Successive time to pregnancy among women experiencing pregnancy loss

Study question: Is time to pregnancy (TTP) similar across successive pregnancy attempts among women experiencing pregnancy loss?

Summary answer: TTP after a loss may be longer compared with TTP before a loss.

What is known already: Two pregnancy cohort studies have reported that TTP is similar across pregnancy attempts in fertile women. However, this has not been investigated among women experiencing pregnancy losses.

Study design, size, duration: Data for this analysis come from the Longitudinal Investigation of Fertility and the Environment Study, a population-based, preconception cohort of couples attempting pregnancy. During 2005-2009, recruitment was targeted to 16 counties in Michigan and Texas with reported exposures to persistent environmental chemicals. A total of 501 couples were recruited and followed for up to 12 months of pregnancy attempts allowing for continued participation of women with pregnancy losses until censoring.

Participants, setting, methods: We assessed TTP among 70 couples recruited upon discontinuing contraception for purposes of becoming pregnant and experiencing ≥1 prospectively observed pregnancy losses during 12 months of trying. There were 61 couples who contributed two pregnancy attempts and 9 who contributed three. Women were instructed in the use of urine-based home fertility monitors to time intercourse relative to ovulation and recorded their bleeding patterns in daily journals. TTP was defined as the number of menstrual cycles taken to achieve pregnancy. Women were also instructed in the use of home digital pregnancy tests and asked to begin pregnancy testing on the day of expected menses. Women recorded the results of their pregnancy tests in a daily journal with a single positive pregnancy test result indicating an hCG-confirmed pregnancy. Pregnancy losses were ascertained from a subsequent recorded negative pregnancy test or clinically confirmed loss. We estimated fecundability odds ratios (FORs) comparing subsequent to first TTP using discrete Cox models with robust standard errors, accounting for cycles off contraception before study entry and adjusting for maternal age, body mass index, reproductive history and time-varying cigarette, alcohol and caffeine usage while trying.

Main results and the role of chance: The mean female age was 30.3 ± 4.3 years; 21% had a prior pregnancy loss before study entry. Of the second and third attempts, 59 and 43%, respectively, were longer compared with the first attempt. FORs <1 suggest reduced fecundability or a longer TTP when comparing the second with the first attempt (0.42, 95% confidence interval (CI): 0.28, 0.65), and similarly for the third relative to the first attempt (0.64, 95% CI: 0.18, 2.36). TTP in the second attempt was a median of 1 cycle longer (interquartile range: 0, 3 cycles) compared with TTP in the first attempt.

Limitations, reasons for caution: As this is the first study to investigate successive TTP exclusively among women experiencing pregnancy loss, our findings await corroboration since most losses occurred early in gestation. As such, the generalizability of our findings for all pregnancy losses awaits further research. We also had limited power to detect a reduction in fecundability for the third compared with first pregnancy attempt.

Wider implications of the findings: Unlike fertile women, TTP in women experiencing early pregnancy losses may trend towards longer subsequent attempts. If the findings are corroborated, women experiencing losses may benefit from counselling regarding trying times.

Study funding/competing interests: This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358). K.J.S. was supported by an Intramural Research Training Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Intramural Population Health Research. The authors have no conflicts of interest to declare.