INTRODUCTION: Approximately 6 million couples in the United States experience infertility. Because few risk factors for infertility are known, identification of modifiable determinants is an important public health goal. Cervical intraepithelial neoplasia, CIN, occurs when the surface cells of the cervical tissue begin to change, and is caused by infection with a high-risk type of human Papillomavirus (HPV). CIN may affect the cervix’s immunological function, resulting in changes in mucus production, reduced protection against infections, and alterations in sperm transport through the cervical canal. CIN can also progress to invasive cervical cancer. There are four main CIN treatment procedures that aim to remove pre-cancerous cells from the cervix; loop excisions, commonly known as electrosurgical excision procedure (LEEP) or large loop excision of the transformative zone (LLETZ); cryosurgery; conization; and laser ablation. Because the goal of these procedures is to remove abnormal cells, healthy cervical cells may inadvertently be removed as well, leading to further changes in cervical mucus production, sperm motility, and reduced protection against infection. Because of the changes to the cervical tissue and its function, CIN and its surgical treatments may affect fecundability. METHODS: We analyzed data from Pregnancy Study Online (PRESTO), a preconception cohort of 5,594 North American pregnancy planners enrolled and followed between 2013 and 2018. At baseline, participants reported whether they had abnormal Pap tests and their age at their first abnormal Pap test, as well as cervical procedures and their age at the procedure. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities models adjusted for sociodemographics, smoking, number of sexual partners, history of sexually transmitted infections/ pelvic inflammatory disease, and HPV vaccination. RESULTS: A history of abnormal Pap test, which we used as a proxy for cervical dysplasia, was positively associated with current and past smoking, gravidity, parity, irregular menses, number of sexual partners, history of chlamydia, genital warts and herpes, as well as a history of pelvic inflammatory disease. Of the women with an abnormal Pap test, the average age at first abnormal Pap test was 23.0 (std=4.5) years and the average number of abnormal Pap tests was 2.1 (std=1.7). We found little association overall between a history of abnormal Pap test and fecundability (FR=1.03, 95% CI: 0.96, 1.11). The results did not differ when the data were examined by number of abnormal Pap tests, or type of procedure. There was also little association between time since the diagnosis or procedure and pregnancy attempt and fecundability. There was however a slight decrease in fecundability within the first 2 years of diagnosis/ procedure, with FRs that tended to increase with increasing time since diagnosis/procedure. DISCUSSION: We found little association overall between a history of abnormal Pap test or cervical dysplasia, including excisional surgeries, and fecundability. These results are consistent with most other studies demonstrating no clear adverse effects of CIN and treatments. Recency of diagnosis or procedure did not appreciably affect these findings. Although we found a very slight decrease in fecundability within the first two years since diagnosis or procedure, fecundability became similar to that of undiagnosed/untreated women after 2 years, and then increased slightly. CONCLUSION: We found little association between a history of abnormal Pap and CIN treatments and fecundability. A major limitation of our study is that the data were self-reported, which may have resulted in non-differential exposure misclassification.

Background: Physical activity (PA) may influence fecundability through alterations in endocrine function. The limited studies that have evaluated PA and fecundability in non-clinical populations have utilized internet-based recruitment, contain potential issues in measurement, and have yielded inconclusive results. Methods: We evaluated the association between PA and time-to-pregnancy in the Effects of Aspirin in Gestation and Reproduction trial, which included 1228 women attempting pregnancy ages 18–40 with prior pregnancy loss. PA was measured at baseline using the short form of the International Physical Activity Questionnaire to determine hours/week of activity (vigorous, moderate, and walking) and hours/day of sedentary (sitting) behavior. Pregnancy was assessed using urine hCG assays. Discrete time Cox models were used to estimate fecundability odds ratios (FORs) adjusted for marital status and parity, accounting for left truncation and right censoring. Results: We observed a positive association between fecundability and vigorous PA of ≥ 4 hrs/week vs. none (FOR= 1.55, 95% CI: 1.17, 2.07) adjusted for marital status and parity. In stratified multivariable models, this association was most pronounced among overweight/obese women reporting vigorous PA of ≥ 4 hrs/week compared to none (FOR=2.27, 1.41, 3.65); however, there was no significant effect modification. Fecundability was not associated with categorical measures of moderate PA, walking, or sitting. Conclusion: In this study, fecundability was positively associated with vigorous PA. Further study is necessary to clarify possible mechanisms to explain the relationship through which vigorous PA might affect time-to-pregnancy; however, such improvements in fecundability may be related to a reduction in ovulatory disorders.