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NCT Number: NCT04989348

Euploid Rate of Blastocyst Derived From PPOS VS Antagonist Protocol

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.

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Key information

Conditions

IVF

Age range

20 year–43 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Shanghai first Maternity and Infant health hospital, Tong Ji University

Shanghai, 200051, China

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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

Treatment and study plan

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

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.

Primary outcomes

  1. euploid blastocyst formation rate

    Time frame: 2 months

    Euploid blastocysts per injected MII oocyte

Secondary outcomes

  1. Number of mature oocytes

    Time frame: 1 month

    M2 oocytes

  2. Number of blastocysts suitable for biopsy and freezing

    Time frame: 1 month

    blastocysts after extented culture

  3. clinical pregnancy of the first FET

    Time frame: an average of 3 months

    presence of intrauterine gestational sac on ultrasound

  4. implantation rate

    Time frame: an average of 3 months

    number of gestational sacs per embryo transferred

  5. ongoing pregnancy of the first FET

    Time frame: an average of 6 months

    viable pregnancy beyond gestation 10 weeks

  6. live birth rate of the first FET

    Time frame: average of 1 year

    A baby born alive after 22 weeks gestation

  7. Serum FSH level

    Time frame: 1 month

    hormone level

  8. Serum AMH level

    Time frame: 1 month

    hormone level

  9. Serum estradiol level

    Time frame: 1 month

    hormone level

  10. Serum progesterone level

    Time frame: 1 month

    hormone level

  11. incidence of premature LH surge

    Time frame: 1 month

    LH ≥10 IU/l

Sponsors and collaborators

Lead sponsor

Shanghai First Maternity and Infant Hospital

Other

Collaborators

  • The University of Hong Kong

Registry information

Official study title

A Randomized Control Trial to Compare the Euploid Rate of Blastocyst Between the Progestin-primed Ovarian Stimulation Protocol and the Gonadotrophin Releasing Hormone Antagonist Protocol in Patients With Undergoing Preimplantation Genetic Testing for Aneuploidy

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Aug 4, 2021
Registry last updated
Feb 28, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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