This application is written in response to RFA-HD-06-008 to participate as a Clinical Site in an ongoing multicenter cooperative program designed to conduct clinical studies investigating problems in reproductive medicine. The application directly addresses the mission of the Reproductive Sciences Branch to ensure the birth of healthy, wanted babies through studies on human fertility and infertility. The long term objectives of the proposed project are to reduce the incidence of multiple pregnancy associated with assisted reproductive technology (ART), to reduce the incidence of excess embryo production and embryo cryopreservation associated with ART, and to reduce the burden on patients of ART therapy. Over 100,000 cycles of ART treatment are performed each year in the US, and ART is now responsible for 1% of all births. Advances in ART have increased its efficacy, but have also led to a large increase in the incidence of multiple pregnancies. The public health impact of ART associated multiple pregnancies cannot be overstated. The majority of ART cycles in the US employ complex treatment regimens entailing self administration of multiple parenteral drugs and intensive outpatient monitoring. These regimens facilitate the creation of multiple embryos, which promotes the transfer and cryopreservation of excess embryos. The proposed project aims to address the shortcomings of conventional ART therapy by examining via a randomized clinical trial design an alternative ovarian stimulation regimen based on the oral administration of the aromatase inhibitor letrozole and minimal monitoring.
The specific aims of the project are to: 1) compare the incidence of multiple pregnancies in letrozole ART cycles with the incidence in conventional ART, 2) determine the incidence of embryo cryopreservation in the two treatment regimens, 3) compare the cumulative live born delivery rate per patient derived from two cycles of letrozole ART compared to one cycle of conventional ART, 4) examine the cumulative cost of two cycles of letrozole ART compared to the cost of a single cycle of conventional ART, and 5) compare self-reported levels of treatment burden and participant concerns between the two regimens. It is hypothesized that the cost savings and reduced treatment burden associated with letrozole therapy compared to conventional ART will allow patients to undergo two cycles of letrozole based ART, which will result in a similar live born delivery rate, a significantly lower incidence of multiple pregnancy and a significantly lower incidence of embryo cryopreservation. The relevance of the project derives from its potential to reduce multiple pregnancies with their attendant costs and risk of death and disability. The proposed examination of treatment costs is relevant given the problem of access to ART care, which limits appropriate utilization in the US. Finally, the project addresses relevant social and ethical concerns regarding embryo cryopreservation.
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