Clinical trial NCT04414761: Live Birth Rate Between PPOS and GnRH Antagonist Protocol in Patients With Anticipated High Ovarian Response
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: IVF
GnRH Antagonist
PPOS
Lead sponsor: ShangHai Ji Ai Genetics & IVF Institute
Sponsor class: OTHER
First posted: 2020-06-04
Enrollment: 784
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: live birth rate
timeFrame: deliveries ≥22 weeks gestation with heartbeat and breath
Secondary outcomes:
measure: positive serum hCG
timeFrame: 2 weeks after FET
measure: clinical pregnancy
timeFrame: 6 weeks' gestation
measure: biochemical pregnancy
timeFrame: 6 weeks' gestation
measure: implantation rate
timeFrame: 6 weeks' gestation
measure: ongoing pregnancy
timeFrame: 12 weeks' gestation
measure: cumulative live birth
timeFrame: 2 years' after FET
measure: number of oocytes retrieved
timeFrame: 1 day after oocyte retrieval
measure: number and grading of blastocysts
timeFrame: 1 week after oocyte retrieval
measure: multiple pregnancy
timeFrame: multiple pregnancy beyond gestation 12 weeks
measure: ectopic pregnancy
timeFrame: ectopic pregnancy during 12 weeks gestation
measure: birthweight of newborns
timeFrame: 1 year after FET
measure: serum baseline FSH
timeFrame: day 2-3 of period
measure: estradiol level on the trigger day
timeFrame: 2 days before oocyte retrieval
measure: progesterone level on the trigger day
timeFrame: 2 days before oocyte retrieval
measure: estradiol and progesterone levels in the follicular fluid
timeFrame: 1 year after FET
measure: miscarriage
timeFrame: 22 weeks of pregnancy
Other outcomes:
Locations:
city: Shanghai
country: China
facility: ShangHai JIAI Genetics&IVF Institute
Study officials:
affiliation: Shanghai JiAi Genetics & IVF Institute
name: XIAOXI SUN, PHD
role: STUDY_DIRECTOR
References:
citation: Begueria R, Garcia D, Vassena R, Rodriguez A. Medroxyprogesterone acetate versus ganirelix in oocyte donation: a randomized controlled trial. Hum Reprod. 2019 May 1;34(5):872-880. doi: 10.1093/humrep/dez034.
citation: Yu S, Long H, Chang HY, Liu Y, Gao H, Zhu J, Quan X, Lyu Q, Kuang Y, Ai A. New application of dydrogesterone as a part of a progestin-primed ovarian stimulation protocol for IVF: a randomized controlled trial including 516 first IVF/ICSI cycles. Hum Reprod. 2018 Feb 1;33(2):229-237. doi: 10.1093/humrep/dex367.
citation: Massin N. New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF. Hum Reprod Update. 2017 Mar 1;23(2):211-220. doi: 10.1093/humupd/dmw047.
citation: Kuang Y, Chen Q, Fu Y, Wang Y, Hong Q, Lyu Q, Ai A, Shoham Z. Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. Fertil Steril. 2015 Jul;104(1):62-70.e3. doi: 10.1016/j.fertnstert.2015.03.022. Epub 2015 May 5.
citation: Dong J, Wang Y, Chai WR, Hong QQ, Wang NL, Sun LH, Long H, Wang L, Tian H, Lyu QF, Lu XF, Chen QJ, Kuang YP. The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial. BJOG. 2017 Jun;124(7):1048-1055. doi: 10.1111/1471-0528.14622.
citation: Alexandru P, Cekic SG, Yildiz S, Turkgeldi E, Ata B. Progestins versus GnRH analogues for pituitary suppression during ovarian stimulation for assisted reproductive technology: a systematic review and meta-analysis. Reprod Biomed Online. 2020 Jun;40(6):894-903. doi: 10.1016/j.rbmo.2020.01.027. Epub 2020 Feb 5.