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BackgroundClinical stigmata of polycystic ovary syndrome include hirsutism, obesity, menstrual disturbances, and infertility. These symptoms impair health-related quality of life. Depression is also common. The relationship among depression, symptom self-perception, and quality of life in polycystic ovary syndrome is poorly understood.ObjectiveWe sought to investigate the relationship between health-related quality of life and depression in women with polycystic ovary syndrome.Study designWe conducted a secondary analysis of a multicenter, randomized clinical trial (Pregnancy in Polycystic Ovary Syndrome II, NCT00719186) comparing clomiphene citrate vs letrozole in the treatment of infertility. Subjects included 732 women ages 18-40 years with polycystic ovary syndrome by modified Rotterdam criteria. The validated Polycystic Ovary Syndrome Health-Related Quality of Life survey was self-administered, assessing the following domains: emotions, body hair, body weight, menstrual problems, and infertility; scores range from 1-7, with lower numbers indicating poorer quality of life. Depression was evaluated via the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire. Quality-of-life scores were compared between depressed and nondepressed women. Multivariate linear regression models analyzed the association between depression and quality-of-life scores, controlling for age, body mass index, hirsutism score, and duration of infertility.ResultsIn all, 64 women (8.4%) met criteria for depression. Depressed women reported reduced quality of life in all domains compared to nondepressed women: mood (3.1 vs 4.6, P < .001), body hair (3.5 vs 4.2, P = .002), weight (2.0 vs 3.5, P < .001), menstrual problems (3.3 vs 4.1, P < .001), and infertility (1.9 vs 3.0, P < .001). Global quality-of-life score was reduced in depressed women (2.8 vs 3.9, P < .001). Impairments in quality of life in depressed women persisted in all domains after controlling for objective parameters including age, body mass index, hirsutism score, and infertility duration.ConclusionDepression is associated with reduced quality of life related to polycystic ovary syndrome symptoms. Disturbances in health-related quality of life in depressed women are not explained by objective measures including body mass index, hirsutism scores, and duration of infertility. Depression may color the experience of polycystic ovary syndrome symptoms and should be considered when there is significant discordance between subjective and objective measures in women with polycystic ovary syndrome.

In 1995, Morris first described cesarean scar defect (CSD) as an "isthmocele" by macroscopy following hysterectomy in women with a prior cesarean delivery. CSD is associated with gynecological symptoms such as abnormal uterine bleeding (AUB), secondary infertility, pelvic pain, and obstetrical complications such as cesarean scar pregnancy, placenta accreta, and uterine rupture. Surgical treatment techniques include hysteroscopic resection, transabdominal repair (laparotomy, laparoscopic, and robotic), and vaginal repair. If the residual myometrial thickness is <3 mm and the patient is symptomatic, consideration is made for defect repair laparoscopically rather than hysteroscopic resection. The advantages of laparoscopic repair include anatomic restoration of myometrial thickness, correction of uterine retroflexion, exploration of other causes of infertility and pelvic pain, and pathological diagnosis of scar tissue with endometriosis. CSD often cannot be visualized from the abdominal cavity; therefore, it is difficult to identify the extent of the defect laparoscopically. Herein, we introduce laparoscopic CSD repair through a surgical video with narration (Video 1). This technique uses a uterine manipulator to distend and help delineate the defect, and a laparoscopic support suture within the defect as a "handle" to place the scar tissue on tension to ensure complete resection of the fibrotic tissue. Temporary uterine artery occlusion can be included to reduce bleeding in the surgical field to support visualization for complete fibrotic tissue removal and to achieve good apposition with a double-layer suture to promote proper anatomic wound healing. Symptom relief was achieved, and the patient became pregnant one year postoperatively. This video demonstrated a feasible, safe, effective procedure for laparoscopic CSD repair in the patient., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The increased use of gestational carriers has expanded family-building opportunities for people and couples unable to carry pregnancies on their own. National American Society of Reproductive Medicine guidelines for gestational carriers have changed over time to reflect advances in reproductive technology and mounting evidence supporting the medical benefits associated with singleton gestations., Objective: Assess changes in gestational carrier cycle practice patterns and resultant pregnancy outcomes in the United States in relation to changing national American Society of Reproductive Medicine guidelines, which changed in 2013 and 2017., Study Design: This retrospective study used data from the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System and included all cycles that were reported from 2014-2020 involving an embryo transfer to a gestational carrier. Binomial regression models evaluated trends in preimplantation genetic testing for aneuploidy, American Society of Reproductive Medicine guideline adherence, number of embryos transferred, and pregnancy outcomes over time., Results: Of the 40,177 gestational carrier transfer cycles from 2014-2020, there was a significant increase in frozen-thawed cycles (41.3% increase), use of assisted hatching (53.4% increase), intracytoplasmic sperm injection (50.0% increase), and preimplantation genetic testing for aneuploidy (155.7% increase). The likelihood of preimplantation genetic testing for aneuploidy was higher in 2020 than in 2014 for autologous oocyte transfers to gestational carriers, both for those aged ≥38 years (adjusted relative risk, 2.38 [95% confidence interval, 2.11-2.70]) and than those aged <38 years (adjusted relative risk, 2.85 [95% confidence interval, 2.58-3.15]). As preimplantation genetic testing for aneuploidy usage increased, single embryo transfer rose for both autologous (adjusted relative risk, 2.22 [95% confidence interval, 1.94-2.50]) and donor cycles (relative risk, 1.91 [95% confidence interval, 1.81-2.02]). This shift toward single embryo transfer corresponded with a decrease in multiple embryo transfer by 79.2% and subsequent decreases in multiple gestations by 68.8% in donor and 73.6% in autologous oocyte cycles from 2014-2020. Gestational carrier cycles remained highly adherent to changing American Society of Reproductive Medicine guidelines throughout the study period. Among live births, there was a 19.4% and 7.9% increase in term deliveries among donor and autologous oocyte cycles, respectively, from 2014 to 2020., Conclusion: Practice patterns have drastically changed throughout the study period, with major increases in the use of preimplantation genetic testing for aneuploidy, intracytoplasmic sperm injection, assisted hatching, and frozen transfers. In response to changing American Society of Reproductive Medicine guidelines, the use of multiple embryo transfers has decreased for gestational carrier cycles with subsequent decreases in multiple gestations and miscarriages and slight increases in live birth rates., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Endocrine disrupting chemicals (EDCs) are defined as exogenous chemicals, or mixtures of chemicals, that can interfere with any aspect of hormone action. The field of endocrine disruption is historically rooted in wildlife biology and reproductive endocrinology where EDCs are demonstrated contributors to infertility, premature puberty, endometriosis, and other disorders. Recently, EDCs have been implicated in metabolic syndrome and obesity. Adipose tissue is a true endocrine organ and, therefore, an organ that is highly susceptible to disturbance by EDCs. A subset of EDCs, called "obesogens," promote adiposity by altering programming of fat cell development, increasing energy storage in fat tissue, and interfering with neuroendocrine control of appetite and satiety. Obesity adds more than $200 billion to US healthcare costs and the number of obese individuals continues to increase. Hence, there is an urgent, unmet need to understand the mechanisms underlying how exposures to certain EDCs may predispose our population to be obese. In this review, we discuss the history of obesogen discovery from its origins in reproductive biology to its latest role in the transgenerational inheritance of obesity in mice. We discuss the development of adipose tissue in an embryo, maintenance of adipocyte number in adults, how EDC disruption programs stem cells to preferentially make more adipocytes, the mechanisms by which chemicals can permanently alter the germline epigenome, and whether there are barriers to EDCs in the gametes.

Objective: This study aimed to determine the efficacy and safety of hyaluronic acid gel for the prevention of intrauterine adhesions and improved fertility after intrauterine surgery., Data Sources: PubMed, EMBASE, Cochrane Library, Web of science, and ClinicalTrials.gov were searched up to November 1, 2023., Study Eligibility Criteria: Randomized controlled trials that reported intrauterine adhesion and fertility outcomes among women who used hyaluronic acid after intrauterine surgery., Methods: The risk of bias was assessed using criteria of the Cochrane Handbook, and the quality of the evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A trial sequential analysis was conducted to assess the outcomes, and Stata 14 was used for sensitivity analyses and publication bias analyses., Results: Data from 16 randomized controlled trials involving 2359 patients were extracted and analyzed. The analysis revealed that hyaluronic acid reduced the incidence of intrauterine adhesion (risk ratio, 0.53; 95% confidence interval, 0.42-0.67; I 2 =48%) and improve pregnancy rates (risk ratio, 1.24; 95% confidence interval, 1.02-1.50; I 2 =0%). A subgroup analysis was conducted to evaluate factors that influence the effect of hyaluronic acid on the incidence of intrauterine adhesion. It was found that a small volume of hyaluronic acid reduced the incidence of intrauterine adhesions. Hyaluronic acid exhibited a protective effect among patients who underwent various intrauterine surgeries and who had different gynecologic medical histories. The protective effect was statistically significant after a follow-up of 6 to 12 weeks. The results of the trial sequential analysis indicated that the effect of hyaluronic acid on the incidence of mild intrauterine adhesions, pregnancy rates, live birth rates, and miscarriage rates after intrauterine surgery may be inconclusive and thus further evaluation is required in the form of additional clinical trials. However, the remaining effects were found to be verifiable and did not require more clinical trials for confirmation., Conclusion: Hyaluronic acid can safely and effectively reduce the incidence of intrauterine adhesions and may improve fertility outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous studies have found that women who undergo cesarean delivery have fewer pregnancies. Cesarean delivery is also more common among women with lower fecundability. The potential role of cesarean delivery in reduced fecundability is not known., Objective: This study aimed to assess the bidirectional relationship between cesarean delivery and fecundability., Study Design: This was a prospective cohort study based on data from the Norwegian Mother, Father, and Child Cohort study linked with the Medical Birth Registry of Norway. We estimated the fecundability ratio (per cycle probability of pregnancy) and relative risk of infertility (time to pregnancy ≥12 months) by mode of delivery in the previous delivery among 42,379 women. For the reverse association, we estimated the relative risk of having a cesarean delivery by fecundability (the number of cycles women needed to conceive) among 74,024 women., Results: The proportion of women with infertility was 7.3% (2707/37,226) among women with a previous vaginal delivery and 9.9% (508/5153) among women with a previous cesarean delivery, yielding an adjusted relative risk of 1.21 (95% confidence interval, 1.10-1.33). Women with a previous cesarean delivery also had a lower fecundability ratio (0.90; 95% confidence interval, 0.88-0.93) than women with a previous vaginal delivery. When assessing the reverse association between fecundability and cesarean delivery, we found that women who did not conceive within 12 or more cycles had a higher risk for cesarean delivery (adjusted relative risk, 1.57; 95% confidence interval, 1.48-1.66) than women who conceived within the first 2 cycles. The associations remained after controlling for sociodemographic and clinical risk factors and were observed across parity groups., Conclusion: Among women with more than 1 child, those who had a previous cesarean delivery subsequently had a lower fecundability ratio and an increased infertility risk than those who had a vaginal delivery. However, women who needed a longer time to conceive were also more prone to be delivered by cesarean delivery, indicating a bidirectional relationship between cesarean delivery and fecundability. This could suggest a common underlying explanatory mechanism and that the surgical procedure itself may not or only partly directly influence fecundability., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

ObjectiveWe sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study.Study designIn this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort.ResultsThe incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57-3.76) and population (AOR, 7.91; 95% CI, 1.69-37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28-4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44-5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32-0.75), parity (AOR, 0.42; 95% CI, 0.28-0.64), and body mass index (AOR, 0.95; 95% CI, 0.93-0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor.ConclusionAn infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.

Background: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies., Objective: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment., Study Design: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m 2 , undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes., Results: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71)., Conclusion: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m 2 . This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are significant racial disparities in in vitro fertilization outcomes, which are poorly explained by individual-level characteristics. Environmental factors such as neighborhood-level socioeconomic factors may contribute to these disparities. However, few studies have directly addressed this research question in a large, racially diverse cohort., Objective: This study aimed to investigate whether neighborhood deprivation is associated with differences in in vitro fertilization outcomes., Study Design: Our retrospective cohort study included 1110 patients who underwent 2254 autologous in vitro fertilization cycles between 2014 and 2019 at an academic fertility center in the Southeastern United States. Neighborhood deprivation was estimated using the Neighborhood Deprivation Index, a composite variable measuring community levels of material capital based on poverty, occupation, housing, and education domains. Using multivariable log-binomial generalized estimating equations with cluster weighting, risk ratios and 95% confidence intervals were estimated for cycle cancellation, miscarriage (defined as spontaneous pregnancy loss before 20 weeks after a confirmed intrauterine gestation), and live birth according to patient Neighborhood Deprivation Index., Results: There were positive associations between increasing Neighborhood Deprivation Index (indicating worsening neighborhood deprivation) and body mass index, as well as increasing prevalence of tubal and uterine factor infertility diagnoses. The crude probability of live birth per cycle was lower among Black (24%) than among White patients (32%), and the crude probability of miscarriage per clinical pregnancy was higher among Black (22%) than among White patients (12%). After adjustment, the Neighborhood Deprivation Index was not significantly associated with risk of cycle cancellation or live birth. Results were consistent when analyses were stratified by race., Conclusion: Our research demonstrates racial disparities between Black and White women in the incidence of miscarriage and live birth following in vitro fertilization. Although the level of neighborhood deprivation was closely related to race, it did not have strong associations with in vitro fertilization outcomes in our population as a whole or within strata of race., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Citing the risks of administering anesthesia to patients with obesity, few fertility centers offer in vitro fertilization as a treatment modality for patients with body mass indexes ≥40 kg/m 2 . Although previous studies have assessed clinical pregnancy and cumulative live birth rates in patients who spontaneously conceive with body mass indexes ≥50 kg/m 2 , there is a paucity of in vitro fertilization, obstetrical, and neonatal outcome data in patients with severe obesity who conceive after in vitro fertilization., Objective: This study aimed to evaluate the impact of increasing body mass index on in vitro fertilization, obstetrical, and neonatal outcomes in patients with obesity undergoing in vitro fertilization., Study Design: This was a retrospective cohort study within an academic fertility center including 2069 fresh in vitro fertilization/intracytoplasmic sperm injection and frozen embryo transfer cycles from January 1, 2012 to April 30, 2020; this cohort was used to determine in vitro fertilization treatment outcomes. A second embedded cohort of 867 fresh in vitro fertilization/intracytoplasmic sperm injection and frozen embryo transfer cycles that resulted in ongoing clinical pregnancies and deliveries within a single tertiary hospital system was used to determine pregnancy, maternal, and neonatal outcomes. All patients with a body mass index ≥40 kg/m 2 underwent consultation with a maternal-fetal medicine specialist before starting treatment and a preoperative evaluation with an anesthesiologist before oocyte retrieval. Cycles were grouped by body mass index at cycle start (30-34.9, 35-39.9, 40-44.9, 45-49.9, and ≥50 kg/m 2 ). Log-binomial regression and Poisson regression with an offset were fitted with body mass index of 30 to 34.9 kg/m 2 as the reference group, adjusting for potential confounders including oocyte age, patient age, embryo quality, transfer type, and coexisting comorbidities. The primary outcome was live birth rate. Secondary outcomes included fertilization rate, blastulation rate, miscarriage rate, incidence of preeclampsia with severe features, gestational diabetes, labor induction, cesarean delivery, preterm delivery, and birthweight., Results: There were 2069 fresh in vitro fertilization/intracytoplasmic sperm injection and frozen embryo transfer cycle starts from January 1, 2012 to April 30, 2020. Of these, 1008 cycles were in the 30 to 34.9 kg/m 2 group, 547 in the 35 to 39.9 kg/m 2 group, 277 in the 40 to 44.9 kg/m 2 group, 161 in the 45 to 49.9 kg/m 2 group, and 76 in the ≥50 kg/m 2 body mass index group. Live birth rate was not significantly different between groups. The body mass index ≥50 kg/m 2 group was significantly more likely to experience preeclampsia with severe features when compared with the 30 to 34.9 kg/m 2 body mass index group (absolute risk reduction, 2.75; 95% confidence interval, 1.13-6.67). Fertilization rate, blastulation rate, miscarriage rate, incidence of gestational diabetes, labor induction, cesarean delivery, preterm delivery, and neonatal birthweights were not significantly different between groups., Conclusion: Among patients with body mass indexes from 30 to 60 kg/m 2 who conceived via in vitro fertilization and received comprehensive prenatal care at a tertiary care hospital, in vitro fertilization, obstetrical, and neonatal outcomes were largely comparable. These data support a collaborative care approach with maternal-fetal medicine specialists and skilled anesthesiologists, reinforcing the notion that in vitro fertilization should not be withheld as a treatment modality from patients with obesity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A proportion of reproductive age women are affected by gynecologic malignancies. This patient population is faced with difficult decisions, related to their cancer care and treatment, as well as future childbearing potential. Therefore, it is important for gynecologists to be familiar with fertility sparing management options in patients with cervical, ovarian, and endometrial cancer. In addition to understanding the surgical approaches available, providers should be able to counsel patients regarding their eligibility for and the indications and limitations of fertility sparing therapy for gynecologic cancer, allowing for appropriate referrals. A comprehensive PUBMED literature search was conducted using the key words "fertility preservation," "cervical cancer," "endometrial cancer," "ovarian cancer," "borderline tumor of the ovary," "germ cell tumor," "obstetrical outcomes," "chemotherapy," and "radiation." The following review summarizes fertility sparing options for patients with cervical, ovarian and endometrial cancer, with an emphasis on appropriate patient selection, oncologic, and obstetric outcomes.

Background: Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood., Objective: This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk., Study Design: This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate., Results: Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding., Conclusion: Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Some reproductive factors (such as age at menarche and parity) have been shown to be associated with age at natural menopause, but there has been little quantitative analysis of the association between infertility, miscarriage, stillbirth, and premature (<40 years) or early menopause (40-44 years). In addition, it has been unknown whether the association differs between Asian and non-Asian women, although the age at natural menopause is younger among Asian women., Objective: This study aimed to investigate the association of infertility, miscarriage, and stillbirth with age at natural menopause, and whether the association differed by race (Asian and non-Asian)., Study Design: This was a pooled individual participant data analysis from 9 observational studies contributing to the InterLACE consortium. Naturally postmenopausal women with data on at least 1 of the reproductive factors (ie, infertility, miscarriage, and stillbirth), age at menopause, and confounders (ie, race, education level, age at menarche, body mass index, and smoking status) were included. A multinomial logistic regression model was used to estimate relative risk ratios and 95% confidence intervals for the association of infertility, miscarriage, and stillbirth with premature or early menopause, adjusting for confounders. Between-study difference and within-study correlation were taken into account by including study as a fixed effect and indicating study as a cluster variable. We also examined the association with number of miscarriages (0, 1, 2, ≥3) and stillbirths (0, 1, ≥2), and tested whether the strength of association differed between Asian and non-Asian women., Results: A total of 303,594 postmenopausal women were included. Their median age at natural menopause was 50.0 years (interquartile range, 47.0-52.0). The percentages of women with premature and early menopause were 2.1% and 8.4%, respectively. The relative risk ratios (95% confidence intervals) of premature and early menopause were 2.72 (1.77-4.17) and 1.42 (1.15-1.74) for women with infertility; 1.31 (1.08-1.59) and 1.37 (1.14-1.65) for women with recurrent miscarriages; and 1.54 (1.52-1.56) and 1.39 (1.35-1.43) for women with recurrent stillbirths. Asian women with infertility, recurrent miscarriages (≥3), or recurrent stillbirths (≥2) had higher risk of premature and early menopause compared with non-Asian women with the same reproductive history., Conclusion: Histories of infertility and recurrent miscarriages and stillbirths were associated with higher risk of premature and early menopause, and the associations differed by race, with stronger associations for Asian women with such reproductive history., (Copyright © 2023. Published by Elsevier Inc.)

Background: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19., Objective: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19., Study Design: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases)., Results: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis., Conclusion: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: As the use of in vitro fertilization continues to increase in the United States, up-to-date models that estimate cumulative live birth rates after multiple oocyte retrievals and embryo transfers (fresh and frozen) are valuable for patients and clinicians weighing treatment options., Objective: This study aimed to develop models that generate predicted probabilities of live birth in individuals considering in vitro fertilization based on demographic and reproductive characteristics., Study Design: Our population-based cohort study used data from the National Assisted Reproductive Technology Surveillance System 2016 to 2018, including 196,916 women who underwent 207,766 autologous embryo transfer cycles and 25,831 women who underwent 36,909 donor oocyte transfer cycles. We used data on autologous in vitro fertilization cycles to develop models that estimate a patient's cumulative live birth rate after all embryo transfers (fresh and frozen) within 12 months after 1, 2, and 3 oocyte retrievals in new and returning patients. Among patients using donor oocytes, we estimated the cumulative live birth rate after their first, second, and third embryo transfers. Multinomial logistic regression models adjusted for age, prepregnancy body mass index (imputed for 18% of missing values), parity, gravidity, and infertility diagnoses were used to estimate the cumulative live birth rate., Results: Among new and returning patients undergoing autologous in vitro fertilization, female age had the strongest association with cumulative live birth rate. Other factors associated with higher cumulative live birth rates were lower body mass index and parity or gravidity ≥1, although results were inconsistent. Infertility diagnoses of diminished ovarian reserve, uterine factor, and other reasons were associated with a lower cumulative live birth rate, whereas male factor, tubal factor, ovulatory disorders, and unexplained infertility were associated with a higher cumulative live birth rate. Based on our models, a new patient who is 35 years old, with a body mass index of 25 kg/m 2 , no previous pregnancy, and unexplained infertility diagnoses, has a 48%, 69%, and 80% cumulative live birth rate after the first, second, and third oocyte retrieval, respectively. Cumulative live birth rates are 29%, 48%, and 62%, respectively, if the patient had diminished ovarian reserve, and 25%, 41%, and 52%, respectively, if the patient was 40 years old (with unexplained infertility). Very few recipient characteristics were associated with cumulative live birth rate in donor oocyte patients., Conclusion: Our models provided estimates of cumulative live birth rate based on demographic and reproductive characteristics to help inform patients and providers of a woman's probability of success after in vitro fertilization., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Systemic administration of soluble factors from bone marrow-derived stem cells combined with activated platelet-rich plasma (SC-PRP) restored ovarian function, mediated through paracrine signaling, in murine models of chemotherapy-induced ovarian damage and human tissue from poor responder patients. However, the effects against age-related infertility and the efficacy of local administration have not been evaluated yet., Objective: This study aimed to assess whether a single intraovarian dose of stem cells combined with activated platelet-rich plasma can recover ovarian function, oocyte quality, and developmental competence in older mice., Study Design: The effects of stem cells combined with activated platelet-rich plasma against age-related infertility were assessed following controlled ovarian stimulation in an aging murine model reproducing 3 physiological stages of women's reproductive life, namely young, advanced maternal age, and menopausal (n=12 animals per group). Female mice were randomized to receive a single intraovarian injection (10 μL/ovary) of either saline, activated platelet-rich plasma, or stem cells combined with activated platelet-rich plasma. Seven days later, the mice were stimulated, naturally mated, and sacrificed to harvest their ovaries for histologic assessment and molecular analysis and their oviducts to evaluate oocyte maturation and to assess early embryo development., Results: A single intraovarian injection of stem cells combined with activated platelet-rich plasma promoted follicle activation and development in young, advanced maternal age, and old mice. Furthermore, stem cells combined with activated platelet-rich plasma rescued fertility in older mice by enhancing the quantity and quality of ovulated mature oocytes and supporting early embryo development to the blastocyst stage in all the evaluated ages. These fertility outcomes were positively associated with mitochondrial quality, treatment-increased mitochondrial DNA copy numbers, and reduced oxidative damage and apoptosis. Finally, the effects observed by histologic analysis were supported at the proteomic level. Functional proteomic analyses revealed molecular mechanisms involved in oocyte maturation and quality, mitochondrial function, and recovery of the ovarian stroma., Conclusion: Bone marrow-derived stem cells combined with activated platelet-rich plasma is a promising treatment with the potential to improve the reproductive outcomes of women with age-related infertility, exceeding the restorative effects of platelet-rich plasma alone. Although further research in human ovarian samples is still required, the autologous nature of stem cell factors collected by noninvasive mobilization, their combination with platelet-rich plasma, and the local administration route suggest that stem cells combined with activated platelet-rich plasma treatment could be a potentially effective and safe application for future clinical practice., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is a recent decrease in fertility rates among the general population in the United States. Female physicians, who are seeking assisted reproductive technology at growing rates often because of delayed childbearing while completing medical training, are included in this statistic. With more than 340,000 practicing female physicians within the United States, female physician infertility is especially relevant. However, despite the increasing number of female physicians seeking assisted reproductive technology, there is a lack of access to adequate insurance coverage for this higher-risk patient subset. This commentary reviewed the importance of increasing infertility rates among female physicians, the associated economic burden, limited insurance coverage, and disparities in access to infertility insurance coverage. Recent studies suggest that up to 25% of female physicians are seeking assisted reproductive technology. Currently, 1 cycle of assisted reproductive technology, or egg retrieval, is estimated at approximately $19,000, with many people needing multiple cycles. Many top academic institutions do not offer enough infertility benefits to cover 1 egg retrieval cycle and the often prerequisite, less invasive procedures. Among those seeking oocyte or embryo cryopreservation for elective fertility preservation, few institutions offer coverage. Addressing and highlighting limited and variable institutional infertility coverage are crucial to gaining equal and accessible reproductive care for female physicians., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Insurance coverage for fertility services may reduce the financial burden of high-cost fertility care such as assisted reproductive technology and improve its utilization. Patients who exit care after failing to reach their reproductive goals report higher rates of mental health problems and a lower sense of well-being. It is important to understand the relationship between state-mandated insurance coverage for fertility services and assisted reproductive technology care discontinuation., Objective: This study aimed to assess whether state-mandated insurance coverage for fertility services is associated with lower rates of care discontinuation after an initial assisted reproductive technology cycle that did not result in a live birth., Study Design: This is a retrospective, population-based cohort study using data from United States fertility clinics reporting to the National Assisted Reproductive Technology Surveillance System during 2016 and 2018. Patients who began their first autologous assisted reproductive technology cycle during 2016 and 2017 and did not have a live birth were included. We describe the rate of assisted reproductive technology care discontinuation (no additional cycle within 12 months of the previous cycle's date of failure). Multivariable analyses were conducted to evaluate factors independently associated with care discontinuation, including the scope of fertility services included in state coverage mandate at assisted reproductive technology cycle initiation that were as follows: comprehensive (≥3 assisted reproductive technology cycles), limited (1, 2, or an unspecified number of assisted reproductive technology cycles), mandate not including assisted reproductive technology, and no mandate., Results: Among 91,324 patients who underwent their first autologous assisted reproductive technology cycle that did not result in live birth, 24,072 (26.4%) discontinued care. Compared with patients who lived in states with mandates for comprehensive assisted reproductive technology coverage, those in states with mandates for fertility services coverage that did not include assisted reproductive technology or states with no mandate were 46% (adjusted relative risk, 1.46; 95% confidence interval, 1.31-1.63) and 26% (adjusted relative risk, 1.26; 95% confidence interval, 1.15-1.39) more likely to discontinue care, respectively, after controlling for patient and cycle characteristics. Increasing patient age, distance from clinic ≥50 miles, previous live birth, fewer oocytes retrieved, and not having embryos cryopreserved were also associated with higher rates of discontinuation. Non-Hispanic Black, non-Hispanic Asian, and Hispanic patients had higher rates of care discontinuation than non-Hispanic White patients regardless of the existence or scope of state-mandated assisted reproductive technology coverage., Conclusion: Comprehensive state-mandated insurance coverage for assisted reproductive technology is associated with lower rates of assisted reproductive technology care discontinuation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: A total of 19 states passed legislation mandating insurance coverage of assisted reproductive technology, and out-of-pocket costs associated with in vitro fertilization vary significantly depending on the region. Consequently, it has been observed that assisted reproductive technology utilization differs regionally and is associated with the presence of an insurance mandate. However, it is unknown whether regional differences exist among patients using donor oocytes., Objective: This study aimed to determine the patient and cycle-specific parameters associated with the use of donor oocytes according to the insurance mandate status of the Society for Assisted Reproductive Technology clinic in which the assisted reproductive technology cycle was performed., Study Design: This study was a retrospective cohort study using national data collected from the Society for Assisted Reproductive Technology registry for 39,338 donor oocyte cycles and 242,555 autologous oocyte cycles performed in the United States from January 1, 2014, to December 31, 2016. Cycles were stratified by insurance mandate of the state in which the assisted reproductive technology cycle was performed: comprehensive (coverage for at least 4 cycles of assisted reproductive technology), limited (coverage limited to 1-3 assisted reproductive technology cycles), offer (insurance mandates exist but exclude assisted reproductive technology treatment), and no mandate. The primary outcome was the number of previous autologous assisted reproductive technology cycles of the recipient. The secondary outcomes included age, serum follicle stimulating hormone level, frozen donor oocyte utilization, day of embryo transfer, number of embryos transferred, clinical pregnancy rate, and live birth rate. Analyses were adjusted for day of transfer, number of embryos transferred, and age of the recipient., Results: Patients in no mandate states underwent fewer autologous assisted reproductive technology cycles (mean, 1.1; standard deviation, 1.6) before using donor oocytes than patients in offer (mean, 1.7; standard deviation, 2.5; P<.01), limited (mean, 1.5; standard deviation, 2.5; P<.01), and comprehensive (mean, 1.7; standard deviation, 2.0; P<.01) states. Patients in no mandate states were more likely to use frozen oocytes than patients in offer (relative risk, 0.54; 95% confidence interval, 0.52-0.57), limited (relative risk, 0.50; 95% confidence interval, 0.46-0.54), and comprehensive (relative risk, 0.94; 95% confidence interval, 0.89-0.99) states. Clinical pregnancy and live birth rates were similar among recipients of donor oocytes, regardless of insurance mandate., Conclusion: Despite similar ages and ovarian reserve parameters, patients without state-mandated insurance coverage of assisted reproductive technology were more likely to use frozen donor oocytes and undergo fewer autologous in vitro fertilization cycles than their counterparts in partial or comprehensive insurance coverage states. These differences in donor oocyte utilization highlight the financial barriers associated with pursuing assisted reproductive technology in uninsured states., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Veterans experience many potentially hazardous exposures during their service, but little is known about the possible effect of these exposures on reproductive health., Objective: This study aimed to assess the association between infertility and environmental, chemical, or hazardous material exposures among US veterans., Study Design: This study examined self-reported cross-sectional data from a national sample of female and male US veterans aged 20 to 45 years separated from service for ≤10 years. Data were obtained via a computer-assisted telephone interview lasting an average of 1 hour and 27 minutes that assessed demographics, general and reproductive health, and lifetime and military exposures. Logistic regression models were used to evaluate associations between exposures to environmental, chemical, and hazardous materials and infertility as defined by 2 different definitions: unprotected intercourse for ≥12 months without conception and trying to conceive for ≥12 months without conception., Results: Of the veterans included in this study, 592 of 1194 women (49.6%) and 727 of 1407 men (51.7%) met the unprotected intercourse definition for infertility, and 314 of 781 women (40.2%) and 270 of 775 men (34.8%) met the trying to conceive definition for infertility. Multiple individual exposure rates were found to be higher in women and men veterans with self-reported infertility, including petrochemicals and polychlorinated biphenyls, which were higher in both the men and women groups reporting infertility by either definition. Importantly, there was no queried exposure self-reported at higher rates in the noninfertile groups. Moreover, veterans reporting infertility reported a higher number of total exposures with a mean±standard deviation of 7.61±3.87 exposures for the women with infertility vs 7.13±3.67 for the noninfertile group (P=.030) and 13.17±4.19 for veteran men with infertility vs 12.54±4.10 for the noninfertile group (P=.005) using the unprotected intercourse definition and 7.69±3.79 for the women with infertility vs 7.02±3.57 for the noninfertile group (P=.013) and 13.77±4.17 for the veteran men with infertility vs 12.89±4.08 for the noninfertile group (P=.005) using the trying to conceive definition., Conclusion: The data identified an association between infertility and environmental, chemical, and hazardous materials that the veterans were exposed to during military service. Although this study was limited by the self-reported and unblinded data collection from a survey, and causation between exposures and infertility cannot be proven, it does show that veterans encounter many exposures during their service and calls for further research into the possible link between veteran exposures and reproductive health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Long-chain omega-3 fatty acids and their food sources have garnered interest as a potential nutrient with wide-range health benefits, including fertility., Objective: This study aimed to investigate the association of women's and men's intake of omega-3 fatty acids and omega-3 rich-foods with semen quality and outcomes of infertility treatment with assisted reproductive technologies., Study Design: Couples presenting to the Massachusetts General Hospital were invited to enroll in a prospective cohort study (2007-2020). Male and female diets were assessed using a validated 131-item food frequency questionnaire. The primary outcomes were implantation, clinical pregnancy, and live birth probabilities. The secondary outcomes included total and clinical pregnancy loss and conventional semen parameters, for males only. We estimated the relationship between intakes of omega-3 fatty acids, nuts, and fish and the probability (95% confidence interval) of study outcomes using generalized linear mixed models to account for repeated treatment cycles per participant while simultaneously adjusting for age, body mass index, smoking status, education, dietary patterns, total energy intake, and male partner diet., Results: A total of 229 couples and 410 assisted reproductive technology cycles were analyzed for primary and secondary outcomes. Of note, 343 men contributing 896 semen samples were included in analyses for semen quality measures. Women's docosahexaenoic acid + eicosapentaenoic acid intake was positively associated with live birth. The multivariable-adjusted probabilities of live birth for women in the bottom and top quartiles of eicosapentaenoic acid + docosahexaenoic acid intake were 0.36 (95% confidence interval, 0.26-0.48) and 0.54 (95% confidence interval, 0.42-0.66) (P trend=.02). Eicosapentaenoic acid + docosahexaenoic acid intake was inversely related to the risk of pregnancy loss, which was 0.53 among women in the lowest quartile of eicosapentaenoic acid + docosahexaenoic acid intake and 0.05 among women in the highest quartile (P trend=.01). Men's intake of total omega-3 fatty acids was positively related to sperm count, concentration, and motility, but unrelated to any assisted reproductive technology outcomes. Similar associations were observed when evaluating the intake of primary food sources of these fatty acids., Conclusion: Women's consumption of omega-3 fatty acids and omega-3-rich foods may improve the probability of conception by decreasing the risk of pregnancy loss. In addition, men's intake of omega-3 fatty acids may influence semen quality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated that state mandated coverage of in vitro fertilization may be associated with increased utilization, fewer embryos per transfer, and lower multiple birth rates, but also lower overall live birth rates. Given new legislation and the delay between enactment and effect, a revisit of this analysis is warranted., Objective: This study aimed to characterize the current impact of comprehensive state in vitro fertilization insurance mandates on in vitro fertilization utilization, live birth rates, multiple birth rates, and embryo transfer practices., Study Design: We conducted a retrospective cohort study of in vitro fertilization cycles reported by the 2018 Centers for Disease Control and Prevention Assisted Reproductive Technology Fertility Clinic Success Rates Report in the United States. In vitro fertilization cycles were stratified according to state mandate as follows: comprehensive (providing coverage for in vitro fertilization with minimal restrictions) and noncomprehensive. The United States census estimates for 2018 were used to calculate the number of reproductive-aged women in each state. Outcomes of interest (stratified by state mandate status) included utilization rate of in vitro fertilization per 1000 women aged 25 to 44 years, live birth rate, multiple birth rate, number of embryo transfer procedures (overall and subdivided by fresh vs frozen cycles), and percentage of transfers performed with frozen embryos. Additional subanalyzes were performed with stratification of outcomes by patient age group., Results: In 2018, 134,997 in vitro fertilization cycles from 456 clinics were reported. Six states had comprehensive mandates; 32,029 and 102,968 cycles were performed in states with and without comprehensive in vitro fertilization mandates, respectively. In vitro fertilization utilization in states with comprehensive mandates was 132% higher than in noncomprehensive states after age adjustment; increased utilization was observed regardless of age stratification. Live birth rate per cycle was significantly higher in states with comprehensive mandates (35.4% vs 33.4%; P<.001), especially among older age groups. Multiple birth rate as a percentage of all births was significantly lower in states with comprehensive mandates (10.2% vs 13.8%; P<.001), especially among younger patients. Mean number of embryos per transfer was significantly lower in states with comprehensive mandates (1.30 vs 1.36; P<.001). Significantly fewer frozen transfers were performed as a percentage of all embryo transfers in states with comprehensive mandates (66.1% vs 76.3%; P<.001). Among fresh embryo transfers, significantly fewer embryos were transferred in comprehensive states among all patients (1.55 vs 1.67; P<.001)., Conclusion: Comprehensive state mandated insurance coverage for in vitro fertilization services is associated with greater utilization of these services, fewer embryos per transfer, fewer frozen embryo transfers, lower multiple birth rates, and higher live birth rates. These findings have important public health implications for reproductive-aged individuals in the United States and present notable opportunities for research on access to fertility care., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Endometriosis and uterine fibroids are common gynecologic conditions associated with a greater risk for infertility. Previous research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially because of increased utilization of fertility treatments., Objective: Our objective was to investigate whether women with a history of endometriosis or fibroids had a greater risk for adverse pregnancy outcomes and whether this risk varied by infertility history and fertility treatment utilization., Study Design: Deliveries (2013-2017) recorded in Massachusetts' vital records were linked to assisted reproductive technology data, hospital stays, and all-payer claims database. We identified endometriosis and fibroids diagnoses via the all-payer claims database before index delivery. Adjusted relative risks for pregnancy complications were modeled using generalized estimating equations with a log link and Poisson distribution. The influence of subfertility or infertility and assisted reproductive technology was also investigated., Results: Among 91,825 deliveries, 1560 women had endometriosis and 4212 had fibroids. Approximately 30% of women with endometriosis and 26% of women with fibroids experienced subfertility or infertility without utilizing assisted reproductive technology, and 34% of women with endometriosis and 21% of women with fibroids utilized assisted reproductive technology for the index delivery. Women with a history of endometriosis or fibroids were at a greater risk for pregnancy-induced hypertension, preeclampsia, or eclampsia (endometriosis relative risk, 1.17; fibroids relative risk, 1.08), placental abnormalities (endometriosis relative risk, 1.65; fibroids relative risk, 1.38), and cesarean delivery (endometriosis relative risk, 1.22; fibroids relative risk, 1.17) than women with no history of those conditions. Neonates born to women with a history of endometriosis or fibroids were also at a greater risk for preterm birth (endometriosis relative risk, 1.24; fibroids relative risk, 1.17). Associations between fibroids and low birthweight varied by fertility status or assisted reproductive technology (P homogeneity=.01) and were stronger among noninfertile women., Conclusion: Endometriosis or fibroids increased the risk for adverse pregnancy outcomes, possibly warranting differential screening or treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Improving in vitro fertilization success is an unmet need. Observational studies have suggested that women with deficient or insufficient vitamin D have lower chances of in vitro fertilization success, but whether supplementation improves clinical pregnancy rate remains unclear., Objective: This study aimed to determine whether oral vitamin D 3 supplementation improves clinical pregnancy in women undergoing an in vitro fertilization cycle., Study Design: The "supplementation of vitamin D and reproductive outcome" trial is a 2-center randomized superiority double-blind placebo-controlled trial. Subjects were recruited between October 2016 and January 2019. Participants were women aged 18 to 39 years with low vitamin D (peripheral 25-hydroxyvitamin D of <30 ng/mL), serum calcium of ≥10.6 mg/dL, body mass index of 18 to 25 kg/m 2 , and antimüllerian hormone levels of >0.5 ng/mL and starting their first, second, or third treatment cycle of conventional in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was the cumulative clinical pregnancy rate per cycle. Pregnancies obtained with both fresh or frozen embryo transfers were included. Clinical pregnancy was defined as an intrauterine gestational sac with a viable fetus. The primary analysis was performed according to the intention-to-treat principle and could also include natural conceptions. Secondary outcomes included total dose of gonadotropins used, embryologic variables (number of oocytes retrieved, number of suitable oocytes retrieved, fertilization rate, and rate of top-quality embryos), and clinical outcomes (miscarriage rate and live birth rate)., Results: Overall, 630 women were randomized 2 to 12 weeks before the initiation of the in vitro fertilization cycle to receive either a single dose of 600,000 IU of vitamin D 3 (n=308) or placebo (n=322). Interestingly, 113 (37%) and 130 (40%) women achieved a clinical pregnancy in the treatment and placebo groups, respectively (P=.37). The risk ratio of clinical pregnancy in women receiving vitamin D 3 was 0.91 (95% confidence interval, 0.75-1.11). Compared with the placebo, vitamin D 3 supplementation did not improve the rate of clinical pregnancy. Exploratory subgroup analyses for body mass index, age, indication to in vitro fertilization, ovarian reserve, interval between drug administration and initiation of the cycle, and basal levels of 25-hydroxyvitamin D failed to highlight any clinical situation that could benefit from the supplementation., Conclusion: In women with normal weight with preserved ovarian reserve and low vitamin D levels undergoing in vitro fertilization cycles, a single oral dose of 600,000 IU of vitamin D 3 did not improve the rate of clinical pregnancy. Although the findings do not support the use of vitamin D 3 supplementation to improve in vitro fertilization success rates, further studies are required to rule out milder but potentially interesting benefits and explore the effectiveness of alternative modalities of supplementation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In the 1970s, numerous medical reports, media coverage, and litigation around the Dalkon Shield intrauterine device led to a perception that all intrauterine devices cause upper genital tract infection and infertility., Objective: This study aimed to assess the association between intrauterine device use and time to conception., Study Design: The Fertility After Contraceptive Termination Study is a multicenter, prospective cohort study of women stopping their contraceptive method to attempt conception. We recruited participants between 2011 and 2017. Participants were a convenience sample of women recruited from academic centers in Philadelphia, PA; Los Angeles, CA; St. Louis, MO; Indianapolis, IN; Aurora, CO; and Salt Lake City, UT. Women were eligible if they stopped their contraceptive method within the past 120 days before enrollment, were between 18 and 35 years of age, had no history of infertility or sterilization, and had at least 6 months of follow-up. Baseline data included demographic and reproductive characteristics, past contraceptive use, nucleic acid amplification testing for sexually transmitted infections, and serology for past infection with Chlamydia trachomatis, Trichomonas vaginalis, and Mycoplasma genitalium. The primary exposure was intrauterine device use (ever); the primary outcome was time to conception. All participants were observed longitudinally for up to 24 months. We used piecewise exponential proportional hazards models with multiple imputation to provide hazard ratios and their respective 95% confidence intervals., Results: Of the 461 participants, mean age was 28.2 years, 178 (38.7%) were Black, 157 (34.1%) were considered as low socioeconomic status, and 275 (59.7%) had a history of intrauterine device use. Without adjusting for any covariates, the median time to conception was shorter for participants who had a history of intrauterine device use (5.1 months) than participants who never used an intrauterine device (7.5 months). After controlling for potential confounders, the association of past intrauterine device use with time to conception was not statistically significant (adjusted hazard ratio, 1.25; 95% confidence interval, 0.99-1.58). In our multivariable model, age, nulligravidity, Black race, low socioeconomic status, and past Mycoplasma genitalium infection were associated with longer times to conception (hazard ratio, 0.76; 95% confidence interval, 0.58-0.99). Conception by 12 months was lower in participants with past Mycoplasma genitalium infection (68% vs 80% without past infection; P=.019)., Conclusion: We found no impairment of fertility with ever use of an intrauterine device. Serologic evidence of past Mycoplasma genitalium infection was associated with longer times to conception and higher rates of infertility. Mycoplasma genitalium infection is a potential modifiable cause of infertility., (Copyright © 2021 Elsevier Inc. All rights reserved.)