Smoking in infertile women with polycystic ovary syndrome: baseline validation of self-report and effects on phenotype

Abstract

Study question: Do women with polycystic ovary syndrome (PCOS) seeking fertility treatment report smoking accurately and does participation in infertility treatment alter smoking?

Summary answer: Self-report of smoking in infertile women with PCOS is accurate (based on serum cotinine levels) and smoking is unlikely to change over time with infertility treatment.

What is known already: Women with PCOS have high rates of smoking and it is associated with worse insulin resistance and metabolic dysfunction.

Study design, size, duration: Secondary study of smoking history from a large randomized controlled trial of infertility treatments in women with PCOS (N = 626) including a nested case-control study (N = 148) of serum cotinine levels within this cohort to validate self-report of smoking.

Participants/materials, setting, methods: Women with PCOS, age 18-40, seeking fertility who participated in a multi-center clinical trial testing first-line ovulation induction agents conducted at academic health centers in the USA.

Main results and the role of chance: Overall, self-report of smoking in the nested case-control study agreed well with smoking status as determined by measure of serum cotinine levels, at 90% or better for each of the groups at baseline (98% of never smokers had cotinine levels <15 ng/ml compared with 90% of past smokers and 6% of current smokers). There were minor changes in smoking status as determined by serum cotinine levels over time, with the greatest change found in the smoking groups (past or current smokers). In the larger cohort, hirsutism scores at baseline were lower in the never smokers compared with past smokers. Total testosterone levels at baseline were also lower in the never smokers compared with current smokers. At end of study follow-up insulin levels and homeostatic index of insulin resistance increased in the current smokers (P < 0.01 for both) compared with baseline and with non-smokers. The chance for ovulation was not associated with smoking status, but live birth rates were increased (non-significantly) in never or past smokers.

Limitations, reasons for caution: The limitations include the selection bias involved in our nested case-control study, the possibility of misclassifying exposure to second hand smoke as smoking and our failure to capture self-reported changes in smoking status after enrollment in the trial.

Wider implications of the findings: Because self-report of smoking is accurate, further testing of smoking status is not necessary in women with PCOS. Because smoking status is unlikely to change during infertility treatment, extra attention should be focused on smoking cessation in current or recent smokers who seek or who are receiving infertility treatment.

Study funding/competing interests: Sponsored by the Eugene Kennedy Shriver National Institute of Child Health and Human Development of the U.S. National Institutes of Health.

Clinical trial registration numbers: ClinicalTrials.gov numbers, NCT00068861 and NCT00719186.

Keywords: anovulation; cigarette smoking; hyperandrogenism; infertility; obesity.

Figure 1

Cotinine levels obtained during the first (C1) and fifth (C5) cycle on study medication (box and whiskers plot displaying the median, the upper and lower quartiles, and the extreme values (outliers)).

Figure 2

Change in smoking status based on serum cotinine levels from cycle 1 (C1) to cycle 5 (C5). Dotted horizontal line is the cutoff of 15 ng/ml between smokers and non-smokers. Red lines indicate individuals having at least one cotinine measurement inconsistent with their self-report. Gray lines indicated those whose cotinine measurements at both time points agreed with their self-report. Multiple subjects are represented at the >=100 mark in the past and current smoker groups.