Effect of Different Ovarian Stimulation Protocols on Endometrial Receptivity
Condition: Infertility, Female; Endometrial Diseases
MeSH terms: Infertility; Infertility, Female; Uterine Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will assess the change in endometrial gene expression signature on the day of
      embryo transfer according to the type of exogenous gonadotropins administered.
    

Detailed description: 
      Late-follicular elevated progesterone (LFEP) following ovarian stimulation for assisted
      reproductive technologies (ART) has been linked to abnormal endometrial receptivity
      expression profiles and lower pregnancy rates. For this reason, physicians frequently propose
      that patients with LFEP avoid performing a fresh embryo transfer, postponing instead it to a
      subsequent unstimulated cycle. Although this strategy may reduce the detrimental effect LFEP
      may have on cumulative ART pregnancy rates, it may also frustrate couples who wish to become
      pregnant as soon as possible.

      With the intent of minimizing potentially-avoidable treatment delays, an increasing number of
      researchers are proposing that physicians revisit their current ovarian stimulation regimens.
      One strategy which may reduce the incidence of LFEP is to decrease the dose of gonadotropins
      administered at the end of stimulation (i.e. a stepdown protocol). A similar approach, using
      corifollitropin alpha (CFA), has also been recently advanced, taking advantage of the
      stepdown-like pharmacodynamic profile of this compound.

      In order to assess the clinical usefulness of these strategies, the investigators propose a
      single-center, open-label, paired, randomized trial. The main objective of this study is to
      assess the changes in the endometrial gene expression profile on the day of fresh embryo
      transfer according to the type of gonadotropins administered for ovarian stimulation. In
      summary, all consenting subjects will first undergo an endometrial biopsy seven days after
      the luteinizing hormone peak in an unmedicated natural cycle. This biopsy will serve as the
      baseline endometrial biopsy (natural cycle biopsy) for a gene expression analysis. Following
      this baseline biopsy, subjects will be randomly allocated to a specific type of ovarian
      stimulation regimen in order to later perform a second endometrial biopsy, this time five
      days after oocyte retrieval (stimulated cycle biopsy). Subjects will be randomized to
      administer, on the third day of their menstrual cycle, either a single dose of 150 IU of CFA
      (study arms 1A and 1B) or a fixed daily dose of 200 or 300 IU of recombinant follicle
      stimulating (rFSH, study arm 2). On the eighth day of stimulation, it is expected that 15% to
      30% of all subjects who performed CFA will have reached the follicular development criteria
      for final oocyte maturation and ovulation triggering.
    

Intervention name(s): CFA; rFSH; Fixed daily rFSH dosing protocol of 200-300 IU; Step-down daily rFSH dose
Intervention type(s): Drug; Drug; Procedure; Procedure
Intervention description(s): Long-acting exogenous ovarian stimulation; Daily rFSH; The dose of daily rFSH is fixed at 200 or 300 IU; The dose of daily rFSH is progressively reduced
Other intervention name(s): Corifollitropin alpha; Puregon; Follitropin beta
Intervention MeSH terms: Follicle Stimulating Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: All consenting subjects will first undergo an endometrial biopsy seven days after the luteinizing hormone (LH) peak in an unmedicated natural cycle. This biopsy will serve as the baseline endometrial biopsy (natural cycle biopsy) for the gene expression signature analysis. Following this baseline biopsy, the subjects will be randomly allocated to a specific type of ovarian stimulation regimen in order to later perform some second endometrial biopsy, five days after oocyte retrieval (stimulated cycle biopsy).
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Endometrial receptivity; Ovarian stimulation