Efficacy of Recombinant FSH/GnRH Antagonist Protocol With and Without LH Adjunct for Egg Bank Donation
Condition: Egg Donation
Study type: Interventional
Phase: Phase 4

Summary: 
      Disprove the null hypothesis as follows:

      Among the investigator's egg bank donors undergoing ovulation induction with recombinant FSH
      medication per treatment protocol outlined below, use of adjunctive LH activity medication
      Menopur ™ , will result in the same number of mature oocytes recovered and cryopreserved as
      from egg donors not treated with Menopur™.

      Objectives:

      Compare efficacy of recombinant FSH (Follistim ™) with and without adjunct LH activity
      medication Menopur ™ for our volunteer egg bank donors.

      Efficacy defined as:

        1. #Days of ovarian stimulation to GnRH agonist trigger.

        2. Peak serum estradiol level on day of GnRH agonist trigger.

        3. Number of follicles >15 mm average diameter on day of GnRH agonist trigger.

        4. Number of mature oocytes recovered and cryopreserved.

      Study type: Randomized prospective clinical trial.

      Patient selection: Voluntary egg donors who have satisfied all screening criteria for FDA and
      the Michigan Egg Bank: Age range 18-to 39 years. BMI 18 to 25. Resting antral follicle count
      of 16 or greater. Cycle day 3 FSH <10 mIU/ml. AMH >2.0 ng/ml.

      Study design:

      Two groups- Group A- Recombinant FSH Follistim only; Group B- Recombinant FSH Follistim and
      adjunct Menopur. Both groups will use GnRH agonist trigger 36 hours prior to egg retrieval.

      Random number generator with patients assigned basd on odd or even numbers.

      Number of subjects: 25 in each group. Total of 50 subjects. This takes into account possible
      cycle cancellation for poor ovarian response or patient elective withdrawal to result in at
      least 20 subjects in each group completing the study.

      Primary measure of outcome: number of mature oocytes recovered and cryopreserved.

      Secondary measures of outcome:

        1. #Days of ovarian stimulation to GnRH agonist trigger.

        2. Peak serum estradiol level on day of GnRH agonist trigger.

        3. Number of follicles >15 mm average diameter on day of GnRH agonist trigger.
    

Detailed description: 
      Background:

      The investigator's Center has been studying human oocyte cryopreservation by vitrification
      since July 1, 2008 (Western Institutional Board Review -WIRB Pro. Nr: 20081080, WIRB Study
      Nr.: 1100421). The first phase of the investigator's study was to assess efficacy of oocyte
      cryopreservation among voluntary egg donors with end points for outcomes including rates of
      oocyte thaw survival, fertilization, embryo development, implantation, clinical pregnancy,
      live birth and infant health. The rationale for starting with egg donors was that they
      represent a population of women most likely to have optimal egg quality and a short
      turnaround time from vitrification to thaw, IVF and embryo transfer into an appropriate egg
      recipient patient. If the investigator could establish good outcomes when egg quality is
      optimal, then there would be good hope to provide reliable egg cryopreservation technology to
      women in need of fertility preservation when facing treatment of cancer; other illnesses for
      which treatments harm their eggs; women choosing personal egg banking and for women who wish
      to avoid excess embryo creation on moral or religious grounds.

      The investigator's study observations were that outcomes with use of previously cryopreserved
      donor eggs was equivalent to fresh donor eggs: 90% of mature oocytes survived the thaw, 76%
      of thawed oocytes fertilized normally with ICSI, 98% of recipient women had a day 5 embryo
      transfer with one or two embryos transferred, implantation rate of 42%, 60% or recipient
      women achieved clinical pregnancy, 58% live birth rate and no birth defects have been
      observed in over 40 babies delivered through this technology at our Center.

      In the beginning of 2012, we opened up the second phase of the investigator's study to
      include women in need of fertility preservation for the indications mentioned above. No
      outcomes are yet known due to the expected time deferment from oocyte cryopreservation to
      use. The favorable outcomes from donor egg bank IVF led to the investigator's establishing
      the Michigan Egg Bank. On October 22, 2012, the American Society for Reproductive Medicine
      announced a new practice guideline that oocyte cryopreservation technology should be
      considered mainstream medical therapy and no long be considered experimental medical care.
      The investigator's closed the WIRB study November, 26, 2012.

      Rationale:

      Ovarian stimulation for egg donation should be provided offering the safest and simplest
      process for our egg donors. Avoiding complications of ovarian hyperstimulation syndrome while
      assuring recruitment and harvest of good quality oocytes is a main goal in caring for the
      investigator's volunteer egg donors. Use of FSH medications with GnRH antagonist and GnRH
      agonist trigger is the protocol of choice for all of the investigator's egg donors. The
      investigator's egg donors have experienced no complications and rapid recovery. GnRH
      antagonists have been shown to suppress endogenous ovarian androgen synthesis. In using GnRH
      antagonist, adjunctive LH or low dose hCG combined with FSH medication has been a mainstream
      assumption to assure sufficient endogenous ovarian testosterone is present as a substrate for
      estrogen synthesis and normal folliculogenesis.

      In an effort to improve patient compliance by simplifying the use of medications for the
      investigator's egg donors, the investigator wishes to examine the efficacy of recombinant FSH
      without additional separate medication of adjunct LH activity in the form Menopur ™.
    

Intervention name(s): Follistim; Ganirelix; Menotropins; Leuprolide; Transvaginal ultrasound guided needle aspiration of oocytes
Intervention type(s): Drug; Drug; Drug; Drug; Procedure
Intervention description(s): Follicle stimulating hormone promotes recruitment of follicles for ovulation.; GnRH antagonist preventing a problematic risk of premature LH surge during ovulation induction therapy.; Combination of follicle stimulating hormone and Luteinizing hormone activity promotes recruitment of follicles for ovulation. Absence or presence of this medication is the difference being tested between the two arms of the study.; Promotes endogenous LH surge signaling oocyte maturation followed by ovulation. This controls timing for oocyte collection.
Other intervention name(s): Follistim AQ; Ganirelix Acetate; Menopur; Lupron; Leuprolide acetate
Intervention MeSH terms: Leuprolide; Menotropins; Ganirelix
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment