Pregnancy Attempt Research Articles

Air pollution and fecundability: Results from a Danish preconception cohort study.

Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. Epidemiologic studies have been restricted largely to couples undergoing fertility treatment or have retrospectively ascertained time-to-pregnancy among pregnant women. We examined the association between residential ambient air pollution and fecundability, the per-cycle probability of conception, in a large preconception cohort of Danish pregnancy planners. During 2007-2018, we used the Internet to recruit and follow women who were trying to conceive without the use of fertility treatment. Participants completed an online baseline questionnaire eliciting socio-demographic characteristics, lifestyle factors, and medical and reproductive histories and follow-up questionnaires every 8weeks to ascertain pregnancy status. We determined concentrations of ambient nitrogen oxides (NOx ), nitrogen dioxide (NO2 ), carbon monoxide (CO), ozone (O3 ), particulate matter <2.5µm (PM2.5 ) and <10µm (PM10 ), and sulphur dioxide (SO2 ) at each participant's residential address. We calculated average exposure during the year before baseline, during each menstrual cycle over follow-up and during the entire pregnancy attempt time. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders and co-pollutants. The analysis was restricted to the 10,183 participants who were trying to conceive for <12 cycles at study entry whose addresses could be geocoded. During 12months of follow-up, 73% of participants conceived. Higher concentrations of PM2.5 and PM10 were associated with small reductions in fecundability. For example, the FRs for a one interquartile range (IQR) increase in PM2.5 (IQR=3.2µg/m3 ) and PM10 (IQR=5.3µg/m3 ) during each menstrual cycle were 0.93 (95% CI: 0.87, 0.99) and 0.91 (95% CI: 0.84, 0.99), respectively. Other air pollutants were not appreciably associated with fecundability. In this preconception cohort study of Danish women, residential exposures to PM2.5 and PM10 were associated with reduced fecundability.

Striving for motherhood after uterus transplantation: a qualitative study concerning pregnancy attempts, and the first years of parenthood after transplantation.

How do women experience attempts to become pregnant, and the first years of motherhood, after uterus transplantation (UTx)? Women who try to become pregnant after UTx experience the general strains typically associated with infertility and childlessness, such as failure of embryo transfer (ET), and specific worries about graft survival but when they become mothers they essentially feel like other mothers, with the associated rewards and stresses. UTx has proven to be a successful treatment for absolute uterine factor infertility (AUFI). Although UTx seems to have a positive effect on self-image there is a lack of knowledge about how women who have received uterine grafts experience pregnancy attempts, pregnancy itself and the first years of motherhood. This prospective cohort study included the seven participants in the first UTx trial who had experienced surgically successful grafts. Pregnancy was attempted using ET 12 months after transplantation. Structured interviews were performed once a year for 5 years after transplantation. Six of the seven participants (mean age 29.3 years at UTx) had AUFI owing to the congenital absence of the uterus, while the seventh woman had undergone a hysterectomy. Post-transplantation, yearly interviews (2013-2018) were performed, comprising a total of 34 interviews. Interview data were analysed thematically. All seven participants achieved pregnancy during the study period and six became mothers. Experiencing the previously unimaginable was classed as an overarching theme with the following underlying themes: The yoke of childlessness; Going through the impossible and Motherhood as surreal and normal. The results showed that the women who try to achieve motherhood after UTx generally describe their situation as manageable and present strains comparable to other women undergoing infertility treatments. The fact that all participants came from one centre is a limitation. There are real psychological strains in motherhood after UTx, such as the concern the women expressed relating to health of the child and the effects of immunosuppressants. These findings are in line with those of other women who became pregnant after transplantation of organs other than the uterus. The results show that extra psychological support and attention should be given to those with repeated pregnancy failures or unsuccessful outcomes. In the cases where women became mothers, attention needs to be given to the possible worries connected to the UTx, but in other respects, they should be treated like any mother-to-be. Funding was received from the Jane and Dan Olsson Foundation for Science; Knut and Alice Wallenberg Foundation. A.L.F. grant from the Swedish state under an agreement between the government and the county councils; Swedish Research Council. The authors have no competing interests. NCT01844362.

Endometrial Factor in Unexplained Infertility and Recurrent Implantation Failure.

Unexplained infertility (UI) and recurrent implantation failure (RIF) are diagnoses based on failed pregnancy attempts within current infertility treatment models. Both diagnoses are made when fertility is unexplained based on current diagnostic methods and has no clear cause; UI is diagnosed when testing is inconclusive, and RIF is diagnosed after three failed in vitro fertilization cycles. In both cases, interventions are often introduced without an understanding of the cause of the infertility, frequently leading to frustration for patients and caregivers. Here, we review evidence to support an influence of endometrial factor in patients given these poorly defined diagnoses and possible treatments targeting the endometrium to improve outcomes in these patients.

Associations between Residential Green Space and Fertility in a North American Preconception Cohort Study

BACKGROUND AND AIM: A growing body of epidemiological literature shows that exposure to green space (natural vegetation) may have positive effects on human health, including reproductive outcomes. Residential green space may improve health via reduced exposure to traffic-related air pollution, reduced depressive symptoms or stress levels, and increased physical activity. We hypothesize that increased exposure to green space may promote fecundability, a sensitive marker of fertility. METHODS: In a North American preconception cohort study (Pregnancy Study Online, PRESTO), we prospectively examined associations between residential green space (measured by satellite normalized difference vegetation index [NDVI] at a 30m resolution) and fecundability (per-cycle probability of conception) (n=8,790). From 2013 through 2019, women aged 21-45 years who were trying to conceive without fertility treatment completed online questionnaires every 8 weeks for up to 12 months. We followed participants until reported pregnancy or a censoring event (loss to follow-up, end of pregnancy attempt, initiation of fertility treatment, or 12 menstrual cycles), whichever event was first. Using geocoded residential addresses, we calculated annual maximum NDVI for 50m, 100m, 250m, and 500m buffers around each residence to quantify green space. We used proportional probabilities regression models to estimate fecundability ratios (FR), adjusting for sociodemographic and lifestyle characteristics. RESULTS:Using life table methods, 67.7% of participants conceived who were in the highest NDVI group for the 250m buffer (NDVI: 0.8-1.0; n=874), compared to only 62.0% of participants with the lowest NDVI group (NDVI: 0.0-0.2; n=162). When comparing participants with the highest to lowest NDVI values in the 250m buffer, adjusted models show an FR of 1.43 (95% CI: 1.04, 1.95). Restricted cubic splines show a nonlinear trend. Results are similar for other distance buffers. CONCLUSIONS:We present the first epidemiologic evidence that residential greenness is positively associated with fecundability. Future work will examine the role of key pathways that may mediate this relationship. KEYWORDS: Green space, Reproductive Outcomes, Female, Built environment, Environmental disparities

Reproductive, Obstetrical and Long-Term Health Outcome after Uterus Transplantation: Results of the First Clinical Trial

Background: Uterus transplantation (UTx) is the first available treatment for absolute uterine factor infertility, caused by absence of the uterus or presence of a non-functional uterus. The proof-of-concept of this new fertility treatment was by the world´s first live birth after UTx in 2014. The present study represents the first report on outcome of a complete study cohort undergoing UTx and provides unique data on efficiency and long-term safety of this novel infertility treatment. Methods: We conducted a prospective clinical trial of nine live-donor UTx procedures at Sahlgrenska University Hospital, Gothenburg, Sweden. Seven grafts achieved long-term survival, thereby allowing pregnancy attempts. Hysterectomies were performed within seven years of UTx. The results of in vitro fertilisation, pregnancies, births, growth trajectory of children born, and the long-term medical and psychological health of patients are reported. Findings: Six women delivered nine healthy babies, with three women giving birth twice (cumulative birth rates of 86% in surgically successful transplants and 67% in performed transplants). The clinical pregnancy rate per embryo transfer (ET) was 32.6%. The livebirth rate per ET was 19.6%. Fetal growth and blood flow were normal in all pregnancies. Times of delivery (median in full pregnancy weeks+days (ranges)) by caesarean section and weight deviations were 35+3 (31+6 - 38+0) and -1% (-13% - +23%), respectively. Three women developed preeclampsia during pregnancy and four children acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. The long-term medical health of uterus donors and recipients was generally good. When UTx resulted in a birth, scores for anxiety, depression and relationship satisfaction were reassuring for both donors and recipients. Interpretations: The results of this first clinical UTx trial show that this is an effective infertility treatment for women with absolute uterine factor infertility, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for live donors and graft recipients. Trial Registration: The prospective, observational study “Uterus transplantation from live donors” was registered as a clinical trial (NCT 01844362) Funding: Jan and Dan Olsson Foundation for Science, Knut and Alice Wallenberg Foundation, Swedish Research Council. Declaration of Interest: None of the authors have any conflict of interest. Ethical Approval: This study was approved by the Regional Ethics Committee of Gothenburg, Sweden (#88-12).

Loss of p57 Expression in Conceptions Other Than Complete Hydatidiform Mole: A Case Series With Emphasis on the Etiology, Genetics, and Clinical Significance.

Combined p57 immunohistochemistry and DNA genotyping refines classification of products of conception specimens into specific types of hydatidiform moles and various nonmolar entities that can simulate them. p57 expression is highly correlated with genotyping and in practice can reliably be used to identify virtually all complete hydatidiform moles (CHM), but aberrant retained or lost p57 expression in rare CHMs and partial hydatidiform moles (PHM), as well as loss in some nonmolar abortuses, has been reported. Among a series of 2329 products of conceptions, we identified 10 cases for which loss of p57 expression was inconsistent with genotyping results (none purely androgenetic). They displayed a spectrum of generally mild abnormal villous morphology but lacked better developed features of CHMs/early CHMs, although some did suggest subtle forms of the latter. For 5 cases, genotyping (4 cases) and/or ancillary testing (1 case) determined a mechanism for the aberrant p57 results. These included 3 PHMs-2 diandric triploid and 1 triandric tetraploid-and 1 nonmolar specimen with loss of p57 expression attributable to partial or complete loss of the maternal copy of chromosome 11 and 1 nonmolar specimen with Beckwith-Wiedemann syndrome. For 5 cases, including 2 diandric triploid PHMs and 3 biparental nonmolar specimens, genotyping did not identify a mechanism, likely due to other genetic alterations which are below the resolution of or not targeted by genotyping. While overdiagnosis of a PHM as a CHM may cause less harm since appropriate follow-up with serum β-human chorionic gonadotropin levels would take place for both diagnoses, this could cause longer than necessary follow-up due to the expectation of a much greater risk of persistent gestational trophoblastic disease for CHM compared with PHM, which would be unfounded for the correct diagnosis of PHM. Overdiagnosis of a nonmolar abortus with loss of p57 expression as a CHM would lead to unnecessary follow-up and restriction on pregnancy attempts for patients with infertility. Genotyping is valuable for addressing discordance between p57 expression and morphology but cannot elucidate certain mechanisms of lost p57 expression. Future studies are warranted to determine whether chromosomal losses or gains, particularly involving imprinted genes such as p57, might play a role in modifying the risk of persistent gestational trophoblastic disease for PHMs and nonmolar conceptions that are not purely androgenetic but have some abnormal paternal imprinting of the type seen in CHMs.

Length-biased semi-competing risks models for cross-sectional data: an application to current duration of pregnancy attempt data.

Cross-sectional length-biased data arise from questions on the at-risk time for an event of interest from those who are at-risk but have yet to experience the event. For example, in the National Survey on Family Growth (NSFG), women who were currently attempting to become pregnant were asked how long they had been attempting pregnancy. Cross-sectional survival analysis methods use the observed at-risk times to make inference on the distribution of the unobserved time-to-failure. However, methodological gaps in these methods remain such as how to handle semi-competing risks. For example, if the women attempting pregnancy had undergone fertility treatment during their current pregnancy attempt. In this paper, we develop statistical methods that extend cross-sectional survival analysis methods to incorporate semi-competing risks. They can be used to estimate the distribution of the length of natural pregnancy attempts (i.e., without fertility treatment) while correctly accounting for women that sought fertility treatment prior to being sampled using cross-sectional data. We demonstrate our approach based on simulated data and an analysis of data from the NSFG. The proposed method results in separate survival curves for: time-to-natural-pregnancy, time-to-fertility treatment, and time-to-pregnancy after fertility treatment.

Trends in time-to-pregnancy in the USA: 2002 to 2017.

Has there been there a temporal change in time-to-pregnancy (TTP) in the USA. Overall, TTP was stable over time, but a longer TTP for women over 30 and parous women was identified. Fertility rates in the USA have declined over the past several years. Although these trends have been attributed to changing reproductive intentions, it is unclear whether declining fecundity (the biologic ability to reproduce measured by TTP in the current report) may also play a role. Indeed, trends based on declining sperm quality and higher utilisation of infertility treatment suggest fecundity may be falling. This cross-sectional survey data from the National Survey of Family Growth was administered from 2002 to 2017. The surveys are based on nationally representative samples of reproductive-aged women in the USA. Interviews were conducted in person or through computer-assisted self-administration of sensitive questions. The study included women who self-reported time spent trying to become pregnant allowing utilisation of the current duration approach to estimate the total duration of pregnancy attempt (i.e. TTP). In all, 1202 participants were analysed over each study period. To estimate a TTP distribution overall and by parity, we used a piecewise constant proportional hazards model that accounts for digit preference. Accelerated-failure-time regression models, which were weighted to account for the sampling design, were used to estimate time ratios (TRs). Models were adjusted for age, BMI, race, education, relationship status, parity, pelvic inflammatory disease treatment and any reproductive problems. Of the participants analysed, the average age was 31.8 and BMI was 28.6, which was similar across the survey periods. Relationship status was the only demographic characteristic that changed over time. All other variables remained constant across the study periods. Overall, TRs comparing TTP between 2002 and 2017 increased slightly (TR: 1.02, 95% CI: 0.99, 1.04). When stratified by parity, parous women had a longer TTP over the later years of the study (TR: 1.04, 95% CI: 1.01, 1.06). TTP remained constant for nulliparous women. Similarly, TTP also increased over time for women over age thirty (TR: 1.02, 1.00, 1.05) but not for women under age thirty. Small changes in data collection over time may have impacted the findings. We accounted for this in sensitivity analyses using imputed data. Overall, TRs were slightly attenuated using the imputed data, but represented similar patterns to the original data. Results for parous women and women over 30 remained consistent in the sensitivity analyses. Consistent with reports of falling fertility rates and sperm counts, this study suggests parous and older couples in the USA may be taking longer to become pregnant. Although trends were suggestive of a small overall increase in TTP, particularly for parous women and women over age thirty, additional data are needed to attempt to understand these trends given the societal, economic and public health implications related to fecundity. Funding was provided by National Institutes of Health grant R03HD097287 to A.C.M. There are no competing interests. N/A.

Accuracy of self-reported birth outcomes relative to birth certificate data in an Internet-based prospective cohort study.

The accuracy of birth outcome data provided by Internet-based cohort study participants has not been well studied. We compared self-reported data on birth characteristics in Pregnancy Study Online (PRESTO), an Internet-based prospective cohort study of North American pregnancy planners, with birth certificate data. At enrolment, participants were aged 21-45years, attempting conception, and not using fertility treatment. Women completed online questionnaires during preconception, early and late pregnancy, and postpartum. We requested birth certificate data during 2014-2019 from seven health departments in states with the most participants. After restricting to singleton births, we assessed specificity, sensitivity, and agreement comparing self-reported data from postpartum questionnaires with birth certificate data for gestational age at delivery (GA) and birthweight (grams). Our primary measure of self-reported GA (weeks) was calculated as [280-(due date-birth date)]/7. We used log-binomial regression to assess predictors of agreement. We linked 85% (771/909) of women in selected states. Median age of women was 30years (range: 21-42), 84% had≥16years of education, nearly 96% were married, 12% had household incomes <$50000, 32% were parous, and 85% identified as non-Hispanic White. Median recall interval was 6months. Among those with self-reported data, 89% reported the same GA as the birth certificate and 98% reported GA within 1week of the birth certificate. Self-report of preterm birth (GA<37weeks) agreed with information from birth certificates for 100% of women; sensitivity was 100%, and specificity was 99%. Self-reported low birthweight (<2500 grams) agreed with birth certificates for 93% of women; sensitivity and specificity were 93% and ≥99%, respectively. Predictors of poorer agreement included higher parity and longer pregnancy attempt time for GA, and lower education and longer recall interval for birthweight. Self-reported data on GA and birthweight from an Internet-based cohort showed high accuracy compared with birth certificates.

Impact of fertility concerns on endocrine therapy decisions in young breast cancer survivors.

The diagnosis and treatment of breast cancer can have profound effects on a young woman's family planning and fertility, particularly among women with hormone receptor-positive breast cancer. The Young Women's Breast Cancer Study was a multicenter cohort of women aged 40 years or younger and newly diagnosed with breast cancer from 2006 to 2016. Surveys included assessments of fertility concerns, endocrine therapy (ET) preferences, and use. Characteristics were compared between women who reported that fertility concerns affected ET decisions and those who did not. Logistic regression was used to identify factors associated with having an ET decision affected by fertility concerns. Of 643 eligible women with hormone receptor-positive, stage I to III breast cancer, one-third (213 of 643) indicated that fertility concerns affected ET decisions. In a multivariable analysis, only parity at diagnosis was significantly associated with fertility concerns affecting ET decisions (odds ratio for nulliparous vs ≥2 children, 6.96; 95% confidence interval, 4.09-11.83; odds ratio for 1 vs ≥2 children, 5.30; 95% confidence interval, 3.03-9.87). Noninitiation/nonpersistence was higher among women with fertility concerns versus those without fertility concerns (40% vs 20%; P < .0001). Among women with fertility-related ET concerns, 7% (15 of 213) did not initiate ET, and 33% (70 of 213) were nonpersistent over 5 years of follow-up. Of these women, 66% (56 of 85) reported 1 or more pregnancies or pregnancy attempts; 27% (15 of 56) had resumed ET at the last available follow-up through 5 years. Concern about fertility is a contributor to adjuvant ET decisions among a substantial proportion of young breast cancer survivors. Ensuring family planning is addressed in the setting of ET recommendations should be a priority throughout the cancer care continuum.

Maternal age at birth and daughter's fecundability.

Do daughters of older mothers have lower fecundability? In this cohort study of North American pregnancy planners, there was virtually no association between maternal age ≥35 years and daughters' fecundability. Despite suggestive evidence that daughters of older mothers may have lower fertility, only three retrospective studies have examined the association between maternal age and daughter's fecundability. Prospective cohort study of 6689 pregnancy planners enrolled between March 2016 and January 2020. Pregnancy Study Online (PRESTO) is an ongoing pre-conception cohort study of pregnancy planners (age, 21-45 years) from the USA and Canada. We estimated fecundability ratios (FR) for maternal age at the participant's birth using multivariable proportional probabilities regression models. Daughters of mothers ≥30 years were less likely to have previous pregnancies (or pregnancy attempts) or risk factors for infertility, although they were more likely to report that their mother had experienced problems conceiving. The proportion of participants with prior unplanned pregnancies, a birth before age 21, ≥3 cycles of attempt at study entry or no follow-up was greater among daughters of mothers <25 years. Compared with maternal age 25-29 years, FRs (95% CI) for maternal age <20, 20-24, 30-34, and ≥35 were 0.72 (0.61, 0.84), 0.92 (0.85, 1.00), 1.08 (1.00, 1.17), and 1.00 (0.89, 1.12), respectively. Although the examined covariates did not meaningfully affect the associations, we had limited information on the participants' mother. Differences by maternal age in reproductive history, infertility risk factors and loss to follow-up suggest that selection bias may partly explain our results. Our finding that maternal age 35 years or older was not associated with daughter's fecundability is reassuring, considering the trend towards delayed childbirth. However, having been born to a young mother may be a marker of low fecundability among pregnancy planners. PRESTO was funded by NICHD Grants (R21-HD072326 and R01-HD086742) and has received in-kind donations from Swiss Precision Diagnostics, FertilityFriend.com, Kindara.com, and Sandstone Diagnostics. Dr Wise is a fibroid consultant for AbbVie, Inc. n/a.

Analysis of female demographics in the United States: life expectancy, education, employment, family building decisions, and fertility service utilization.

To discuss changes in female demographic parameters in the US and associated increase in utilization of fertility services. Fractions of women earning bachelor's, master's, and doctoral degrees increased from 1970 to 2018 (32.6 vs 64.8; 7.9 vs 27.3; 0.54 vs 5.7 per 10,000 women; P < .001; respectively). This was associated with decrease in percentage of married women (61.9% vs 50.8%) and increase in median age at first marriage (20.8 vs 27.8). In parallel, mean age of mothers at first birth increased (21.4 vs 26.8), and pregnancy rates of women aged 35-39 and 40-44 years doubled between 1980 and 2010 (0.036 vs 0.077; 0.009 vs 0.019 per 1,000 women). With later pregnancy attempts, female fertility rates decreased from 1970 to 2017 (87.9% vs 60.3%; P < .001). Women undergoing assisted reproductive technologies (ART) treatment with a DOR diagnosis increased (12% vs 31%), and ART cycles using donor eggs increased (16,161 vs 24,300), between 2005 and 2016. Participation of women in education is paralleled by increased female employment, later occurrence of marriage, increased age of childbearing, decreased fertility rates, and increased DOR diagnosis.

Conception after chemotherapy: post-chemotherapy method of conception and pregnancy outcomes in breast cancer patients.

As the paradigm shifts towards improving cancer survivorship, an important concern for reproductive-aged women diagnosed with cancer is how their disease and its treatment will affect their future fertility. We sought to characterize pregnancy attempts and outcomes in breast cancer patients following chemotherapy. We conducted a prospective cohort study of women diagnosed with breast cancer seen between 2010 and 2019. A questionnaire was administered following cancer treatment with questions regarding oncologic and reproductive history and attempts and method of conception. Of 181 participants, 46 (25.4%) attempted to conceive following chemotherapy. Thirty-five patients (76.1%) had return of ovarian function. Of those, 34 patients (mean age 32.8 years) first attempted to conceive by intercourse, and 22 (64.7%) became pregnant, resulting in 17 live births. Of the remaining 12 who did not successfully conceive through intercourse, eight went on to try other methods, resulting in five additional pregnancies and one live birth. Twelve patients (mean age 34.6 years) proceeded directly to ART; of those, eight (66.7%) became pregnant, resulting in six live births. In breast cancer patients with return of ovarian function after chemotherapy, half were able to conceive by intercourse alone. In order to maximize reproductive potential in patients who have return of ovarian function, providers should offer natural conception as a reasonable option prior to the use of cryopreserved tissue. For those who did not attempt to conceive on their own, the use of pre-treatment cryopreserved eggs or embryos had a high likelihood of success.

The Use of Time to Pregnancy for Estimating and Monitoring Human Fecundity From Demographic and Health Surveys.

Available studies on the prevalence of infertility have proved to have certain limitations, with a scarcity of population-based studies and inconsistent reporting from surveys in countries at all income levels. We wanted to test the applicability of the current duration approach to data from the important Demographic and Health Surveys (DHS) program, funded by USAID since its inception in 1985, https://dhsprogram.com/. The current duration approach assumes that there is a well-defined time of initiation of attempts to get pregnant and defines the current duration of a still ongoing pregnancy attempt as the time interval from initiation to interview. The DHS interviews do not have an explicit question about initiation. We focused on nullipari and substituted date of "establishment of relationship with current partner" for initiation. Our study used the current duration approach on 15 datasets from DHS during 2002-2016 in eight different countries from sub-Saharan Africa, Asia, and Latin America. Well-established statistical techniques for current duration data yielded results that for some countries postulated surprisingly long median times to pregnancy and surprisingly high estimates of infertility prevalence. Further study of the data structures revealed serious deviations from expected patterns, in contrast to our earlier experience from surveys in France and the United States where participants were asked explicitly about time of initiation of attempts to become pregnant. Using cohabitation as a proxy for the initiation of attempts to get pregnant is too crude. Using the current duration approach with DHS data will require more explicit questions during the DHS interviews about initiation of pregnancy attempt.

Serum ferritin level is inversely related to number of previous pregnancy losses in women with recurrent pregnancy loss

To study whether low serum ferritin (s-ferritin) levels are associated with recurrent pregnancy loss (RPL), and whether low s-ferritin predicts the risk of another pregnancy loss or the ability to conceive. Cohort study. Fertility clinic at a university hospital. Eighty-four women referred to the RPL Unit and 153 women of reproductive age with no known fertility problem. s-Ferritin levels were measured in serum samples taken before pregnancy attempt. None. s-Ferritin levels were correlated to pregnancy history, ability to conceive, and time to conception during the first 2 years after sampling. Furthermore, s-ferritin levels were correlated to outcome of the first pregnancy after referral for RPL. Women with RPL had lower s-ferritin than the comparison group, 39.9 μg/L versus 62.2 μg/L, and had a higher prevalence of low iron stores (s-ferritin <30 μg/L), 35.7% versus 13.7%. We found an inverse relationship between s-ferritin level and number of pregnancy losses before referral. We did not find s-ferritin level to be associated with ability to conceive or time to pregnancy in either group. Nor did s-ferritin level predict the risk of losing the first pregnancy after referral for RPL. The inverse relationship between s-ferritin levels and previous pregnancy losses suggests that low s-ferritin is associated with a more severe reproductive disturbance in women with RPL. Whether low s-ferritin is causally related to RPL and if such women could benefit from iron supplementation to achieve a live birth warrants further investigation.

Changes in Behavior with Increasing Pregnancy Attempt Time: A Prospective Cohort Study.

The extent to which couples change their behaviors with increasing pregnancy attempt time is not well documented. We examined change in selected behaviors over pregnancy attempt time in a North American preconception cohort study. Eligible females were ages 21-45 years and not using fertility treatment. Participants completed baseline and bimonthly follow-up questionnaires for up to 12 months or until pregnancy. Among 3,339 females attempting pregnancy for 0-1 cycles at enrollment, 250 contributed 12 months of follow-up without conceiving. Comparing behaviors at 12 months versus baseline, weighted for loss-to-follow-up, we observed small-to-moderate reductions in mean caffeine intake (-19.5 mg/day, CI = -32.7, -6.37), alcohol intake (-0.85 drinks/week, CI = -1.28, -0.43), marijuana use (-3.89 percentage points, CI = -7.33, 0.46), and vigorous exercise (-0.68 hours/week, CI = -1.05, -0.31), and a large increase in activities to improve conception chances (e.g., ovulation testing) (21.7 percentage points, CI = 14.8, 28.6). There was little change in mean cigarette smoking (-0.27 percentage points, CI = -1.58, 1.04), perceived stress scale score (-0.04 units, CI = -0.77, 0.69), or other factors (e.g., sugar-sweetened soda intake, moderate exercise, intercourse frequency, and multivitamin use), but some heterogeneity within subgroups (e.g., 31% increased and 32% decreased their perceived stress scores by ≥2 units; 14% reduced their smoking but none increased their smoking by ≥5 cigarettes/day). Although many behaviors changed with increasing pregnancy attempt time, mean changes tended to be modest for most variables. The largest differences were observed for the use of caffeine, alcohol, and marijuana, and methods to improve conception chances.

Safer conception for female sex workers living with HIV in Dar es Salaam, Tanzania: Cross-sectional analysis of needs and opportunities in integrated family planning/HIV services.

BackgroundWith the advent of effective treatment, women living with HIV can plan for pregnancy while minimizing risk of transmission to infants and seronegative partners. Family planning (FP) services tend to focus solely on addressing contraceptive need, but HIV-positive women—including female sex workers—often plan to have children someday. Various “safer conception” strategies are now available to support women living with HIV achieve fertility intentions, and integrated HIV/FP services may be a promising platform to offer these services.MethodsAt integrated community-based HIV/FP service delivery sites operated by Jhpiego’s Sauti project in Dar es Salaam, we conducted exit interviews with 300 HIV-positive female sex workers. Descriptive analyses were conducted to describe their desire for children, use of condoms and other modern contraceptive methods, self-reported viral suppression, and knowledge of and interest in safer conception strategies. We conducted bivariate and multivariate logistic regression analysis to examine correlates of fertility desire among respondents.ResultsMedian age of participants was 32. Nearly one-third wished to have a child within two years. Seventy-two percent had heard of having the HIV-positive partner taking ART to reduce sexual transmission during pregnancy attempts. Thirty-one percent felt the amount of FP content covered in the consultation was “too little.” Factors significantly associated with desire for children were having a nonpaying partner (adjusted odds ratio [AOR] 2.18, 95% confidence interval [CI]1.13–4.20) and having fewer children (AOR 0.65, 95% CI 0.48–0.87). Viral suppression was not associated with fertility desire.ConclusionsSex workers living with HIV attending integrated HIV/FP services have need for both contraception as well as safer conception counseling. This integrated service delivery modality is a promising platform for providing safer conception services. FP counseling for HIV-positive women should be broadened to broach the topic of safer pregnancy, as well as explicit counseling on strategies to minimize risk of sexual transmission to partners.

Night Shift Work and Fecundability in Late Reproductive-Aged African American Women.

Background: We estimated the association between night shift work and fecundability among African American women. Methods: Black Women's Health Study participants (n = 560) aged 30-45 years reported their history of night shift work in 2005. Time to pregnancy for all pregnancies resulting in a livebirth was reported in 2011. We estimated the fecundability ratio (FR) and 95% confidence interval (CI) using proportional probabilities regression, accounting for multiple observations of individual women using generalized estimating equations. Results: We observed 4,417 months of pregnancy attempt time resulting in 390 births. After adjustment for covariates, women who reported ever working night shifts had 20% lower fecundability compared with those who never reported night shift work (FR = 0.80, 95% CI: 0.59-1.04). The FR for women reporting night shift work with a frequency of ≥1 time per month and a duration of ≥2 years was 0.65 (95% CI: 0.47-0.94) relative to women reporting no shift work. We observed a decrease in fecundability associated with ever working night shifts (FR = 0.74, 95% CI: 0.56-0.96) among women aged ≥35 years, but not among younger women (FR = 1.33, 95% CI: 0.78-2.28). Conclusion: A history of working night shifts was associated with reduced fecundability among older reproductive-aged African American women attempting pregnancy.

Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study.

STUDY QUESTIONHow efficacious and safe are the current approaches to controlled ovarian stimulation (COS) aimed at fertility preservation (FP) in women with breast cancer (BC)?SUMMARY ANSWERIn women with BC undergoing COS aiming at egg/embryo cryopreservation, letrozole-based protocols and those randomly started were equally effective compared with conventional COS, and the overall survival was similar between the women that proceeded to FP and those who did not.WHAT IS KNOWN ALREADYCryopreservation of oocytes and embryos is an established method for FP in women with BC. Recent improvements to COS protocols include concomitant use of letrozole, random-cycle start day of stimulation and the use of GnRHa for the egg maturation trigger. To date, limited sample size of the available studies has not allowed investigation of differences in the efficacy of the different approaches to COS for FP in this patient population.STUDY DESIGN, SIZE, DURATIONA prospective multicenter study with national coverage including 610 women with BC counseled between 1 January 1995 and 30 June 2017 at six Swedish FP regional programs.PARTICIPANTS/MATERIALS, SETTING, METHODSAfter counseling, 401 women elected to undergo COS. Treatments differed in the use or not of concomitant letrozole, a conventional or random-cycle day COS initiation and the use of hCG versus GnRHa trigger for oocyte maturation. Numbers of cryopreserved oocytes and embryos were defined as primary outcome. Pregnancy attempts, reproductive outcomes and long-term survival, investigated by the linking of individuals of the cohort to the total population register of the Swedish Tax Agency (up to 25 November 2018), were evaluated.MAIN RESULTS AND THE ROLE OF CHANCEUsing letrozole or not resulted in similar numbers of oocytes and embryos cryopreserved (meanoocytes = 9.7 versus 10 and meanembryos 4.0 versus 5.3, respectively), similar to COS with random versus conventional start (meanoocytes 9.0 versus 10.6 and meanembryos 4.8 versus 4.8). In COS with letrozole, a GnRHa trigger was associated with a higher number of oocytes retrieved (P < 0.05) and embryos cryopreserved (P < 0.005), compared with conventional hCG trigger. Of 99 women who returned to fertility clinics after cancer treatment, 32 proceeded to thawing of oocytes or embryos and 10 of them had live births. The all-cause survival between the women that underwent COS and those who did not was similar and did not differ between the two groups.LIMITATIONS, REASONS FOR CAUTIONData on tumor characteristics and estrogen receptor (ER) status were not known for all women at the time of FP counseling and planning of COS, thus protocols with letrozole have been used for both estrogen-sensitive and non-estrogen-sensitive BC. For the same reason, subsequent adjustment for ERs in the BC or tumor characteristics as potential confounders were not performed as these parameters were not available and did not influence the provision of FP through COS.WIDER IMPLICATIONS OF THE FINDINGSThe results of our study support the premise that recently introduced potential improvements to COS protocols for FP in women with BC are efficacious and safe.STUDY FUNDING/COMPETING INTEREST(S) This study was supported by research grants from the Swedish Cancer Society, the Stockholm County Council, the Percy Falk Stiftelsen, Radiumhemmets Forskningsfonder, The Swedish Breast Cancer Association and Karolinska Institutet to K.A.R.W. J.B. reports grants from Amgen, AstraZeneca, Pfizer, Roche, Sanofi-Aventis and Merck, outside the submitted work, and payment from UpToDate to Asklepios Medicine HB for a chapter on BC prediction and prognostication. All the other authors have no competing interests to report.

Serum omega-3 and omega-6 fatty acid concentrations and natural fertility.

Are serum omega-3 and omega-6 essential fatty acid concentrations associated with the probability of conceiving? There is no strong association between serum concentrations of omega-3 and omega-6 fatty acids and the probability of conceiving naturally. Omega-3 and omega-6 fatty acid serum concentrations have been shown to play an important role in reproduction in animal models, while conflicting results have been reported in human studies of infertile women. It is unknown to what extent omega fatty acid serum concentrations impact natural fertility. A nested, case-control study was conducted consisting of 200 participants [fertile: conceived within 3cycles of attempt (n= 50), subfertile: conceived within 4 and 12cycles of attempt (n= 100) and infertile: did not conceive within 12cycles of attempt (n= 50)] randomly selected from the Time to Conceive cohort, a prospective time-to-pregnancy study (2008 to 2015). In the Time to Conceive study, women aged 30-44years who were trying to conceive for <3months and had no history of infertility were recruited and followed until the end of their pregnancy or ~1year of pregnancy attempt. For this study, serum collected early in the woman's pregnancy attempt was analysed for anti-Müllerian hormone (AMH) and omega-3 and omega-6 fatty acid concentrations by liquid chromatography-mass spectrometry. The primary outcome was a positive home pregnancy test. The secondary outcomes were miscarriage and serum AMH level. A discrete-time Cox proportional hazards model was used to estimate the fecundability ratio. The odds ratios for miscarriage were calculated using logistic regression. The association between serum omega fatty acid concentrations and AMH level (natural log transformed) was analysed using Pearson's Correlation. A total of 200 women provided 1321cycles for analysis.Mean omega-3, omega-6 and omega-6:omega-3 ratios did not significantly differ between the fertile, subfertile and infertile groups. There were no associations (all fecundability ratios ~1.0) between pregnancy and individual omega-3 fatty acid concentrations, including alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, or omega-6 fatty acids, including linoleic acid (LA), dihommo-gamma linolenic acid and arachidonic acid. There was no significant association between any individual omega fatty acid serum concentration and the age-adjusted odds of miscarriage. No association was found between any serum omega fatty acid concentration and AMH. This study is limited by the sample size. Omega-3 and omega-6 fatty acid concentrations were derived from serum provided at a single timepoint in the first cycle of enrollment. Serum concentrations may therefore not be representative of all critical timepoints in the menstrual cycle or throughout their attempts to conceive. Additionally, women enrolled in this study were 30years of age and older, and therefore the findings may not apply to younger women. These data would suggest that omega-3 and omega-6 serum levels are not associated with natural fertility or risk of miscarriage. However, due to the above-mentioned limitations, future investigation is still needed to determine whether omega-3 fatty acid supplementation may benefit women planning to conceive naturally. This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, by the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01) and, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). Dr. Jukic received vitamin D supplements for a research study from Theralogix, Inc. The authors have no other conflicts of interest to disclose. N/A.