Elagolix for Fertility Enhancement Clinical Trial
Condition: Endometriosis; Unexplained Infertility
MeSH terms: Infertility; Endometriosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Studies suggest that undiagnosed endometriosis results in poor reproductive outcomes in the
      setting of In Vitro Fertilization and Embryo Transfer (IVF-ET). Biomarkers that predict
      endometriosis including B-cell lymphoma (BCL6) and Sirtuin 1 (SIRT1) are associated with
      reduced pregnancy rates following IVF-ET. Treatment with gonadotropin releasing hormone
      (GnRHr) receptor agonists (leuprolide acetate depot) has been shown to improve pregnancy
      rates following embryo transfer (ET). In this randomized controlled trial, a new generation
      GnRHr antagonist, elagolix, will be compared to oral contraceptives (OCPs) for suppression of
      suspected endometriosis prior to ET. Both groups will receive two months of treatment prior
      to frozen embryo transfer of a single euploid embryo. Outcomes will include pregnancy rate,
      miscarriage rate and ongoing and live birth rate following treatment. Patients experiencing
      unanticipated problems or who experience adverse events such that they do not tolerate the
      treatment they are assigned, will be allowed to discontinue treatment and be provided the
      opportunity to use the other treatment if they so choose. The outcomes of such cycles would
      be collected separately and included as observational data only and not included in the
      randomized data analysis. Alternatively, they can simply drop out of the study and resume
      medical therapy as appropriate or pursue frozen embryo transfer as previously planned.
    

Detailed description: 
      Although meta-analyses have not demonstrated an effect of endometriosis on IVF outcomes, most
      women with endometriosis undergoing IVF have not been diagnosed or treated for their disease.
      Recent evidence suggests that biomarkers for endometriosis predict IVF failure and
      miscarriage. Further suppression of endometriosis prior to IVF has been shown to dramatically
      improve pregnancy rates in unexplained infertility with suspected endometriosis. Elagolix
      (Orilissa) is a new generation FDA approved orally active GnRHr antagonist that is rapidly
      reversible, for the treatment of endometriosis and pelvic pain. There have been no studies on
      the efficacy of elagolix for the treatment of endometriosis-associated infertility. Given the
      recent study in Fertility and Sterility demonstrating IVF outcome prediction using BCL6 as a
      biomarker for the presence of endometriosis and subsequent preliminary data showing benefit
      using surgery and GnRH agonist therapy, there is adequate rationale to examine the use of the
      orally active, non-peptide compound (elagolix) for estrogen suppression prior to frozen
      embryo transfer in women who test positive for BCL6 and an associated protein, SIRT1. In this
      multi-central randomized controlled trial (RCT), the EFFECT Trial, the investigators plan to
      recruit 100 subjects with prior unexplained IVF failure with positive endometrial BCL6/SIRT1
      expression. To qualify all subjects will need to have a preimplantation genetic testing
      (PGT-A) tested euploid embryo and intentions to undergo frozen embryo transfer. Subjects will
      be randomized to receive elagolix (200 mg BID) or OCPs for 2 months prior to standardized
      FET. Primary study outcomes will be pregnancy outcome.
    

Intervention name(s): Elagolix; Oral Contraceptive
Intervention type(s): Drug; Drug
Intervention description(s): This orally active, reversible GnRH antagonist will be used to suppress endometriosis by lowering estrogen levels for 2 months prior to FET; Oral contraceptive prescribed by physician.
Intervention MeSH terms: Contraceptive Agents; Contraceptives, Oral
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects in the OCP group who fail FET but have remaining euploid embryos will be offered 2 additional months of elagolix followed by another FET
Masking: None (Open Label)
Primary purpose: Treatment