Women with a 0- to 3-month compared with greater than 3-month inter-trying interval were more likely to achieve a pregnancy (68.6% compared with 51.1%) and achieve a pregnancy leading to a live birth (53.2% compared with 36.1%) (Table 2). Median (interquartile range) for time to pregnancy among women with 0–3 months compared with greater than 3 months was five cycles (three, eight) compared with six cycles (three, nine) and time to pregnancy leading to live birth, five cycles (three, eight) compared with six cycles (four, nine). After adjusting for age, race, BMI, education, and subfertility, women with a 0- to 3-month compared with greater than 3-month inter-trying interval had a shorter time to pregnancy (fecundability OR 1.58 [95% CI 1.25–2.00]) and shorter time to pregnancy leading to a live birth (fecundability OR 1.71 [95% CI 1.30–2.25]) (Table 3). There was no significant increased risk for any pregnancy complication (including pregnancy loss, preterm birth, preeclampsia, and gestational diabetes) among women with an inter-trying interval 0–3 months compared with greater than 3 months. Additional adjustment for other demographic and reproductive history potential confounders including partner's age, smoking, alcohol intake, parity, previous number of losses, recency of loss, gestational age of last loss, age of first intercourse, age of menarche, and dilation and curettage performed for last loss did not alter fecundability OR (1.52 [95% CI 1.20–1.92]) or fecundability OR leading to a live birth (1.65 [95% CI 1.26–2.16]) nor did further adjustment for low-dose aspirin (Table 4).
In regard to alternative cut points for inter-trying intervals, compared with an inter-trying interval of greater than 3–6 months, women with an inter-trying interval of 0–3 months had a shorter time to pregnancy, with a fecundability OR of 1.24 (0.90–1.72). Women with longer inter-trying intervals had longer times to pregnancy (inter-trying interval greater than 6–9 months: fecundability OR 0.90, 95% CI 0.44–1.83; inter-trying interval greater than 9–12 months: fecundability OR 0.83, 95% CI 0.38–1.81; inter-trying interval greater than 12 months: fecundability OR 0.60, 95% CI 0.38–0.95) after adjusting for age, race, BMI, education, and subfertility. Similar decreased success in achieving pregnancy leading to live birth was seen with increasing inter-trying intervals (data not shown).
In the sensitivity analysis using multiply imputed values for the misspecified inter-trying intervals, women with a 0- to 3-month compared with a greater than 3-month inter-trying interval had an attenuated but still significantly shorter time to pregnancy (fecundability OR 1.31 [95% CI 1.03–1.67]) and time to pregnancy leading to live birth (fecundability OR 1.49 [95% CI 1.13–1.99]). Similar shorter time to pregnancy was observed after applying Monte Carlo simulation techniques to randomly assign time at risk for those couples who had included time before their loss when reporting how long they had been trying to conceive (average fecundability OR for pregnancy 1.35, 95% CI 1.07–1.73) and pregnancy leading to a live birth (fecundability OR 1.56, [95% CI 1.18–2.06]).
In a preconception cohort of women with a history of one to two spontaneous pregnancy losses, women who waited 3 months or less, compared with longer, from their most recent pregnancy loss to start trying again had higher live birth rates. Notably, women with the longest inter-trying interval of greater than 12 months had reduced fecundability compared with women with an inter-trying interval of 0–3 or greater than 3–6 months. Our findings also demonstrated no increased risk for pregnancy complications, including peri-implantation losses, among women with short intervals. Our results indicate that there is no physiologic basis for delaying pregnancy attempt after a nonectopic, nonmolar, less than 20-week gestational age pregnancy loss. Recommendations to delay pregnancy attempts for at least 3–6 months among couples who are psychologically ready to begin trying4,26,27 may be unwarranted and should be revisited.
Although several professional women's health organizations concur on the recommended interval of at least 24 months after a live birth before attempting another pregnancy,27 there are no consistent guidelines on how long a woman should wait after experiencing a pregnancy loss. The “depletion hypothesis” may partially explain potential detrimental effects for a short interval between a live birth, but not a pregnancy loss, and a subsequent pregnancy.11,28 This hypothesis proposes that decreasing levels of folate in the mother from the fifth month of gestation, continuing into the postpartum period during breastfeeding, lead to poorer birth outcomes including neural tube defects, intrauterine growth restriction, and preterm birth among women with short interpregnancy intervals. Because most pregnancy losses occur before 20 weeks of gestation, like in our study in which greater than 99% occurred before 20 weeks of gestation, women conceiving after an early pregnancy loss are not at risk for depletion of vital nutrients and consequently not likely at risk for adverse outcomes. Hypothesized advantages to attempting pregnancy immediately after a pregnancy loss include enhanced growth-supporting capacities and increased uterine blood volume and flow.7
Although our study supports the hypothesis that there is no physiologic reason for delaying pregnancy attempt after a loss, whether a couple needs time to heal emotionally after a loss may be dependent on many factors. Although emotional compared with physical readiness may require individual couple assessment, previous research has found that a speedy new pregnancy and birth of a living child lessens grief among couples who are suffering from a pregnancy loss.29
Our study has many strengths and is an improvement over previous studies given that we enrolled women preconceptionally; obtained detailed demographic, lifestyle, and reproductive history information before conception; and closely followed participants through delivery with details of pregnancy outcomes carefully and objectively determined. Although these differences in demographic and reproductive history characteristics were statistically different, they are unlikely to be clinically meaningful. Nevertheless, our study is not without limitations. Although information on prior loss was obtained through medical records, our assessment of starting to try to conceive after the last loss was obtained by self-report and thus subject to recall error. However, there is no other source of these data than self-report. Additionally, there may be differences between women with equivalent inter-trying intervals in regard to time at risk of pregnancy as a result of such factors as fertility tracking or intercourse frequency. Future studies that enroll women preconceptionally immediately after a loss and follow them prospectively through pregnancy outcome are needed to corroborate our findings. Finally, although low-dose aspirin was shown to neither confound nor modify the relationship between inter-trying intervals and pregnancy outcomes, it is currently not part of routine care among women with an early pregnancy loss and thus additional studies are warranted to corroborate our findings.
In summary, we previously reported that women in the Effects of Aspirin in Gestation and Reproduction trial who achieved pregnancy within 3 compared with greater than 3 months of their last loss had no significant differences in live birth rates or adverse pregnancy outcomes.18 In the present study we demonstrate that couples who begin trying to achieve pregnancy within 3 months have just as fast, if not faster, time to pregnancy leading to a live birth, with no risk of pregnancy complications, as those who wait until after 3 months to start trying. Additionally, we found that women with long inter-trying intervals, greater than 12 months compared with 0–3 or greater than 3–6 months, had significantly lower fecundability after taking into account many confounding factors including a history of subfertility. Taken together, our findings suggest that the traditional recommendation to wait at least 3 months after a pregnancy loss before attempting to conceive may be unwarranted.
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