Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response

Study Overview
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Brief Summary
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Progestin can inhibit the pituitary LH surge during ovarian stimulation and various studies show progestin-primed ovarian stimulation (PPOS) is effective in blocking the LH surge in IVF. More and more centers in China are using PPOS because this regimen appears simpler and cheaper.A randomized trial to compare the effectiveness of PPOS and GnRH antagonist protocol in IVF in terms of the live birth rate is urgently needed. Trial objectives: To compare the live birth rate between the PPOS protocol and the antagonist protocol used for ovarian stimulation during IVF Eligible women will be randomised into one of the two groups: Antagonist group : Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger. PPOS group: Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger. There will be no fresh transfer. Only one blastocyst will be allowed to replaced in the first FET and a maximum of two blastocysts will be replaced in the subsequent FET cycles. The primary outcome is the live birth rate of the first frozen-thawed transfer cycle.

Official Title
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A Randomized Control Trial to Compare the Live Birth Rate Between the Progestin-primed Ovarian Stimulation Protocol and the GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response Undergoing IVF

Conditions
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IVF, GnRH Antagonist, PPOS

Intervention / Treatment
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* Drug: Progesterone
* Drug: GnRH Antagonist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of women <43 years at the time of ovarian stimulation for IVF The first IVF cycle Antral follicle count (AFC) >15 on day 2-5 of the period Exclusion Criteria: Presence of a functional ovarian cyst with E2>100 pg/mL Recipient of oocyte donation Undergoing preimplantation genetic testing Presence of hydrosalpinx or endometrial polyp which is not surgically treated

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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: Antagonist group<br>Women will receive antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger. | Drug: GnRH Antagonist<br>* GnRH antagonist (Cetrorelix or Ganirelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger<br>* Other names: Ganirelix;|
| Experimental: PPOS group<br>Women will receive oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger. | Drug: Progesterone<br>* oral medroxyprogesterone 10 mg daily or duphaston 10mg bd daily from Day 3 till the day of ovulation trigger<br>* Other names: duphaston;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| live birth rate | live birth rate of the first frozen embryo transfer cycle | deliveries ≥22 weeks gestation with heartbeat and breath | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| positive serum hCG | serum β-hCG ≥10 mIU/mL of the first FET | 2 weeks after FET | 
| clinical pregnancy | presence of intrauterine gestational sac by trans-vaginal ultrasound at 6 gestational weeks of the first FET | 6 weeks' gestation | 
| biochemical pregnancy | positive serum hCG not followed by clinical pregnancy of the first FET | 6 weeks' gestation | 
| implantation rate | the number of gestational sacs per blastocyst transferred of the first FET | 6 weeks' gestation | 
| ongoing pregnancy | a viable pregnancy beyond 12 weeks' gestation of the first FET | 12 weeks' gestation | 
| cumulative live birth | cumulative live birth within 6 months of randomization | 2 years' after FET | 
| number of oocytes retrieved | number of oocytes retrieved | 1 day after oocyte retrieval | 
| number and grading of blastocysts | number and grading of blastocysts suitable for biopsy and freezing | 1 week after oocyte retrieval | 
| multiple pregnancy | more than one intrauterine sacs on scanning | multiple pregnancy beyond gestation 12 weeks | 
| ectopic pregnancy | pregnancy outside the uterine cavity | ectopic pregnancy during 12 weeks gestation | 
| birthweight of newborns | the birth weight of newborns | 1 year after FET | 
| serum baseline FSH | baseline FSH of period day 2-3 | day 2-3 of period | 
| estradiol level on the trigger day |  | 2 days before oocyte retrieval | 
| progesterone level on the trigger day |  | 2 days before oocyte retrieval | 
| estradiol and progesterone levels in the follicular fluid | estradiol and progesterone levels in the follicular fluid | 1 year after FET | 
| miscarriage | clinically recognised pregnancy loss before 22 weeks of pregnancy. | 22 weeks of pregnancy |