Proteome asymmetry in mouse and human embryos before fate specification.

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.

A comparison of letrozole regimens for ovulation induction in women with polycystic ovary syndrome.

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/m2 (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.

Obstetric Characteristics and Outcomes of Gestational Carrier Pregnancies: A Systematic Review and Meta-Analysis.

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.

Obstetric outcomes of women with congenital uterine anomalies in the United States.

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.

Pregnancy with endometriosis: Assessment of national-level trends, characteristics, and maternal morbidity at delivery.

OBJECTIVE: To examine pregnancy characteristics and maternal morbidity at delivery among pregnant patients with a diagnosis of endometriosis. STUDY DESIGN: This cross-sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample. Study population was 17,796,365 hospital deliveries from 2016 to 2020, excluded adenomyosis and uterine myoma. The exposure was endometriosis diagnosis. Main outcome measures were clinical and pregnancy characteristics and severe maternal morbidity at delivery related to endometriosis, assessed with multivariable regression model. RESULTS: Endometriosis was diagnosed in 17,590 patients. The prevalence of endometriosis increased by 24 % from one in 1,191 patients in 2016 to one in 853 patients in 2020 (adjusted-odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.19-1.30). Clinical and pregnancy characteristics that had greater than two-fold association to endometriosis included polycystic ovary syndrome, placenta previa, cesarean delivery, maternal age of ≥30 years, prior pregnancy loss, and anxiety disorder. Pregnant patients with endometriosis were more likely to have the diagnosis of measured severe maternal morbidity during the index hospitalization for delivery (47.8 vs 17.3 per 1,000 deliveries, aOR 1.91, 95%CI 1.78-2.06); these associations were more prominent following vaginal (aOR 2.82, 95%CI 2.41-3.30) compared to cesarean (aOR 1.85, 95%CI 1.71-2.00) deliveries. Among the individual morbidity indicators, endometriosis was most strongly associated with thromboembolism (aOR 5.05, 95%CI 3.70-6.91), followed by sepsis (aOR 2.39, 95%CI 1.85-3.09) and hysterectomy (aOR 2.18, 95%CI 1.85-2.56). When stratified for endometriosis anatomical site, odds of thromboembolism was increased in endometriosis at distant site (aOR 9.10, 95%CI 3.76-22.02) and adnexa (aOR 7.37, 95%CI 4.43-12.28); odds of sepsis was most increased in endometriosis at multi-classifier locations (aOR 7.33, 95%CI 2.93-18.31) followed by pelvic peritoneum (aOR 5.54, 95%CI 2.95-10.40); and odds of hysterectomy exceeded three-fold in endometriosis at adnexa (aOR 3.00, 95%CI 2.30-3.90), distant site (aOR 5.36, 95%CI 3.48-8.24), and multi-classifier location (aOR 4.46, 95%CI 2.11-9.41). CONCLUSION: The results of this nationwide analysis suggest that pregnancy with endometriosis is uncommon but gradually increasing over time in the United States. The data also suggest that endometriosis during pregnancy is associated with increased risk of severe maternal morbidity at delivery, especially for thromboembolism, sepsis, and hysterectomy. These morbidity risks differed by the anatomical location of endometriosis.

Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

OBJECTIVE: To describe population-level utilization of fertility-sparing surgery and outcome of reproductive-aged patients with early epithelial ovarian cancer who underwent fertility-sparing surgery in the United States. METHODS: This retrospective study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study included 3,027 patients younger than age 50 years with stage I epithelial ovarian cancer receiving primary surgical therapy from 2007 to 2020. Fertility-sparing surgery was defined as preservation of one ovary and the uterus for unilateral lesion and preservation of the uterus for bilateral lesions. Temporal trend of fertility-sparing surgery was assessed with linear segmented regression with log-transformation. Overall survival associated with fertility-sparing surgery was assessed with Cox proportional hazard regression model. RESULTS: A total of 534 patients (17.6%) underwent fertility-sparing surgery. At the cohort level, the utilization of fertility-sparing surgery was 13.4% in 2007 and 21.8% in 2020 ( P for trend=.009). Non-Hispanic White individuals (2.8-fold), those with high-grade serous histology (2.2-fold), and individuals with stage IC disease (2.3-fold) had a more than twofold increase in fertility-sparing surgery utilization during the study period (all P for trend<.05). After controlling for the measured clinicopathologic characteristics, patients who received fertility-sparing surgery had overall survival comparable with that of patients who had nonsparing surgery (5-year rates 93.6% vs 92.1%, adjusted hazard ratio 0.87, 95% CI, 0.57-1.35). This survival association was consistent in high-grade serous (5-year rates 92.9% vs 92.4%), low-grade serous (100% vs 92.2%), clear cell (97.5% vs 86.1%), mucinous (92.1% vs 86.6%), low-grade endometrioid (95.7% vs 97.7%), and mixed (93.3% vs 83.7%) histology (all P >.05). In high-grade endometrioid tumor, fertility-sparing surgery was associated with decreased overall survival (5-year rates 71.9% vs 93.8%, adjusted hazard ratio 2.90, 95% CI, 1.09-7.67). Among bilateral ovarian lesions, fertility-sparing surgery was not associated with overall survival (5-year rates 95.8% vs 92.5%, P =.364). Among 41,914 patients who had epithelial ovarian cancer with any age and stage, those younger than age 50 years with stage I disease increased from 8.6% to 10.9% during the study period ( P for trend=.002). CONCLUSION: Nearly one in five reproductive-aged patients with stage I epithelial ovarian cancer underwent fertility-sparing surgery in recent years in the United States. More than 90% of reproductive-aged patients with stage I epithelial ovarian cancer who underwent fertility-sparing surgery were alive at the 5-year timepoint, except for those with high-grade endometrioid tumors.

Nationwide assessment of practice variability in the utilization of hysteropexy at laparoscopic apical suspension for uterine prolapse.

BACKGROUND: Although hysteropexy has been used to preserve the uterus during uterine prolapse surgery for a long time, there is a scarcity of data that describe the nationwide patterns of use of this surgical procedure. OBJECTIVE: This study aimed to examine the national-level use and characteristics of hysteropexy at the time of laparoscopic apical suspension surgery for uterine prolapse in the United States. STUDY DESIGN: This cross-sectional study used data from the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample. The study population included 55,608 patients with a diagnosis of uterine prolapse who underwent laparoscopic apical suspension surgery from 2016 to 2019. Patients who had a hysterectomy were assigned to the hysterectomy group, and those who did not have a hysterectomy were assigned to the hysteropexy group. The main outcome was clinical characteristics associated with hysteropexy, assessed using a multivariable binary logistic regression model. A classification tree was further constructed to assess the use pattern of hysteropexy during laparoscopic apical suspension procedures. The secondary outcome was surgical morbidity, including urinary tract injury, intestinal injury, vascular injury, and hemorrhage. RESULTS: A hysteropexy was performed in 6500 (11.7%) patients. In a multivariable analysis, characteristics associated with increased use of a hysteropexy included (1) patient factors, such as older age, Medicare coverage, private insurance, self-pay, and medical comorbidity; (2) pelvic floor dysfunction factor of complete uterine prolapse; and (3) hospital factors, including medium bed capacity center and location in the Southern United States (all P<.05). Conversely, (1) the patient factor of higher household income; (2) gynecologic factors such as uterine myoma, adenomyosis, and benign ovarian pathology; (3) pelvic floor dysfunction factor with stress urinary incontinence; and (4) hospital factors including Midwest and West United States regions and rural setting center were associated with decreased use of a hysteropexy (all P<.05). A classification tree identified a total of 14 use patterns for hysteropexies during laparoscopic apical suspension procedures. The strongest factor that dictated the use of a hysteropexy was the presence or absence of uterine myomas; the rate of hysteropexy use was decreased to 5.6% if myomas were present in comparison with 15% if there were no myomas (P<.001). Second layer factors were adenomyosis and hospital region. Patients who did not have uterine myomas or adenomyosis and who underwent surgery in the Southern United States had the highest rate of undergoing a hysteropexy (22.6%). Across the 14 use patterns, the percentage rate difference between the highest and lowest uptake patterns was 22.0%. Patients who underwent a hysteropexy were less likely to undergo anteroposterior colporrhaphy, posterior colporrhaphy, and sling procedures (all P<.05). Hysteropexy was associated with a decreased risk for measured surgical morbidity (3.0 vs 5.4 per 1000 procedures; adjusted odds ratio, 0.57; 95% confidence interval, 0.36-0.90). CONCLUSION: The results of these current, real-world practice data suggest that hysteropexies are being performed at the time of ambulatory laparoscopic apical suspension surgery for uterine prolapse. There is substantial variability in the application of hysteropexy based on patient, gynecologic, pelvic floor dysfunction, and hospital factors. Developing clinical practice guidelines to address this emerging surgical practice may be of use.

Assessment of obstetric characteristics and outcomes associated with pregnancy with Turner syndrome.

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.

Increasing utilization of intrauterine device insertion at hysteroscopic endometrial evaluation for patients with endometrial hyperplasia.

PURPOSE: To examine the utilization and characteristics related to the use of hysteroscopy at the time of endometrial evaluation for endometrial hyperplasia in the outpatient surgery setting. METHODS: This cross-sectional study queried the Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample. The study population was 3218 patients with endometrial hyperplasia who underwent endometrial evaluation from January 2016 to December 2019. Performance and clinical characteristics of hysteroscopic endometrial evaluation were assessed with multivariable binary logistic regression models. RESULTS: A total of 2654 (82.5%) patients had hysteroscopic endometrial tissue evaluation. Patients with postmenopausal bleeding, heavy menstrual bleeding, and polycystic ovary syndrome were more likely to undergo hysteroscopic endometrial evaluation in multivariable analysis (all, adjusted-P < 0.001). Uterine injury occurred in 4.9 per 1000 hysteroscopic endometrial evaluations; none had uterine injury in the non-hysteroscopy cohort. Among the 2654 patients who had hysteroscopic endometrial evaluation, 106 (4.0%) patients had intrauterine device insertion at surgery, and the utilization increased from 2.9 to 5.8% during the study period (P-trend < 0.001). Younger age, more recent year surgery, and obesity were independently associated with increased utilization of intrauterine device insertion at hysteroscopic endometrial evaluation (all, adjusted-P < 0.05). Among 2023 reproductive-age patients with endometrial hyperplasia, 1666 (82.4%) patients underwent hysteroscopic endometrial evaluation. On multivariable analysis, patients with heavy menstrual bleeding were more likely to have hysteroscopic endometrial evaluation (adjusted-P < 0.05). Intrauterine device insertion increased from 3.7% in 2016 to 8.0% in 2019 (P-trend = 0.007). CONCLUSION: This nationwide analysis suggests that the insertion of intrauterine devices at the time of hysteroscopic endometrial tissue evaluation for endometrial hyperplasia is increasing among reproductive-age population.

Pregnancy following assisted reproductive technology in morbidly obese patients: assessment of feto-maternal outcomes.

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.

Pregnant patients undergoing cholecystectomy: nationwide assessment of clinical characteristics and outcomes.

BACKGROUND: Gallstone disease in pregnancy is one of the most common indications for nonobstetrical surgery during pregnancy. National-level data on contemporary surgical practice and outcomes are limited. OBJECTIVE: This study aimed to assess the clinical characteristics and outcomes of patients undergoing cholecystectomy during pregnancy. STUDY DESIGN: This cross-sectional study examined the Healthcare Cost and Utilization Project's 2 nationwide databases in the United States: the National Inpatient Sample and the Nationwide Ambulatory Surgery Sample. The study population included 18,630 patients who had cholecystectomy during pregnancy from January 2016 to December 2020. The exposure was gestational age, grouped sequentially into the following 5 groups: first trimester (<14 weeks), early second trimester (14-20 weeks), late second trimester (21-27 weeks), early third trimester (28-36 weeks), and late third trimester (≥37 weeks). The main outcomes were clinical demographics, medical comorbidities, surgical information, and pregnancy characteristics and outcomes, assessed by gestational age. RESULTS: Cholecystectomy was most common in the early second trimester (32.1%), followed by the first trimester (25.2%), late second trimester (23.1%), early third trimester (12.4%), and late third trimester (7.2%). Patients in the first-trimester group were more likely to be aged ≥35 years, to smoke, and to have acute cholecystitis, severe hyperemesis gravidarum including metabolic disturbance, pregestational diabetes, multifetal gestation, and sepsis/shock (P<.001). Patients in the early-third-trimester group were more likely to be obese and have gestational diabetes, Charlson Comorbidity Index of ≥1, premature rupture of membranes, and intrauterine growth restriction, whereas those in the late-third-trimester group were more likely to have gallstone pancreatitis, biliary colic, chorioamnionitis, gestational hypertension, preeclampsia, and severe maternal morbidity including sepsis (P<.001). At the cohort level, a laparoscopic approach was used in most cholecystectomy procedures (97.5%), and bile duct injury was uncommon (<0.1%). Delivery during the admission occurred in 0.3%, 0%, 0.6%, 17.8%, and 60.6% in the 5 gestational age groups, respectively (P<.001). Among the cases that had delivery in the early- and late-third-trimester groups, the delivery event preceded cholecystectomy in 61.4% and 86.2%, respectively, whereas both delivery and cholecystectomy occurred on the same day in 34.3% and 13.8%, respectively. CONCLUSION: This nationwide analysis suggests that clinical and pregnancy characteristics and outcomes of patients undergoing cholecystectomy differ by pregnancy stage with a bimodal distribution. Although patients in the first and third trimesters have distinct medical conditions, more clinically significant pregnancy and maternal outcomes were found in both groups compared with patients in the second trimester.

Contraception and sterilization selection at delivery among pregnant patients with malignancy.

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.