Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation
Condition: Pregnancy; Unexplained Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 3

Summary: 
      The objective of this application is to identify a pharmacologic agent which helps couples in
      whom the female partner ovulates regularly successfully obtain their goal of delivering a
      healthy child, whose use will result in low rates of multiple gestations. The central
      hypothesis is that, in infertile ovulatory women undergoing ovarian stimulation (OS) and
      intrauterine insemination (IUI), the use of aromatase inhibitors (AI) will stimulate the
      ovaries sufficiently to produce no reduction in the rate of pregnancy, while significantly
      reducing the numbers of multiple gestational pregnancies that result from stimulation with
      clomiphene citrate (CC) or follicle stimulating hormone (FSH). The rationale for the proposed
      research is that reduction of multiple pregnancy rates could significantly reduce maternal
      and neonatal morbidity and mortality, as well as the cost of healthcare for these individuals
      and society.
    

Detailed description: 
      Patient Population

      The population will consist of 900 women up to and including women ≥18 to ≤40 years years of
      age (at time of randomization) desirous of conceiving who will be recruited over
      approximately a two year period from the Reproductive Medicine Network (RMN) clinical sites
      and possibly from the Specialized Cooperative Center Programs in Reproductive Research
      (SCCPIR) sites, through public notification programs.

      Study Design

      This will be a multi-center, prospective, partially blinded clinical trial of gonadotropins
      vs. clomiphene citrate vs. aromatase inhibitors. The randomization scheme will be coordinated
      through the data coordination center (DCC) and the randomization will be stratified by each
      participating site and within each site for ages 18-34 and 35-40.

      Treatment

      Patients will be randomized to receive either FSH, CC, or an AI according to randomization
      tables generated by a computer randomization program. Treatment assignments will be blocked
      by site and age group. Subjects randomized to pill treatment will receive medication in
      double blinded fashion, receiving one type of pill (overcoated CC or AI). Subjects randomized
      to injectable medication(FSH) will receive vials of medication.

      Primary efficacy parameter

      Multiple gestation rate following recruitment of multiple follicular development with an AI,
      as compared to CC and FSH.

      Secondary efficacy parameters

      Rate of pregnancy obtained, live birth rate, and time to pregnancy following administration
      of an aromatase inhibitor, as compared to CC and FSH as well as the live birth rate of
      multiple gestation pregnancies.
    

Intervention name(s): Letrozole (aromatase inhibitor); Clomiphene Citrate; Follicle Stimulating Hormone (gonadotropin)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A daily dose of 5 mg of the AI, letrozole, will be administered orally for five days starting on day three of the menstrual cycle. Future cycles can be started at 2.5-7.5 mg/d. FDA approval (IND) will be obtained.; CC will be administered at a dose of 100 mg/d on cycle days 3-7. Future cycles can be started at 50-150 mg/d.; A daily injection of 150 IU of FSH will be administered subcutaneously starting on day three of the menstrual cycle and continuing until the day of hCG administration. Dosage will be able to be increased or decreased 37.5-75 IU/d beginning cycle day 7. Future cycles can be started at doses ranging from 75-225 IU/d. The same type of FSH injections will be used.
Intervention MeSH terms: Letrozole; Clomiphene; Enclomiphene; Zuclomiphene; Hormones; Follicle Stimulating Hormone; Aromatase Inhibitors
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Pregnancy; Infertility; Ovarian stimulation; Aromatase inhibitors; Follicle Stimulating Hormone