Immediate Versus Postponed Freeze-all Embryo Transfer in Hyperresponders

Study Overview
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Brief Summary
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This is a multicenter, randomised controlled trial. The investigators plan to randomise 836 participants to the immediate FET or the postponed FET from the day of oocyte retrieval to the last day of that menstrual cycle in a 1:1 rate. Primary outcome will be the live birth rate after the embryo transfer.

Detailed Description
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It is postulated that postponing embryo transfer for at least one menstrual cycle after a freeze-all cycle can minimise the possible residual negative effect caused by ovarian stimulation and can promote the resumption of a normal ovulatory cycle and the receptivity of endometrium. Nevertheless, emerging evidence suggests a higher live birth rate in the immediate freeze-all embryo transfer (FET) cycles compared to that in the delayed group. It is unclear the whether postponed FET is superior in hyperresponders. The investigators hypothesize the success rate in the postponed FET for at least one menstrual cycle after oocyte retrieval is higher than in the immediate FET in hyperresponders. Objective: To evaluate whether the postponed FET for at least one menstrual cycle after oocyte retrieval is superior to the immediate FET in the first menstrual cycle after oocyte retrieval in hyperresponders in terms of live birth rates. Design: a multicenter, randomised controlled trial Patients: The investigators plan to randomise participants to the immediate FET and the postponed FET from the day of oocyte retrieval to the last day of that menstrual cycle. Primary outcome: live birth rate after the embryo transfer. Patients who get pregnant will be followed up until 6 weeks after delivery. Sample size: The investigators plan to enroll 836 participants in a 1:1 rate.

Official Title
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Immediate Versus Postponed Freeze-all Embryo Transfer in Hyperresponders, A Multicenter Randomised Controlled Trial

Conditions
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IVF

Intervention / Treatment
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* Biological: the timing of embryo transfer in freeze-all cycles


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 20 to 42 years old; Written informed consent; Women scheduled for freeze-all embryo transfer; Women with the number of oocyte collected higher than 15. Exclusion Criteria: Women with a history of at lease three failed transfer cycles; Women with an endometrial thickness less than 7 mm on the triggering day; Severe uterine malformations.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate FET group<br>Freeze-all embryo transfer will be carried out in the menstrual cycle immediately following oocyte retrieval. | Biological: the timing of embryo transfer in freeze-all cycles<br>* Immediate FET group Freeze-all embryo transfer will be carried out in the menstrual cycle immediately following oocyte retrieval. Postponed FET group Freeze-all embryo transfer will be carried out during the second menstrual cycle to 6 months after oocyte retrieval.<br>|
| Experimental: Postponed FET group<br>Freeze-all embryo transfer will be carried out during the second menstrual cycle to 6 months after oocyte retrieval. | Biological: the timing of embryo transfer in freeze-all cycles<br>* Immediate FET group Freeze-all embryo transfer will be carried out in the menstrual cycle immediately following oocyte retrieval. Postponed FET group Freeze-all embryo transfer will be carried out during the second menstrual cycle to 6 months after oocyte retrieval.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth after the first embryo transfer | Live birth is defined as the delivery of at least one baby after 22 weeks of gestation that exhibits any sign of life. | At least 22 months gestation after the first embryo transfer cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy | defined as at least one gestational sac on ultrasound at around 7 weeks' gestation with the detection of heart-beat activity | around 7 weeks' gestation after the first embryo transfer cycle | 
| Ongoing pregnancy | defined as pregnancy with detectable heart rate at 12 weeks' gestation or beyond | 12 weeks' gestation or beyond after the first embryo transfer cycle | 
| Biochemical pregnancy | defined as a positive pregnancy test | about 12 days after embryo transfer | 
| Ectopic pregnancy | defined as embryo implanted at any site other than the endometrial lining of the uterus cavity | about 6 weeks after embryo transfer | 
| Miscarriage | defined as spontaneous loss of a clinical pregnancy before 22 completed weeks of gestational age, in which the embryo(s) or fetus(es) is/are nonviable or is/are absorbed or expelled from the uterus. | 6-22 weeks of gestation | 
| Cumulative live birth | the cumulative rate of live born children conceived within six months of the first FET cycle. | 6 month after the first embryo transfer | 
| Pre-eclampsia | defined as the development of gestational hypertension with proteinuria (≥300 mg/24-hour urine collection or 30 mg/dL in single urine sample) of new onset after 20 weeks of gestation | after 20 weeks of gestation | 
| Gestational hypertension | defined as the development of blood pressure greater than 140/90 mmHg after pregnancy without proteinuria or other signs of preeclampsia | after 20 weeks of gestation | 
| Gestational diabetes mellitus | defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy as determined from the diagnosis in the obstetrical medical record | after 24 weeks of gestation | 
| Premature rupture of membrane (PROM) rate | defined as rupture of the amniotic membranes before the onset of labor including PROM at term and preterm PROM | the day of delivery | 
| Preterm delivery | defined as delivery of a fetus at less than 37 weeks' gestational age | less than 37 and more than 21 weeks' gestational age | 
| Placenta previa | defined as a placenta that is implanted over or very close to the internal cervical orifice | the day of delivery | 
| Postpartum hemorrhage | defined as the loss of 500 ml of blood or more after completion of the third stage of labor | the day of delivery | 
| Birth weight | Birth weight | the day of delivery | 
| Stillbirth | defined as the absence of signs of life at or after birth | the day of delivery | 
| Mode of delivery | Vaginal birth or Caesarean Section | the day of delivery |