Preconceptional thyroid stimulating hormone level and fecundity: a community-based cohort study of time to pregnancy.

OBJECTIVE: To investigate the association between preconception thyroid stimulating hormone (TSH) level and time to pregnancy within a community-based population. DESIGN: A community-based cohort study. SETTING: Two free preconception check-up centers. PATIENT(S): Women who enrolled in the National Free Preconception Check-up Projects from January 1, 2018 to December 31, 2018 in Tianhe and Zengcheng districts of Guangzhou city. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to pregnancy. RESULT(S): A total of 1,478 women were eligible for the analysis; of these, 1,401 had a preconception TSH level within the range of 0.50 and 5.59 mIU/L (2.5th-97.5th percentiles) were taken as target study population. Among them, 968 (69.1%) couples achieved pregnancy within the first 6 months and 1,082 (77.2%) within 12 months. Dichotomized by the recommended cut-off value of 2.5 mIU/L, the percentage of women conceived in the high TSH level category (2.50-5.59 mIU/L) was comparable to that of the low category (0.50-2.49 mIU/L) (79.0% vs. 78.1%), with a crude fecundity odd ratio of 0.99 (95% confidence interval at 0.87-1.13). No statistically significant difference was observed after the adjustment in all models. Continuous TSH level was further examined, and the nonlinear association between TSH level and fecundity odds ratios was of no statistical significance. CONCLUSION(S): Preconception TSH level was not associated with fecundity in a healthy community-based population. Women attempting pregnancy with a TSH level ≥ 2.5 mIU/L can be reassured that they are unlikely to have an increased time to pregnancy.

Cultivable vaginal Lactobacillus is not associated with fecundability in Kenyan women attempting to conceive.

OBJECTIVE: To examine the association between cultivable vaginal Lactobacillus and fecundability in Kenyan women attempting nonmedically assisted conception. DESIGN: Prospective preconception cohort. SETTING: Nairobi and Mombasa, Kenya. PATIENT(S): Women trying to conceive who reported ≤3 months of pre-enrollment conception attempt time. INTERVENTION(S): Cultivable Lactobacillus (primary), Lactobacillus morphotypes on Gram stain (secondary). MAIN OUTCOME MEASURE(S): Participants reported the first day of their last menstrual period and recent sexual behavior, underwent pregnancy testing, and provided vaginal specimen samples for Lactobacillus culture and Gram stain at ≤6 monthly preconception visits. The outcome was fecundability-the per-menstrual cycle probability of pregnancy. Associations between cultivable Lactobacillus and Lactobacillus morphotypes on Gram stain at the visit before each pregnancy test and fecundability were estimated using proportional probabilities models to generate fecundability ratios (FRs). RESULT(S): A total of 458 women contributed 1,376 menstrual cycles. At enrollment, 65.3% (n = 299) of participants had cultivable Lactobacillus, 47.4% (n = 217) had cultivable hydrogen peroxide producing Lactobacillus, and 64.6% (n = 296) had Lactobacillus detected on Gram stain. In unadjusted analysis, there was no association between cultivable Lactobacillus at the prior visit and fecundability (FR, 0.92; 95% CI, 0.73-1.16); results were similar after adjustment for age, frequency of condomless sex, and study site (adjusted FR, 0.92; 95% CI, 0.72-1.18). Lactobacillus on Gram stain at the visit prior was associated with modestly higher fecundability (adjusted FR, 1.18; 95% CI, 0.92-1.51). CONCLUSION(S): Cultivable Lactobacillus was not associated with fecundability, although Lactobacillus morphotypes detected on Gram stain were somewhat associated with increased fecundability. The relationship between vaginal Lactobacillus and fecundity may be species-specific.

Time to conceive after myomectomy: should we advise a minimum time interval? A systematic review.

The optimal time interval between myomectomy and pregnancy is unclear and no specific guidelines exist. The aim of this review was to study the time interval from myomectomy to pregnancy and the occurrence of uterine rupture after myomectomy. Randomized controlled trials, cohort studies and retrospective studies were used to assess the primary objective, and case reports, cases series or letters to the editor for the secondary objective. Only articles reporting myomectomy performed via the vaginal route, laparotomy, laparoscopy or robot-assisted surgery were selected for inclusion. Among 3852 women who wanted to become pregnant after the surgery, 2889 became pregnant, accounting for 3000 pregnancies (77.9%) and 2097 live births (54.4%). Mean time between myomectomy and pregnancy was estimated at 17.6 months (SD 9.2) for 2451 pregnant women. Among 1016 women, a third were advised to delay attempting to conceive for between 3 and 6 months and another third for between 6 and 12 months. A total of 70 spontaneous uterine ruptures with a mean gestational age of 31 weeks at occurrence were identified. No linear relationship was found between gestational age at the event and time interval from myomectomy to conception (P = 0.706). There are insufficient data to advise a minimal time interval between myomectomy and conception.

Couples' prepregnancy body mass index and time to pregnancy among those attempting to conceive their first pregnancy.

OBJECTIVE: To explore the relationship between couples' prepregnancy body mass index (BMI) and time to pregnancy (TTP) among those with no prior gravidity. DESIGN: Retrospective cohort study. SETTING: Local maternal/child health care or family-planning service institutions. PATIENT(S): A total of 2,301,782 eligible couples participating in the National Free Preconception Check-up Projects from January 1, 2015 to December 31, 2017. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to pregnancy. RESULT(S): Underweight, overweight, or obese status in women and underweight status in men were associated with couples' prolonged TTP. The optimal BMI levels were 20.61-23.06 kg/m2 and 22.69-27.74 kg/m2 for women and men, respectively. Compared with couples in whom both partners had a normal BMI, the pregnancy rates were reduced by 10% (fecundability odds ratio [FOR] 0.90; 95% confidence interval [CI], 0.88-0.92) and 19% (FOR 0.81; 95% CI, 0.78-0.84) for couples in whom both partners were underweight or obese, respectively. The combination of women with a normal BMI and overweight men had the greatest fertility (FOR 1.03; 95% CI, 1.02-1.03), and the combination of obese women and underweight men had the lowest fertility (FOR 0.70; 95% CI, 0.65-0.76). CONCLUSION(S): Abnormal prepregnancy BMIs in either women or men were associated with prolonged TTP among couples with no prior gravidity. Scientific management of couples' prepregnancy BMI could improve their fertility.

Pre-pregnancy body mass index and time to pregnancy among couples pregnant within a year: A China cohort study.

BACKGROUND: Extreme pre-pregnancy body mass index (BMI) values have been associated with reduced fecundability and prolonged time to pregnancy in previous studies. However, the effect in fertile couples is unclear. OBJECTIVES: This study aimed to evaluate the association between pre-pregnancy BMI and fecundability, measured as time to pregnancy (TTP), among couples that achieved pregnancy within 1 year. METHODS: This was a retrospective cohort study of 50,927 couples wishing to conceive, enrolled in the National Free Preconception Health Examination Project (NFPHEP) in Chongqing, China, during 2012-2016. Participants' weight and height were measured by NFPHEP-trained preconception guidance physicians. TTP measured in months was used to determine subfecundity (TTP >6 months). The strength of association between BMI and TTP/subfecundity was measured with fecundability odds ratios (FOR)/odds ratios (OR) and their corresponding 95% confidence intervals (CI), calculated with Cox and logistic regression analysis. We used restricted cubic spline regression (RCS) to test the observed FOR trends. RESULTS: Compared to women with normal BMI, women with pre-pregnancy overweight/obesity had longer TTP (FOR = 0.96, 95% CI: 0.94-0.99) and increased risk of subfecundity (OR = 1.08, 95% CI: 1.00-1.17). There was no association between TTP and male BMI. RCS trends varied when data were stratified by male pre-pregnancy BMI, with the greatest change detected in pre-pregnancy underweight men. CONCLUSIONS: Pre-pregnancy overweight/obesity was associated with longer TTP and subfecundity among women who became pregnant within 1 year; this effect was likely mediated by their partners' pre-pregnancy BMI. These findings indicate that BMI could affect fecundability, independently of affecting the risk of sterility. Advice on weight management and maintaining healthy weight should be included in couples' preconception guidance.

Thinness and fecundability: Time to pregnancy after adolescent marriage in rural Bangladesh.

Undernutrition may affect fecundability, but few studies have quantified this relationship. In rural Bangladesh, where newlywed couples face strong pressures to become pregnant, we assessed fecundability, estimated by time to pregnancy (TTP), and its association with preconceptional thinness among nulligravid, newlywed female adolescents. During 2001-2002, 5,516 newlywed women aged 12-19 years participated in a home-based, 5-weekly surveillance system for 5-6 years to enrol pregnant women into an antenatal vitamin A or ß-carotene supplementation trial. Thinness was defined as a left mid-upper arm circumference (MUAC) ≤21.5 versus >21.5 cm. At each visit, staff obtained a monthly history of menstruation. Report of amenorrhea prompted a human chorionic gonadotropin urine test to confirm pregnancy. We derived hazard ratios (with 95% confidence intervals [CI]) for pregnancy and Kaplan-Meier curves for TTP. Ages of women at marriage and pregnancy detection (mean ± standard deviation) were 15.3 ± 1.9 and 17.0 ± 1.9 years, respectively. A total of 82.7% of thinner and 87.3% of better nourished women became pregnant. The unadjusted and multivariable relative hazard of ever becoming pregnant was 0.84 (95% CI [0.78, 0.89]) and 0.86 (95% CI [0.81, 0.92]), respectively, and TTP was 12 weeks longer (median [95% CI]: 63 [58-68] vs. 51 [49-54]) in women whose MUAC was ≤21.5 versus >21.5 cm. In rural Bangladesh, thin adolescent newlywed girls have a lower probability of becoming pregnant and experience a longer time to pregnancy.

Comparison of woman-picked, expert-picked, and computer-picked Peak Day of cervical mucus with blinded urine luteinising hormone surge for concurrent identification of ovulation.

BACKGROUND: Previous research has demonstrated that women instructed in fertility awareness methods can identify the Peak Day of cervical mucus discharge for each menstrual cycle, and the Peak Day has high agreement with other indicators of the day of ovulation. However, previous studies enrolled experienced users of fertility awareness methods or were not fully blinded. OBJECTIVE: To assess the agreement between cervical mucus Peak Day identified by fertile women without prior experience on assessing cervical mucus discharge with the estimated day of ovulation (1 day after urine luteinising hormone surge). METHODS: This study is a secondary analysis of data from a randomised trial of the Creighton Model FertilityCareTM System (CrM), conducted 2003-2006, for women trying to conceive. Women who had no prior experience tracking cervical mucus recorded vulvar observations daily using a standardised assessment of mucus characteristics for up to seven menstrual cycles. Four approaches were used to identify the Peak Day. The referent day was defined as one day after the first identified day of luteinising hormone (LH) surge in the urine, assessed blindly. The percentage of agreement between the Peak Day and the referent day of ovulation was calculated. RESULTS: Fifty-seven women with 187 complete cycles were included. A Peak Day was identified in 117 (63%) cycles by women, 185 (99%) cycles by experts, and 187 (100%) by computer algorithm. The woman-picked Peak Day was the same as the referent day in 25% of 117 cycles, within ±1 day in 58% of cycles, ±2 days in 84%, ±3 days in 87%, and ±4 days in 92%. The ±1 day and ± 4 days' agreement was 50% and 90% for the expert-picked and 47% and 87% for the computer-picked Peak Day, respectively. CONCLUSIONS: Women's daily tracking of cervical mucus is a low-cost alternative for identifying the estimated day of ovulation.

Uterine fibroids increase time to pregnancy: a cohort study.

Objectives: The primary purpose of the study was to investigate a possible association between uterine fibroids and time to pregnancy (TTP), and, secondly, to explore the effect of myomectomy on TTP.Methods: This historical cohort study used data from the Danish National Birth Cohort and the Danish National Patient Registry. The study population consisted of 86,323 women with 92,696 pregnancies. The main outcome was TTP; groups were compared using a binary outcome: TTP >12 months or TTP ≤12 months.Results: Women who had a fibroid diagnosis code before attempting to conceive (n = 92) had an increased risk of TTP >12 months compared with women without a fibroid diagnosis code (n = 87,358) (adjusted odds ratio [OR] 1.67; 95% confidence interval [CI] 1.05, 6.68). Women who had a fibroid diagnosis code after pregnancy (n = 963) also had an increased risk of TTP >12 months compared with women without a fibroid diagnosis code (adjusted OR 1.24; 95% CI 1.04, 1.47).Conclusion: We found an association between having a uterine fibroid diagnosis code and TTP >12 months. We were not able to make a valid assessment of the effect of myomectomy on TTP.

Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study.

OBJECTIVE: To quantify the frequency of use of selected fertility awareness indicators and to assess their influence on fecundability. DESIGN: Web-based prospective cohort study. SETTING: Not applicable. PATIENT(S): Female pregnancy planners, aged 21-45 years, attempting conception for ≤6 cycles at study entry. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We ascertained time to pregnancy, in menstrual cycles, with bimonthly questionnaires. We estimated adjusted fecundability ratios (FRs) and confidence intervals (CIs) using proportional probabilities models, controlling for age, income, education, smoking, intercourse frequency, and other lifestyle and reproductive factors. RESULT(S): A total of 5,688 women were analyzed, with a mean age of 29.9 years and mean time trying of 2.1 cycles at baseline; 30% had ever been pregnant. At baseline, 75% were using one or more fertility indicators (counting days or charting menstrual cycles [71%], measuring basal body temperature [BBT, 21%], monitoring cervical fluid [39%], using urine LH tests [32%], or feeling for changes in position of the cervix [12%]). Women using any fertility indicator at baseline had higher subsequent fecundability (adjusted FR 1.25, 95% CI 1.16-1.35) than those not using any fertility indicators. For each individual indicator, adjusted FRs ranged from 1.28-1.36, where 1.00 would indicate no relation with fecundability. The adjusted FR for women using a combination of charting days, cervical fluid, and urine LH was 1.48 (95% CI 1.31-1.67) relative to women using no fertility indicators. CONCLUSION(S): In a North American preconception cohort study, use of fertility indicators indicating the fertile window was common, and was associated with greater fecundability.

Association between diminished ovarian reserve and luteal phase deficiency.

OBJECTIVE: To determine the association between biomarkers of ovarian reserve and luteal phase deficiency (LPD). DESIGN: Secondary analysis of a prospective time-to-conceive cohort study. SETTING: Not applicable. PATIENT(S): Women attempting conception, aged 30-44 years, without known infertility. INTERVENTION(S): Measurement of early follicular phase serum levels of antimüllerian hormone, FSH, inhibin B, and E2. MAIN OUTCOME MEASURE(S): The primary outcome was LPD, defined by luteal bleeding (LB) (≥1 day of LB) or a short luteal phase length (≤11 days). RESULT(S): Overall, 755 women provided information on 2,171 menstrual cycles and serum for measurement of at least one biomarker of ovarian reserve. There were 2,096 cycles from 754 women in the LB cohort, of which 40% experienced LB. After adjusting for age, race, previous miscarriages, and previous pregnancies, diminished ovarian reserve (DOR) was not significantly associated with LB. Low early follicular phase FSH levels increased the odds of LB (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.25-2.71), as did high early follicular phase E2 levels (OR 1.59; 95% CI 1.26-2.01). A total of 608 cycles from 286 women were included in the analysis of luteal phase length, of which 13% had a short luteal phase. After adjusting for age, there was no significant association between DOR and a short luteal phase. The risk of a short luteal phase decreased with increasing inhibin B (OR 0.61; 95% CI 0.45-0.81). CONCLUSION(S): Although DOR is not associated with LPD, hormone dysfunction in the early follicular phase may contribute to LPD in women of older reproductive age.

Predicting the chances of having a baby with or without treatment at different time points in couples with unexplained subfertility.

STUDY QUESTION: Can we develop a prediction model that can estimate the chances of conception leading to live birth with and without treatment at different points in time in couples with unexplained subfertility? SUMMARY ANSWER: Yes, a dynamic model was developed that predicted the probability of conceiving under expectant management and following active treatments (in vitro fertilisation (IVF), intrauterine insemination with ovarian stimulation (IUI + SO), clomiphene) at different points in time since diagnosis. WHAT IS KNOWN ALREADY: Couples with no identified cause for their subfertility continue to have a realistic chance of conceiving naturally, which makes it difficult for clinicians to decide when to intervene. Previous fertility prediction models have attempted to address this by separately estimating either the chances of natural conception or the chances of conception following certain treatments. These models only make predictions at a single point in time and are therefore inadequate for informing continued decision-making at subsequent consultations. STUDY DESIGN, SIZE, DURATION: A population-based study of 1316 couples with unexplained subfertility attending a regional clinic between 1998 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: A dynamic prediction model was developed that estimates the chances of conception within 6 months from the point when a diagnosis of unexplained subfertility was made. These predictions were recomputed each month to provide a dynamic assessment of the individualised chances of conception while taking account of treatment status in each month. Conception must have led to live birth and treatments included clomiphene, IUI + SO, and IVF. Predictions for natural conception were externally validated using a prospective cohort from The Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 554 (42%) couples started fertility treatment within 2 years of their first fertility consultation. The natural conception leading to live birth rate was 0.24 natural conceptions per couple per year. Active treatment had a higher chance of conception compared to those who remained under expectant management. This association ranged from weak with clomiphene to strong with IVF [clomiphene, hazard ratio (HR) = 1.42 (95% confidence interval, 1.05 to 1.91); IUI + SO, HR = 2.90 (2.06 to 4.08); IVF, HR = 5.09 (4.04 to 6.40)]. Female age and duration of subfertility were significant predictors, without clear interaction with the relative effect of treatment. LIMITATIONS, REASONS FOR CAUTION: We were unable to adjust for other potentially important predictors, e.g. measures of ovarian reserve, which were not available in the linked Grampian dataset that may have made predictions more specific. This study was conducted using single centre data meaning that it may not be generalizable to other centres. However, the model performed as well as previous models in reproductive medicine when externally validated using the Dutch cohort. WIDER IMPLICATIONS OF THE FINDINGS: For the first time, it is possible to estimate the chances of conception following expectant management and different fertility treatments over time in couples with unexplained subfertility. This information will help inform couples and their clinicians of their likely chances of success, which may help manage expectations, not only at diagnostic workup completion but also throughout their fertility journey. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck, and Guerbet. None of the other authors declare any conflicts of interest.

Metabolic syndrome and time to pregnancy: a retrospective study of nulliparous women.

OBJECTIVE: To determine: (1) the association between metabolic syndrome (MetS), time to pregnancy (TTP), and infertility; (2) associations between individual and an increasing number of MetS components, TTP, and infertility; and (3) whether these relationships differ by body mass index (BMI < 30 kg/m2 versus BMI ≥ 30 kg/m2 ). DESIGN: Retrospective cohort study. SETTING: Multiple centres (in Australia, Ireland, New Zealand, and the UK). POPULATION: Five thousand five hundred and nineteen low-risk nulliparous pregnant women. METHODS: Data on retrospectively reported TTP (number of months to conceive) and a blood sample to assess metabolic health were collected between 14 and 16 weeks of gestation. MetS was defined according to the International Diabetes Federation criteria. Accelerated failure time models with log-normal distribution were conducted to estimate time ratios (TRs) and 95% CIs. Differences in MetS on infertility (TTP > 12 months) were compared using a generalised linear model (Poisson distribution) with robust variance estimates (relative risks, RRs; 95% CIs). All analyses (entire cohort and split by BMI) were controlled for a range of maternal and paternal confounding factors. MAIN OUTCOME MEASURES: Time to pregnancy and infertility. RESULTS: Of the 5519 women included, 12.4% (n = 684) had MetS. Compared with women without MetS, women with MetS had a longer TTP (adjusted TR 1.30; 95% CI 1.15-1.46), which was similar in women who were obese and in women who were not obese. Marginal estimates for median TTP in women with MetS versus without MetS was 3.1 months (3.0-3.3 months) versus 4.1 months (3.6-4.5 months), respectively. Women with MetS were at a 62% greater risk for infertility and were at a greater risk for infertility whether they were obese (adjusted RR 1.62; 95% CI 1.15-2.29) or not (adjusted RR 1.73; 95% CI 1.33-2.23). Reduced high-density lipoprotein cholesterol (HDL-C) and raised triglycerides (TGs) were the main individual components associated with risk for infertility. CONCLUSION: Metabolic syndrome is associated with longer TTP and infertility, independent of obesity. Additional studies, before pregnancy, are required to support our findings and to determine the applicability of which combinations of metabolic abnormalities pose the greatest risk to delayed fertility, or whether individual components are amenable to modification. TWEETABLE ABSTRACT: Metabolic syndrome is associated with longer time to pregnancy and infertility, independent of obesity.

Reducing time to pregnancy and facilitating the birth of healthy children through functional analysis of embryo physiology†.

An ever-increasing number of couples rely on assisted reproductive technologies (ART) in order to conceive a child. Although advances in embryo culture have led to increases in the success rates of clinical ART, it often takes more than one treatment cycle to conceive a child. Ensuring patients conceive as soon as possible with a healthy embryo is a priority for reproductive medicine. Currently, selection of embryos for transfer relies predominantly on the morphological assessment of the preimplantation embryo; however, morphology is not an absolute link to embryo physiology, nor the health of the resulting child. Non-invasive quantitation of individual embryo physiology, a key regulator of both embryo viability and health, could provide valuable information to assist in the selection of the most viable embryo for transfer, hence reducing the time to pregnancy. Further, according to the Barker Hypothesis, the environment to which a fetus is exposed to during gestation affects subsequent offspring health. If the environment of the preimplantation period is capable of affecting metabolism, which in turn will affect gene expression through the metaboloepigenetic link, then assessment of embryo metabolism should represent an indirect measure of future offspring health. Previously, the term viable embryo has been used in association with the potential of an embryo to establish a pregnancy. Here, we propose the term healthy embryo to reflect the capacity of that embryo to lead to a healthy child and adult.

Parental subfertility and hypospadias and cryptorchidism in boys: results from two Danish birth cohorts.

OBJECTIVE: To study if parental subfertility is related to the occurrence of the male genital anomalies, cryptorchidism and hypospadias. DESIGN: Population-based cohort study. SETTING: Not applicable. PATIENT(S): A total of 80,220 singleton boys and their mothers from the Danish National Birth Cohort and the Aarhus Birth Cohort. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The two congenital anomalies; cryptorchidism and hypospadias, registered within the Danish National Patient Register up until December 31, 2012. RESULT(S): By means of Cox regression analyses, we found no associations between waiting time-to-pregnancy (TTP) and cryptorchidism or hypospadias among those who conceived spontaneously. The highest hazard ratio for cryptorchidism was seen among boys of couples with a TTP>12 months who conceived after fertility treatment (adjusted hazard ratio [aHR] 1.19, 95% confidence interval 0.92-1.55). For hypospadias, we found that boys of couples with a TTP>12 months who conceived after fertility treatment, had a 71% higher risk of hypospadias (aHR 1.71, [95% confidence interval 1.24-3.36]) as compared with boys of couples with a TTP<5 months. CONCLUSION(S): The findings from this study showed that boys of couples with TTP>12 months who conceived after fertility treatment, had a higher occurrence of hypospadias than boys conceived spontaneously of couples with a short TTP. Among those who conceived spontaneously, TTP was not associated with hypospadias or cryptorchidism. These findings indicate that fertility treatment or severity of subfertility is related to hypospadias.

Preconception Plasma Phospholipid Fatty Acids and Fecundability.

Context: Fatty acids (FAs) are important for reproductive processes, including steroidogenesis, though associations with fecundability, as measured by time to pregnancy (TTP), are unclear. Objective: To investigate the relationship between preconception plasma phospholipid FA (PPFA) levels and time to human chorionic gonadotropin-pregnancy among women with prior pregnancy loss. Design, Setting, and Participants: Prospective cohort of 1228 women attempting pregnancy (aged 18 to 40 years, with one or two prior pregnancy losses) followed for up to six cycles at four US university medical centers during 2006 to 2012. PPFA levels were measured at baseline. Main Outcome Measures: Associations with fecundability overall and by body mass index (BMI) group after adjusting for confounders were estimated using fecundability odds ratios (FORs) and 95% CIs. False discovery rate (FDR) was used to account for multiple comparisons. Results: Monounsaturated fatty acids (MUFAs) were associated with increased fecundability or shorter TTP [FOR, 1.08 (95% CI, 1.01 to 1.16) per unit increase in percentage of total FAs], whereas polyunsaturated fatty acids (PUFAs) were associated with decreased fecundability or longer TTP [FOR, 0.95 (95% CI, 0.91 to 1.00) per 1% change], though associations only remained significant after FDR adjustment among women with BMI <25 kg/m2. Saturated FA and trans FA were not associated with fecundability. Omega-3 FAs and omega-6 linoleic acid were not associated with fecundability. Conclusion: We observed associations between preconception MUFA and PUFA levels and fecundability among women with normal BMI, highlighting the importance of FA composition among normal-weight women with prior pregnancy loss.

First Trimester Urinary Bisphenol and Phthalate Concentrations and Time to Pregnancy: A Population-Based Cohort Analysis.

Background: Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogs, and phthalate metabolites with time to pregnancy (TTP). Methods: Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates [median gestational age, 12.9 weeks (interquartile range, 12.1, 14.4)]. We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested. Results: In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally [respective fecundability ratios per each natural log increase were 0.90 (95% CI, 0.81 to 1.00) and 0.88 (95% CI, 0.79 to 0.99)]. Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high-molecular-weight phthalate metabolites. Conclusions: We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.

Association between use of marijuana and time to pregnancy in men and women: findings from the National Survey of Family Growth.

OBJECTIVE: To determine if regular use of marijuana has an impact on time to pregnancy. DESIGN: Retrospective review of cross-sectional survey data from male and female respondents aged 15-44 years who participated in the 2002, 2006-2010, and 2011-2015 National Survey of Family Growth. SETTING: Not applicable. PARTICIPANT(S): The National Survey of Family Growth is a nationally representative population-based sample derived from stratified multistage area probability sampling of 121 geographic areas in the U.S. Our analytic sample was participants who were actively trying to conceive. INTERVENTION(S): Exposure status was based on the respondents' answers regarding their marijuana use in the preceding 12 months. MAIN OUTCOME MEASURE(S): The main outcome was estimated time to pregnancy, which was hypothesized before analysis to be delayed by regular marijuana use. RESULT(S): A total of 758 male and 1,076 female participants responded that they were actively trying to conceive. Overall, 16.5% of men reported using any marijuana while attempting to conceive, versus 11.5% of women. The time ratio to pregnancy for never smokers versus daily users of marijuana in men was 1.08 (95% confidence interval 0.79-1.47) and in women 0.92 (0.43-1.95), demonstrating no statistically significant impact of marijuana use on time to pregnancy. CONCLUSION(S): Our study suggests that neither marijuana use nor frequency of marijuana use was associated with time to pregnancy for men and women.

Pregnancy after bariatric surgery: the effect of time-to-conception on pregnancy outcomes.

BACKGROUND: At our medical center, female patients who have undergone bariatric surgery are advised to defer pregnancy for 2 years after surgery to avoid the following complications and their potential consequences for the fetus: inadequate gestational weight gain, inadequate postsurgical weight loss, hyperemesis gravidarum, nutritional deficiencies, gestational diabetes, and gestational hypertension. OBJECTIVES: To examine the effect of time from surgery to conception on pregnancy course and outcomes in bariatric patients. SETTING: University. METHODS: We identified 73 pregnancies in 54 women who became pregnant after undergoing bariatric surgery. Surgery to conception interval was compared between pregnancies that were carried to delivery and 8 pregnancies that resulted in spontaneous abortion. Of 41 pregnancies that were carried to delivery, 26 occurred in women who had undergone surgery less than 2 years before conception, and 15 occurred in women who had undergone surgery greater than 2 years before conception. Gestational age at delivery, number of neonatal intensive care unit admissions, gestational weight gain, hyperemesis gravidarum, nutritional deficiencies, gestational diabetes, and gestational hypertension during pregnancy were compared for the 2 groups. RESULTS: Eight patients who had spontaneous abortion had a significantly shorter time from surgery to conception. There were no significant differences between our 2 groups in rates of preterm deliveries, neonatal intensive care unit admission, gestational weight gain, hyperemesis, nutritional deficiencies, gestational diabetes, or gestational hypertension. CONCLUSIONS: Becoming pregnant within the first 2 years after bariatric surgery appears to have no effect on pregnancy course and outcomes. Women who miscarried had a significantly lower mean surgery to conception interval. These results fail to show an increased rate of pregnancy complications during the first 2 years after bariatric surgery.

The influence of age at menarche, menstrual cycle length and bleeding duration on time to pregnancy: a large prospective cohort study among rural Chinese women.

OBJECTIVE: To investigate the relations among age at menarche (AAM), menstrual cycle length, menstrual bleeding duration and time to pregnancy in a large cohort of rural Chinese women. DESIGN: A prospective cohort study. SETTING: Local family-planning service agencies and maternal/child care service centres. POPULATION: A total of 391 320 rural women of reproductive age who participated in the National Free Pre-pregnancy Checkups and were planning to conceive were enrolled. METHODS: Menstrual characteristics were collected via face-to-face interviews. The Cox proportional hazards model were used to estimate the fecundability ratios (FRs) and 95% confidence intervals for each measure relative to its reference category. MAIN OUTCOME MEASURES: Time to pregnancy. RESULTS: Women with an AAM later than 14 years of age were less likely become pregnant compared with women with AAM at 13-14 years of age (FR 0.93, 95% CI 0.92-0.94). Those with menstrual cycle lengths >29 days were less likely to come pregnant (FR 0.91, 95% CI 0.90-0.92) compared with the reference cycle length of 27-29 days. Women with bleeding durations of <4 (FR 0.88; 95% CI 0.86-0.91) or >5 days (FR 0.91; 95% CI 0.90-0.91) showed lower FRs compared with those reporting 4-5 days of bleeding. The associations were independent of maternal age, ethnicity, education level, occupation, tobacco use, alcohol use and body mass index. CONCLUSION: A later onset of menarche, longer menstrual cycle length, both shorter (<4 days) and longer (>5 days) bleeding duration were associated with a lower FR and longer time to pregnancy in rural Chinese women. TWEETABLE ABSTRACT: A later menarche, longer cycle, shorter or longer bleeding duration were associated with lower fecundity.