Maximal Stimulation and Delayed Fertilization for Diminished Ovarian Reserve: a Randomized Pilot Study
Condition: Infertility
MeSH terms: Infertility
Intervention: clomiphene plus gonadotropins; Leuprolide flare
Intervention description: clomiphene plus gonadotropin ovulation induction; Leuprolide flare ovulation induction
Intervention MeSH terms: Leuprolide; Clomiphene
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: infertility; diminished ovarian reserve; fertilization in vitro; ovulation inducion; vitrification

Summary:

      The purpose of the study is (A) to determine if the following novel approach improves the
      live birth rate with In-Vitro Fertilization (IVF) for women with a poor prognosis due to
      diminished ovarian reserve:

        -  ovarian stimulation with medications that are effective in women with diminished ovarian
           reserve but adversely affect the endometrium

        -  oocyte retrieval and vitrification

        -  fertilization and embryo transfer in a subsequent cycle with controlled endometrial
           preparation B) To determine the optimal stimulation protocol for women with diminished
           ovarian reserve incorporating oocyte vitrification

      Women who are not eligible to participate in the Carolinas Medical Center (CMC) Assisted
      Reproductive Therapy program because of an extremely poor prognosis will be recruited for a
      prospective, randomized, open-label study to determine if a novel approach improves the live
      birth rate with traditional IVF "poor prognosis" stimulation protocols. The novel approach
      will incorporate one of two protocols utilizing medications that provide maximal ovarian
      stimulation but have a temporary detrimental fertility-reducing effect on the endometrium. If
      ovarian stimulation is adequate, oocyte retrieval will be performed and viable oocytes
      vitrified (stored in a "glass-like" state in liquid nitrogen). At a later time, oocyte
      warming and fertilization will be performed in a subsequent cycle, in which the endometrium
      has been prepared.

      Key points include:

        -  Randomization to one of two ovarian stimulation protocols that have been shown to have a
           detrimental effect on the endometrium, and therefore are rarely used in a "fresh" IVF
           cycle

        -  Oocyte vitrification is considered to be an investigational procedure by the American
           Society of Reproductive Medicine (ASRM), and should only be performed under the
           supervision of an IRB. With oocyte vitrification, ovarian stimulation and oocyte
           retrieval can "unlinked" from embryo transfer, allowing embryo transfer to occur in a
           more optimal environment

        -  Endometrial preparation is routine for frozen embryo transfer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Basal FSH 17 IU/mL (highest ever)

          -  Basal FSH 15-17 (highest ever) and failed EFORT test

          -  Age > 43 at the time of expected retrieval

          -  Failure to conceive with a prior "poor prognosis" IVF stimulation protocol (microdose
             leuprolide flare or GnRH antagonist cycle) if administered because of evidence of
             diminished ovarian reserve

          -  Failure to conceive with 3 or more IVF cycles at CMC

        Exclusion Criteria:

          -  Contraindications to IVF

          -  Contraindication to pregnancy

          -  Allergy or contraindication to medications used for IVF or embryo transfer

          -  Use for a gestational carrier

          -  Uncorrected or untreatable uterine infertility

          -  Smoking or substance abuse within 3 months of initiating stimulation for IVF