participating in another IVF study at the same time
Exclusion Criteria:
- Oocyte donation cycles
- Pre-implantation genetic diagnosis (PGD) cycles
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: IVM (in vitro maturation)
Receiving FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and an ultrasound scan will be performed subsequently.
Oocytes retrieval will be performed 42 hours after the last injection.
Pre-maturation will last for 24-30 hours.
ICSI will be used for insemination.
Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred
|
Patients in IVM group will receive FSH (Menopur, Ferring) for 2 days on day 2/3 of the menstrual cycle (spontaneous/ OCP administration) and the ultrasound scan will be performed subsequently.
Oocytes retrieval will be performed 42 hours after the last injection.
Pre-maturation will last for 24-30 hours.
ICSI will be used for insemination.
Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred.
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Active Comparator: IVF (in vitro fertilization)
Undergoing controlled ovarian hyperstimulation for in vitro Fertilization (IVF) with recombinant FSH (Menopur, Ferring) in GnRH antagonist protocol, treatment monitoring using ultrasound scans and blood tests.
GnRH agonist triggering will be used for final oocytes maturation.
ICSI will be used for insemination.
Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred.
|
Patients in IVF arm will undergo controlled ovarian hyperstimulation with recombinant FSH (Menopur, Ferring) in GnRH antagonist protocol, treatment monitoring using ultrasound scans and blood tests.
GnRH agonist will be used for final oocytes maturation.
ICSI will be used for insemination.
Freeze-only on day 3 and frozen embryo transfer will be performed on the subsequent cycle using HRT protocol with a maximum of 2 embryos transferred.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Live birth after the first embryo transfer of the started treatment cycle
Time Frame: 12 weeks of gestation
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Live birth is defined as the birth of at least one newborn after 24 weeks' gestation that exhibits any sign of life (twins will be a single count).
To allow assessment of the timing of live birth, the rate of ongoing pregnancy at 12 weeks will be used in calculations, conditional on the fact that this ongoing pregnancy results in live birth.
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12 weeks of gestation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Positive pregnancy test
Time Frame: at 2 weeks after the embryo placement after the completion of the first transfer
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Serum human chorionic gonadotropin level greater than 5 mIU/mL
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at 2 weeks after the embryo placement after the completion of the first transfer
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Clinical pregnancy
Time Frame: 5 weeks after embryo placement after the completion of the first transfer
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at least one gestational sac on ultrasound at 7 weeks' gestation with the detection of heart beat activity
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5 weeks after embryo placement after the completion of the first transfer
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Implantation rate
Time Frame: 3 weeks after embryo transferred after the completion of the first transfer
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as the number of gestational sacs per number of embryos transferred
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3 weeks after embryo transferred after the completion of the first transfer
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Time from randomisation to ongoing pregnancy
Time Frame: 12 weeks of gestation after the completion of the first transfer
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Time from randomization to ongoing pregnancy after the completion
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12 weeks of gestation after the completion of the first transfer
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Ongoing pregnancy
Time Frame: at 10 weeks or beyond after the embryo placement after the completion of the first transfer
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Pregnancy with detectable heart rate at 12 weeks' gestation or beyond
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at 10 weeks or beyond after the embryo placement after the completion of the first transfer
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Number of top quality embryos
Time Frame: 3 days after oocytes pick-up day in IVF or 5 days in IVM
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Top quality embryos are defined followed Istanbul consensus
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3 days after oocytes pick-up day in IVF or 5 days in IVM
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Number of freezable embryos
Time Frame: 3 days after oocytes pick-up day in IVF or 5 days in IVM after the completion of the first transfer
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Number of frozen embryos
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3 days after oocytes pick-up day in IVF or 5 days in IVM after the completion of the first transfer
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Cumulative ongoing pregnancy at 6 months
Time Frame: at 6 months after randomization
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After 6 months, most patients doing IVM have finished all their frozen embryos.
If they still fail, they usually change to IVF.
We lose the comparison; therefore, we consider this time point for analyzing the cumulative ongoing pregnancy rate.
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at 6 months after randomization
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Cumulative ongoing pregnancy at 12 months
Time Frame: at 12 months after randomization
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After 12 months, most patients doing IVF have finished all their frozen embryos; therefore, we consider this time point for analyzing the cumulative ongoing pregnancy rate.
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at 12 months after randomization
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cost-effectiveness
Time Frame: Two year after randomization
|
Including direct and indirect costs; costs related to complications treatment.
Cost data will be collected for a supplementary analysis and will be reported in a separated paper.
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Two year after randomization
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Ovarian hyperstimulation syndrome (OHSS)
Time Frame: at 03 days after oocytes pick-up and 14 days after embryo transfer
|
Routine assessments for OHSS were performed on day 3 post oocyte retrieval in both groups.
At other times, OHSS was evaluated if symptoms were reported by the patient.
OHSS was classified using the flow diagram developed by Humaidan and colleagues for use in clinical trial settings
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at 03 days after oocytes pick-up and 14 days after embryo transfer
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Ectopic pregnancy
Time Frame: at 12 weeks of gestation after the completion of the first transfer
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a pregnancy in which implantation takes place outside the uterine cavity after the completion of the first transfer
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at 12 weeks of gestation after the completion of the first transfer
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Hypertensive disorders of pregnancy
Time Frame: at 20 weeks of gestation or beyond after the completion of the first transfer
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Pregnancy-induced hypertension, pre-eclampsia and eclampsia
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at 20 weeks of gestation or beyond after the completion of the first transfer
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Gestational diabetes mellitus
Time Frame: at 24 weeks of gestation after the completion of the first transfer
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using a 75g oral glucose tolerance test
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at 24 weeks of gestation after the completion of the first transfer
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Preterm delivery
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer
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Multiple definitions, defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer
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Birth weight
Time Frame: at the time of delivery
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Weight of singletons and twins
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at the time of delivery
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Congenital anomaly
Time Frame: At birth after the completion of the first transfer
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Any congenital anomaly will be included
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At birth after the completion of the first transfer
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Admission to NICU
Time Frame: 7 days after delivery after the completion of the first transfer
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The admittance of the newborn to NICU
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7 days after delivery after the completion of the first transfer
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Ectopic pregnancy
Time Frame: at 6 months after randomisation
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A pregnancy in which implantation takes place outside the uterine cavity
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at 6 months after randomisation
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Ectopic pregnancy
Time Frame: at 12 months after randomisation
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A pregnancy in which implantation takes place outside the uterine cavity
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at 12 months after randomisation
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Miscarriage
Time Frame: at 24 weeks of gestation after the completion of the first transfer
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pregnancy loss at < 12 weeks
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at 24 weeks of gestation after the completion of the first transfer
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Miscarriage
Time Frame: At 6 months after randomisation
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pregnancy loss at < 12 weeks
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At 6 months after randomisation
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Miscarriage
Time Frame: at 12 months after randomisation
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pregnancy loss at < 12 weeks
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at 12 months after randomisation
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Hypertensive disorders of pregnancy
Time Frame: at 20 weeks of gestation or beyond at 6 months after randomisation
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Pregnancy-induced hypertension, pre-eclampsia and eclampsia
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at 20 weeks of gestation or beyond at 6 months after randomisation
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Hypertensive disorders of pregnancy
Time Frame: at 20 weeks of gestation or beyond at 12 months after randomisation
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Pregnancy-induced hypertension, pre-eclampsia and eclampsia
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at 20 weeks of gestation or beyond at 12 months after randomisation
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Gestational diabetes mellitus
Time Frame: at 24 weeks of gestation at 6 months after randomisation
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using a 75g oral glucose tolerance test
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at 24 weeks of gestation at 6 months after randomisation
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Gestational diabetes mellitus
Time Frame: at 24 weeks of gestation at 12 months after randomisation
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using a 75g oral glucose tolerance test
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at 24 weeks of gestation at 12 months after randomisation
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Preterm delivery
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation at 6 months after randomisation
|
Multiple definitions, defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation at 6 months after randomisation
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Preterm delivery
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation at 12 months after randomisation
|
Multiple definitions, defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation at 12 months after randomisation
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Multiple pregnancy
Time Frame: after the completion of the first transfer
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Defined as presence of more than one sac at early pregnancy ultrasound (6-8 weeks gestation)
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after the completion of the first transfer
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Multiple pregnancy
Time Frame: at 6 months after randomisation
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Defined as presence of more than one sac at early pregnancy ultrasound (6-8 weeks gestation)
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at 6 months after randomisation
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Multiple pregnancy
Time Frame: at 12 months after randomisation
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Defined as presence of more than one sac at early pregnancy ultrasound (6-8 weeks gestation)
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at 12 months after randomisation
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Multiple delivery
Time Frame: 22 weeks of gestation or beyond after the completion of the first transfer
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Birth of more than one baby beyond 24 weeks
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22 weeks of gestation or beyond after the completion of the first transfer
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Multiple delivery
Time Frame: 22 weeks of gestation or beyond at 6 months after randomisation
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Birth of more than one baby beyond 24 weeks
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22 weeks of gestation or beyond at 6 months after randomisation
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Multiple delivery
Time Frame: 22 weeks of gestation or beyond at 12 months after randomisation
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Birth of more than one baby beyond 24 weeks
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22 weeks of gestation or beyond at 12 months after randomisation
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Antepartum haemorrhage
Time Frame: After the completion of the first transfer
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Including placenta previa, placenta accreta and unexplained
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After the completion of the first transfer
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Antepartum haemorrhage
Time Frame: At 6 months after randomisation
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Including placenta previa, placenta accreta and unexplained
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At 6 months after randomisation
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Antepartum haemorrhage
Time Frame: At 12 months after randomisation
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Including placenta previa, placenta accreta and unexplained
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At 12 months after randomisation
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Spontaneous preterm birth
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer
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Defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer
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Spontaneous preterm birth
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation at 6 months after randomisation
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Defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation at 6 months after randomisation
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Spontaneous preterm birth
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation at 12 months after randomisation
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Defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation at 12 months after randomisation
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Iatrogenic preterm birth
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer
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Defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation after the completion of the first transfer
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Iatrogenic preterm birth
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation at 6 months after randomisation
|
Defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation at 6 months after randomisation
|
Iatrogenic preterm birth
Time Frame: at 24, 28, 32 weeks and 37 weeks of gestation at 12 months after randomisation
|
Defined as delivery at <24, <28, <32, <37 completed weeks
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at 24, 28, 32 weeks and 37 weeks of gestation at 12 months after randomisation
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Large for gestational age
Time Frame: at the time of delivery after the completion of the first transfer
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birth weight >90th percentile
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at the time of delivery after the completion of the first transfer
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Large for gestational age
Time Frame: at the time of delivery at 6 months after randomisation
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birth weight >90th percentile
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at the time of delivery at 6 months after randomisation
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Large for gestational age
Time Frame: at the time of delivery at 12 months after randomisation
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birth weight >90th percentile
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at the time of delivery at 12 months after randomisation
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Small for gestational age
Time Frame: at the time of delivery after the completion of the first transfer
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birth weight < 10th percentile
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at the time of delivery after the completion of the first transfer
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Small for gestational age
Time Frame: at the time of delivery at 6 months after randomisation
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birth weight < 10th percentile
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at the time of delivery at 6 months after randomisation
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Small for gestational age
Time Frame: at the time of delivery at 12 months after randomisation
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birth weight < 10th percentile
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at the time of delivery at 12 months after randomisation
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Low birth weight
Time Frame: at birth after the completion of the first transfer
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Weight < 2500 gm at birth
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at birth after the completion of the first transfer
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Low birth weight
Time Frame: at 6 months after randomisation
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Weight < 2500 gm at birth
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at 6 months after randomisation
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Low birth weight
Time Frame: at 12 months after randomisation
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Weight < 2500 gm at birth
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at 12 months after randomisation
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Very low birth weight
Time Frame: at birth after the completion of the first transfer
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Weight < 1500 gm at birth
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at birth after the completion of the first transfer
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Very low birth weight
Time Frame: at 6 months after randomisation
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Weight < 1500 gm at birth
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at 6 months after randomisation
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Very low birth weight
Time Frame: at 12 months after randomisation
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Weight < 1500 gm at birth
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at 12 months after randomisation
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High birth weight
Time Frame: at birth after the completion of the first transfer
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Weight >4000 gm at birth
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at birth after the completion of the first transfer
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High birth weight
Time Frame: at 6 months after randomisation
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Weight >4000 gm at birth
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at 6 months after randomisation
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High birth weight
Time Frame: at 12 months after randomisation
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Weight >4000 gm at birth
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at 12 months after randomisation
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Very high birth weight
Time Frame: at birth after the completion of the first transfer
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Weight >4500 gm at birth
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at birth after the completion of the first transfer
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Very high birth weight
Time Frame: at 6 months after randomisation
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Weight >4500 gm at birth
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at 6 months after randomisation
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Very high birth weight
Time Frame: at 12 months after randomisation
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Weight >4500 gm at birth
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at 12 months after randomisation
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Congenital anomaly
Time Frame: At 6 months after randomisation
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Any congenital anomaly will be included
|
At 6 months after randomisation
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Congenital anomaly
Time Frame: At 12 months after randomisation
|
Any congenital anomaly will be included
|
At 12 months after randomisation
|
Admission to NICU
Time Frame: At 6 months after randomisation
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The admittance of the newborn to NICU
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At 6 months after randomisation
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Admission to NICU
Time Frame: At 12 months after randomisation
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The admittance of the newborn to NICU
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At 12 months after randomisation
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Genetic and epigenetic analysis of newborn
Time Frame: 1 day (Prior to the initiation of IVF/IVM) and 1 day ( at the time of delivery)
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Maternal whole blood; newborn's materials including cord blood, neonatal buccal smear, and placental tissue will be collected
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1 day (Prior to the initiation of IVF/IVM) and 1 day ( at the time of delivery)
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lan N Vuong, MD,PhD, Mỹ Đức Hospital
Publications and helpful links
General Publications
- Vuong LN, Ho VNA, Ho TM, Dang VQ, Phung TH, Giang NH, Le AH, Pham TD, Wang R, Smitz J, Gilchrist RB, Norman RJ, Mol BW. In-vitro maturation of oocytes versus conventional IVF in women with infertility and a high antral follicle count: a randomized non-inferiority controlled trial. Hum Reprod. 2020 Nov 1;35(11):2537-2547. doi: 10.1093/humrep/deaa240.
- Vuong LN, Ho VNA, Ho TM, Dang VQ, Phung TH, Giang NH, Le AH, Pham TD, Wang R, Norman RJ, Smitz J, Gilchrist RB, Mol BW. Effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilisation in women with high antral follicle count: study protocol for a randomised controlled trial. BMJ Open. 2018 Dec 9;8(12):e023413. doi: 10.1136/bmjopen-2018-023413.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- CS/MD/17/11
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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