DATA COORDINATING CENTER FOR LOW-COST INTERVENTION TO AUGMENT INFERTILITY TREATMENT SUCCESS: PREPARATIOIN AND TRAINING

The Emmes Company, Llc, Rockville MD

Investigators

Abstract

Recent evidence from the Division of Intramural Population Health Research (DIPHR) Effects of Aspirin in Gestation and Reproduction (EAGeR) trial indicates that low grade inflammation, as indicated by elevated high sensitivity C-reactive protein (hsCRP), may contribute to a reduction in spontaneous conceptions among fecund women. However, low dose aspirin (LDA, 81 mg), appeared to restore normal rates of pregnancy and live birth among women with higher hsCRP. Because low-grade inflammation is also linked to several disorders that contribute to infertility, aspirin therapy may be a viable approach to help improve infertility treatment outcomes at a low cost. Furthermore, among women with higher hsCRP, LDA was associated with a substantial increase in pregnancy rates among lean women, more so than women with excess adiposity who may be plagued with greater inflammatory burden and metabolic disturbances. Indeed, higher circulating lipid levels are also associated with a decreased chance of pregnancy in women in the EAGeR trial and in prior studies. Given these collective results, it is hypothesized that improving pregnancy rates among women with low-grade inflammation coupled with greater adiposity may require a dual treatment that provides a stronger anti-inflammatory effect and a supplemental lipid-lowering effect by using a combined aspirin + statin therapy. Evaluating a potential intervention effect interaction by race-ethnicity is also critical to successful clinical translation, given evidence of somewhat lower effectiveness of some statin drugs in black patients with hyperlipidemia, and of lower infertility treatment success rates and higher hsCRP observed among certain minority groups. Therefore, the overarching goal of this trial is to determine if an intervention comprising aspirin with and without statin improves pregnancy and live birth rates in women with low grade inflammation undergoing OI/IUI treatment with lower and higher central adiposity. If efficacious and safe, such an intervention would have considerable public health impact and afford clinicians a simple and inexpensive treatment option for improving OI/IUI success rates which have been flat for decades. The specific trial objective is to enroll up to 2770 racially- and ethnically-diverse women with elevated hsCRP and normal versus higher waist circumference who are undergoing ovulation induction (OI) and/or intrauterine insemination (IUI) in a block-randomized, double-blind, placebo-controlled clinical trial to evaluate the effect of an adjunct therapy of ?half-dose? aspirin (162 mg) with and without the addition of statin (pravastatin, 40 mg) on cumulative pregnancy and live birth rates after 3 cycles of OI/IUI. Specifically, in Stage 1 of the trial, the aim is to enroll 330 women with lower waist circumference to be allocated to all three treatment arms (aspirin with statin, aspirin alone, placebo) and 530 women with higher waist circumference to be allocated to two treatment arms (aspirin with statin, placebo). At the completion of Stage 1, an interim analysis of women with high waist circumference will be conducted to determine whether Stage 2 of the trial will proceed, which would aim to enroll an additional 1910 high waist women. Stage 1 will estimate the effect of aspirin with statin versus placebo. Stage 2 would determine the superiority of aspirin STATEMENT OF WORK ? TASK ORDER 1 2 ATTACHMENT 1 with statin versus aspirin alone, as well as the effect of aspirin alone versus placebo in high waist women. The following study aims underlie successful attainment of the overarching research goal: Stage 1: 1. To determine the effect of aspirin with and without statin versus placebo on the cumulative rate of 12-wk pregnancy and live birth achieved following up to 3 cycles of OI and/or IUI infertility treatment in women with elevated hsCRP and waist circumference < 88 cm. 2. To determine the effect of aspirin with statin versus placebo on the cumulative rate of 12-wk pregnancy achieved following up to 3 cycles of OI and/or IUI infertility treatment in women with elevated hsCRP and waist circumference ? 88 cm. Stage 2: Results and recruitment rates of Stage 1 will be used to determine the utility, feasibility, and final design of Stage 2: 3. To determine the effect of aspirin with and/without statin (including the effect of aspirin alone vs. placebo, and the superiority of aspirin with statin vs. aspirin alone) on the cumulative rate of 12-wk pregnancy and live birth achieved following up to 3 cycles of OI and/or IUI infertility treatment in women with elevated hsCRP and waist circumference ? 88 cm. 4. To determine the effect of aspirin with and without statin versus placebo on treatment and pregnancy outcomes (including pregnancy loss, preeclampsia, preterm birth) among women with elevated hsCRP undergoing up to 3 cycles of OI/IUI infertility treatment.