Euploid Rate of Blastocyst Derived From PPOS VS Antagonist Protocol

NCT04989348 | Completed DMC

• 1 other identifier: shanghaiFMIH-20210729
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

In-vitro fertilization (IVF) involves multiple follicular development, oocyte retrieval and embryo transfer after fertilization. Despite recent advances in ovarian stimulation, the method of assisted fertilization and improved culture conditions, the implantation potential of embryos remains around 30-35% for a long time. Gonadotrophin releasing hormone (GnRH) agonists have been used in IVF to prevent the LH surge and the premature ovulation and are given in the luteal phase of the preceding cycle or in the follicular phase of the treatment cycle i.e. the long GnRH agonist. GnRH antagonists are now commonly used during IVF. In addition to the advantage of its simplicity, the use of antagonist is associated with a substantial reduction in ovarian hyperstimulation syndrome without reducing the chance of achieving live birth when compared with the long agonist protocols. \[1\] 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 \[2-5\]. More and more centers in China are using PPOS because this regimen appears simpler and cheaper. Because of its negative effect on the endometrium, fresh transfer of embryos is not possible and elective freezing of all embryos is required. PPOS protocol is indicated in women who freeze all embryos because of various reasons such as undergoing preimplantation genetic testing for aneuploidy or the risk of ovarian hyperstimulation syndrome. One prospective non-randomized study comparing the PPOS vs short GnRH agonist protocol shows similar oocytes retrieved between the two protocols, and the incidence of premature LH surge, clinical pregnancy rate and live birth rates shows no significant difference. \[2\] A recent randomized trial comparing medroxyprogesterone and GnRH antagonist in an oocyte donation program showed a similar number of mature oocytes but reported lower ongoing pregnancy rate and live birth rate of recipients of oocyte donors who had received medroxyprogesterone in IVF \[6\]. However, the oocyte recipients in that trial were not randomized. Therefore, it is not possible to conclude the effect of progestin used in IVF on the pregnancy outcomes. It is possible that the PPOS protocol may have an adverse effect on the euploid rate of embryos, leading to a lower live birth rate.

Conditions

IVF

Keywords

ppos; antagonist protocol; PGT-A; Euploid Rate of Blastocyst

Outcome Measures

Primary Outcomes (1)

• euploid blastocyst formation rate

  Euploid blastocysts per injected MII oocyte

  2 months

Secondary Outcomes (11)

• Number of mature oocytes

  1 month

• Number of blastocysts suitable for biopsy and freezing

  1 month

• clinical pregnancy of the first FET

  an average of 3 months

• implantation rate

  an average of 3 months

• ongoing pregnancy of the first FET

  an average of 6 months

Study Arms (2)

Antagonist group

PLACEBO COMPARATOR

Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.

Procedure: Gonadotrophin releasing hormone antagonist protocol

PPOS group

ACTIVE COMPARATOR

Women will receive oral medroxyprogesterone 10 mg daily or Duphaston 10mg bd from Day 3 till the day of ovulation trigger. Gonadotrophin (human menopausal gonadotrophin or recombinant FSH) injections will be started. Ovarian response will be monitored by transvaginal scanning with or without serum hormonal level. Human chorionic gonadotrophin (hCG 1,000 IU) and GnRH agonist (decepepty 0.2mg) will be given for triggering of final maturation when at least 3 follicles reach \>17mm in diameter. Blood will be checked for serum estradiol and progesterone levels. Transvaginal USS-guided oocyte retrieval will be performed 36 hours after the trigger.

Procedure: Progestin-primed ovarian stimulation protocol

Interventions

Gonadotrophin releasing hormone antagonist protocol PROCEDURE

Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger or

Antagonist group

Progestin-primed ovarian stimulation protocol PROCEDURE

Women will receive oral medroxyprogesterone 10 mg daily or Duphaston 10mg bd from Day 3 till the day of ovulation trigger.

PPOS group

Eligibility Criteria

• Age: 20 Years - 43 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age of women \<43 years at the time of ovarian stimulation for IVF
• PGT-A indicated for advanced maternal age (\>40 years), recurrent miscarriage (\>=2 or 3 consecutive miscarriage and repeated implantation failure (\>=4 embryos replaced or \>=2 blastocysts replaced without success)

You may not qualify if:

• Presence of a functional ovarian cyst with E2\>100 pg/mL
• use of donor eggs/sperm,
• Presence of hydrosalpinx or endometrial polyp which is not surgically treated
• moderate or severe endometriosis

Sponsors & Collaborators

• Shanghai First Maternity and Infant Hospital: lead
• The University of Hong Kong: collaborator

Study Sites (1)

Shanghai first Maternity and Infant health hospital, Tong Ji University

Shanghai, 200051, China

Location

Related Publications (8)

• Al-Inany HG, Youssef MA, Aboulghar M, Broekmans F, Sterrenburg M, Smit J, Abou-Setta AM. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011 May 11;(5):CD001750. doi: 10.1002/14651858.CD001750.pub3.

  PMID: 21563131 RESULT

• 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.

  PMID: 25956370 RESULT

• 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.

  PMID: 28276192 RESULT

• 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.

  PMID: 28062551 RESULT

• 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.

  PMID: 29300975 RESULT

• 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.

  PMID: 30927417 RESULT

• Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.

  PMID: 25432917 RESULT

• Wang L, Wang JY, Zhang Y, Qian C, Wang XH, Ng EHY, Ai A, Chen ZQ. Comparison of the euploidy rate in preimplantation genetic testing for aneuploidy cycles following progestin-primed versus gonadotropin-releasing hormone antagonist protocol: a randomized controlled study. Reprod Biol Endocrinol. 2025 May 13;23(1):67. doi: 10.1186/s12958-025-01404-0.

  PMID: 40361159 DERIVED

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: clinical doctor in chief

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 4, 2021
• Study Start: August 4, 2021
• Primary Completion: March 1, 2023
• Study Completion: February 20, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

CN (1)