Immunomodulatory Effects of Rapamycin on Pregnancy Rate of Patient With Recurrent Implantation Failure
Condition: Recurrent Implantation Failure
MeSH terms: Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      Repeated implantation failure (RIF) is determined as failure to achieve pregnancy following
      at least 3 embryo transfers of high quality embryos in IVF cycles. Successful implantation
      and pregnancy depend on the activity of a variety of factors such as adhesion molecules,
      cytokines and immune cells.The process by which the foreign conceptus is accepted requires
      the appropriate function of regulatory T cells (Treg), which are known as the mediators of
      immune regulation. Tregs are capable of inducing maternal tolerance toward the fetus and
      their systemic expansion has been observed in early pregnancy. Furthermore, Th17 cells that
      play important roles in mounting inflammation are involved in the maintenance of pregnancy as
      a subset of effector T cells.The mammalian target of rapamycin (mTOR) inhibitors are
      immunosuppressive agents used after solid organ transplantation. Sirolimus as the most common
      mTOR inhibitor is able to effectively prevent allograft rejection and possesses significant
      antitumor properties. Pregnancy is a state of immunosuppression and the dysregulated immune
      responses has been observed in women with RIF. Accordingly, modulation of the immune system
      by an immunosuppressant drug may present an approach to overcome implantation failure. In
      this context, the use of Sirolimus might offer promise to achieve a better pregnancy outcome
      among women with implantation failure who undergo IVF. Based on previous findings, we
      hypothesized that Sirolimus may be beneficial for the improvement of pregnancy rate in women
      with IVF failure.

      In the current study, we performe randomized phase II clinical trial to determine whether
      Sirolimus could be used as a bona fide treatment to increase the success rate of IVF in women
      with RIF of immune etiologies.A total 121 patients with a history of at least 3 RIF after
      IVF/ET cycles that will refer to Eastern Azerbaijan ACECR ART center, Alzahra Hospital of
      Tabriz University of Medical Sciences and Infertility Treatment center ACER Qom from July
      2017 to June 2018 were select and enroll in this multicenter, randomized, double-blind, phase
      II study.

      Normal ranges for Th17/Treg cell ratios establish using 50 normal fertile women who had a
      history of normal delivery by natural conception.

      In patients with elevated Th17/Treg ratios, half of them treat with Sirolimus (Rapamune®;
      Pfizer, UK) and rest of patients not treat (control group). The patients in the treatment
      group will began Sirolimus 2 days prior to embryo transfer (ET) and will continue until the
      day of pregnancy test (15 day after ET), for a total of 17 days Sirolimus administe in a
      daily dose of 2mg.
    


Intervention name(s): Rapamycin
Intervention type(s): Drug
Intervention description(s): Patients will take Rapamycin 2 days before IVF until 15 days after IVF
Other intervention name(s): Treatment group
Intervention MeSH terms: Sirolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Recurrent Implantation Failure; Rapamycin; Pregnancy Rate