C-Reactive protein in relation to fecundability and anovulation among eumenorrheic women

Abstract

Objective: To assess systemic inflammation in relation to fecundability and anovulation.

Design: Prospective cohort study among participants in the Effects of Aspirin in Gestation and Reproduction trial who were assigned to the placebo.

Setting: Academic medical centers.

Patient(s): Healthy eumenorrheic women (n = 572), 18-40 years of age, with one or two pregnancy losses, attempting spontaneous pregnancy.

Intervention(s): Baseline serum high-sensitivity C-reactive protein (hsCRP) values <10 mg/L were categorized into tertiles.

Main outcome measure(s): Discrete Cox proportional hazards models estimated the fecundability odds ratio (FOR) and 95% confidence interval (CI) and adjusted for potential confounders. Log-binomial regression estimated the risk ratio (RR) and 95% CI of anovulation. The algorithm to define anovulation used data on urinary concentrations of hCG, pregnanediol-3-glucuronide, and LH as well as fertility monitor readings.

Result(s): Higher hsCRP was associated with reduced fecundability but not with an increased risk of anovulation.

Conclusion(s): Among healthy women attempting pregnancy after one or two pregnancy losses, we found preliminary evidence that systemic inflammation is associated with reduced fecundability, but not independently from adiposity. Sporadic anovulation did not appear to drive this association.

Clinical trial registration number: ClinicalTrials.gov: NCT00467363.

Keywords: C-Reactive protein; anovulation; fertility; inflammation; prospective studies.

Conflict of interest statement

Conflicts of interest: Dr. Pollack reports payment from ICF Global Consulting for work performed while consulting on a project about preterm birth and spontaneous abortion for the US Environmental Health and Protection Agency and payment from Triway Chinese Delegation for development of an educational presentation on environmental factors affecting female reproductive health. All other authors report no potential conflicts of interest.

Published by Elsevier Inc.

Figures

Figure 1

The Fecundability Odds Ratio (FOR) and 95% CI for the second tertile (open circle) and third tertile (closed circle) of hsCRP relative to the first tertile. Results are restricted to 572 women assigned to placebo. Model 1 is adjusted for cycles trying at enrollment. Model 2 is adjusted for cycles trying at enrollment, age (linear variable), race (white, non-white), marital status (married, living as married or other) and the time from last pregnancy loss to study enrollment (≤4 months, 5-8 months, 9-12 months, >12 months). Model 3 is adjusted for cycles trying at enrollment, age (linear variable), race (white, non-white), marital status (married, living as married or other) the time from last pregnancy loss to study enrollment (≤4 months, 5-8 months, 9-12 months, >12 months), and BMI (linear variable).

Figure 2

The Risk Ratio (RR) and 95% CI for anovulation for the second tertile (open circle) and third tertile (closed circle) of hsCRP relative to the first tertile. Results are restricted to 572 women assigned to placebo. Model A is adjusted for cycles of follow-up. Model B is adjusted for cycles of follow-up, age (18-24 years, 25-34, 35-40), marital status (married, living as married or other) and the time from last pregnancy loss to study enrollment (≤4 months, 5-8 months, 9-12 months, >12 months). Model C is adjusted for cycles of follow-up, age (18-24 years, 25-34, 35-40), marital status (married, living as married or other) the time from last pregnancy loss to study enrollment (≤4 months, 5-8 months, 9-12 months, >12 months), and BMI (linear variable).

Figure 3

Simplified directed acyclic graphs to illustrate the potential causal structure of C-reactive protein, body mass index, and pregnancy. Figure 3A: Body mass index is a common cause of C-reactive protein and pregnancy, and therefore can be considered a confounder of the relationship between inflammation and fecundability. Figure 3B: Body mass index is an intermediate on the causal path from C-reactive protein to pregnancy, and therefore adjustment for adiposity would partially obscure the total effect of inflammation on fecundability.