Letrozole Therapy for IVF/ET: Effects on Multiple Pregnancy and Treatment Burden

描述(由申请人提供)：本申请是为了响应RFA-HD-06-008，作为临床站点参与正在进行的多中心合作计划，旨在进行临床研究，调查生殖医学中的问题。该应用程序直接涉及生殖科学处的使命，即通过对人类生育和不孕不育的研究，确保健康、想要的婴儿的出生。拟议项目的长期目标是减少与辅助生殖技术(ART)相关的多胎妊娠的发生率，减少与ART相关的过多胚胎生产和胚胎冷冻的发生率，并减轻ART治疗患者的负担。在美国，每年进行超过10万个周期的抗逆转录病毒治疗，现在抗逆转录病毒治疗占所有新生儿的1%。抗逆转录病毒疗法的进步提高了其疗效，但也导致多胎妊娠的发生率大幅增加。抗逆转录病毒治疗相关的多胎妊娠对公众健康的影响怎么强调都不为过。美国的大多数抗逆转录病毒治疗周期采用复杂的治疗方案，包括多种非肠道药物的自我给药和密集的门诊监测。这些方案有助于产生多个胚胎，从而促进多余胚胎的移植和冷冻保存。该项目旨在解决传统ART疗法的缺点，通过随机临床试验设计，研究一种基于口服芳香酶抑制剂来曲唑和最低限度监测的替代卵巢刺激方案。该项目的具体目标是：1)比较来曲唑抗逆转录病毒治疗周期中多胎妊娠的发生率与传统抗逆转录病毒疗法的发生率，2)确定两种治疗方案中胚胎冷冻保存的发生率，3)比较来自两个来曲唑抗逆转录病毒治疗周期和一个传统抗逆转录病毒疗法周期的每个患者的累计活产率，4)检查两个周期来曲唑抗逆转录病毒疗法的累积成本与传统抗逆转录病毒疗法单周期的成本，以及5)比较两种治疗方案之间自我报告的治疗负担水平和参与者的担忧。据推测，与传统的ART相比，与来曲唑治疗相关的成本节约和治疗负担将允许患者接受两个周期的来曲唑ART，这将导致类似的活产分娩率，多胎妊娠的发生率显著降低，胚胎冷冻保存的发生率显著降低。该项目的相关性源于它有可能减少多胎妊娠及其随之而来的费用和死亡和残疾风险。考虑到获得抗逆转录病毒治疗的问题，拟议的治疗费用审查是相关的，这限制了美国的适当利用。最后，该项目解决了有关胚胎冷冻保存的相关社会和伦理问题。

DESCRIPTION (provided by applicant): 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.