Objective sleep duration and timing predicts completion of in vitro fertilization cycle.

PURPOSE: To examine associations between objectively measured sleep duration and sleep timing with odds of completion of an in vitro fertilization (IVF) cycle. METHODS: This prospective cohort study enrolled 48 women undergoing IVF at a large tertiary medical center between 2015 and 2017. Sleep was assessed by wrist-worn actigraphy, 1-2 weeks prior to initiation of the IVF cycle. Reproductive and IVF cycle data and demographic and health information were obtained from medical charts. Sleep duration, midpoint, and bedtime were examined in relation to IVF cycle completion using logistic regression models, adjusted for age and anti-Müllerian hormone levels. A sub-analysis excluded women who worked non-day shifts to control for circadian misalignment. RESULTS: The median age of all participants was 33 years, with 29% of women >35 years. Ten women had an IVF cycle cancelation prior to embryo transfer. These women had shorter sleep duration, more nocturnal awakenings, lower sleep efficiency, and later sleep timing relative to those who completed their cycle. Longer sleep duration was associated with lower odds of uncompleted IVF cycle (OR = 0.88; 95%CI 0.78, 1.00, per 20-min increment of increased sleep duration). Women with later sleep midpoint and later bedtime had higher odds of uncompleted cycle relative to those with earlier midpoint and earlier bedtime; OR = 1.24; 95%CI 1.09, 1.40 and OR = 1.33; 95%CI 1.17, 1.53 respectively, for 20-min increments. These results were independent of age, anti-Müllerian hormone levels, or sleep duration, and remained significant after exclusion of shift-working women. CONCLUSIONS: Shorter sleep duration and later sleep timing increase the odds of uncompleted cycles prior to embryo transfer.

Impact of Laparoscopic Hysterectomy on Quality of Life.

There is an ongoing debate regarding the benefits and drawbacks of the various routes of hysterectomy. A number of studies have examined overall quality of life outcomes as well as specific patient-reported outcomes including physical, psychosocial, and sexual functioning after hysterectomy. Existing studies have used varied methodologies with widely heterogeneous results, but patient satisfaction appears to be very high after laparoscopic hysterectomy, with many studies favoring the laparoscopic approach over other routes of hysterectomy. There are many opportunities for further investigation into the impact of laparoscopic hysterectomy on quality of life-an outcome measure that may be 1 of the most important in surgeries for benign indications.

Fertility and fertility preservation: knowledge, awareness and attitudes of female graduate students.

PURPOSE: To evaluate the general knowledge of female graduate students on reproductive aging and fertility preservation options, as well as to investigate the perceptions, personal beliefs, and desires regarding fertility and preservation modalities. MATERIALS AND METHODS: A cross-sectional online survey study of female graduate students and medical trainees from academic institutions in Ohio was performed. Women were excluded if the online survey was incomplete or if they were >45 years. RESULTS: Analysis of 590 surveys was performed (response rate of 26.3%). Ninety-four percent (557/590) of subjects were between 20 and 35 years. Our respondents tended to be nulliparous (87%), married or in a relationship (51%) and interested in future fertility (77%). The reasons cited for delaying childbearing were multi-factorial, with career building noted most commonly (69%). Nearly 60% of women reported they would consider fertility preservation in the future; however, the majority (87%) cited two or more barriers. When asked about their desire for information on fertility preservation, 28% desired to receive education on their choices and 36% wanted their Ob/Gyn to discuss fertility preservation options. Women >30 years were significantly more likely to desire future fertility, want more fertility preservation education and consider pursuing fertility preservation in the future. CONCLUSIONS: Graduate-level women often delay childbearing for professional pursuits. This study demonstrates a need for increased fertility preservation awareness and education, especially by Ob/Gyn providers.

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review.

PURPOSE: To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART. METHODS: A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars. RESULTS: Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion. CONCLUSION: The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

LiverMap pipeline for 3D imaging of human liver reveals volumetric spatial dysregulation of cirrhotic vasculobiliary architecture.

The liver contains an intricate microstructure that is critical for liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, 2D histopathology - the gold standard for pathological understanding of many liver diseases - can misrepresent or leave gaps in our understanding of complex 3D structural features. Here, we utilized immunostaining, tissue clearing, microscopy, and computational software to create 3D multilobular reconstructions of both non-fibrotic and cirrhotic human liver tissue. We found that spatial architecture in human cirrhotic liver samples with varying etiologies had sinusoid zonation dysregulation, reduction in glutamine synthetase-expressing pericentral hepatocytes, regression of central vein networks, disruption of hepatic arterial networks, and fragmentation of biliary networks, which together suggest a pro-portalization/decentralization phenotype in cirrhotic tissue. Further implementation of 3D pathological analyses may provide a deeper understanding of cirrhotic pathobiology and inspire novel treatments for liver disease.

Hymenal Anomalies Interfering with Dilation in Women with Mullerian Agenesis: A Case Series.

BACKGROUND: Women with Mullerian agenesis, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), have aplasia or hypoplasia of the uterus and vagina. Regular use of dilators can successfully create a functional vagina in up to 95% of cases. We present 3 women with Mullerian agenesis who failed dilation therapy due to pain and were subsequently found to have hymenal anomalies. CASES: Patients presented at age 16 or 17 to initiate dilation. Initial attempts were discontinued due to pain. On examination, a septate hymen was identified in 2 patients and a microperforate hymen in 1 patient. All patients underwent hymenectomy and thereafter continued dilation with less discomfort. SUMMARY AND CONCLUSION: These cases illustrate the importance of recognizing and treating hymenal anomalies in women with Mullerian agenesis to prevent pain, leading to unsuccessful dilation.

Temporal Dynamics of Metabolic Acquisition in Grafted Engineered Human Liver Tissue.

Liver disease affects millions globally, and end-stage liver failure is only cured by organ transplant. Unfortunately, there is a growing shortage of donor organs as well as inequitable access to transplants across populations. Engineered liver tissue grafts that supplement or replace native organ function can address this challenge. While engineered liver tissues have been successfully engrafted previously, the extent to which these tissues express human liver metabolic genes and proteins remains unknown. Here, it is built engineered human liver tissues and characterized their engraftment, expansion, and metabolic phenotype at sequential stages post-implantation by RNA sequencing, histology, and host serology. Expression of metabolic genes is observed at weeks 1-2, followed by the cellular organization into hepatic cords by weeks 4-9.5. Furthermore, grafted engineered tissues exhibited progressive spatially restricted expression of critical functional proteins known to be zonated in the native human liver. This is the first report of engineered human liver tissue zonation after implantation in vivo, which can have important translational implications for this field.

Highly Parallel Tissue Grafting for Combinatorial In Vivo Screening.

Material- and cell-based technologies such as engineered tissues hold great promise as human therapies. Yet, the development of many of these technologies becomes stalled at the stage of pre-clinical animal studies due to the tedious and low-throughput nature of in vivo implantation experiments. We introduce a 'plug and play' in vivo screening array platform called Highly Parallel Tissue Grafting (HPTG). HPTG enables parallelized in vivo screening of 43 three-dimensional microtissues within a single 3D printed device. Using HPTG, we screen microtissue formations with varying cellular and material components and identify formulations that support vascular self-assembly, integration and tissue function. Our studies highlight the importance of combinatorial studies that vary cellular and material formulation variables concomitantly, by revealing that inclusion of stromal cells can "rescue" vascular self-assembly in manner that is material-dependent. HPTG provides a route for accelerating pre-clinical progress for diverse medical applications including tissue therapy, cancer biomedicine, and regenerative medicine.

Risks for Recurrent Vulvovaginal Candidiasis Caused by Non-Albicans Candida Versus Candida Albicans.

Background: Vulvovaginal candidiasis (VVC) is the second most common vulvovaginitis (VV). About 20% of women will experience recurrent infections in their lifetime with non-albicans Candida (NAC) species being one of the causative agents. Although studies have looked at risk factors for recurrent VVC they are limited in scope. In this study, we explore whether risks of recurrent VVC are increased with NAC infections compared to Candida albicans infections. Methods: Through an institutional review board-approved retrospective chart review, we identified 174 women with positive yeast cultures and followed their charts to assess recurrent visits and treatments. We also assessed several baseline variables such as race, age, body mass index (BMI), obstetric history, probiotic use, contraceptive use, mycological therapy, steroid use, hormone replacement therapy, menopausal status, and medical comorbidities. Results: Women with NAC VV were more likely to have multiple visits for recurring infections compared to women who had C. albicans VV (66% vs. 34%). The women with multiple recurrences were younger, had a lower BMI, had lower parity, and endorsed higher use of probiotics. Conclusion: Women with positive NAC cultures were more likely to have multiple visits to their physicians for VV complaints. Identifying the causative species using vaginal fungal cultures can more accurately guide therapy and lead to better outcomes for these patients.

Trends in Emergency Department Utilization Among Women With Leiomyomas in the United States.

OBJECTIVE: To describe trends in emergency department (ED) visits in the United States with a primary diagnosis of leiomyomas, subsequent admissions, and associated charges. METHODS: The Healthcare Cost and Utilization Project Nationwide Emergency Department Sample database was used to retrospectively identify all ED visits from 2006 to 2017 among women aged 18-55 years with a primary diagnosis of leiomyomas as indicated by International Classification of Diseases (ICD) diagnosis codes. Trends in ED visits and subsequent admissions were analyzed and stratified by patient and hospital characteristics. Secondary ICD codes, Current Procedural Terminology codes, and hospital charges were analyzed. A multivariate regression model was used to identify predictors of admission. RESULTS: Although the number of ED visits for leiomyomas increased from 28,732 in 2006 to 65,685 in 2017, the admission rate decreased, from 23.9% in 2006 to 11.1% in 2017. Emergency department visits for leiomyomas were highest among women who were aged 36-45 years (44.5%), in the lowest income quartile (36.1%), privately insured (38.3%), and living in the South (46.2%). Admission was more likely at nonteaching hospitals (odds ratio [OR] 1.23, 95% CI 1.08-1.39) or those located in the Northeast (OR 1.39, 95% CI 1.15-1.68). Patient characteristics associated with admission included older age (26-35 years: OR 1.42, 95% CI 1.21-1.66; 36-45 years: OR 2.01, 95% CI 1.72-2.34; 46-55 years: OR 2.60, 95% CI 2.23-3.03) and bleeding-related complaints (OR 14.92, 95% CI 14.00-15.90). Admission was least likely in uninsured patients (Medicare: OR 1.37, 95% CI 1.21-1.54; Medicaid: OR 1.26, 95% CI 1.16-1.36; private: OR 1.44, 95% CI 1.32-1.56). CONCLUSION: Although ED visits for leiomyomas are increasing, admission rates for these visits are decreasing. The substantial decline in admissions suggests many of these visits could potentially be addressed in a non-acute-care setting. However, when women with leiomyomas present with a bleeding-related complaint, the odds of admission increase 15-fold. There is an apparent disparity in likelihood of admission based on insurance type.

Medical transition for gender diverse patients.

Purpose of review: The purpose of this review is to provide an up-to-date overview of gender-affirming hormone therapy, including the various hormone regimens available, the efficacy and potential risks of these treatments, and considerations for surveillance and long-term care. Recent findings: Recent studies reaffirm that hormone therapy has positive physical and psychological effects for many transgender individuals. The overall risks of treatment are low. Transgender women may have an increased risk of venous thromboembolism and breast cancer based on recent cohort studies, but these findings have yet to be confirmed with randomized controlled trials. Important long-term considerations include metabolic, cardiovascular, and skeletal health. Summary: High-quality, long-term studies on the effectiveness and safety of various gender-affirming hormone treatment regimens are lacking, but the currently available evidence suggests that it is overall safe and effective with appropriate oversight.

Liver stage malaria infection is controlled by host regulators of lipid peroxidation.

The facets of host control during Plasmodium liver infection remain largely unknown. We find that the SLC7a11-GPX4 pathway, which has been associated with the production of reactive oxygen species, lipid peroxidation, and a form of cell death called ferroptosis, plays a critical role in control of Plasmodium liver stage infection. Specifically, blocking GPX4 or SLC7a11 dramatically reduces Plasmodium liver stage parasite infection. In contrast, blocking negative regulators of this pathway, NOX1 and TFR1, leads to an increase in liver stage infection. We have shown previously that increased levels of P53 reduces Plasmodium LS burden in an apoptosis-independent manner. Here, we demonstrate that increased P53 is unable to control parasite burden during NOX1 or TFR1 knockdown, or in the presence of ROS scavenging or when lipid peroxidation is blocked. Additionally, SLC7a11 inhibitors Erastin and Sorafenib reduce infection. Thus, blocking the host SLC7a11-GPX4 pathway serves to selectively elevate lipid peroxides in infected cells, which localize within the parasite and lead to the elimination of liver stage parasites.

Effects of myomas and myomectomy on assisted reproductive technology outcomes.

OBJECTIVE: To determine the effects of fibroids, and their removal, on ART outcomes. MATERIALS AND METHODS: Single institution retrospective cohort study of infertility patients who underwent myomectomy prior to either in vitro fertilization (IVF) or intrauterine insemination (IUI) between August 2006 and October 2015 (N = 49). Two separate control groups were established: 1) women with fibroids left in situ during the ART process (N = 76), and 2) women with no fibroids (N = 103). The study was powered to detect a difference between a 42%, 11%, and 25% live birth (LB) rate in the myomectomy, fibroids in situ, and no fibroids groups at P < 0.05. RESULTS: There were no significant differences in IVF cycle parameters between groups. Fibroids that were either submucosal or intramural with associated cavity distortion were significantly more likely to be removed. Amongst women undergoing IVF, the cumulative incidence of clinical pregnancy (CP) was significantly higher in the myomectomy group than the in situ or no fibroids groups. Women who underwent pre-IVF myomectomy also achieved CP more quickly. Cumulative LB rates did not differ significantly amongst women undergoing IVF. CP and LB rates per cycle were similar between myomectomy, in situ, and no fibroids groups (CP 49% vs. 37.5% vs. 54.4%, P = 0.21; LB 41.7% vs. 27.1% vs. 43.9%, P = 0.17). DISCUSSION: IVF outcomes appear to be improved by judicious removal of clinically significant fibroids. Further prospective studies are required to confirm the role of fibroids, and their removal, on ART outcomes before advocating for routine myomectomy amongst women with fibroids undergoing ART.

Multivascular networks and functional intravascular topologies within biocompatible hydrogels.

Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.

Alternatives to hysterectomy: The burden of fibroids and the quality of life.

Uterine fibroids are the most common benign tumor in reproductive-aged women. While the majority of women are asymptomatic, those with symptoms may suffer from abnormal uterine bleeding, infertility, pelvic pain or pressure, and urinary dysfunction. Fibroids represent a significant healthcare burden for women and society as a whole. Women with fibroids have compromised overall quality of life and impairment in many specific domains including work productivity, sexuality, self-image, relationships, and social emotional and physical well-being. Many women are reluctant to ask for help and delay seeking treatment. To date, myomectomy remains the gold standard for treating fibroid-related symptoms in reproductive-aged women. However, many less invasive uterine preserving approaches have been developed. Quality of life is improved in many women following treatment for fibroids. This article aims to provide an overview of the substantial impact of fibroids on health-related quality of life.

Human Organ-Specific Endothelial Cell Heterogeneity.

The endothelium first forms in the blood islands in the extra-embryonic yolk sac and then throughout the embryo to establish circulatory networks that further acquire organ-specific properties during development to support diverse organ functions. Here, we investigated the properties of endothelial cells (ECs), isolated from four human major organs-the heart, lung, liver, and kidneys-in individual fetal tissues at three months' gestation, at gene expression, and at cellular function levels. We showed that organ-specific ECs have distinct expression patterns of gene clusters, which support their specific organ development and functions. These ECs displayed distinct barrier properties, angiogenic potential, and metabolic rate and support specific organ functions. Our findings showed the link between human EC heterogeneity and organ development and can be exploited therapeutically to contribute in organ regeneration, disease modeling, as well as guiding differentiation of tissue-specific ECs from human pluripotent stem cells.

In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease.

Control of both tissue architecture and scale is a fundamental translational roadblock in tissue engineering. An experimental framework that enables investigation into how architecture and scaling may be coupled is needed. We fabricated a structurally organized engineered tissue unit that expanded in response to regenerative cues after implantation into mice with liver injury. Specifically, we found that tissues containing patterned human primary hepatocytes, endothelial cells, and stromal cells in a degradable hydrogel expanded more than 50-fold over the course of 11 weeks in mice with injured livers. There was a concomitant increase in graft function as indicated by the production of multiple human liver proteins. Histologically, we observed the emergence of characteristic liver stereotypical microstructures mediated by coordinated growth of hepatocytes in close juxtaposition with a perfused vasculature. We demonstrated the utility of this system for probing the impact of multicellular geometric architecture on tissue expansion in response to liver injury. This approach is a hybrid strategy that harnesses both biology and engineering to more efficiently deploy a limited cell mass after implantation.

Increased Length of Awareness of Assisted Reproductive Technologies Fosters Positive Attitudes and Acceptance among Women.

BACKGROUND: The field of infertility medicine has witnessed a surge of scientific developments in recent years, but research on public attitudes towards infertility treatments has remained minimal. This study examined the social and demographic factors that affect women's attitudes towards assisted reproductive technology (ART) in general, as well as their opinions of specific issues related to ART. MATERIALS AND METHODS: This cross-sectional study was conducted from March 2011 to April 2011 by means of an online survey administered to a sample of 287 women. RESULTS: Women with a longer length of awareness of ART had significantly greater attitudinal favorability towards ART. Political affiliation was also significantly related to general attitudes, as well as several specific aspects of ART issues. CONCLUSION: The results of this study suggest that several factors influence attitudes that women hold in regards to ART. Identifying some of these factors serves as a crucial starting point for devising strategies to increase public acceptance of ART.

Predisposing factors to post-operative adhesion development.

BACKGROUND: Adhesion development is the most common sequelae of intra-abdominal and pelvic surgery and represents a significant, yet poorly understood, cause of morbidity among post-operative patients. It remains unclear, for example, exactly why adhesions form more frequently in certain tissues and/or patients, or at specific locations within them, as opposed to others. This review contributes to the growing knowledge pool by elucidating factors that potentially predispose to the development of adhesions. Given the strong correlation between a hypofibrinolytic state and adhesion formation, this review article will examine not only those factors that have been shown to directly predispose to adhesion development, but also those that are likely do so indirectly by means of altering the coagulation/fibrinolytic profile. METHODS: A literature search was performed using the PubMed database for all relevant English language articles up to February 2014. All of the identified articles were reviewed with particular attention to predisposing factors to post-operative adhesion development. In addition, the reference lists of each article were reviewed to identify additional relevant articles. RESULTS: Various factors have been shown to directly increase the risk of post-operative adhesion development; namely, certain genetic polymorphisms in the interleukin-1 receptor antagonist, increased estrogen exposure, and endometriosis. In addition, numerous factors are known to increase the risk of fibrosis, therefore likely increasing the risk of adhesion development indirectly. These factors include genetic polymorphisms in plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor, diabetes mellitus, metabolic syndrome, hyperglycemia, obesity, depression, binge alcohol consumption, anti-Parkinsonian medications, oral hormone therapy, pregnancy, and cancer. CONCLUSIONS: The literature reviewed in this paper will help to direct future research aimed at understanding the mechanisms that underlie the association of certain factors with adhesion development. This information will be crucial in the creation of adequate preventative and treatment strategies.