Racial and socioeconomic disparities in fertility treatment provision for patients with polycystic ovary syndrome.

OBJECTIVE: To assess whether provision of fertility treatment for patients with polycystic ovary syndrome (PCOS) varies by patient and physician level demographics. DESIGN: Retrospective cohort study SUBJECTS: Patients at a university health system seeking care for PCOS and infertility from 2007-2021. EXPOSURE: Patient age, BMI, race, ethnicity, estimated household income, primary insurance payor, provider sex, and provider medical specialty. MAIN OUTCOME MEASURES: Prescriptions for fertility treatment, including clomiphene citrate, letrozole, and injectable gonadotropins. Differences in patient and physician demographics between patients who did and did not receive a prescription were identified with univariable analysis. Multilevel mixed-effects logistic regression was performed to determine associations between patient and physician demographics and prescription receipt. RESULTS: 3,435 patients with PCOS and infertility were identified with a mean age of 31.1 +/- 5.7 years. Of the 68.8% of patients who received a prescription, 47.8% of prescriptions were clomiphene citrate, 38.6% letrozole, and 13.7% injectable gonadotropins. There were lower odds of prescription receipt for Black patients compared to White patients (aOR 0.75, 95% CI 0.61-0.93), those with estimated household income below the federal poverty level (FPL) compared to above the national median (aOR 0.71, 95% CI 0.46-0.97), and those with public compared to commercial insurance (aOR 0.53, 95% CI 0.40-0.71). These disparities persisted in a subanalysis of patients prescribed oral medications only with lower odds of prescription receipt for Black compared to White patients (aOR 0.74, 95% CI 0.57-0.95), those with estimated household income below the FPL compared to above the national median (aOR 0.93, 95% CI 0.87-0.98), and those with public compared to commercial insurance (aOR 0.57, 95% CI 0.42-0.76). Black patients waited on average 153.3 days longer than White patients from initial visit to prescription receipt. Patients had lower odds of receiving any prescription from family medicine physicians (aOR 0.36, 95% CI 0.24-0.52) and general internal medicine physicians (aOR 0.55, 95% CI 0.42-0.73) compared to reproductive endocrinologists. CONCLUSION: Racial and socioeconomic disparities exist in the provision of infertility treatments for patients with PCOS. Fewer primary care physicians engaged in first-line fertility treatment, indicating an opportunity for physician education to improve access to fertility care.

Operative Time and Accrual of Postoperative Complications in Minimally Invasive Versus Open Myomectomy.

STUDY OBJECTIVE: To compare the prevalence and accrual of 30-day postoperative complications by operative time for open myomectomy (OM) and minimally invasive myomectomy (MIM). DESIGN: Retrospective cohort study SETTING: Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2021. PATIENTS: Female patients aged ≥18 years undergoing OM or MIM. INTERVENTIONS: Patients were categorized into OM and MIM cohorts. Covariates associated with operative time and composite complications were identified using general linear model and chi-square or Fisher's exact test as appropriate. Adjusted spline regression was performed as a test of linearity between operative time and composite complications. Adjusted risk ratios of 30-day postoperative individual, minor, major, and composite complications by 60-minute operative time increments were estimated using Poisson regression with robust error variance. MEASUREMENTS AND MAIN RESULTS: Of 27 728 patients, 11 071 underwent MIM and 16 657 underwent OM. Mean operative times (SD) were 164.6 (82.0) for MIM and 129.2 (67.0) for OM. Raw composite complication rates were 5.5% for MIM and 15.8% for OM. Adjusted spline regression demonstrated linearity between operative time and relative risk of composite postoperative complications for both MIM and OM. MIM had higher adjusted relative risk (aRR, 95% CI) compared to OM of blood transfusion (1.55, 1.45-1.64 versus 1.29, 1.25-1.34), overall minor complications (1.13, 1.03-1.23 versus 1.01, 0.92-1.10), and overall major complications (1.43, 1.35-1.51 versus 1.27, 1.12-1.32). Operative time had greater impact on risk of composite complications for MIM than OM, reaching aRR 2.0 at 296 minutes versus 461 minutes for OM. CONCLUSION: OM has a higher overall rate of composite, minor, and major complications compared to MIM. While operative time is independently and linearly associated with postoperative complications with myomectomy regardless of approach, optimizing surgical efficiency for MIM may be more critical than for OM.

Safety of Same-Day Discharge Versus Hospital Admission in Minimally Invasive Myomectomy.

STUDY OBJECTIVE: To compare postoperative complication rates between same-day discharge patients and patients admitted to hospital after minimally invasive myomectomy, stratified by patient demographics and perioperative variables including myoma burden. DESIGN: Retrospective cohort study. Setting Hospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2019. PATIENTS: Female patients aged ≥18 years undergoing minimally invasive myomectomy. INTERVENTIONS: Patients were categorized into either the same-day discharge or admitted patient cohort. Univariate comparisons of demographics, perioperative variables, and 30-day postoperative complications were performed. Multivariate logistic regression was used to 1) identify demographic and perioperative factors associated with admission, and 2) compare postoperative complication rates of same-day discharge patients with those of admitted patients while adjusting for demographic and perioperative factors. MEASUREMENTS AND MAIN RESULTS: Eight thousand one hundred patients were recruited during the study period. The overall rate of same-day discharge was 57.2% in 2015 and 65.0% in 2019. The same-day discharge rate was 64.6% for patients with a smaller myoma burden (1-4 fibroids and ≤250 grams, Current Procedural Terminology 58545) and 56.8% for larger myoma burden (≥5 fibroids or >250 grams, Current Procedural Terminology 58546). Age, race, American Society of Anesthesiologists classification III or IV, preoperative hematocrit <36%, hypertension, diabetes, bleeding disorder, and increasing operative time were associated with admission to hospital. After adjusting for these variables, composite postoperative complication rates were similar between admitted patients and patients who were discharged the same day regardless of myoma burden (adjusted OR [aOR], 0.66; 95% confidence interval [CI] 0.18-2.47 for low myoma burden and aOR, 0.91; 95% CI 0.18-4.63 for high myoma burden). Admitted patients with both low (aOR, 9.1; 95% CI 2.27-37.04) and high (aOR, 8.24; 95% CI 1.59-42.49) myoma burdens were significantly more likely to receive a blood transfusion compared to same-day discharge patients. CONCLUSION: Same-day discharge after minimally invasive myomectomy, regardless of myoma burden, is associated with low complication rates. Our findings may aid in shared decision making on discharge planning.

Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Prior research suggests that women with endometriosis are at greater risk of coronary heart disease. Therefore, our objective was to prospectively investigate the association between laparoscopically confirmed endometriosis and risk of incident stroke during 28 years of follow-up. METHODS: Participants in the NHSII cohort study (Nurses' Health Study II) were followed from 1989 when they were between the ages of 25 to 42 until 2017 for development of incident stroke (ischemic and hemorrhagic). Cox proportional hazard models were used to calculate hazard ratios and 95% CI, with adjustment for potential confounding variables (alcohol intake, body mass index at age 18, current body mass index, age at menarche, menstrual cycle pattern in adolescence, current menstrual cycle pattern, parity, oral contraceptive use history, smoking history, diet quality, physical activity, NSAID use, aspirin use, race/ethnicity, and income). We estimated the proportion of the total association mediated by history of hypertension, hypercholesterolemia, hysterectomy/oophorectomy, and hormone therapy. We also tested for effect modification by age (<50, ≥50 years), infertility history, body mass index (<25, ≥25 kg/m2), and menopausal status. RESULTS: We documented 893 incident cases of stroke during 2 770 152 person-years of follow-up. Women with laparoscopically confirmed endometriosis had a 34% greater risk of stroke in multivariable-adjusted models (hazard ratio, 1.34 [95% CI, 1.10-1.62]), compared to those without a history of endometriosis. Of the total association of endometriosis with risk of stroke, the largest proportion was attributed to hysterectomy/oophorectomy (39% mediated [95% CI, 14%-71%]) and hormone therapy (16% mediated [95% CI, 5%-40%]). We observed no differences in the relationship between endometriosis and stroke by age, infertility history, body mass index, or menopausal status. CONCLUSIONS: We observed that women with endometriosis were at elevated risk of stroke. Women and their health care providers should be aware of endometriosis history, maximize primary cardiovascular prevention, and discuss signs and symptoms of cardiovascular disease.

Realization of the T Lineage Program Involves GATA-3 Induction of Bcl11b and Repression of Cdkn2b Expression.

The zinc-finger transcription factor GATA-3 plays a crucial role during early T cell development and also dictates later T cell differentiation outcomes. However, its role and collaboration with the Notch signaling pathway in the induction of T lineage specification and commitment have not been fully elucidated. We show that GATA-3 deficiency in mouse hematopoietic progenitors results in an early block in T cell development despite the presence of Notch signals, with a failure to upregulate Bcl11b expression, leading to a diversion along a myeloid, but not a B cell, lineage fate. GATA-3 deficiency in the presence of Notch signaling results in the apoptosis of early T lineage cells, as seen with inhibition of CDK4/6 (cyclin-dependent kinases 4 and 6) function, and dysregulated cyclin-dependent kinase inhibitor 2b (Cdkn2b) expression. We also show that GATA-3 induces Bcl11b, and together with Bcl11b represses Cdkn2b expression; however, loss of Cdkn2b failed to rescue the developmental block of GATA-3-deficient T cell progenitor. Our findings provide a signaling and transcriptional network by which the T lineage program in response to Notch signals is realized.

Research priorities for neuroimmunology: identifying the key research questions to be addressed by 2030.

Neuroimmunology in the broadest sense is the study of interactions between the nervous and the immune systems. These interactions play important roles in health from supporting neural development, homeostasis and plasticity to modifying behaviour. Neuroimmunology is increasingly recognised as a field with the potential to deliver a significant positive impact on human health and treatment for neurological and psychiatric disorders. Yet, translation to the clinic is hindered by fundamental knowledge gaps on the underlying mechanisms of action or the optimal timing of an intervention, and a lack of appropriate tools to visualise and modulate both systems. Here we propose ten key disease-agnostic research questions that, if addressed, could lead to significant progress within neuroimmunology in the short to medium term. We also discuss four cross-cutting themes to be considered when addressing each question: i) bi-directionality of neuroimmune interactions; ii) the biological context in which the questions are addressed (e.g. health vs disease vs across the lifespan); iii) tools and technologies required to fully answer the questions; and iv) translation into the clinic. We acknowledge that these ten questions cannot represent the full breadth of gaps in our understanding; rather they focus on areas which, if addressed, may have the most broad and immediate impacts. By defining these neuroimmunology priorities, we hope to unite existing and future research teams, who can make meaningful progress through a collaborative and cross-disciplinary effort.

Risk factors for atypical hyperplasia and endometrial cancer in the infertility population: a case-control study.

OBJECTIVE: To estimate the incidence and identify risk factors for atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in American women undergoing infertility evaluation. DESIGN: Case-control study. SETTING: Academic reproductive endocrinology and infertility practice. PATIENTS: Female patients (18-50 years) seeking infertility evaluation from January 1, 2009 to December 1, 2018. Patients with known genetic predisposition to cancer or prior cancer diagnosis were excluded. Cases were defined as patients diagnosed with AH or EC during infertility workup (n = 22). Controls without AH or EC were randomly selected in a 10:1 ratio (n = 220) from all women undergoing infertility evaluation in the same year. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Incidence of AH or EC and odds of AH or EC accounting for age, race, body mass index (BMI), and ovulatory dysfunction. RESULTS: Twenty-two cases of AH or EC were identified among 11,569 women undergoing infertility evaluation (incidence 2 per 1,000 women, 95% confidence interval [CI] 1.2-2.9 per 1,000). Of these women, 68% had a BMI ≥30 kg/m2 compared with 25% of controls. In multivariable analyses, women with a BMI ≥30 kg/m2 were 5.9 times more likely to be diagnosed with AH or EC (adjusted odds ratio 5.9, 95% CI 2.0-17.2). Women with ovulatory dysfunction were 3.4 times more likely to be diagnosed with AH or EC (adjusted odds ratio 3.4, 95% CI 1.1-10.1). CONCLUSIONS: The incidence of AH and EC in a population of women undergoing infertility evaluation is 10 times that in the general population of premenopausal women. Obesity is the strongest independent risk factor for AH and EC in women with infertility.

Maximising the potential of neuroimmunology.

Technological developments in recent years have led to a surge in advances in neuroimmunology, making real progress towards improving human health. With the scale of the challenges ahead, realising this potential requires a collaborative effort. The neuroscience, immunology and wider scientific community, both academia and industry, must come together to pool together ideas, experiences and resources.

Surgical simulation supplements reproductive endocrinology and infertility fellowship training.

OBJECTIVE: To assess if a surgical boot camp improves laparoscopic skill among reproduction endocrinology and infertility (REI) fellows and increases fellow desire to incorporate surgical skills into practice and to examine whether fellowship in vitro fertilization (IVF) volume correlates with surgical efficiency. DESIGN: Prospective evaluation. SETTING: Simulation Center. PATIENTS: Forty REI fellows. INTERVENTIONS: Fellows were timed before and after training in laparoscopic suturing and knot tying and while using virtual simulators. Fellows were surveyed before boot camp on prior experience with IVF and reproductive surgery, and immediately and 1 month after boot camp on their desire to incorporate surgical skills into practice. MAIN OUTCOME MEASURES: Efficiency of laparoscopic suturing and knot tying before and after boot camp; likelihood and persistence of incorporating surgical skills into practice immediately and 1 month after boot camp; and correlation between fellowship IVF volume and fellow surgical efficiency. RESULTS: Fellows experienced significant improvement in laparoscopic suturing (44 sec), intracorporeal knot tying (82 sec), and extracorporeal knot tying (71 sec). Fellows reported being more likely to incorporate operative hysteroscopy (89%), operative laparoscopy (87%), and laparoscopic suturing (84%) into practice immediately following boot camp with no difference 1 month later. Fifty-four percent of fellows reported being more likely to perform robotic surgery after the boot camp, increasing to 70% 1 month later. There were weak correlations between IVF case volume and efficiency in laparoscopic suturing or hysteroscopic polypectomy (Spearman correlation coefficients, -0.14 and -0.03). CONCLUSIONS: An intensive surgical boot camp enhances surgical skill among REI fellows.

The Epidemiology of Brachial Plexus Birth Palsy in the United States: Declining Incidence and Evolving Risk Factors.

BACKGROUND: The epidemiology of brachial plexus birth palsy (BPBP) in the United States may be changing over time due to population-level changes in obstetric care. METHODS: The Kids' Inpatient Database from 1997 to 2012 was analyzed. Annual estimates of BPBP incidence and disease determinant distribution were calculated for the general population and the study population with BPBP. Long-term trends were analyzed. A multivariate logistic regression model was used to quantify the risk associated with each determinant. RESULTS: The database yielded a combined total of 5,564,628 sample births extrapolated to 23,385,597 population births. The population incidence of BPBP dropped 47.1% over the 16-year study period, from 1.7 to 0.9 cases per 1000 live births (P<0.001). Female, black, and Hispanic subgroups had moderately increased risks of BPBP. Among children with BPBP, 55.0% had no identifiable risk factor. Shoulder dystocia was the strongest risk factor for BPBP in the regression model [odds ratio (OR), 113.2; P<0.001], although the risk of sustaining a BPBP in the setting of shoulder dystocia decreased from 10.7% in 1997 to 8.3% in 2012 (P=0.006). Birth hypoxia was independently associated with BPBP (OR, 3.1; P<0.001). Cesarean delivery (OR, 0.16; P<0.001) and multiple gestation birth (OR, 0.45; P<0.001) were associated with lower incidence of BPBP. Notably, the rate of cesarean delivery increased by 62.8% during the study period, from 20.9% in 1997 to 34.0% in 2012 (P<0.001). CONCLUSIONS: Over a 16-year period, the incidence of BPBP fell dramatically, paralleled by a significant increase in the rate of cesarean delivery. Systemic changes in obstetric practice may have contributed to these trends. As more than half of BPBP cases have no identifiable risk factor, prospective investigation of established risk factors and characterization of new disease determinants are needed to more reliably identify infants at greatest risk. Racial and geographic inequalities in disease burden should be investigated to identify interventional targets. LEVEL OF EVIDENCE: Level III-case series.

Association of Patient Race With Surgical Practice and Perioperative Morbidity After Myomectomy.

OBJECTIVE: To compare surgical approach, operative time, and perioperative morbidity after myomectomy by patient race. METHODS: In this retrospective cohort study, data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program database on 8,438 women undergoing myomectomy between January 1, 2012, and December 31, 2015. Myoma burden and approach to myomectomy were determined based on Current Procedural Terminology coding. Surgical approach and perioperative morbidity were examined in African American, Asian American, and Hispanic American women using non-Hispanic Caucasian women as the referent population. Adjusted means and odds ratios (ORs) with 95% CI were calculated using propensity score matching accounting for age, ethnicity, body mass index (BMI), myoma burden, preoperative anemia, hypertension, smoking, and operative time. RESULTS: Data were available for 2,533 Caucasian, 3,359 African American, 664 Asian American, and 700 Hispanic American women. Smoking, BMI, hypertension, myoma burden, and anemia varied by race (P<.001, all comparisons). In adjusted analysis, African American women were twice as likely to undergo abdominal myomectomy (adjusted OR 1.9, 95% CI 1.7-2.0), Asian American women were more than twice as likely (adjusted OR 2.3, 95% CI 1.8-2.8), and Hispanic American women were 50% more likely to undergo abdominal myomectomy (adjusted OR 1.5, 95% CI 1.2-1.9) when compared with Caucasian women. African American women were 50% more likely to experience composite morbidity after abdominal myomectomy (adjusted OR 1.5, 95% CI 1.2-1.7) and Asian American women were more than three times as likely to experience composite morbidity after laparoscopic myomectomy (adjusted OR 3.7, 95% CI 1.7-8.1) compared with Caucasian women. There were no differences in composite morbidity in other racial groups. CONCLUSION: Minority women are substantially more likely to undergo abdominal myomectomy when compared with Caucasian women. African American women had 50% increased odds of morbidity after abdominal myomectomy, and Asian American women were more than three times as likely to experience morbidity after laparoscopic myomectomy. Further examination into the etiology and prevention of these racial disparities is needed.

Difference between mean gestational sac diameter and crown-rump length as a marker of first-trimester pregnancy loss after in vitro fertilization.

OBJECTIVE: To investigate whether the difference between mean gestational sac diameter and crown-rump length (mGSD - CRL) is associated with first-trimester pregnancy loss or adverse pregnancy outcomes after in vitro fertilization (IVF) and to determine if mGSD - CRL is a better predictor of pregnancy loss than either measurement alone. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): A total of 1,243 IVF cycles with fresh or cryopreserved autologous embryo transfers resulting in singleton gestations performed at the University of Iowa Hospitals and Clinics from January 2005 through December 2014. Cycles included ultrasound measurements of mGSD and CRL at 45-56 days' gestation. INTERVENTION(S): Mean gestational sac diameter to crown-rump length difference. MAIN OUTCOME MEASURE(S): Primary outcomes were first-trimester pregnancy loss and gestational age at delivery. Secondary outcomes were infant birth weight and pregnancy complications. RESULT(S): First-trimester pregnancy loss rates were significantly higher in pregnancies with mGSD - CRL <5 mm (43.7%) compared with 5-9.99 mm (15.8%), 10-14.99 mm (9.9%), and ≥15 mm (7.1%). No correlations were found with infant birth weight, gestational age at delivery, or other pregnancy complications. mGSD - CRL was not a better predictor of pregnancy loss than mGSD or CRL alone. CONCLUSION(S): There is a strong inverse relationship between mGSD - CRL and first-trimester pregnancy loss in IVF patients, although the incidence of pregnancy loss with a mGSD - CRL <5 mm was significantly lower than previously reported. Small mGSD - CRL was not associated with an increased risk of complications in pregnancies that continued beyond 20 weeks. The association between mGSD, CRL, and miscarriage is complex.

Fertility preservation training for obstetrics and gynecology fellows: a highly desired but non-standardized experience.

BACKGROUND: Despite a large body of data suggesting that delivery of fertility care to cancer patients is inconsistent and frequently insufficient, there is a paucity of literature examining training in fertility preservation for those physicians expected to discuss options or execute therapy. The study objective was to compare fertility preservation training between Reproductive Endocrinology & Infertility (REI) and Gynecologic Oncology (GYN ONC) fellows and assess the need for additional education in this field. METHODS: A 38-item survey was administered to REI and GYN ONC fellows in the United states in April 2014. Survey items included: 1) Clinical exposure, perceived quality of training, and self-reported knowledge in fertility preservation; 2) an educational needs assessment of desire for additional training in fertility preservation. RESULTS: Seventy-nine responses were received from 137 REI and 160 GYN ONC fellows (response rate 27%). REI fellows reported seeing significantly more fertility preservation patients and rated their training more favorably than GYN ONC fellows (48% of REI fellows versus 7% of GYN ONC fellows rated training as 'excellent', p < 0.001). A majority of all fellows felt discussing fertility preservation was 'very important' but fellows differed in self-reported ability to counsel patients, with 43% of REI fellows and only 4% of GYN ONC fellows able to counsel patients 'all the time' (p = 0.002). Seventy-six percent of all fellows felt more education in fertility preservation was required, and 91% felt it should be a required component of fellowship training. CONCLUSION: Significant variability exists in fertility preservation training for REI and GYN ONC fellows, with the greatest gap seen for GYN ONC fellows, both in perceived quality of fertility preservation training and number of fertility preservation patients seen. A majority of fellows in both disciplines support the idea of a standardized multi-disciplinary curriculum in fertility preservation.

Changes in Myomectomy Practice After the U.S. Food and Drug Administration Safety Communication on Power Morcellation.

OBJECTIVE: To examine the association between the 2014 U.S. Food and Drug Administration (FDA) safety communication on power morcellation and surgical approach and morbidity after myomectomy. METHODS: In this retrospective cohort study, data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program database on 3,160 myomectomies between April 2012 and December 2013 (pre-FDA) and 4,378 between April 2014 and December 2015 (post-FDA). Aims were to 1) compare rates of abdominal and laparoscopic myomectomy pre-FDA and post-FDA (primary outcome), 2) directly compare the morbidity of abdominal and laparoscopic myomectomy during each time period (secondary outcome 1), and 3) compare the morbidity after all myomectomies performed pre-FDA and post-FDA (secondary outcome 2). Adjusted means, odds ratios, and rate ratios with 95% confidence intervals were calculated using linear, logistic, and Poisson regression, respectively, adjusting for age, race, ethnicity, body mass index, and myoma burden. RESULTS: Myomectomies performed post-FDA were more likely to be abdominal (60.0%, 95% confidence interval [CI] 58.6-61.5%) than laparoscopic (40.0%, 95% CI 38.5-41.4%) as compared with myomectomies pre-FDA, which were equally divided between surgical approaches (49.1% abdominal, 95% CI 47.4-50.9% compared with 50.9% laparoscopic, 95% CI 49.1-52.6%; P<.001). When directly compared with laparoscopic myomectomy, abdominal myomectomy was associated with longer hospitalizations, higher readmission rates, and greater morbidity both pre-FDA and post-FDA (P<.05, all comparisons). Adjusted models demonstrated shorter operative times post-FDA for all myomectomies (P<.001), although composite morbidity was similar between myomectomies performed pre-FDA and post-FDA (P=.809). CONCLUSIONS: The FDA safety communication on power morcellation was associated with an 11% absolute increase in the use of abdominal myomectomy. Although morbidity is consistently higher after abdominal as compared with laparoscopic myomectomy, the increased reliance on abdominal myomectomy post-FDA did not result in clinically significant changes in morbidity in this cohort.

Association Between Body Mass Index, Uterine Size, and Operative Morbidity in Women Undergoing Minimally Invasive Hysterectomy.

STUDY OBJECTIVE: Although the selection of an approach to minimally invasive hysterectomy is relatively straightforward in an ideal patient scenario, it is more difficult in patients who pose operative challenges such as high body mass index (BMI) and enlarged uteri. The objective of this study was to explore the association between surgical approach and operative morbidity after minimally invasive hysterectomy and examine whether the association varies based on patient BMI and uterine size. DESIGN: Retrospective cohort (Canadian Task Force classification II-2). SETTING: Data abstracted from the American College of Surgeons National Safety and Quality Improvement Project registry. PATIENTS: Thirty-six thousand seven hundred fifty-seven women undergoing vaginal, laparoscopic-assisted vaginal, or total laparoscopic hysterectomy for benign indications between January 2005 and December 2012. INTERVENTIONS: Associations between surgical approach, BMI, and operative morbidity were examined, stratifying by uterine size (< or >250 g) and adjusting for covariates. Adjusted means, rate ratios, or odds ratios with 95% confidence intervals (CI) were calculated using linear, Poisson, or logistic regression. MEASUREMENTS AND MAIN RESULTS: Operative times were shortest in women undergoing vaginal hysterectomy regardless of BMI or uterine size (all p < .02). Although operative time increased with BMI, the association varied with uterine size in women undergoing vaginal hysterectomy; increasing BMI had a minimal impact on operative time with small uteri <250 g but lengthened operative time in uteri >250 g. Compared with vaginal hysterectomy, total laparoscopic hysterectomy had lower odds of blood transfusion (all p < .02) and shorter hospitalizations (all p < .03) regardless of uterine size or BMI. Stratifying by uterine size, the association was strongest in morbidly obese women with small uteri; women with uteri <250 g and BMI >40 kg/m2 had 76% lower odds of blood transfusion (95% CI, 0.10-0.54) and 18% shorter hospitalization (95% CI, 0.75-0.90) after laparoscopic hysterectomy compared with vaginal hysterectomy. CONCLUSION: Major operative morbidity after minimally invasive hysterectomy is rare regardless of the surgical approach. A vaginal approach to hysterectomy is associated with the shortest operative times, but increasing BMI results in a rapid escalation of operative time in women with large uteri. Total laparoscopic hysterectomy is associated with shorter hospitalizations and lower odds of blood transfusion across the BMI spectrum, particularly in women with small uteri. Laparoscopic-assisted vaginal hysterectomy appears to confer no specific advantage over the vaginal or laparoscopic approaches.

Lapse in embryo transfer training does not negatively affect clinical pregnancy rates for reproductive endocrinology and infertility fellows.

OBJECTIVE: To compare rates of clinical pregnancy (CPR) and live birth (LBR) following embryo transfer (ET) performed by reproductive endocrinology and infertility (REI) fellows before and after a prolonged lapse in clinical training due to an 18-month research rotation. DESIGN: Retrospective cohort study. SETTING: Not applicable. PATIENT(S): All women undergoing in vitro fertilization (IVF) and IVF-intracytoplasmic sperm injection (ICSI) cycles with ET performed by REI fellows from August 2003 to July 2012. INTERVENTION: Eighteen-month lapse in clinical training of REI fellows. MAIN OUTCOME MEASURE(S): CPR and LBR before and after the lapse in clinical training were calculated and compared per fellow and as a composite group. Alternating logistic regression models were used to calculate the odds of clinical pregnancy and live birth following transfers performed before and after the lapse in training. RESULT(S): Unadjusted odds of clinical pregnancy and live birth were similar between the two time periods both for individual fellows and for the composite group. Alternate logistic regression analysis revealed no significant difference in CPR (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.83-1.07) or LBR (OR 1.05, 95% CI 0.94-1.18) after the lapse in training compared with before. CONCLUSION(S): A research rotation is common in REI fellowship training programs. This prolonged departure from clinical training does not appear to negatively affect pregnancy outcome following fellow ET.

An overview of the intrathymic intricacies of T cell development.

The generation of a functional and diverse repertoire of T cells occurs in the thymus from precursors arriving from the bone marrow. In this article, we introduce the various stages of mouse thymocyte development and highlight recent work using various in vivo, and, where appropriate, in vitro models of T cell development that led to discoveries in the regulation afforded by transcription factors and receptor-ligand signaling pathways in specifying, maintaining, and promoting the T cell lineage and the production of T cells. This review also discusses the role of the thymic microenvironment in providing a niche for the successful development of T cells. In particular, we focus on advances in Notch signaling and developments in Notch ligand interactions in this process.

Pharmacokinetics of human chorionic gonadotropin injection in obese and normal-weight women.

CONTEXT: Obese women have poorer in vitro fertilization outcomes, but underlying mechanisms remain unclear. OBJECTIVE: The objectives of the study were to compare the pharmacokinetics of human chorionic gonadotropin (hCG) and ovarian steroid hormone production, after subcutaneous (s.c.) and intramuscular (i.m.) injection of hCG in obese and normal-weight women. DESIGN AND SETTING: This was a randomized, experimental study. PATIENTS OR OTHER PARTICIPANTS: Twenty-two women aged 18-42 years with body mass index of 18.5-24.9 (normal) or 30-40 kg/m(2) (obese). INTERVENTIONS: Participants received im urinary hCG or s.c. recombinant hCG and returned for a second injection type after a 4-week washout. Intramuscular injections were performed under ultrasound guidance. Blood was taken 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 36 hours after injection. MAIN OUTCOME MEASURES: hCG was measured at each time point; estradiol, progesterone, 17-hydroxyprogesterone (17-OHP), testosterone (T), dehydroepiandrosterone, and SHBG were measured at 0 and 36 hours. RESULTS: Twenty-two women completed the study. In both normal-weight and obese women, peak serum concentration (Cmax), area under the curve (AUC), and average hCG concentration were higher after i.m. injection as compared with s.c. injection (all P < .003). Obese women had markedly lower Cmax, AUC, and average hCG concentration after s.c. injection as compared with normal-weight women (P = .02, P = .009, and P = .008, respectively). After i.m. injection, Cmax, AUC, and average concentration were similar for normal-weight and obese women (P = .31, P = .25, and P = .18, respectively). Thirty-six percent of obese women had muscular layers beyond the reach of a standard 1.5 inch needle. hCG caused a significant rise in 17-OHP in both obese and normal-weight women and an increase in T in obese but not normal-weight women (all P < .04). CONCLUSIONS: Subcutaneous injection yields lower hCG levels in obese women. Standard-length needles are insufficient to administer i.m. injections in many obese women.