Study protocol for the implementation of Centering Patients with Fibroids, a novel group education and empowerment program for patients with symptomatic uterine fibroids.

BACKGROUND: Black women and people with uteri have utilized collectivistic and relational practices to improve health outcomes in the face of medical racism and discrimination for decades. However, there remains a need for interventions to improve outcomes of uterine fibroids, a condition that disproportionately impacts Black people with uteri. Leveraging personalized approaches alongside evidence that demonstrates the positive impact of social and peer support on health outcomes, we adapted from CenteringPregnancy, an evidence based group prenatal care intervention, for the education and empowerment of patients with uterine fibroids. METHODS: The present report provides  an overview of the study design and planned implementation of CPWF in cohorts at Boston Medical Center and Emory University / Grady Memorial Hospital. After receiving training from the Centering Healthcare Institute (CHI), we adapted the 10-session CenteringPregnancy curriculum to an 8-session hybrid group intervention called Centering Patients with Fibroids (CPWF). The study began in 2022 with planned recruitment of six cohorts of 10-12 participants at each institution. We will conduct a mixed methods evaluation of the program using validated survey tools and qualitative methods, including focus groups and 1:1 interviews. DISCUSSION: To date, we have successfully recruited 4 cohorts at Boston Medical Center and are actively implementing BMC Cohort 5 and the first cohort at Emory University / Grady Memorial Hospital. Evaluation of the program is forthcoming.

Fibroids are non-cancerous smooth muscle tumors that disproportionate impact black women and gender expansive people. Our team adapted CenteringPregnancy, a group based model of prenatal care, to an education and empowerment program for peple with fibroids called Centering Patients with Fibroids (CPWF). This paper describes the development and implemation of the program at two academic hospitals serving diverse patients in Boston, Massachusetts and Atlanta, Georgia. To evaluate the successes and challenges of the program, we ask participants to complete surveys to learn more about their experience with having fibroids and also invite them to group feedback sessions or focus groups. We also interview other healthcare providers, team members, and hospital leadership on their knowledge and thoughts about the program. We hope to use the feedback to improve the program and make it available to more people across the country.

OSR1 disruption contributes to uterine factor infertility via impaired Müllerian duct development and endometrial receptivity.

Three sisters, born from consanguineous parents, manifested a unique Müllerian anomaly characterized by uterine hypoplasia with thin estrogen-unresponsive endometrium and primary amenorrhea, but with spontaneous tubal pregnancies. Through whole-exome sequencing followed by comprehensive genetic analysis, a missense variant was identified in the OSR1 gene. We therefore investigated OSR1/OSR1 expression in postpubertal human uteri, and the prenatal and postnatal expression pattern of Osr1/Osr1 in murine developing Müllerian ducts (MDs) and endometrium, respectively. We then investigated whether Osr1 deletion would affect MD development, using WT and genetically engineered mice. Human uterine OSR1/OSR1 expression was found primarily in the endometrium. Mouse Osr1 was expressed prenatally in MDs and Wolffian ducts (WDs), from rostral to caudal segments, in E13.5 embryos. MDs and WDs were absent on the left side and MDs were rostrally truncated on the right side of E13.5 Osr1-/- embryos. Postnatally, Osr1 was expressed in mouse uteri throughout their lifespan, peaking at postnatal days 14 and 28. Osr1 protein was present primarily in uterine luminal and glandular epithelial cells and in the epithelial cells of mouse oviducts. Through this translational approach, we demonstrated that OSR1 in humans and mice is important for MD development and endometrial receptivity and may be implicated in uterine factor infertility.

Preconception contraceptive use and miscarriage: prospective cohort study.

Objectives: To evaluate the association between preconception contraceptive use and miscarriage. Design: Prospective cohort study. Setting: Residents of the United States of America or Canada, recruited from 2013 until the end of 2022. Participants: 13 460 female identified participants aged 21-45 years who were planning a pregnancy were included, of whom 8899 conceived. Participants reported data for contraceptive history, early pregnancy, miscarriage, and potential confounders during preconception and pregnancy. Main outcome measure: Miscarriage, defined as pregnancy loss before 20 weeks of gestation. Results: Preconception use of combined and progestin-only oral contraceptives, hormonal intrauterine devices, copper intrauterine devices, rings, implants, or natural methods was not associated with miscarriage compared with use of barrier methods. Participants who most recently used patch (incidence rate ratios 1.34 (95% confidence interval 0.81 to 2.21)) or injectable contraceptives (1.44 (0.99 to 2.12)) had higher rates of miscarriage compared with recent users of barrier methods, although results were imprecise due to the small numbers of participants who used patch and injectable contraceptives. Conclusions: Use of most contraceptives before conception was not appreciably associated with miscarriage rate. Individuals who used patch and injectable contraceptives had higher rates of miscarriage relative to users of barrier methods, although these results were imprecise and residual confounding was possible.

Optimizing preconception care and interventions for improved population health.

There is growing literature indicating that optimal preconception health is associated with improved reproductive, perinatal, and pediatric outcomes. Given that preconception care is recommended for all individuals planning a pregnancy, medical providers and public health practitioners have a unique opportunity to optimize care and improve health outcomes for reproductive-aged individuals. Knowledge of the determinants of preconception health is important for all types of health professionals, including policy makers. Although some evidence-based recommendations have already been implemented, additional research is needed to identify factors associated with favorable health outcomes and to ensure that effective interventions are made in a timely fashion. Given the largely clinical readership of this journal, this piece is primarily focused on clinical care. However, we acknowledge that optimizing preconception health for the entire population at risk of pregnancy requires broadening our strategies to include population-health interventions that consider the larger social systems, structures, and policies that shape individual health outcomes.

Periconceptional antibiotic use and spontaneous abortion: A prospective cohort study.

BACKGROUND: Many reproductive-aged North Americans use antibiotics in the weeks preceding conception or during early pregnancy. Antibiotic use may influence risk of spontaneous abortion (SAB) by disrupting the reproductive tract microbiome or treating harmful infections. However, this association has not been extensively studied. OBJECTIVE: To determine the extent to which periconceptional antibiotic use is associated with the risk of SAB. METHODS: We analysed data from an internet-based preconception cohort study of pregnancy planners. Eligible participants self-identified as female, were aged 21-45 years, resided in the USA or Canada, and conceived during 12 months of follow-up (n = 7890). Participants completed an enrolment questionnaire during June 2013-September 2021 and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. Pregnant participants completed questionnaires in early (~8-9 weeks) and late (~32 weeks) gestation. We assessed antibiotic use, including type (penicillins, nitrofurantoin, cephalosporins and macrolides) and indication for use, during the previous 4 weeks on preconception questionnaires. Participants reported pregnancies and SAB on follow-up and pregnancy questionnaires. We used Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between periconceptional antibiotic use and SAB, controlling for potential demographic, medical, and lifestyle confounders. RESULTS: Nineteen percent (n = 1537) of pregnancies ended in SAB. Participants reported periconceptional antibiotic use in 8% of pregnancies ending in SAB and 7% not ending in SAB. Periconceptional antibiotic use was not appreciably associated with SAB (adjusted HR 1.06, 95% CI 0.88, 1.28). We observed no strong associations between antibiotic type, indication for use, or recency of exposure and SAB risk. CONCLUSIONS: Periconceptional antibiotic use was not appreciably associated with SAB in this study. This association is likely complicated by antibiotic type and dosage, timing of conception, and the individual's overall health.

Impact of race versus ethnicity on infertility diagnosis between Black American, Haitian, African, and White American women seeking infertility care: a retrospective review.

Objective: To determine whether infertility diagnoses differ between Black ethnic subgroups. Design: Retrospective review. Setting: an urban safety-net hospital. Patients: Women seeking infertility care between 2005 and 2015. Interventions: Charts of women with infertility and polycystic ovary syndrome (International Classification of Diseases, Ninth Revision diagnoses) were reviewed to confirm diagnoses. Data were stratified by race and subsequently by ethnicity to evaluate the differences in infertility diagnoses between Black American, Black Haitian, and Black African women. White American women were used as the comparison group. Main Outcome Measures: Infertility diagnoses between Black ethnic subgroups and White women. Results: A total of 358 women met the inclusion criteria, including 99 Black American, 110 Black Haitian, 61 Black African, and 88 White American women. Anovulation/polycystic ovary syndrome was the most common diagnosis in each ethnic group, accounting for 40% of infertility among White American, 57% among Black American, 25% among Black Haitian, and 21% among Black African women. There were no significant differences in the individual infertility diagnoses between Black and White women. Between ethnic subgroups, multivariate analysis showed significantly higher odds of infertility because of anovulation/polycystic ovary syndrome in Black American women compared with Black African women (odds ratio [OR], 4.9; 95% confidence interval [CI], 1.4-17.0). Compared with Black African women, higher odds of tubal factor infertility were observed in Black American (OR, 4.7; 95% CI, 1.16-18.7) and Black Haitian women (OR, 4.0; 95% CI, 1.1-14.0). Conclusions: Infertility diagnoses were not homogeneous across Black ethnic groups. Studies examining infertility should specify the ethnic subgroups within a race because this may affect results.

Boston Birth Cohort profile: rationale and study design.

In1998, the Boston Birth Cohort (BBC) was initiated at Boston Medical Center (BMC) in response to persistently high rates of preterm birth (PTB, defined as birth before 37 weeks of gestation) in the US population and the longstanding profound PTB disparity among Black, Indigenous, and people of color (BIPOC). The BBC encompasses two linked study protocols: The PTB Study serves as the baseline recruitment in the BBC. It aims to address fundamental questions about the causes and consequences of PTB. The study oversamples preterm babies using a case/control study design, in which cases are defined as mothers who deliver a preterm and/or low birthweight baby (<2500 grams regardless of gestational age). Controls are enrolled at a 2:1 control/case ratio and matched by maternal age (±5 years), self-reported race and ethnicity, and date of delivery (± 7 days for case delivery). From inception, it was designed as a comprehensive gene-environmental study of PTB. As a natural extension, the Children's Health Study, under a separate but linked Institutional Review Board protocol, is a longitudinal follow-up study of the participants who were recruited at birth in the PTB Study and who continue pediatric care at BMC. This linked model allows for investigation of early life origins of pediatric and chronic disease in a prospective cohort design. The BBC is one of the largest and longest National Institutes of Health-funded prospective birth cohort studies in the United States, consisting of 8733 mother-child dyads enrolled in the PTB Study at birth, and of those, 3592 children have been enrolled in the Children's Health Study, with a median follow-up of 14.5 years. The BBC mirrors the urban, underresourced, and underrepresented BIPOC population served by BMC. A high proportion of BBC children were born prematurely and had chronic health conditions (e.g., asthma, obesity, and elevated blood pressure) in childhood. The BBC's long-term goal has been to build a large, comprehensive database (epidemiological, clinical, and multiomics) and biospecimen repository to elucidate early life origins of pediatric and chronic diseases and identify modifiable upstream factors (e.g., psychosocial, environmental, and nutritional) to improve health across the life course for BIPOC mothers and children.

Uterine fibroids and incidence of depression, anxiety and self-directed violence: a cohort study.

BACKGROUND: Depression and anxiety are prevalent among women with uterine fibroids (UF). The rate of mental health diagnoses in women with UF has not been studied. METHODS: Women aged 18-50 years with diagnosed UF were identified in the Optum Clinformatics commercial insurance claims database (OptumInsight, Eden Prairie, Minnesota) from 1 May 2000 to 31 March 2020 (n=313 754) and were matched 1:2 on age and calendar time to women without (n=627 539). Cox proportional hazards models estimated HRs and 95% CIs between UF and diagnosed depression, anxiety and self-directed violence, adjusting for demographics and comorbidities. Among women with diagnosed UF, the association between hysterectomy and mental health outcomes was estimated. RESULTS: After adjusting for confounders, women with diagnosed UF had a higher rate of depression (HR: 1.12; 95% CI 1.10 to 1.13), anxiety (HR: 1.12; 95% CI 1.10 to 1.13) and self-directed violence (HR: 1.46; 95% CI 1.29 to 1.64) than women without. Among women with pain symptoms and heavy menstrual bleeding, the HR comparing women with diagnosed UF to women without was 1.21 (95% CI 1.18 to 1.25) for depression, 1.18 (95% CI 1.15 to 1.21) for anxiety and 1.68 (95% CI 1.35 to 2.09) for self-directed violence. Among women with diagnosed UF, the HR comparing women who underwent a hysterectomy to women who did not was 1.22 (95% CI 1.17 to 1.27) for depression, 1.13 (95% CI 1.09 to 1.17) for anxiety and 1.86 (95% CI 1.39 to 2.49) for self-directed violence. CONCLUSIONS: Rates of depression, anxiety and self-directed violence were higher among women with diagnosed UF, particularly among those who experienced pain symptoms or who underwent hysterectomy.

Chlamydia trachomatis Infection, when Treated during Pregnancy, Is Not Associated with Preterm Birth in an Urban Safety-Net Hospital.

Preterm birth is a major public health problem, occurring in more than half a million births per year in the United States. A number of maternal conditions have been recognized as risk factors for preterm birth, but for the majority of cases, the etiology is not completely understood. Chlamydia trachomatis is one of the most prevalent sexually transmitted infections in the world. However, its role in adverse pregnancy outcome in women is still debated. In order to determine if genitourinary tract infection with C. trachomatis during pregnancy was associated with preterm birth, we conducted a case-control study on women who delivered at Boston Medical Center, an urban "safety-net" hospital that serves a socioeconomically disadvantaged and racially diverse population. Women with known risk factors for preterm birth or immune suppression were excluded. Variables collected on enrolled subjects included demographics; diagnosis of C. trachomatis during or prior to pregnancy; tobacco, alcohol, and illicit substance use; gestational age; and birthweight and gender of the newborn. We also collected urine for chlamydia testing at the time of delivery and placental biopsies for nucleic acid amplification and histological studies. A total of 305 subjects were enrolled: 100 who delivered preterm and 205 who delivered full term. Among those subjects, we identified 19 cases of pregnancy-associated C. trachomatis infection: 6/100 preterm and 13/205 full term, a difference which was not statistically significant. Only two cases of untreated chlamydia infection were identified postpartum, and both occurred in women who delivered at term. We conclude that genitourinary tract infection with C. trachomatis during pregnancy, when appropriately treated, is not associated with preterm birth.

Vaginal cuff dehiscence following transvaginal oocyte retrieval: a case report.

BACKGROUND: Vaginal cuff dehiscence (VCD) is a rare but potentially serious complication following hysterectomy with an estimated incidence of 0.14-1.4%. There is a wide range of risk factors thought to contribute to VCD, but due to its rare occurrence, much still remains to be learned about the true impact of risk factors leading to dehiscence. We present here the second known report of VCD to occur in a patient undergoing transvaginal oocyte retrieval during her fertility treatment. This case highlights what may become a more common clinical scenario as more premenopausal women are diagnosed with reproductive tract cancers and access assisted reproductive therapies to preserve fertility. CASE PRESENTATION: Our patient is a 35-year-old G1 P0 A1 who had undergone ovary-sparing total laparoscopic hysterectomy (TLH) following diagnosis of endometrial adenocarcinoma. She underwent two in-vitro fertilization (IVF) cycles after TLH to bank frozen blastocysts, the first vaginal oocyte retrieval (VOR) taking place 12 weeks following hysterectomy. She experienced VCD during her second VOR that occurred 17 weeks after TLH, the second case of VCD to be reported in the literature during fertility preservation treatment following hysterectomy. The patient underwent an emergent and uncomplicated repair of the defect vaginally the same day. CONCLUSIONS: Currently there are no guidelines in place for women who have undergone hysterectomy with regard to when they can begin fertility treatment in the post-operative period. Based on now two case reports, it is worth considering extension of the typical 6-week timeline of avoidance of vaginal procedures to allow for full cuff healing. Infertility providers should also be mindful of limiting transvaginal ultrasounds where possible to reduce force along the cuff.

Biomaterials and Contraception: Promises and Pitfalls.

The present state of reproductive and sexual health around the world reveals disparities in contraceptive use and effectiveness. Unintended pregnancy and sexually transmitted infection transmission rates remain high even with current prevention methods. The 20th century saw a contraceptive revolution with biomedical innovation driving the success of new contraceptive technologies with central design concepts and materials. Current modalities can be broadly categorized according to their mode of function: reversible methods such as physical/chemical barriers or hormonal delivery devices via systemic (transdermal and subcutaneous) or localized (intrauterine and intravaginal) administration, and nonreversible sterilization procedures such as tubal ligation and vasectomy. Contraceptive biomaterials are at present dominated by well-characterized elastomers such as polydimethylsiloxane and ethylene vinyl acetate due to their favorable material properties and versatility. Contraceptives alter the normal function of cellular components in the reproductive systems to impair fertility. The purpose of this review is to highlight the bioengineering design of existing methods, explore novel adaptations, and address notable shortcomings in current contraceptive technologies.

Impact of circadian rhythms on female reproduction and infertility treatment success.

PURPOSE OF REVIEW: In recent years, new studies have investigated the role and influence of sleep on female fertility and early pregnancy outcomes, providing a growing body of knowledge demonstrating how regulation by sleep of hormones are important to reproduction, and how disruptions in sleep, circadian rhythms, and genes regulating circadian rhythmicity can negatively impact fertility and early pregnancy outcomes. This review aims to summarize the most recent research on the relationship among circadian rhythms, fertility, and early pregnancy outcomes in women, and to explore possible fertility interventions. RECENT FINDINGS: Recent studies have found altered levels of FSH, LH, and prolactin with sleep disturbance or circadian dysrhythmia. Disruption of circadian rhythms in the form of shift work, jet lag, and daylight savings time changes have been associated with poorer fertility and early pregnancy outcomes. Alterations in the expression of circadian rhythm-regulating circadian locomotor output cycles kaput (CLOCK) genes have been associated with decreased fertility and increased rates of miscarriage. SUMMARY: Overall, undisrupted sleep and circadian rhythmicity appear to optimize fertility and early pregnancy outcomes and may play an important role in the success of fertility treatment.

Congenital Zika syndrome arising from sexual transmission of Zika virus, a case report.

BACKGROUND: Sexual transmission of Zika virus is well documented and pregnant women are advised to abstain or use barrier protection if a sexual partner has risk for Zika infection. However, to date there has not been a documented case of the congenital Zika syndrome resulting from sexual transmission. CASE PRESENTATION: A 32 year-old woman who had not traveled to any area with local Zika transmission in years became pregnant via frozen embryo transfer. Her husband traveled to Haiti several times prior to embryo transfer and during the pregnancy. Neither partner was ever symptomatic. In her second trimester when recommendations were published by the Centers for Disease Control and Prevention (CDC) regarding prevention of sexual transmission during pregnancy she was counseled to abstain or use barrier protection with her partner. At delivery, the infant head circumference measured less than the first percentile. Placental samples were sent to the CDC and all were positive for Zika RNA by RT-PCR. Evaluation for other causes of microcephaly was negative. Consistent with the most up to date diagnostic parameters for congenital Zika, including viral infection of the placenta, the baby was diagnosed with congenital Zika syndrome. CONCLUSIONS: Transmission via sexual contact during assisted reproductive therapies (ART) and pregnancy can result in Zika fetopathy. This case supports recommendations to counsel women undergoing ART and pregnant women to use barrier protection with partners with Zika exposure regardless of their symptoms.

Current clinical applications of antimullerian hormone.

PURPOSE OF REVIEW: Determine if literature supports the use of anti-Müllerian hormone (AMH) as a useful biomarker of reproductive potential when cumulative live birth rates (CLBRs) per retrieval are used as the outcome variable. RECENT FINDINGS: Advances in technology used in in-vitro fertilization (IVF) permit the use of single embryo transfer to achieve expected pregnancy success rates. Many IVF cycles result in the creation of more than a single embryo suitable for transfer per oocyte retrieval. Cryopreservation permits subsequent use of other embryos with no loss in total reproductive potential from single retrievals. Therefore, an emerging concept in IVF is the CLBR per retrieval as an indicator of the patient's reproductive potential. Using the total reproductive potential from a single retrieval may help patients decide on IVF. As such, any predictor of success that relies upon the live birth rate for a single transfer, as opposed to CLBR per retrieval, is inadequate to estimate the true reproductive potential for patient. AMH has been proposed as a biomarker for reproductive potential, but most studies have correlated an AMH value to a single embryo transfer. SUMMARY: A more appropriate way to use AMH levels may be to correlate the AMH with CLBR per retrieval. AMH may thus prove to be a useful biomarker when counseling patients about what to expect from their treatment.

Cost-effectiveness of preexposure prophylaxis for HIV prevention for conception in the United States.

OBJECTIVE: The aim of this study was to investigate the value of coformulated Tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) for preexposure prophylaxis (PrEP) for conception in the U.S. and to identify scenarios in which 'Undetectable = Untransmittable' (U = U) may not be adequate, and rather, PrEP or assisted reproduction would improve outcomes. DESIGN: We developed a Markov cohort simulation model to estimate the incremental benefits and cost-effectiveness of PrEP compared with alternative safer conception strategies, including combination antiretroviral therapy (cART) alone for the HIV-infected partner and assisted reproductive technologies. We modelled various scenarios in which HIV RNA suppression in the male partner was less than perfect. SETTING: U.S. healthcare sector perspective. PARTICIPANTS: Serodiscordant couples in the U.S. was composed of an HIV-infected male and HIV-uninfected female seeking conception. INTERVENTION: Economic analysis. MAIN OUTCOME MEASURE(S): Cumulative risks of HIV transmission to women and babies, maternal life expectancy, discounted quality-adjusted life years (QALY), discounted lifetime medical costs and incremental cost-effectiveness ratios. RESULTS: cART with condomless intercourse limited to ovulation was the preferred HIV prevention strategy among women seeking to conceive with an HIV-infected partner who is HIV-suppressed. PrEP was not cost-effective for women who had partners who were virologically suppressed. When the probability of male partner HIV suppression was low and we assumed generic pricing of PrEP, PrEP was cost-effective, and sometimes even cost-saving compared with cART alone. CONCLUSION: From a U.S. healthcare sector perspective, when the male partner was not reliably suppressed, PrEP became economically attractive, and in some cases, cost-saving.

Physician-scientists in obstetrics and gynecology: predictors of success in obtaining independent research funding.

BACKGROUND: Obstetrics and gynecology departments receive the smallest amount of National Institutes of Health research funding and have significantly lower application success rates compared to pediatric, internal medicine, and surgery departments. The development of mentored early career development training grants (K awards) has been one strategy implemented by the National Institutes of Health to help aspiring physician-scientists establish independent research careers. OBJECTIVE: The purpose of this study is to describe the cohort of obstetrics and gynecology physician-scientists who were K08, K12, and K23 recipients from 1988 through 2015 and to identify predictors of success in obtaining independent federal funding, as defined by acquisition of an R01, R21, R34, U01, U54, P01, or P50 award. We hypothesized that sex, subspecialty, type of K award, and dual MD/PhD would impact success rates. STUDY DESIGN: K08, K12, and K23 recipients from 1988 through 2015 were identified from the National Institutes of Health Research Portfolio Online Reporting Tools, the office of the National Institutes of Health Freedom of Information Act, and the website of the Reproductive Scientist Development Program. Data were stratified by sex, educational degree, subspecialty, and type of K award. Data were analyzed using the Pearson χ2 and Fisher exact tests. The Kaplan-Meier estimator was used to determine rates of conversion to independent funding over time. RESULTS: A total of 388 K recipients were identified. Women accounted for 66% of K awards while men accounted for 34%. Among K recipients, 82% were MDs, while 18% were MD/PhDs. K12 awards accounted for 82% of all K awards, while K08 and K23 awards accounted for 10% and 8%, respectively. Subspecialists in maternal-fetal medicine and reproductive endocrinology and infertility received the highest proportion of K awards, followed by generalists and gynecologic oncologists. Altogether, the 3 subspecialty groups accounted for 68% of all K awards. R01 awards made up the bulk of independent funding. Among recipients who received their first K award between 1988 and 2009, 63 of 288 (22%) were successful at obtaining an R01. Rates of R21 (n = 22), U01 (n = 15), U54 (n = 12), P01 (n = 5), R34 (n = 1), and P50 (n = 1) acquisition ranged from 0.35-7.6%. In all, 118 K scholars (41%) were successful at achieving independent funding of any type compared to 1219 of 7535 (16.2%) obstetrics and gynecology non-K scholars. K08 recipients received the largest proportion of R01 awards compared to K12 and K23 recipients (32% vs 20%; P = .12), while 21% of K12 recipients and 17% of K23 recipients achieved an R01. There were no differences in the rates of independent funding success among K12 programs. K23 recipients were more likely to obtain an R21 (22% vs 6%, P = .008) compared to K12 and K08 recipients. The mean time to R01 acquisition was 6.8 years, while the mean time to independent funding of any type was 6.4 years. There were no significant differences in independent funding success rates by sex, educational degree, or subspecialty, although generalists received the highest proportion of R01 awards (29%). CONCLUSION: Mentored early career development K programs enable aspiring obstetrics and gynecology physician-scientists to achieve higher rates of National Institutes of Health-based independent research funding compared to non-K recipients.

Impact of daylight savings time on spontaneous pregnancy loss in in vitro fertilization patients.

Transition into daylight savings time (DST) has studied negative impacts on health, but little is known regarding impact on fertility. This retrospective cohort study evaluates DST impact on pregnancy and pregnancy loss rates in 1,654 autologous in vitro fertilization cycles (2009 to 2012). Study groups were identified based on the relationship of DST to embryo transfer. Pregnancy rates were similar in Spring and Fall (41.4%, 42.2%). Pregnancy loss rates were also comparable between Spring and Fall (15.5%, 17.1%), but rates of loss were significantly higher in Spring when DST occurred after embryo transfer (24.3%). Loss was marked in patients with a history of prior spontaneous pregnancy loss (60.5%).

Differential expression of toll-like receptors in the human placenta across early gestation.

Toll-like receptors (TLRs) are an essential component of the innate immune system. While a number of studies have described TLR expression in the female reproductive tract, few have examined the temporal expression of TLRs within the human placenta. We hypothesized that the pattern of TLR expression in the placenta changes throughout the first and second trimester, coincident with physiological changes in placental function and the demands of innate immunity. We collected first and second trimester placental tissue and conducted quantitative PCR analysis for TLRs 1-10, followed by immunohistochemistry to define the cell specific expression pattern of a subset of these receptors. Except for the very earliest time points, RNA expression for TLRs 1-10 was stable out to 20 weeks gestation. However, the pattern of protein expression evolved over time. Early first trimester placenta demonstrated a strong, uniform pattern predominantly in the inner villous cytotrophoblast layer. As the placenta matured through the second trimester, both the villous cytotrophoblasts and the pattern of TLR expression within them became disorganized and patchy, with putative Hofbauer cells now identifiable in the tissue also staining positive. We conclude from this data that placental TLR expression changes over the course of gestation, with a tight barrier of TLRs forming a wall of defense along the cytotrophoblast layer in the early first trimester that breaks down as pregnancy progresses. These data are relevant to understanding placental immunity against pathogen exposure throughout pregnancy and may aid in our understanding of the vulnerable period for fetal exposure to pathogens.

Brief Report: Cesarean Delivery and Subsequent Fecundability.

BACKGROUND: Studies have shown that cesarean delivery is associated with fewer subsequent births relative to vaginal delivery, but it is unclear whether confounding by pregnancy intention or indication for surgery explained these results. We evaluated the association between cesarean delivery and subsequent fecundability among 910 primiparous women after singleton live birth. METHODS: In a cohort of Danish women planning pregnancy (2007-2012), obstetrical history was obtained via registry linkage; time-to-pregnancy and covariate data were collected via questionnaire. Fecundability ratios (FRs) and 95% confidence intervals (CIs) were adjusted for potential confounders. RESULTS: Relative to spontaneous vaginal delivery, emergency cesarean delivery with cephalic presentation showed little association with fecundability (FR = 1.0, 95% CI = 0.83, 1.3), but cesarean delivery with breech presentation (FR = 0.72, 95% CI = 0.53, 0.97) and planned cesarean delivery with cephalic presentation (FR = 0.51, 95% CI = 0.25, 1.0) were associated with reduced fecundability. CONCLUSIONS: The cesarean-fecundability association varied by previous fetal presentation and emergency status.

History of uterine leiomyoma and risk of endometrial cancer in black women.

BACKGROUND: Previous studies have found an association between uterine leiomyomata (UL) and uterine malignancies. This relation has not been studied in black women, who are disproportionately affected by UL. METHODS: We investigated prospectively the association between self-reported physician-diagnosed UL and endometrial cancer in the Black Women's Health Study. During 1995-2013, 47,267 participants with intact uteri completed biennial health questionnaires. Reports of endometrial cancer were confirmed by pathology data from medical records and cancer registries. Cox regression was used to derive incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: There were 300 incident endometrial cancer cases during 689,546 person-years of follow-up. In multivariable models, UL history was associated with a 42% greater incidence of endometrial cancer compared with no such history (95% CI 1.12-1.80). IRRs for cancer diagnosed 0-2, 3-9, and ≥10 years after UL diagnosis were 3.20 (95% CI 2.06-4.98), 0.95 (95% CI 0.60-1.52), and 1.35 (95% CI 1.03-1.77), respectively. Stronger overall associations between UL history and endometrial cancer were observed for later stages at cancer diagnosis (IRR = 2.25, 95% CI 1.09-4.63) and type II/III cancers (IRR = 3.13, 95% CI 1.64-5.99). CONCLUSIONS: In this large cohort of black women, a history of UL was positively associated with endometrial cancer, particularly type II/III tumors. The strongest association was observed for cancer diagnosed within 2 years of UL diagnosis, a finding that might be explained by greater surveillance of women with UL or misdiagnosis of cancer as UL. However, an association was also observed for cancer reported ≥10 years after UL diagnosis.