Effects of common pharmacologic agents on reproductive outcomes among male and female pregnancy planners
McInerney, Kathryn A.
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Infertility and spontaneous abortion (SAB) affect up to one-third of couples planning a family.1–3 While common, there are few known risk factors. Medication use may play a role but the extent is unknown because, for most agents, use during reproduction has been understudied. The objective of this dissertation was to examine the associations between use of common pharmacologic agents and reproductive outcomes in three interrelated prospective cohort studies of pregnancy planners in Denmark, the United States, and Canada. In study 1, we examined fecundability, the average per-cycle probability of conception and a measure of time-to-pregnancy (TTP), in relation to past contraceptive use. Exposures of interest included oral contraceptives, IUDs (hormonal, copper), rings, implants, patches, injectables, natural methods, and barrier methods. Among 9,350 female pregnancy planners, we first examined TTP by the last method of contraception used before pregnancy attempt. We then examined the association between total lifetime duration of use of hormonal contraceptive methods and TTP. On average, injectable users had the longest delay in the return of fertility (8 cycles), followed by OC, ring, implant and patch (3 cycles), hormonal IUD (2 cycles), and copper IUD users (1 cycle). We did not find any evidence that long-term use of these methods was detrimental to fecundability. Study 2 examined the association between male use of pain medications and fecundability among 1,065 couples planning pregnancy in North America. Medications examined include ibuprofen, acetaminophen, naproxen, and aspirin. We examined fecundability in relation to any use and cumulative monthly dose of each of these medications. Our study showed little evidence of a deleterious effect of male preconception use of common pain medications on fecundability. In study 3, we examined use of pain medications between pregnancy conception and 12 gestational weeks and risk of SAB. Medications examined include ibuprofen, acetaminophen, naproxen, aspirin, and opioids. In the three cohorts of women recruited before conception, we observed 9,196 pregnancies and 1,597 SABs (17.4%). We found that low-dose use of ibuprofen, naproxen, or opioids before 12 weeks of gestation was associated with slightly increased risk of SAB. Overall, low-dose use of acetaminophen or aspirin did not appreciably increase risk of SAB.