Disproportionate multimorbidity among veterans in middle age.

BACKGROUND: Little is known about the prevalence of multimorbidity among middle-aged veterans. Multimorbidity holds implications for planning for a population with high health care utilization, poor quality of life and marked need for interdisciplinary care. METHODS: The current study used the US 2017 Behavior Risk Factor Surveillance System to measure multimorbidity in three ways: (1) reporting two or more health conditions, (2) reporting two or more conditions controlling for demographic characteristics (e.g. income) and health risk behaviors (e.g. smoking) and (3) a weighted index using health-related quality of life. RESULTS: After age 25, veterans' risk for multimorbidity increased across all age groups. The increased odds of reporting multimorbidity was highest when comparing veterans aged 35-44 to non-veterans of the same ages. Veterans aged 35-44 are 50% (adjusted odds ratios (AOR) 1.50, 95% confidence interval (CI) 1.16, 1.94) to 80% (AOR 1.80, 95% CI 1.46, 2.23) more likely to report multimorbidity when compared with same aged non-veterans. CONCLUSIONS: Younger veterans may benefit from comprehensive interdisciplinary services to aid in the treatment of multiple medical conditions. Failure to account for the impact of chronic conditions on quality of life may lead to an underestimate of the health care needs of veterans across the lifespan.

Fertility awareness and attitudes among resident physicians across different specialties.

PURPOSE: To evaluate knowledge of age-related fertility decline and oocyte cryopreservation among resident physicians in obstetrics and gynecology (ob-gyn) compared to residents in other specialties. METHODS: An online survey was sent to the US residency program directors for ob-gyn, internal medicine, emergency medicine, family medicine, general surgery, pediatrics, and psychiatry. They were asked to forward the survey to their respective residents. The survey consisted of three sections: fertility knowledge, oocyte cryopreservation knowledge, and attitudes toward family building and fertility preservation. Multivariable logistic regression models were used to compare outcomes between ob-gyn and non-ob-gyn residents. RESULTS: Of the 2,828 completed surveys, 450 (15.9%) were by ob-gyn residents and 2,378 (84.1%) were by residents in other specialties. 66.3% of respondents were female. The median number of correct answers was 2 out of 5 on the fertility knowledge section and 1 out of 3 on the oocyte cryopreservation knowledge section among both ob-gyn and non-ob-gyn residents. After adjusting for covariates, residents in ob-gyn were no more likely to answer these questions correctly than residents in other specialties (fertility knowledge, adjusted OR .97, 95% CI .88-1.08; oocyte cryopreservation knowledge, adjusted OR 1.05, 95% CI .92-1.19). Ob-gyn residents were significantly more likely than non-ob-gyn residents to feel "somewhat supported" or "very supported" by their program to pursue family building goals (83.5% vs. 75.8%, OR 1.62, 95% CI 1.23-2.14). CONCLUSIONS: Resident physicians, regardless of specialty, have limited knowledge of natural fertility decline and the opportunity to cryopreserve oocytes. These data suggest need for improved fertility education.

Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability.

Genetic studies of intellectual disability and identification of monogenic causes of obesity in humans have made immense contribution toward the understanding of the brain and control of body mass. The leptin > melanocortin > SIM1 pathway is dysregulated in multiple monogenic human obesity syndromes but its downstream targets are still unknown. In ten individuals from six families, with overlapping 6q16.1 deletions, we describe a disorder of variable developmental delay, intellectual disability, and susceptibility to obesity and hyperphagia. The 6q16.1 deletions segregated with the phenotype in multiplex families and were shown to be de novo in four families, and there was dramatic phenotypic overlap among affected individuals who were independently ascertained without bias from clinical features. Analysis of the deletions revealed a ∼350 kb critical region on chromosome 6q16.1 that encompasses a gene for proneuronal transcription factor POU3F2, which is important for hypothalamic development and function. Using morpholino and mutant zebrafish models, we show that POU3F2 lies downstream of SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. Our work helps to further delineate the neuro-endocrine control of energy balance/body mass and demonstrates that this molecular pathway is conserved across multiple species.

Factors associated with internal medicine physician job attitudes in the Veterans Health Administration.

BACKGROUND: US healthcare organizations increasingly use physician satisfaction and attitudes as a key performance indicator. Further, many health care organizations also have an academically oriented mission. Physician involvement in research and teaching may lead to more positive workplace attitudes, with subsequent decreases in turnover and beneficial impact on patient care. This article aimed to understand the influence of time spent on academic activities and perceived quality of care in relation to job attitudes among internal medicine physicians in the Veterans Health Administration (VHA). METHODS: A cross-sectional survey was conducted with inpatient attending physicians from 36 Veterans Affairs Medical Centers. Participants were surveyed regarding demographics, practice settings, workplace staffing, perceived quality of care, and job attitudes. Job attitudes consisted of three measures: overall job satisfaction, intent to leave the organization, and burnout. Analysis used a two-level hierarchical model to account for the nesting of physicians within medical centers. The regression models included organizational-level characteristics: inpatient bed size, urban or rural location, hospital teaching affiliation, and performance-based compensation. RESULTS: A total of 373 physicians provided useable survey responses. The majority (72%) of respondents reported some level of teaching involvement. Almost half (46%) of the sample reported some level of research involvement. Degree of research involvement was a significant predictor of favorable ratings on physician job satisfaction and intent to leave. Teaching involvement did not have a significant impact on outcomes. Perceived quality of care was the strongest predictor of physician job satisfaction and intent to leave. Perceived levels of adequate physician staffing was a significant contributor to all three job attitude measures. CONCLUSIONS: Expanding opportunities for physician involvement with research may lead to more positive work experiences, which could potentially reduce turnover and improve system performance.

Developmental expression of estrogen receptor beta in the brain of prairie voles (Microtus ochrogaster).

Here, for the first time, the expression of estrogen receptor beta (ERß) is characterized in the brains of the highly prosocial prairie vole (Microtus ochrogaster). ERß immunoreactivity was compared in weanlings (postnatal Day 21) and adult males and females. The results indicate several major findings. First, unlike ERα, ERß expression is not sexually dimorphic. Second, the adult pattern of ERß-IR is established at the time of weaning, as there were no age-dependent effects on distribution. Finally, ERß does not appear to be as widely distributed in voles compared with rats and mice. High levels of ERß-IR were observed in several regions/nuclei within the medial pre-optic area, ventrolateral pre-optic nuclei, and in the hypothalamus, especially in the paraventricular and supraoptic nuclei. The visualization of ERß in prairie voles is important as the socially monogamous prairie vole functions as a human relevant model system for studying the expression of social behavior and social deficit disorders. Future studies will now be able to determine the effect of treatments on the expression and/or development of ERß in this highly social species.

Fertility and infertility in rheumatoid arthritis.

PURPOSE OF REVIEW: Despite decades of evidence suggesting that women with rheumatoid arthritis (RA) have fewer children than their healthy peers, this information is not widely known among clinicians. The causes of decreased fertility in this population have been largely unexplored, but likely revolve around altered inflammation, increased age when conception is attempted, limited sexual function, and possibly medications limiting ovarian function. RECENT FINDINGS: Several large Scandinavian cohorts and a cohort study in the United States demonstrate that women with RA have smaller families and are slower to conceive compared with other women. Personal choice to limit family size plays some role, as does infertility. Sexual function in women with RA is hampered by pain and fatigue, perhaps decreasing the opportunity for conception. Finally, data about the role of NSAIDs in preventing ovulation suggest that continued use of these medications may hinder conception. SUMMARY: Infertility in women with RA is an under-recognized, but remarkably common phenomenon. Although research continues into the underlying causes, physicians can discuss this topic and refer women to reproductive endocrinology when needed, thereby helping patients to build the families that they desire.

Embryo transfer by reproductive endocrinology fellows vs attending physicians: are live birth rates comparable?

OBJECTIVE: To compare live birth rates following ultrasound-guided embryo transfer (ET) by reproductive endocrinology and infertility fellows versus attending physicians. STUDY DESIGN: Women who underwent their first day-3, fresh, nondonor ET between Oct. 1, 2005, and April 1, 2011, at our academic center were included in this retrospective cohort study. Embryos were designated high quality if they had 8 cells, less than 10% fragmentation, and no asymmetry. ET was performed with the afterload technique under ultrasound guidance. Categorical variables were evaluated with the χ(2) test and continuous variables with the Student t test. Logistic regression was performed to assess the relationship between ET physician and live birth rate while adjusting for potential confounders. RESULTS: Seven hundred sixty women underwent ET by an attending physician, and 104 by a fellow. Baseline characteristics were similar between the groups. The live birth rate was 31% following ET by an attending physician, compared with 34% following ET by a fellow (P = .65). Logistic regression adjusting for potential confounders demonstrated no significant association between ET physician and live birth rate. CONCLUSION: This retrospective study demonstrated no significant difference in live birth rates following ultrasound-guided ET by fellows vs attending physicians at our institution. These data suggest that academic practices using the afterload method and ultrasound guidance can train fellows to perform ET without compromising success rates.

Addressing Privacy Concerns Surrounding Oocyte Donation in the United States: Gone With Anonymity.

Oocyte donation has greatly expanded in the past several decades since the first procedure was performed in 1983. According to the Centers for Disease Control, the number of cycles using donor oocytes increased from 18,011 cycles in 2010 to 27,131 cycles in 2019. Oocyte donation has become an important reproductive option for women with diminished ovarian reserve, recurrent failed in vitro fertilization, or heritable genetic conditions. It is also particularly important for single men, same-sex male couples, and men with a transgender woman partner. More recently, societal changes accompanying the expansion of social media and broader access to direct-to-consumer DNA testing have raised concerns about privacy and anonymity. In this article, we review two specific aspects of donor privacy: privacy related to personal identifiers provided by clinics or donor egg bank websites and privacy related to direct-to-consumer genetic testing. We also provide clinical recommendations specific to the United States for working with oocyte donors and donor oocyte recipients.

Racial Disparities in Fertility Care: A Narrative Review of Challenges in the Utilization of Fertility Preservation and ART in Minority Populations.

Significant ethnic and racial disparities exist in the utilization and outcomes of assisted reproductive technology (ART) in the United States. The popularity of fertility preservation (FP) procedures, a specific application of ART for those desiring to delay childbearing, has increased; however, many minority populations have seen a less rapid uptake of these services. Minority patients pursuing ART are more likely to have poorer in vitro fertilization (IVF) and pregnancy outcomes. These outcomes are used to predict success after FP and may lessen the appeal of such procedures in these populations. Suboptimal outcomes are further compounded by challenges with receiving referrals to, accessing, and paying for FP services. Resolving these disparities in minority populations will require culturally appropriate education surrounding the benefits of ART and FP, the demonstration of favorable outcomes in ART and FP through continued research engaging minority participants, and continued advocacy for expanded access to care for patients.

The Status of Fertility Preservation (FP) Insurance Mandates and Their Impact on Utilization and Access to Care.

Fertility preservation (FP) is the use of a specific medical intervention to protect the fertility of individuals whose disease or disease treatment may lead to infertility. These medical interventions include the cryopreservation of oocytes, embryos, ovarian tissue, sperm, and testicular tissue; oocyte and embryo cryopreservation are the most widely used interventions in the United States. Although guidelines recommend FP prior to undergoing gonadotoxic treatments, cost barriers are high. For example, the average cost of an oocyte cryopreservation cycle in the United States exceeds $10,000. High cost and lack of insurance coverage are two of the most cited reasons explaining the low Reproductive Endocrinology and Infertility (REI) referral rates and limited FP utilization. Broadening insurance mandates for FP prior to gonadotoxic treatments could improve utilization and provide cancer survivors with improved quality of life post treatment.

An investigation of racial and ethnic disparities in donor sperm availability in the United States.

OBJECTIVE: To determine whether the racial and ethnic distribution of sperm donors contributing to US sperm banks differs from the demographics of the US population and those of US donor sperm recipients undergoing treatment with in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). DESIGN: Cross-sectional study. SETTING: United States donor sperm banks, US Census, and fertility clinics reporting to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. PATIENTS: Sperm donors from 18 banks, men aged 18-39 years on the basis of the 2021 Census Current Population Survey, and recipients of donor sperm for IVF and ICSI treatments in clinics reporting to the Assisted Reproductive Technology Clinic Outcome Reporting System from January 1, 2018, to December 31, 2020. INTERVENTION: None. MAIN OUTCOME MEASURE: Proportions of sperm donors and donor sperm recipients undergoing IVF and ICSI treatments identifying as each racial and ethnic group. RESULTS: Eighteen donor sperm banks were identified, encompassing 1,503 donors. Of these donors, 60.9% identified as White compared with 55.1% of the US male population and 67.7% of donor sperm recipients. Proportions of donors identifying as Asian or 2 or more races were larger than those of US men and donor sperm recipients (Asian: 18.6% vs. 6.5%, and 18.6% vs. 10.2%; 2 or more races: 11.6% vs. 2.2%, and 11.6% vs. 1.7%). In contrast, Black donors were underrepresented when compared with the US population of men and donor sperm recipients (2.8% vs. 12.9% and 2.8% vs. 13.0%). Hispanic donors were underrepresented when compared with the US population of men (6.0% vs. 22.2%). The percentages of Hispanic sperm donors and donor sperm recipients were similar (6.0% vs. 7.0%). CONCLUSION: The racial and ethnic distribution of sperm donors differs significantly from the demographics of the US male population and donor sperm recipients undergoing IVF and ICSI treatments. These findings suggest a need for targeted recruitment efforts for Black sperm donors.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Dysregulation of FHL1 spliceforms due to an indel mutation produces an Emery-Dreifuss muscular dystrophy plus phenotype.

Emery-Dreifuss muscular dystrophy (EDMD) is characterised by early-onset joint contractures, progressive muscular weakness and wasting and late-onset cardiac disease. The more common X-linked recessive form of EDMD is caused by mutations in either EMD (encoding emerin) or FHL1 (encoding four and a half LIM domains 1), while mutations in LMNA (encoding lamin A/C), SYNE1 (encoding nesprin-1) and SYNE2 (encoding nesprin-2) lead to autosomal dominant forms of the condition. Here, we identify a three-generation family with an extended EDMD phenotype due to a novel indel mutation in FHL1 that differentially affects the relative expression of the three known transcript isoforms produced from this locus. The additional phenotypic manifestations in this family-proportionate short stature, facial dysmorphism, pulmonary valvular stenosis, thoracic scoliosis, brachydactyly, pectus deformities and genital abnormalities-are reminiscent of phenotypes seen with dysregulated Ras-mitogen-activated protein kinase (RAS-MAPK) signalling [Noonan syndrome (NS) and related disorders]. The misexpression of FHL1 transcripts precipitated by this mutation, together with the role of FHL1 in the regulation of RAS-MAPK signalling, suggests that this mutation confers a complex phenotype through both gain- and loss-of-function mechanisms. This indel mutation in FHL1 broadens the spectrum of FHL1-related disorders and implicates it in the pathogenesis of NS spectrum disorders.

Amniocytes can serve a dual function as a source of iPS cells and feeder layers.

Clinical barriers to stem-cell therapy include the need for efficient derivation of histocompatible stem cells and the zoonotic risk inherent to human stem-cell xenoculture on mouse feeder cells. We describe a system for efficiently deriving induced pluripotent stem (iPS) cells from human and mouse amniocytes, and for maintaining the pluripotency of these iPS cells on mitotically inactivated feeder layers prepared from the same amniocytes. Both cellular components of this system are thus autologous to a single donor. Moreover, the use of human feeder cells reduces the risk of zoonosis. Generation of iPS cells using retroviral vectors from short- or long-term cultured human and mouse amniocytes using four factors, or two factors in mouse, occurs in 5-7 days with 0.5% efficiency. This efficiency is greater than that reported for mouse and human fibroblasts using similar viral infection approaches, and does not appear to result from selective reprogramming of Oct4(+) or c-Kit(+) amniocyte subpopulations. Derivation of amniocyte-derived iPS (AdiPS) cell colonies, which express pluripotency markers and exhibit appropriate microarray expression and DNA methylation properties, was facilitated by live immunostaining. AdiPS cells also generate embryoid bodies in vitro and teratomas in vivo. Furthermore, mouse and human amniocytes can serve as feeder layers for iPS cells and for mouse and human embryonic stem (ES) cells. Thus, human amniocytes provide an efficient source of autologous iPS cells and, as feeder cells, can also maintain iPS and ES cell pluripotency without the safety concerns associated with xenoculture.

Association of thyroid, breast and renal cell cancer: a population-based study of the prevalence of second malignancies.

BACKGROUND: Analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results data has shown that the incidence of thyroid cancer is higher in patients with a preexisting malignancy and that the incidence of other malignancies is higher in patients with thyroid cancer. The purpose of this study was to evaluate the prevalence of a second malignancy in patients treated for thyroid, breast or renal cell cancer and determine what associations, if any, exist between these cancers. METHODS: This study utilized the novel data system, Explorys, as its population base. Patient cohorts were constructed using ICD-9 codes, and prevalence rates were obtained for each cancer. Rates of second malignancy were obtained and compared to the baseline prevalence for a particular malignancy. RESULTS: Female thyroid cancer patients had a 0.67- and twofold increase in prevalence of a subsequent breast and renal cell cancer. Female breast and renal cell cancer patients had a twofold and 1.5-fold increase in the prevalence of thyroid cancer, respectively. Male patients with thyroid cancer had a 29- and 4.5-fold increase in prevalence of subsequent breast and renal cell cancer. Male patients with breast and renal cell cancer had an increased prevalence of subsequent thyroid cancer, 19- and threefold, respectively. CONCLUSIONS: Our study demonstrated a bidirectional association between thyroid, breast and renal cancer in both male and female patients. This may have important implications for patient follow-up and screening after treatment of a primary cancer.

Maternal education and its association with maternal and neonatal adverse outcomes in live births conceived using medically assisted reproduction (MAR).

BACKGROUND: To examine the association between maternal education and adverse maternal and neonatal outcomes in women who conceived using medically assisted reproduction, which included fertility medications, intrauterine insemination, or in vitro fertilization. METHODS: We conducted a retrospective cohort study utilizing the US Vital Statistics data set on national birth certificates from 2016 to 2020. Women with live, non-anomalous singletons who conceived using MAR and had education status of the birthing female partner recorded were included. Patients were stratified into two groups: bachelor's degree or higher, or less than a bachelor's degree. The primary outcome was a composite of maternal adverse outcomes: intensive care unit (ICU) admission, uterine rupture, unplanned hysterectomy, or blood transfusion. The secondary outcome was a composite of neonatal adverse outcomes: neonatal ICU admission, ventilator support, or seizure. Multivariable modified Poisson regression models with robust error variance adjusted for maternal age, race, marital status, prenatal care, smoking during pregnancy, neonatal sex, and birth year estimated the relative risk (RR) of outcomes with a 95% confidence interval (CI). RESULTS: 190,444 patients met the inclusion criteria: 142,943 had a bachelor's degree or higher and 47,501 were without a bachelor's degree. Composite maternal adverse outcomes were similar among patients with a bachelor's degree (10.1 per 1,000 live births) and those without a bachelor's degree (9.4 per 1,000 live births); ARR 1.05, 95% CI (0.94-1.17). However, composite adverse neonatal outcomes were significantly lower in women with a bachelor's degree or higher (94.1 per 1,000 live births) compared to women without a bachelor's degree (105.9 per 1,000 live births); ARR 0.91, 95% CI (0.88-0.94). CONCLUSIONS: Our study demonstrated that lower maternal education level was not associated with maternal adverse outcomes in patients who conceived using MAR but was associated with increased rates of neonatal adverse outcomes. As access to infertility care increases, patients who conceive with MAR may be counseled that education level is not associated with maternal morbidity. Further research into the association between maternal education level and neonatal morbidity is indicated.

Body mass index is negatively associated with a good perinatal outcome after in vitro fertilization among patients with polycystic ovary syndrome: a national study.

Objective: To evaluate the association between body mass index (BMI) and good perinatal outcomes after in vitro fertilization (IVF) among women with polycystic ovary syndrome (PCOS). Design: Retrospective cohort study using 2012-2015 Society for Assisted Reproductive Technology Clinic Outcomes Reporting System data. Setting: Fertility clinics. Patients: To identify patients most likely to have PCOS, we included women with a diagnosis of ovulation disorder and serum antimüllerian hormone >4.45 ng/mL. Exclusion criteria included age ≥ 41 years, secondary diagnosis of diminished ovarian reserve, preimplantation genetic testing, and missing BMI or primary outcome data. Interventions: None. Main Outcome Measures: Good perinatal outcome, defined as a singleton live birth at ≥ 37 weeks with birth weight ≥ 2,500 g and ≤ 4,000 g. Results: The analysis included 9,521 fresh, autologous IVF cycles from 8,351 women. Among women with PCOS, the proportion of cycles with a good perinatal outcome was inversely associated with BMI: underweight 25.1%, normal weight 22.7%, overweight 18.9%, class I 18.4%, class II 14.9%, and class III or super obesity 12.2%. After adjusting for confounders, women in the highest BMI category had 51% reduced odds of a good perinatal outcome compared with normal weight women (adjusted odds ratio 0.49, 95% confidence interval 0.36-0.67). Conclusions: Among women with PCOS undergoing fresh, autologous IVF, the odds of a good perinatal outcome decline with increasing BMI. Women with PCOS should be counseled that the odds of achieving a good perinatal outcome decrease as their weight increases.

Organizational effects of oxytocin on serotonin innervation.

Oxytocin (OT) has an organizational effect within the central nervous system and can have long-lasting effects on the expression of social behavior. OT has recently been implicated in modulating the release of serotonin through activation of receptors in the raphe nuclei. Here we test the hypothesis that OT can have an organizational effect on the serotonergic system. Male prairie voles received an intraperitoneal injection on postnatal day 1 with 3.0 or .3 µg OT, an OT antagonist, or a saline control. Brains were collected on day 21 and immunostained for serotonin. Serotonin axons were quantified in the anterior hypothalamus, cortical amygdala, medial amygdala, paraventricular nucleus of the hypothalamus, and ventromedial hypothalamus. Males treated with 3.0 µg OT displayed significantly higher serotonin axon length densities in the anterior hypothalamus, cortical amygdala, and the ventromedial hypothalamus than control males. These results support the hypothesis that OT has an organizational effect on the serotonin system during the neonatal period, and that these effects are site-specific.

Impact of increasing antimüllerian hormone level on in vitro fertilization fresh transfer and live birth rate.

Objective: The objective of our study was to assess the association between AMH and live birth among women with elevated AMH undergoing first fresh IVF. Serum antimüllerian hormone (AMH) correlates with oocyte yield during in vitro fertilization (IVF). However, there are limited data regarding IVF outcomes in women with elevated AMH levels. Design: Retrospective cohort study using the Society for Assisted Reproductive Technology Clinical Outcomes Reporting System database from 2012-2014. Setting: Fertility clinics reporting to Society for Assisted Reproductive Technology. Patients: First, fresh, autologous IVF cycles with elevated AMH levels (≥5.0 ng/mL). Subanalyses were performed to examine patients with or without polycystic ovary syndrome (PCOS). Interventions: None. Main Outcome Measures: Odds of live birth. Results: Our cohort included 10,615 patients with elevated an AMH level, including 2,707 patients with PCOS only. The adjusted odds of live birth per initiated cycle were significantly lower per each unit increase in the AMH level (odds ratio, 0.97; 95% confidence interval, 0.96-0.98). Increasing AMH level was associated with increased cancellation of fresh transfer (odds ratio, 1.12; 95% confidence interval, 1.10-1.15) up to an AMH level of 12 ng/mL. The decrease in the live birth rate appears to be caused by the increasing incidence of cancellation of fresh transfer because the live birth rate per completed transfer was maintained. Similar trends were observed in the PCOS and non-PCOS subanalyses. Conclusions: Among patients with AMH levels of ≥5 ng/mL undergoing fresh, autologous IVF, each unit increase in AMH level is associated with a 3% decrease in odds of live birth because of the increased incidence of fresh embryo transfer cancellation.