Conditions: Pregnancy Unexplained Infertility
Keywords: Pregnancy Infertility Ovarian stimulation Aromatase inhibitors Follicle Stimulating Hormone
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 900
Healthy volunteers: no

Brief 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.

Arms:
arm 1: 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. arm 2: 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. arm 3: 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.

Interventions: intervention 1: Letrozole (aromatase inhibitor) intervention 2: Clomiphene Citrate intervention 3: Follicle Stimulating Hormone (gonadotropin)
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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.

Protocol document: