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The zona pellucida binding assay assesses the ability of spermatozoa to bind to the zona pellucida. The present study investigated the influence of: (i) prior oocyte exposure to spermatozoa on subsequent sperm-zona pellucida binding in vitro; and (ii) cryopreservation of oocytes. Only oocytes obtained from fertile donors were used and the binding capacity of non-inseminated, cryopreserved oocytes was compared with both inseminated/unfertilized, cryopreserved oocytes and inseminated/unfertilized, non-cryopreserved oocytes recovered from in-vitro fertilization cultures on sperm-zona pellucida binding using an intact zona model. There was no statistically significant difference in sperm-zona binding between non-inseminated, cryopreserved oocytes (range 9.6-23.2), inseminated/unfertilized, cryopreserved oocytes (range 15.0-16.0) and inseminated/ unfertilized, non-cryopreserved oocytes (range 3.3-23.0). The coefficient of variation for sperm binding to all oocyte groups was very large (range 37-121%). We conclude that neither prior exposure of human oocytes to human spermatozoa nor cryopreservation of human oocytes influences the subsequent binding of a different population of spermatozoa to the zona pellucida. However, large oocyte-to-oocyte variation of sperm-zona binding may diminish the usefulness of this assay in clinical practice and as a research tool. [ABSTRACT FROM AUTHOR]

Purpose: To assess national trends, characteristics, and delivery outcomes associated with gestational carriers (GC) pregnancies., Methods: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was 14,312,619 deliveries between 2017 and 2020. Obstetric characteristics and outcomes associated with GC pregnancies were assessed with inverse probability of treatment weighting propensity score., Results: There were 1965 GCs (13.7 per 100,000) included for national estimates. The prevalence rate of GC pregnancies increased by 55.0% over a 4-year period from 11.8 to 18.2 per 100,000 deliveries (P-trend < .001). In the weighted model, GCs were more likely to have a multiple gestation pregnancy (14.7% vs 1.8%, adjusted odds ratio [aOR] 7.83, 95% confidence interval [CI] 6.54-9.38, P < .001), placental abruption (3.5% vs 1.1%, aOR 2.98, 95%CI 2.12-4.19), and low-lying placenta (1.6% vs 0.2%, aOR 5.14, 95%CI 3.10-8.52). Among singleton delivery, odds of late-preterm (10.8% vs 6.4%, aOR 1.79, 95%CI 1.44-2.23) and periviable (1.1% vs 0.4%, aOR 2.54, 95%CI 1.32-4.89) deliveries and postpartum hemorrhage (12.2% vs 4.1%, aOR 3.27, 95%CI 2.67-4.00) were increased for GC compared to non-GCs whereas odds of cesarean delivery (23.6% vs 31.6%, aOR 0.59, 95%CI 0.51-0.69) were decreased. These associations were less robust in multi-fetal gestations., Conclusion: The results of the current nationwide assessment suggest that GC pregnancies are rare but gradually increasing in the United States. This study shows that GC pregnancies have usually favorable pre-pregnancy patient characteristics compared to non-GC pregnancies, with mixed obstetric outcomes including increased odds of preterm delivery, placental abnormalities, and postpartum hemorrhage and decreased odds of cesarean delivery in singleton pregnancies., Competing Interests: Declarations. Details of ethics approval: University of Southern California Institutional Review Board (HS-16–00481). Attestation statements: The manuscript’s corresponding authors affirm that the manuscript is an honest, accurate, and transparent account of the study being reported, that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. The National Inpatient Sample is developed for the Healthcare Cost and Utilization Project that is sponsored by the Agency for Healthcare Research and Quality, and the program is the source of the de-identified data used; race/ethnicity was grouped by the program; and the program has not verified and is not responsible for the statistical validity of the data analysis or the conclusions derived by the study team. Declaration of AI and AI-assisted technologies in the writing process: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Access to state-of-the-art ART can be viewed as a marker of societal development. The recent Alabama Supreme Court ruling represents a major local setback in the access to state-of-the-art ART. If this isolated local incident becomes a national trend, the USA will lose ground in this emerging area of healthcare, and its citizens will be left with substandard treatment options for the redress of infertility., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pre-patterning of the embryo, driven by spatially localized factors, is a common feature across several non-mammalian species 1-4 . However, mammals display regulative development and thus it was thought that blastomeres of the embryo do not show such pre-patterning, contributing randomly to the three lineages of the blastocyst: the epiblast, primitive endoderm and trophectoderm that will generate the new organism, the yolk sac and placenta respectively 4-6 . Unexpectedly, early blastomeres of mouse and human embryos have been reported to have distinct developmental fates, potential and heterogeneous abundance of certain transcripts 7-12 . Nevertheless, the extent of the earliest intra-embryo differences remains unclear and controversial. Here, by utilizing multiplexed and label-free single-cell proteomics by mass-spectrometry 13 , we show that 2-cell mouse and human embryos contain an alpha and a beta blastomere as defined by differential abundance of hundreds of proteins exhibiting strong functional enrichment for protein synthesis, transport, and degradation. Such asymmetrically distributed proteins include Gps1 and Nedd8, depletion or overexpression of which in one blastomere of the 2-cell embryo impacts lineage segregation. These protein asymmetries increase at 4-cell stage. Intriguingly, halved mouse zygotes display asymmetric protein abundance that resembles alpha and beta blastomeres, suggesting differential proteome localization already within zygotes. We find that beta blastomeres give rise to a blastocyst with a higher proportion of epiblast cells than alpha blastomeres and that vegetal blastomeres, which are known to have a reduced developmental potential, are more likely to be alpha. Human 2-cell blastomeres also partition into two clusters sharing strong concordance with clusters found in mouse, in terms of differentially abundant proteins and functional enrichment. To our knowledge, this is the first demonstration of intra-zygotic and inter-blastomere proteomic asymmetry in mammals that has a role in lineage segregation.

Background: Due to the rarity, congenital uterine anomaly type-specific evaluation of pregnant women has been relatively understudied., Objective: To describe national-level obstetric outcomes in women with congenital uterine anomalies., Study Design: This cross-sectional study queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. Pregnant women with diagnosis of congenital uterine anomalies who had hospital delivery between 2016 and 2019 were examined. The World Health Organization's International Classification of Disease, 10th revision coding was used to delineate type of congenital uterine anomaly, diagnoses, and procedures performed during the index admission. Primary outcomes included pregnancy outcome, which was classified as full-term live birth, preterm live birth, abortion/stillbirth, or ectopic pregnancy. Secondary outcomes included obstetric comorbidities and severe maternal morbidity, which were compared between different subtypes of congenital uterine anomalies with multivariable logistic regression model., Results: A total of 50,180 pregnant women with congenital uterine anomalies were identified. Bicornuate was the most common subtype (73.5%), followed by arcuate (13.5%) and unicornuate (10.0%). 70.6% of women with congenital uterine anomalies had a full-term live birth, 26.8% had a preterm live birth, 2.1% had an abortion or stillbirth, and 0.4% had an ectopic pregnancy. 61.8% of preterm births occurred between 33 and 36 weeks, 16.9% between 30 and 32 weeks, and 21.3% at <30 weeks. There were 1,440 (2.9%) periviable births. The preterm (34.5%) and periviable (6.9%) birth rates were highest in the uterine didelphys group. Overall, two-thirds (65.7%) of patients with congenital uterine anomalies were delivered via cesarean section. When compared to arcuate uterus, risk of severe maternal morbidity in septate uterus (4.8% vs 2.6%, adjusted-odds ratio [aOR] 2.60, 95% confidence interval [CI] 1.49-4.52) was increased, including hemorrhage (14.5% vs 7.7%, aOR 2.16, 95% CI 1.51-3.07). This was followed by uterine didelphys (4.2% vs 2.6%, aOR 1.75, 95% CI 1.24-2.47), unicornuate uterus (3.8% vs 2.6%, aOR 1.61, 95% CI 1.29-2.01), and bicornuate uterus (3.0% vs 2.6%, aOR 1.23, 95% CI 1.04-1.47)., Conclusion: While the majority of patients with congenital uterine anomalies result in full-term viable deliveries, each subtype of congenital uterine anomalies confers different obstetric risks. Uterine didelphys was associated with the highest risk of preterm birth, while septate uterus was associated with the highest risk of severe maternal morbidity. While this hospital delivery dataset likely overrepresents bicornuate uteri, this populational data may help inform patients with congenital anomalies considering pregnancy. El resumen está disponible en Español al final del artículo., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess national-level trends, characteristics, and outcomes of pregnancies with Turner syndrome in the United States., Design: Cross-sectional study., Setting: The Healthcare Cost and Utilization Project's National Inpatient Sample., Subjects: A total of 17,865,495 hospital deliveries from 2016-2020., Exposure: A diagnosis of Turner syndrome, identified according to the World Health Organization's International Classification of Disease 10th revision code of Q96., Main Outcome Measures: Obstetrics outcomes related to Turner syndrome, assessed with inverse probability of treatment weighting cohort and multivariable binary logistic regression modeling., Results: The prevalence of pregnant patients with Turner syndrome was 7.0 per 100,000 deliveries (one in 14,235). The number of hospital deliveries with patients who have a diagnosis of Turner syndrome increased from 5.0 to 11.7 per 100,000 deliveries during the study period (adjusted-odds ratio [aOR] for 2020 vs. 2016; 2.18, 95% confidence interval [CI] 1.83-2.60). Pregnant patients with Turner syndrome were more likely to have a diagnosis of pregestational hypertension (4.8% vs. 2.8%; aOR 1.65; 95% CI 1.26-2.15), uterine anomaly (1.6% vs. 0.4%; aOR, 3.01; 95% CI 1.93-4.69), and prior pregnancy losses (1.6% vs. 0.3%; aOR 4.70; 95% CI 3.01-7.32) compared with those without Turner syndrome. For the index obstetric characteristics, Turner syndrome was associated with an increased risk of intrauterine fetal demise (10.9% vs. 0.7%; aOR 8.40; 95% CI 5.30-13.30), intrauterine growth restriction (8.5% vs. 3.5%; aOR 2.11; 95% CI 1.48-2.99), and placenta accreta spectrum (aOR 3.63; 95% CI 1.20-10.97). For delivery outcome, pregnant patients with Turner syndrome were more likely to undergo cesarean delivery (41.6% vs. 32.3%; aOR 1.53; 95% CI 1.26-1.87). Moreover, the odds of periviable delivery (22-25 weeks: 6.1% vs. 0.4%; aOR 5.88; 95% CI 3.47-9.98) and previable delivery (<22 weeks: 3.3% vs. 0.3%; aOR 2.87; 95% CI 1.45-5.69) were increased compared with those without Turner syndrome., Conclusions: The results of contemporaneous, nationwide assessment in the United States suggest that although pregnancy with Turner syndrome is uncommon this may represent a high-risk group, particularly for intrauterine fetal demise and periviable delivery. Establishing a society-based approach for preconception counseling and antenatal follow-up would be clinically compelling., Competing Interests: Declaration of Interests Z.S.A. has nothing to disclose. A.D.M. has nothing to disclose. L.S.A. has nothing to disclose. R.S.M. has nothing to disclose. K.V.E. has nothing to disclose. S.M. received research funding from Merck. D.B. has nothing to disclose. R.J.P. has nothing to disclose. J.G.O. has nothing to disclose. K.M. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: Advancements in assisted reproductive technology (ART) have led to an increase in gestational carrier (GC) pregnancies. However, the perinatal outcomes of GC pregnancies remain understudied, necessitating a deeper understanding of their associated risks., Objective: To assess maternal characteristics and obstetric outcomes associated with GC pregnancies., Data Sources: A comprehensive systematic search of publications published before October 31, 2023, using PubMed, Web of Science, Scopus, and Cochrane Library databases was conducted., Study Selection: Two authors selected studies examining obstetric characteristics and outcomes in GC pregnancies with 24 or more weeks' gestation. Studies with insufficient outcome information, unavailable data on gestational surrogacies, and non-English language studies were excluded., Data Extraction and Synthesis: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, 2 investigators extracted and synthesized both quantitative and qualitative data. Both fixed-effect and random-effect analysis were used to pool data., Main Outcomes and Measures: The primary outcomes were obstetric characteristics and outcomes, including hypertensive disorders, preterm birth, and low birth weight. Secondary outcomes included severe maternal morbidity and mortality associated with GC pregnancies., Results: Six studies from 2011 to 2023 involving 28 300 GC pregnancies and 1 270 662 non-GC pregnancies were included. GCs accounted for 2.5% of in vitro fertilization cycles (59 502 of 2 374 154 cycles) and 3.8% of ART pregnancies (26 759 of 701 047 ART pregnancies). GC pregnancies were more likely to be conceived by frozen embryo transfer compared with non-GC ART pregnancies (odds ratio [OR], 2.84; 95% CI, 1.56-5.15), and rates of single embryo transfer were similar between the 2 groups (OR, 1.18; 95% CI, 0.94-1.48). GCs were rarely nulliparous (6 of 361 patients [1.7%]) and were more likely to have multifetal pregnancies compared with non-GC ART patients (OR, 1.18; 95% CI, 1.02-1.35). Comparator studies revealed lower odds of cesarean delivery (adjusted OR [aOR], 0.42; 95% CI, 0.27-0.65) and comparable rates of hypertensive disorders (aOR, 0.86; 95% CI, 0.45-1.64), preterm birth (aOR, 0.82; 95% CI, 0.68-1.00), and low birth weight (aOR, 0.79; 95% CI, 0.50-1.26) in GC pregnancies vs non-GC ART pregnancies. Comparatively, GC pregnancies had higher odds of hypertensive disorders (aOR, 1.44; 95% CI, 1.13-1.84) vs general (non-GC ART and non-ART) pregnancies with comparable cesarean delivery risk (aOR, 1.06; 95% CI, 0.90-1.25). Preterm birth and low birth weight data lacked a comparative group using multivariate analysis. Severe maternal morbidity and maternal mortality were rare among GCs., Conclusions and Relevance: In this systematic review and meta-analysis, although GC pregnancies had slightly improved outcomes compared with non-GC ART pregnancies, they posed higher risks than general pregnancies. Contributing factors may include ART procedures and increased rates of multiple gestations which influence adverse perinatal outcomes in GC pregnancies.

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body., Competing Interests: Declaration of interests N.A. is the founder and CEO of Progenesis Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To describe patterns and variations in the medical and procedural management of early pregnancy loss (EPL) among reproductive endocrinology and infertility specialists, with attention to mifepristone use., Design: Cross-sectional., Setting: Online survey., Patients: Society for Reproductive Endocrinology and Infertility members., Intervention: Not applicable., Main Outcome Measure: Preferred management for EPL., Results: Of 101 completed surveys (response rate: 12.2%), 70.3% of respondents reported diagnosing EPL at least once per week. Half (50.5%) of respondents preferred medical management compared with 27.7% who preferred procedural management and 21.8% who preferred expectant management. Approximately one-quarter (26.7%) of respondents offer mifepristone for medical management of EPL. The most common reason cited for not prescribing mifepristone was a lack of access to the medication. Mifepristone prescribers were more likely to work in a hospital or university setting than private practice. Increasing years in practice was also associated with mifepristone use. The use of mifepristone for EPL did not vary by the respondent's age, gender, prior abortion training, or practice region., Conclusion: The most effective method of medical management uses both mifepristone and misoprostol. However, nearly three-quarters of reproductive endocrinology and infertility physicians do not offer mifepristone, which may be linked to access issues., Competing Interests: Z.S.A. has nothing to disclose. R.J.P. is the Editor-in-Chief for F&S Reports and was not involved in the editorial review or the decision to publish this article. B.T.N. is on the research advisory boards of Sebela Pharmaceuticals and Myovant Sciences, the products of which are unrelated to the subject of this research., (© 2024 The Author(s).)

Purpose: To examine feto-maternal characteristics and outcomes of morbidly obese pregnant patients who conceived with assisted reproductive technology (ART)., Methods: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 48,365 patients with ART pregnancy from January 2012 to September 2015, including non-obesity (n = 45,125, 93.3%), class I-II obesity (n = 2445, 5.1%), and class III obesity (n = 795, 1.6%). Severe maternal morbidity at delivery per the Centers for Disease and Control Prevention definition was assessed with multivariable binary logistic regression model., Results: Patients in the class III obesity group were more likely to have a hypertensive disorder (adjusted-odds ratio (aOR) 3.03, 95% confidence interval (CI) 2.61-3.52), diabetes mellitus (aOR 3.08, 95%CI 2.64-3.60), large for gestational age neonate (aOR 3.57, 95%CI 2.77-4.60), and intrauterine fetal demise (aOR 2.03, 95%CI 1.05-3.94) compared to those in the non-obesity group. Increased risks of hypertensive disease (aOR 1.35, 95%CI 1.14-1.60) and diabetes mellitus (aOR 1.39, 95%CI 1.17-1.66) in the class III obesity group remained robust even compared to the class I-II obesity group. After controlling for priori selected clinical, pregnancy, and delivery factors, patients with class III obesity were 70% more likely to have severe maternal morbidity at delivery compared to non-obese patients (8.2% vs 4.4%, aOR 1.70, 95%CI 1.30-2.22) whereas those with class I-II obesity were not (4.1% vs 4.4%, aOR 0.87, 95%CI 0.70-1.08)., Conclusions: The results of this national-level analysis in the United States suggested that morbidly obese pregnant patients conceived with ART have increased risks of adverse fetal and maternal outcomes., (© 2024. The Author(s).)

Introduction: Since malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long-acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery., Material and Methods: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long-acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics., Results: When compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long-acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long-acting reversible contraception. Among pregnant patients aged <30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged <30 with melanoma (aOR 5.36) was also increased., Conclusions: The results of this nationwide assessment in the United States suggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To determine the optimal letrozole regimen for ovulation induction (OI) in women with polycystic ovary syndrome (PCOS)., Design: Retrospective cohort study., Setting: Single academic fertility clinic from 2015-2022., Patients: A total of 189 OI cycles in 52 patients with PCOS., Interventions: Patients were prescribed 1 of 4 letrozole regimens (group 1: 2.5 mg for 5 days, group 2: 2.5 mg for 10 days, group 3: 5 mg for 5 days, and group 4: 5 mg for 10 days)., Main Outcome Measures: The primary outcome was ovulation, and secondary outcomes included multifollicular development, and clinical pregnancy rate, which were analyzed with binary logistic regression. Kaplan-Meier cumulative response curves and a Cox proportional hazard regression model were used for time-dependent analyses., Results: Mean age was 30.9 years (standard deviation [SD], 3.6) and body mass index was 32.1 kg/m 2 (SD, 4.0). Group 2 (odds ratio [OR], 9.12; 95% confidence interval [CI], 1.92-43.25), group 3 (OR, 3.40; 95% CI, 1.57-7.37), and group 4 (OR, 5.94; 95% CI, 2.48-14.23) had improved ovulation rates after the starting regimen as compared with group 1. Cumulative ovulation rates exceeded 84% in all groups, yet those who received 5 mg and/or 10 days achieved ovulation significantly sooner. Multifollicular development was not increased in groups 2-4 as compared with group 1. Groups 2-4 also demonstrated improved time to pregnancy., Conclusions: Ovulation rates are improved when starting with letrozole at 5 mg and/or a 10-day extended course as compared with the frequently-used 2.5 mg for 5 days. This may shorten time to ovulation and pregnancy., Competing Interests: R.S.M. has nothing to disclose. R.A. has nothing to disclose. S.M. has nothing to disclose. C.J.V. has nothing to disclose. S.W. has nothing to disclose. D.S. has nothing to disclose. K.M. has nothing to disclose. R.J.P. has nothing to disclose. M.M.Q. has nothing to disclose., (© 2024 The Authors.)

Culture media play an essential role in the success of IVF. Their composition has undergone major modifications over the 45 years since the birth of Louise Brown. Most IVF programmes now rely on commercially produced media, which they buy in small vials, guaranteed to be sterile and non-embryotoxic. Unfortunately, information about the components of the culture media and their concentrations is no longer available. Arguing that culture media recipes are proprietary, relevant commercial interests have stopped labelling their products with this vital information. Given the critical role that is played by culture media in the success of IVF, as well as the subsequent health of the children who are born after IVF, this information should not remain a 'company secret'. Clinicians and scientists working in IVF must insist that the labelling of culture media includes all of the constituents and their concentrations. Only in this way can we monitor the influence of culture media on IVF outcomes, innovate and continue to advance the field of IVF., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Chronic oxidative stress impairs the normal functioning of the retinal pigment epithelium (RPE), leading to atrophy of this cell layer in cases of advance age-related macular degeneration (AMD). The purpose of our study was to determine if buspirone, a partial serotonin 1A (5-HT1A) receptor agonist, protected against oxidative stress-induced changes in the RPE. We exposed differentiated human ARPE-19 cells to paraquat to induce oxidative damage in culture, and utilized a mouse model with sodium iodate (NaIO 3 )-induced oxidative injury to evaluate the effect of buspirone. To investigate buspirone's effect on protective gene expression, we performed RT-PCR. Cellular toxicities and junctional abnormalities due to paraquat induction in ARPE-19 cells and buspirone's impact were assessed via WST-1 assays and ZO-1 immunostaining. We used spectral-domain optical coherence tomography (SD-OCT) and ZO-1 immunostaining of RPE/choroid for structural analysis. WST-1 assays showed dose-dependent protection of viability in buspirone-treated ARPE-19 cells in culture and preservation of RPE junctional integrity under oxidative stress conditions. In the NaIO 3 model, daily intraperitoneal injection (i.p.) of buspirone (30 mg/kg) for 12 days improved the survival of photoreceptors compared to those of vehicle-treated eyes. ZO-1-stained RPE flat-mounts revealed the structural preservation of RPE from oxidative damage in buspirone-treated mice, as well as in buspirone-induced Nqo1 , Cat , Sqstm1 , Gstm1 , and Sod2 genes in the RPE/choroid compared to untreated eyes. Since oxidative stress is implicated in the pathogenesis AMD, repurposing buspirone, which is currently approved for the treatment of anxiety, might be useful in treating or preventing dry AMD.

Our primary objective is to verify or refute a 2013 study by Connolly et al. which showed that in early pregnancy, a gestational sac was visualized 99% of the time on transvaginal ultrasound when the HCG level reached 3510 mIU/mL. Our secondary objective was to make clinical correlations by assessing the relationship between human chorionic gonadotropin (HCG) level in early pregnancy when a gestational sac is not seen and pregnancy outcomes of live birth, spontaneous abortion, and ectopic pregnancy. This retrospective study includes 144 pregnancies with an outcome of live birth, 87 pregnancies with an outcome of spontaneous abortion, and 59 ectopic pregnancies. Logistic regression is used to determine the probability of visualizing a gestational sac and/or yolk sac based on the HCG level. A gestational sac is predicted to be visualized 50% of the time at an HCG level of 979 mIU/mL, 90% at 2421 mIU/mL, and 99% of the time at 3994 mIU/mL. A yolk sac was predicted to be visualized 50% of the time at an HCG level of 4626 mIU/mL, 90% at 12,892 mIU/mL, and 99% at 39,454 mIU/mL. A total of 90% of ectopic pregnancies presented with an HCG level below 3994 mIU/mL. These results are in agreement with the study by Connolly et al. Since most early ectopic pregnancies had an HCG value below the discriminatory level for gestational sac visualization, other methods for the evaluation of pregnancy of unknown location such as repeat HCG values are clinically important., (© 2023. The Author(s).)

Objective: To examine the association between assisted reproductive technology (ART) and abnormal placentation., Methods: This is a retrospective cohort study querying the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample. The study population included 14, 970, 064 deliveries for national estimates from January 2012 to September 2015. The exposure was 48, 240 pregnancies after ART. The main outcome measure encompassed three abnormal placentation pathologies (placenta previa [PP], placenta accreta spectrum [PAS], and vasa previa [VP]). Propensity score matching was performed to assess the exposure-outcome association., Results: Pregnancy after ART was more likely to have a diagnosis of PAS (2.8 vs 1.0 per 1000 deliveries; adjusted odds ratio [aOR], 2.06 [95% confidence interval (CI), 1.44-2.93]), PP (24.5 vs 8.6 per 1000; aOR, 2.98 [95% CI, 2.64-3.35]), and VP (2.3 vs <0.3 per 1000; aOR, 11.3 [95% CI, 5.86-21.8]) compared with pregnancy without ART. Similarly, pregnancy after ART was associated with an increased likelihood of having multiple types of abnormal placentation, including VP with PP (aOR, 15.4 [95% CI, 6.15-38.4]) and PAS with PP (aOR, 2.80 [95% CI, 1.32-5.92]) compared with non-ART pregnancy., Conclusions: This national-level analysis suggests that pregnancy after ART is associated with a significantly increased risk of abnormal placentation, including PAS, PP, and VP., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To compare the consistency of endometrial receptivity array (ERA) and histologic dating among 3 spatially distinct endometrial samples obtained during a cycle of exogenous estrogen and progesterone., Design: Prospective blinded study., Setting: University practice., Patients: Twelve patients undergoing a mock frozen embryo transfer cycle., Intervention: Endometrial biopsy was performed in a manner that provided a spatially organized endometrial specimen, corresponding to the fundus, middle, and lower segment. Each of these 3 sections was further divided into immediately adjacent specimens for ERA and histology., Main Outcome Measure: Consistency of the ERA and histology results among fundal, mid, and lower endometrial biopsy specimens., Results: The ERA showed variability in outcome among different patients but dated all specimens originating from the same patient identically. Histologic dating showed variability between patients as well as between different locations within the uterus. When comparing average dating results for each patient, we saw a positive correlation between histologic and ERA dating (Spearman Rho = 0.45); however, this did not reach statistical significance. The ERA results from upper, mid, and lower uterine biopsy specimens were identical for each autologous biopsy, whereas histologic dating showed variability with an average standard deviation of 0.71 days., Conclusions: The increased heterogeneity of histologic dating is likely to be attributed to the subjectivity of the test. Furthermore, we did not observe a consistent lag or advancement in histologic or ERA dating between the fundal or lower uterine biopsies. Overall, clinicians should be reassured that endometrial tissue will return consistent ERA results independent of the location within the uterus in which it was obtained., Competing Interests: T.L.P. has nothing to disclose. R.A. has nothing to disclose. P.N. has nothing to disclose. S.W. has nothing to disclose. L.K.M. has nothing to disclose. P.K. has nothing to disclose. J.C.F. has nothing to disclose. R.J.P. has nothing to disclose., (© 2023 The Authors.)

Introduction: This study examined obstetric outcomes in patients diagnosed with uterine adenomyosis., Material and Methods: This historical cohort study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. The study population was all hospital deliveries in women aged 15-54 years between January 2016 and December 2019. The exposure was a diagnosis of uterine adenomyosis. The main outcome measures were obstetric characteristics, including placenta previa, placenta accreta spectrum, and placental abruption. Secondary outcomes were delivery complications including severe maternal morbidity. Analytic steps to assess these outcomes included (i) a 1-to-N propensity score matching to mitigate and balance prepregnancy confounders to assess obstetric characteristics, followed by (ii) an adjusting model with preselected pregnancy and delivery factors to assess maternal morbidity. Sensitivity analyses were also performed with restricted cohorts to account for prior uterine scar, uterine myoma, and extra-uterine endometriosis., Results: After propensity score matching, 5430 patients with adenomyosis were compared to 21 720 patients without adenomyosis. Adenomyosis was associated with an increased odds of placenta accreta spectrum (adjusted-odds ratio [aOR] 3.07, 95% confidence interval [CI] 2.01-4.70), placenta abruption (aOR 3.21, 95% CI: 2.60-3.98), and placenta previa (aOR 5.08, 95% CI: 4.25-6.06). Delivery at <32 weeks of gestation (aOR 1.48, 95% CI: 1.24-1.77) and cesarean delivery (aOR 7.72, 95% CI: 7.04-8.47) were both increased in women with adenomyosis. Patients in the adenomyosis group were more likely to experience severe maternal morbidity at delivery compared to those in the nonadenomyosis group (aOR 1.86, 95% CI: 1.59-2.16). Results remained robust in the aforementioned several sensitivity analyses., Conclusions: This national-level analysis suggests that a diagnosis of uterine adenomyosis is associated with an increased risk of placental pathology (placenta accreta spectrum, placenta abruption, and placental previa) and adverse maternal outcomes at delivery., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Purpose: To examine patient and hospital characteristics related to seasonal fluctuation in in vitro fertilization (IVF)., Methods: This retrospective cohort study examined 33,077 oocyte retrievals identified in the National Ambulatory Surgery Sample. Exposure assignment was monthly IVF encounters: low-volume months (<25%ile), mid-volume months (≥25/<75%ile), and high-volume months (>75%ile). Main outcomes were patient and hospital characteristics related to the exposure groups, assessed with a multinomial regression model., Results: The median IVF encounters were 977 per month, ranging from 657 to 1074 (absolute-difference 417). January, July, and December were the lowest-quartile volume months, ranging from 657 to 710 encounters per month (low-volume months). May, August, and November were the top-quartile volume months, ranging from 1049 to 1074 encounters per month (high-volume months). In a multivariable analysis, patients undergoing IVF in the low-volume months were younger and less likely to have infertility or comorbidities. Patients undergoing IVF in the high-volume months were more likely to have lower household income and receive IVF at urban teaching facilities. Northeastern residents were less likely to have IVF in the low-volume months but more likely to have IVF in the high-volume months. Sensitivity analyses showed that the lowest-to-highest variability in monthly IVF encounters was higher in Northeast region compared to other regions (320 vs 50-128); infertility patients compared to those without (317 vs 190); privately insured patients compared to self-pay (227 vs 156); and older patients compared to younger (234 vs 192)., Conclusion: This study suggests substantial seasonal fluctuation in IVF oocyte retrieval in the USA based on patient and hospital factors., (© 2023. The Author(s).)

Introduction: Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients., Areas Covered: This clinical opinion provides a summary of recent studies exploring risk factors for the development of malignant endometrial pathology including obesity, PCOS, and T2DM. Studies assessing efficacy of fertility-sparing treatment of malignant endometrial pathology are reviewed, and a potential new adjunct treatment approach to LNG-IUD is explored., Expert Opinion: There is an unmet-need for a personalized treatment approach in cases of first-line progestin treatment failure. Glucagon-like peptide 1 receptor agonists are a class of anti-diabetic agents, but may have a role in fertility-sparing treatment of obese patients with malignant endometrial pathology by reducing weight, decreasing inflammation, and decreasing insulin resistance; these changes may also improve chances of subsequent pregnancy. This hypothesis warrants further exploration.

Many studies have sought to explore the impact of high-dose gonadotropin on stimulation outcomes based on a hypothesis that higher doses of follicle-stimulating hormone may harm the quantity or quality of oocytes and, therefore, be counterproductive. Herein, we describe the results of a narrative review aimed at elucidating any harm associated with "excess" follicle-stimulating hormone dosing in poor-to-moderate responders. Additionally, we sought to describe the outcomes associated with mild ovarian stimulation, with an eye toward determining whether this approach is superior. We concluded that there is no apparent harm to higher-dose gonadotropin stimulation for poor-to-moderate responders. Simultaneously, we did not find compelling data to suggest that mild stimulation is superior. Finally, we close by presenting data that suggest that more gonadotropin may be beneficial in specific clinical scenarios., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the relationship between prior obstetrical history and gestational age at delivery in a twin pregnancy., Design: Retrospective cohort study using the United States Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database., Setting: Clinic-based data., Patients: Patients undergoing in vitro fertilization (IVF) in the United States with live delivery of twins., Interventions: None., Main Outcome Measures: The main outcome measures are median gestational age at delivery and rate of preterm delivery (before 37 weeks)., Results: The median gestational age at delivery of IVF-conceived twins was 36.3 (interquartile rate 34.4, 37.6) weeks for nulliparous women, 35.9 (34.0, 37.1) weeks for parous women with a prior preterm birth, and 36.7 (35.1, 37.7) weeks for parous women without a prior preterm birth. The rate of preterm delivery was 61% for nulliparous women, 70% for parous women with a prior preterm birth, and 55% for parous women without a prior preterm birth., Conclusions: Parous women without a history of preterm delivery had lower rates of preterm delivery in a subsequent twin pregnancy than nulliparous women. Nulliparous women had lower rates of preterm delivery compared with parous women with a history of preterm delivery., (© 2023 The Author(s).)

Background: Several studies have investigated the effectiveness of intrauterine device placement at cesarean delivery as a contraceptive method. However, national-level use and outcomes of a postplacental intrauterine device at cesarean delivery are currently understudied in the United States., Objective: This study aimed to examine the trends, characteristics, and outcomes of patients who received a postplacental intrauterine device at cesarean delivery., Study Design: This retrospective cohort study used the National Inpatient Sample. The study cohort included patients who underwent cesarean delivery from October 2015 to December 2018. The exclusion criteria included hemorrhage, chorioamnionitis, uterine anomaly, hysterectomy, and permanent surgical sterilization. Eligible cases were grouped on the basis of the use of a postplacental intrauterine device at cesarean delivery. The primary outcome measures were temporal trends and characteristics associated with the use of a postplacental intrauterine device at cesarean delivery, assessed using the generalized estimating equation model in multivariable analysis. The secondary outcome measure was perioperative morbidity (leukocytosis, endometritis, myometritis, and sepsis). Propensity score matching was used to balance the baseline characteristics., Results: Among 2,983,978 patients who met the inclusion criteria, 10,145 patients (0.3%) received a postplacental intrauterine device at cesarean delivery. The use of a postplacental intrauterine device increased from 0.1% in the fourth quarter of 2015 to 0.6% in the fourth quarter of 2018 ( P <.001). In a multivariable analysis, the use of a postplacental intrauterine device increased by 14% every quarter-year (adjusted odds ratio, 1.14; 95% confidence interval, 1.13-1.15). In addition, (1) patient characteristics of young age, non-White race, obesity, tobacco use, lowest quartile median household income, and insured with Medicaid; (2) hospital characteristics of large bed capacity and urban teaching setting in Northeast region; and (3) pregnancy characteristics of early gestational age at cesarean delivery, hypertensive disease, previous cesarean delivery, multifetal pregnancy, grand multiparity, placenta previa, and nonelective cesarean delivery represented the independent characteristics associated with the use of a postplacental intrauterine device (all P <.05). A regression tree model identified 35 discrete patterns of the use of a postplacental intrauterine device based on 8 factors (time, race or ethnicity, primary expected payer, obesity, hospital bed capacity, hospital teaching status, hospital region, and previous cesarean delivery). There were 9 patterns, representing 8.8% of the study population, exhibiting a use rate of ≥1.0%, whereas there were 7 patterns, representing 16.0% of the study population, exhibiting no use of a postplacental intrauterine device (absolute rate difference from the highest group to the lowest group, 4.7%). In a propensity score-matched model, postplacental intrauterine device placement at cesarean delivery was not associated with increased risk of measured morbidity (any, 1.8% vs 1.7%; odds ratio, 1.06; 95% confidence interval, 0.66-1.69; P =.812), including postpartum endometritis (1.2% vs 1.0%; odds ratio, 1.19; 95% confidence interval, 0.67-2.14; P =.554)., Conclusion: The use of a postplacental intrauterine device at cesarean delivery increased significantly in recent years in the United States., (© 2023 The Authors.)

Objective: The association between early surgical menopause and increased mortality has been well demonstrated. Prior studies have also demonstrated that ovarian conservation is not associated with worse oncologic outcomes in early-stage cervical cancer. This study examined the contemporary trends and characteristics of ovarian conservation at time of hysterectomy in young women with cervical cancer., Methods: This is a retrospective cohort study examining the National Inpatient Sample. The study population was 4900 women aged ≤50 years with cervical cancer who had hysterectomy-based surgical treatment from 10/2015 to 12/2018. The exposure allocation was the adnexal procedure status (ovarian conservation versus oophorectomy). The main outcome measures were temporal trends of ovarian conservation over time and per patient age. Multivariable binary logistic regression model was fitted to identify independent characteristics associated with ovarian conservation. A classification-tree was constructed by recursive partitioning analysis to examine the utilization patterns of ovarian conservation., Results: A total of 2,940 (60.0%) women underwent ovarian conservation at hysterectomy. Ovarian conservation rates remained stable until age 37 years, ranging from 82.5% to 77.9% (P = 0.502), after which time the rate sharply and significantly decreased by 7.4% (95% confidence interval 5.4-9.3, P < 0.001) in one-year age increments from 77.9% at age 37 years to 28.7% at age 50 years. The rate of ovarian conservation increased from 54.7% in Q4/2015 to 64.4% in Q4/2018 (P = 0.002). In multivariable analysis, recent surgery remained an independent factor for ovarian conservation (adjusted-odds ratio per year-quarter 1.04, 95% confidence interval 1.03-1.06). A classification-tree model identified 24 unique patterns of ovarian conservation based on patient factor (age, race/ethnicity, primary expected payer, and year of surgery), surgical factor (minimally invasive hysterectomy), and facility factor (hospital bed capacity and region), ranging from <20% to 90% (absolute percentage difference, >80%)., Conclusion: Increasing rates of ovarian conservation at the time of hysterectomy in women undergoing surgical management of cervical cancer is encouraging; however, the marked decrease noted in patients in their mid-30s as well as substantial variability in ovarian conservation based on patient, surgical, and hospital factors are striking and warrant further consideration in clinical practice guidelines., (Copyright © 2022 Elsevier B.V. All rights reserved.)