Female physician infertility: the lack of adequate insurance coverage.

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

Synthesis of stereochemically and skeletally diverse fused ring systems from functionalized C-glycosides.

A diversity-oriented synthesis (DOS) strategy was developed for the synthesis of stereochemically diverse fused-ring systems containing a pyran moiety. Each scaffold contains an amine and methyl ester for further diversification via amine capping and amide coupling. Scaffold diversity was evaluated in comparison to previously prepared scaffolds by a shape-based principal moments of inertia (PMI) analysis.

Treatment of acute-onset hypertension in pregnancy: A network meta-analysis of randomized controlled trials comparing anti-hypertensives and route of administration.

BACKGROUND: Consensus on the relative efficacy of available antihypertensive agents used in pregnancy is lacking. OBJECTIVE: To compare treatment success with antihypertensives and categorize by route of administration. SEARCH STRATEGY: MEDLINE, Embase, PubMed, Web of Science, Scopus, CINAHL, and clinicaltrials.gov were searched without date restriction. DATA COLLECTION: Peer-reviewed randomized controlled trials (RCTs) comparing pharmacologic agents used to treat hypertension in parturients were included. Evaluated treatment groups included IV-labetalol (BBIV), IV-hydralazine (DIV), oral-nifedipine (CCBPO), sublingual nifedipine (CCBSL), IV-calcium channel blocker (nonspecific)(CCBIV), IV-nitroglycerine (NTG), epoprostenol infusion (PRO), IV-ketanserin (5HT2B), IV-diazoxide (BZO), oral-nifedipine + methyldopa (CCBAG), oral-methyl-dopa (AAG), and oral prazosin (ABPO). ANALYSIS: Seventy-four studies (8324 patients) were eligible post PRISMA guidelines screening. Results were pooled using a Bayesian-approach for success of treatment (study defined target blood pressure), time to achieve target pressure, and neonatal intensive-care admissions. RESULTS: Treatment success (primary outcome, 55 trials with 5518 patients) was analyzed. Surface under the cumulative ranking curve (SUCRA) was categorized for 13 drugs, CCBPO (0.84) followed by CCBSL (0.78) were most likely to be effective in achieving target blood pressure. After sub-grouping by presence/absence of preeclampsia, CCB-PO ranked highest for both [(0.82) vs. (0.77), respectively]. Serotonin antagonists (0.99) and nitroglycerin (0.88) ranked highest for time to target pressure. NICU admissions were lowest for alpha-2 agonists (0.89), followed by BB PO (0.82) and hydralazine IV (0.49). CONCLUSION: Oral calcium-channel blockers ranked highest for treatment success. Ketanserin achieved target blood pressure fastest, warranting additional research. The results should be interpreted with caution as SUCRA values may not indicate whether the differences between interventions have clinically meaningful effect sizes.

Practical asymmetric synthesis of ß-hydroxy γ-amino acids via complimentary aldol reactions.

Orthogonally protected chiral ß-hydroxy-γ-amino acids can be accessed in >100 g quantities from readily available starting materials and reagents in 3-4 steps. These chiral synthons contain two adjacent stereocenters along with suitably protected functional groups (O-TBS, N-Boc) for downstream reactivity. Implementation of two existing aldol technologies allows rapid access to all possible stereoisomers of 1. The guiding principles during reaction optimization were reaction scalability and operational efficiency. Conversion of the amino acids to a variety of chiral building blocks in 1-2 steps demonstrates their synthetic utility.

Management of Fontan circulation in pregnancy: a multidisciplinary approach to care.

The Fontan operation was first performed in 1968 and is a palliative procedure for children born with single ventricle forms of congenital heart disease. Today, 70,000 patients worldwide have Fontan circulation today, half of them women, and with an expected 30-year survival of >80%, this population is expected to double in the next 20 years. The Fontan operation surgically redirects systemic venous blood return directly to the pulmonary circulation, bypassing the single ventricle. This abnormal anatomy results in significant challenges for the cardiovascular system and is marked by a sustained, abnormally elevated systemic venous pressure combined with decreased cardiac output. As more women with Fontan circulation reach childbearing age, understanding the unique risks of pregnancy to the mother and fetus and how to best provide clinical care for these women during pregnancy is imperative. However, there are limited clinical data to guide counseling and management in this population. This expert review offers an analysis of the literature about Fontan circulation during pregnancy and describes our center's current multidisciplinary approach to care for these women in the preconception, antepartum, intrapartum, and postpartum periods.

Trial of Labor After Two Prior Cesarean Deliveries: Patient and Hospital Characteristics and Birth Outcomes.

OBJECTIVE: Trial of labor after cesarean delivery has been mostly studied in the setting of one prior cesarean delivery; controversy remains regarding the risks and benefits of trial of labor for women with two prior cesarean deliveries. This study aimed to examine utilization, success rate, and maternal and neonatal outcomes of trial of labor in this population. METHODS: Using linked hospital discharge and birth certificate data, we retrospectively analyzed a cohort of mothers with nonanomalous, term, singleton live births in California between 2010-2012 and had two prior cesarean deliveries and no clear contraindications for trial of labor. We measured whether they attempted labor and, if so, whether they delivered vaginally. Association of patient and hospital characteristics with the likelihood of attempting labor and successful vaginal birth was examined using multivariable regressions. We compared composite severe maternal morbidities and composite severe newborn complications in those who underwent trial of labor as opposed to planned cesarean delivery using a propensity score-matching approach. RESULTS: Among 42,771 women who met sample eligibility criteria, 1,228 (2.9%) attempted labor, of whom 484 (39.4%) delivered vaginally. There was no significant difference in the risk of composite severe maternal morbidities, but there was a modest increase in the risk of composite severe newborn complications among women who attempted labor compared with those who did not (2.0% vs 1.4%, P=.04). After accounting for differences in patient and hospital characteristics, propensity score-matched analysis showed no significant association between trial of labor and the risk of composite severe maternal morbidities (odds ratio [OR] 1.16, 95% CI 0.70-1.91), but trial of labor was associated with a higher risk for the composite of severe newborn complications (OR 1.78, 95% CI 1.04-3.04). CONCLUSION: Among women with two prior cesarean deliveries, trial of labor was rarely attempted and was successful in 39.4% of attempts. Trial of labor in this population was associated with a modest increase in severe neonatal morbidity.

Deep-learned placental vessel segmentation for intraoperative video enhancement in fetoscopic surgery.

INTRODUCTION: Twin-to-twin transfusion syndrome (TTTS) is a potentially lethal condition that affects pregnancies in which twins share a single placenta. The definitive treatment for TTTS is fetoscopic laser photocoagulation, a procedure in which placental blood vessels are selectively cauterized. Challenges in this procedure include difficulty in quickly identifying placental blood vessels due to the many artifacts in the endoscopic video that the surgeon uses for navigation. We propose using deep-learned segmentations of blood vessels to create masks that can be recombined with the original fetoscopic video frame in such a way that the location of placental blood vessels is discernable at a glance. METHODS: In a process approved by an institutional review board, intraoperative videos were acquired from ten fetoscopic laser photocoagulation surgeries performed at Yale New Haven Hospital. A total of 345 video frames were selected from these videos at regularly spaced time intervals. The video frames were segmented once by an expert human rater (a clinician) and once by a novice, but trained human rater (an undergraduate student). The segmentations were used to train a fully convolutional neural network of 25 layers. RESULTS: The neural network was able to produce segmentations with a high similarity to ground truth segmentations produced by an expert human rater (sensitivity = 92.15% ± 10.69%) and produced segmentations that were significantly more accurate than those produced by a novice human rater (sensitivity = 56.87% ± 21.64%; p < 0.01). CONCLUSION: A convolutional neural network can be trained to segment placental blood vessels with near-human accuracy and can exceed the accuracy of novice human raters. Recombining these segmentations with the original fetoscopic video frames can produced enhanced frames in which blood vessels are easily detectable. This has significant implications for aiding fetoscopic surgeons-especially trainees who are not yet at an expert level.

Catalytic scaffolding ligands: an efficient strategy for directing reactions.

The design and application of a scaffolding ligand that promotes branch and diastereoselective hydroformylation of terminal olefins as well as the regio- and diastereoselective hydroformylation of disubstituted olefins is reported. It is shown that the ligand covalently and reversibly bonds to the substrate, allowing for directed hydroformylation. As the substrate ligand interaction is dynamic, hydroformylations are catalytic in ligand and do not require any additional synthetic steps to add or remove the directing group. Using a catalytic quantity of a scaffolding ligand (20-25 mol %), excellent regioselectivity for disubstituted olefins (up to 98:2) and high branch selectivity (up to 88:12) for terminal olefins were obtained.

Regioselective hydroformylation of sulfonamides using a scaffolding ligand.

A highly regioselective hydroformylation of allylic sulfonamides has been developed by employing a catalytic directing group. The reaction tolerates a wide range of electronically and sterically modified olefins, and only 10% of the scaffolding ligand is required to effectively control the regioselectivity.

Preeclampsia and small-for-gestational age are associated with decreased concentrations of a factor involved in angiogenesis: soluble Tie-2.

OBJECTIVE: An anti-angiogenic state has been described in patients with preeclampsia, small-for-gestational age (SGA) fetuses and fetal death, and changes in the concentration of circulating angiogenic and anti-angiogenic factors can precede the clinical recognition of preeclampsia and SGA by several weeks. Gene deletion studies demonstrate that a selective group of endothelial growth factors are required for vascular development, including members of the vascular endothelial growth factor (VEGF) family, as well as angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2), both ligands for the tyrosine kinase endothelial cell receptor Tie-2. These angiogenic factors have been proposed to promote angiogenesis in a coordinated and complementary fashion. Soluble Tie-2 (sTie-2) is the soluble form of the Tie-2 receptor, which is detectable in biological fluids. The purpose of this study was to determine whether patients with preeclampsia and mothers who deliver a SGA neonate have changes in the plasma concentrations of sTie-2. STUDY DESIGN: This cross-sectional study included patients in the following groups: (1) non-pregnant women (n = 40), (2) women with normal pregnancies (n = 135), (3) patients with preeclampsia (n = 112), and (4) patients who delivered an SGA neonate (n = 53). Maternal plasma concentrations of sTie-2 were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis. RESULTS: (1) The median maternal plasma concentration of sTie-2 was lower in normal pregnant women than in non-pregnant women [median 16.0 ng/mL (range 5.0-71.6) vs. median 20.7 ng/mL (range 10.8-52.4), respectively; p = 0.01)). (2) Plasma sTie-2 concentrations in normal pregnancy changed significantly as a function of gestational age. (3) Patients with preeclampsia and those who delivered SGA neonates had a lower median maternal plasma concentration of sTie-2 than those with a normal pregnancy [preeclampsia: median 14.9 ng/mL (range 4.9-67.3); SGA: median 10.9 ng/mL (range 5.1-29.1); normal pregnancy: median 16.0 ng/mL (range 5.0-71.6); p = 0.048 and p < 0.001, respectively]. (4) Patients with SGA neonates had a lower median plasma concentration of sTie-2 than that of those with preeclampsia [median 10.9 ng/mL (range 5.1-29.1) vs. median 14.9 ng/mL (range 4.9-67.3), respectively; p < 0.001]. (5) Patients with early-onset preeclampsia (34 weeks) median of delta values: -0.13 ng/mL (range -0.47-0.58) vs. median of delta values: -0.09 ng/mL (range: -0.60-0.58), respectively; p = 0.043]. In contrast, there were no significant differences in the maternal plasma sTie-2 concentration between women with severe and mild preeclampsia (p = 0.6). CONCLUSION: Patients with preeclampsia and those with SGA fetuses have lower median plasma concentrations of soluble Tie-2 than women with normal pregnancies.