Euploid Rate of Blastocyst Derived From PPOS VS Antagonist Protocol

Not Applicable

Completed

• Conditions: IVF
• Interventions: Procedure: Gonadotrophin releasing hormone antagonist protocol; Procedure: Progestin-primed ovarian stimulation protocol

• Registration Number: NCT04989348
• Lead Sponsor: Shanghai First Maternity and Infant Hospital

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.

Detailed Description

The inability to assess embryo quality and select those with the highest potential for implantation on the basis of morphology has led to the concept of preimplantation genetic testing for aneuploidy (PGT-A). PGT-A involves biopsy of a few cells from an embryo and assessment of the chromosome copy numbers. While PGT-A cannot create a healthy embryo or improve the health of an embryo, it provides a method of selecting embryos with a normal number of chromosomes for transfer. This in turn has the potential to increase the chance of having a healthy live birth and reduce the risk of miscarriage or an abnormal fetus caused by an abnormal number of chromosomes. Aneuploidy screening of all chromosomes is necessary to determine whether an embryo is chromosomally normal.

As the turnaround time of PGT-A with next generation sequencing is about a week, it is not possible to transfer blastocyst in the stimulated cycle. All blastocysts will be frozen post biopsy and the blastocysts with normal genetic makeup will be thawed and replaced in a subsequent menstrual cycle. Cryopreservation of blastocysts and replacing the frozen blastocysts after thawing in subsequent cycles become a common practice with vitrification as the cryopreservation method. A systematic review (7) of the clinical utility of PGT-A with comprehensive chromosome screening found that three small randomised controlled trials demonstrated benefit in young and good prognosis patients in terms of clinical pregnancy rates and the use of single embryo transfer.

This randomized trial aims to compare the euploid rate of blastocysts between PPOS and GnRH antagonist protocols in patients undergoing PGT-A.

Study Timeline

• Study First Submitted: 2021-07-30
• Study First Submitted QC: 2021-08-03
• Study Start: 2021-08-04
• Study First Posted: 2021-08-04
• Primary Completion: 2023-03-01
• Status Verified: 2024-02
• Study Completion: 2024-02-20
• Last Update Submitted: 2024-02-23
• Last Update Posted: 2024-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 240

Inclusion Criteria

1. Age of women <43 years at the time of ovarian stimulation for IVF
2. 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)

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antagonist group	Gonadotrophin releasing hormone antagonist protocol	Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger.
PPOS group	Progestin-primed ovarian stimulation protocol	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.

Primary Outcome Measures

Name	Time	Method
euploid blastocyst formation rate	2 months	Euploid blastocysts per injected MII oocyte

Secondary Outcome Measures

Name	Time	Method
ongoing pregnancy of the first FET	an average of 6 months	viable pregnancy beyond gestation 10 weeks
Serum FSH level	1 month	hormone level
Number of mature oocytes	1 month	M2 oocytes
Serum progesterone level	1 month	hormone level
incidence of premature LH surge	1 month	LH ≥10 IU/l
Number of blastocysts suitable for biopsy and freezing	1 month	blastocysts after extented culture
implantation rate	an average of 3 months	number of gestational sacs per embryo transferred
Serum estradiol level	1 month	hormone level
clinical pregnancy of the first FET	an average of 3 months	presence of intrauterine gestational sac on ultrasound
live birth rate of the first FET	average of 1 year	A baby born alive after 22 weeks gestation
Serum AMH level	1 month	hormone level

Trial Locations

Locations (1)

Shanghai first Maternity and Infant health hospital, Tong Ji University; 🇨🇳 Shanghai, China