Euploid Rate of Blastocyst Derived From PPOS VS Antagonist Protocol
Condition: IVF
Study type: Interventional

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.
    

Intervention name(s): Gonadotrophin releasing hormone antagonist protocol; Progestin-primed ovarian stimulation protocol
Intervention type(s): Procedure; Procedure
Intervention description(s): Women will receive antagonist (Cetrorelix 0.25mg) once subcutaneously daily from day 6 of ovarian stimulation till the day of the ovulation trigger or; Women will receive oral medroxyprogesterone 10 mg daily or Duphaston 10mg bd from Day 3 till the day of ovulation trigger.
Intervention MeSH terms: Hormones; Progestins; Hormone Antagonists
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: ppos; antagonist protocol; PGT-A; Euploid Rate of Blastocyst