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Polycystic ovary syndrome (PCOS) is the most common cause of anovulation. A key feature of PCOS is arrest of follicles at the small- to medium-sized antral stage. To provide further insight into the mechanism of follicle arrest in PCOS, we profiled (i) gonadotropin receptors; (ii) characteristics of aberrant steroidogenesis; and (iii) expression of anti-Müllerian hormone (AMH) and its receptor in granulosa cells (GCs) from unstimulated, human small antral follicles (hSAFs) and from granulosa lutein cells (GLCs). GCs from hSAFs were collected at the time of cryopreservation of ovarian tissue for fertility preservation and GLCs collected during oocyte aspiration before in vitro fertilization/intracytoplasmic sperm injection. We collected hSAF GCs from 31 women (98 follicles): 10 with polycystic ovaries (PCO) and 21 without. GLCs were collected from 6 women with PCOS and 6 controls undergoing IVF. Expression of the following genes: LHCGR, FSHR, AR, INSR, HSD3B2, CYP11A1, CYP19, STAR, AMH, AMHR2, FST, INHBA, INHBB in GCs and GLCs were compared between women with PCO and controls. GCs in hSAFs from women with PCO showed higher expression of LHCGR in a subset (20%) of follicles. Expression of FSHR (P < 0.05), AR (P < 0.05), and CYP11A1 (P < 0.05) was lower, and expression of CYP19A1 (P < 0.05), STAR (P < 0.05), HSD3B2 (P = NS), and INHBA (P < 0.05) was higher in PCO GCs. Gene expression in GL cells differed between women with and without PCOS but also differed from that in GCs. Follicle arrest in PCO is characterized in GCs by differential regulation of key genes involved in follicle growth and function.

Members of the TGF-β family have been implicated in aberrant follicle development in women with polycystic ovaries (PCO). Are there quantitative differences in the concentrations of TGF-β family members in fluid from human small antral follicles (hSAFs) in women with or without PCO? Follicle fluids (FFs) were collected from 4- to 11-mm hSAFs obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. FFs from 16 women with PCO (FF = 93) and 33 women without PCO (FF = 92). Intrafollicular concentrations of growth differentiation factor-9 (GDF9); anti-Müllerian hormone (AMH); inhibin-A and inhibin-B; total inhibin; activin-A, activin-B, and activin-AB; follistatin; follistatin-like-3; estradiol; and testosterone. Activin-B concentrations were reported in hSAFs, and concentrations were 10 times higher than activin-A and activin-AB concentrations. Activin-B showed significant associations with other growth factors. Concentrations of inhibin-A and inhibin-B were significantly lower in FFs from women with PCO, especially in hSAFs <8 mm in diameter. AMH concentrations did not differ between the groups in hSAFs <8 mm; however, AMH remained high in hSAFs >8 mm in women with PCO but decreased in women without PCO. Estradiol was significantly lower in FFs from women with PCO and showed significant associations with AMH. Concentrations of GDF9 showed significantly higher concentrations in PCO FFs of follicles >6 mm. Altered concentrations of TGF-β family members in hSAFs from women with PCO highlight altered growth factor signaling as a potential mechanism for follicle growth arrest.

Context: Members of the TGF-[beta] family have been implicated in aberrant follicle development in women with polycystic ovaries (PCO). Objective: Are there quantitative differences in the concentrations of TGF-[beta] family membersin fluid from human small antral follicles (hSAFs) in women with or without PCO? Design and Setting: Follicle fluids (FFs) were collected from 4- to 11-mm hSAFs obtained from women undergoing ovarian tissue cryopreservation for fertility preservation. Patients: FFs from 16 women with PCO (FF = 93) and 33 women without PCO (FF = 92). Main Outcome Measures: Intrafollicular concentrations of growth differentiation factor-9 (GDF9); anti-Mullerian hormone (AMH); inhibin-A and inhibin-B; total inhibin; activin-A, activin-B, and activin-AB; follistatin; follistatin-like-3; estradiol; and testosterone. Results: Activin-B concentrations were reported in hSAFs, and concentrations were 10 times higher than activin-A and activin-AB concentrations. Activin-B showed significant associations with other growth factors. Concentrations of inhibin-A and inhibin-B were significantly lower in FFs from women with PCO, especially in hSAFs <8 mm in diameter. AMH concentrations did not differ between the groups in hSAFs <8 mm; however, AMH remained high in hSAFs >8 mm in women with PCO but decreased in women without PCO. Estradiol was significantly lower in FFs from women with PCO and showed significant associations with AMH. Concentrations of GDF9 showed significantly higher concentrations in PCO FFs of follicles >6 mm. Conclusions: Altered concentrations of TGF-[beta] family members in hSAFs from women with PCO highlight altered growth factor signaling as a potential mechanism for follicle growth arrest. (J Clin Endocrinol Metab 104: 6371-6384, 2019)

Background: The Covid-19 pandemic has profoundly affected the lives of the global population. It is known that periods of stress and psychological distress can affect women’s menstrual cycles. We, therefore, performed an observational study of women’s reproductive health over the course of the pandemic. Materials & Methods: An anonymous digital survey was shared by the authors via social media in September 2020. All women of reproductive age were invited to complete the survey. Results: 1031 women completed the survey. The mean age was 36.7 ± 6.6 years. 693/70% reported recording their cycles using an app or diary. 233/23% were using hormonal contraception. 441/46% reported a change in their menstrual cycle since the beginning of the pandemic. 483/53% reported worsening premenstrual symptoms, 100/18% reported new menorrhagia (p=0.003) and 173/30% new dysmenorrhea (p<0.0001) compared to before the pandemic. 72/9% reported missed periods who not previously missed periods (p=0.003) and the median number of missed periods was 2 (IQR 1-3). 17/21% of those who ‘occasionally’ missed periods pre-pandemic missed periods ‘often’ during the pandemic. 467/45% reported a reduced libido. There was no change in the median cycle length (28 days) or days of bleeding (5) but there was a wider variability of cycle length (p=0.01) and a 1-day median decrease in the minimum (p<0.0001) and maximum (p=0.009) cycle length. Women reported a median 2kg increase in self-reported weight and a 30-minute increase in median weekly exercise. 517/50% of women stated that their diet was worse and 232/23% that it was better than before the pandemic. 407/40% reported working more and 169/16% were working less. Women related a significant increase in low mood (p<0.0001), poor appetite (p<0.0001), binge eating (p<0.0001), poor concentration (p<0.0001), anxiety (p<0.0001), poor sleep (p<0.0001), loneliness (p<0.0001) and excess alcohol use (p<0.0001). Specific stressors reported included work stress (499/48%), difficulty accessing healthcare (254/25%), change in financial (201/19%) and living (169/16%) situation, difficulties with homeschooling children (191/19%), family or partner conflict (170/16%), family illness or bereavement (156/15%), and difficulties accessing or providing childcare (99/10%). Conclusions: The Covid-19 pandemic has significantly impacted the reproductive health of women. The long term health implications of this are yet to be determined and future studies should address this.

Mechanical circulatory support is an invaluable tool in the care of children with severe refractory cardiac and or pulmonary failure. Two forms of mechanical circulatory support are currently available to neonates, infants, and smaller children, namely extracorporeal membrane oxygenation and use of a ventricular assist device, with each technique having unique advantages and disadvantages. The intra-aortic balloon pump is a third form of mechanical support that has been successfully used in larger children, adolescents, and adults, but has limited applicability in smaller children. In this review, we discuss the current experiences with extracorporeal membrane oxygenation and ventricular assist devices in children with cardiac disease. A variety of forms of mechanical circulatory support are available for children with cardiopulmonary dysfunction refractory to conventional management. These devices require extensive resources, both human and economic. Extracorporeal membrane oxygenation can be effectively used in a variety of settings to provide support to critically-ill patients with cardiac disease. Careful selection of patients and timing of intervention remains challenging. Special consideration should be given to children with cardiac disease with regard to anatomy, physiology, cannulation, and circuit management. Even though exciting progress is being made in the development of ventricular assist devices for long-term mechanical support in children, extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation. As the familiarity and experience with extracorporeal membrane oxygenation has grown, new indications have evolved, including emergent resuscitation. This utilization has been termed extracorporeal cardiopulmonary resuscitation. The literature supporting emergent cardiopulmonary support is mounting. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Due to the limitations of conventional circuits for extracorporeal membrane oxygenation, some centres have developed novel systems for rapid cardiopulmonary support. Many centres previously considered a functionally univentricular circulation to be a contraindication to extracorporeal membrane oxygenation, but improved results have been achieved recently with this complex subset of patients. The registry of the Extracorporeal Life Support Organization recently reported the outcome of extracorporeal life support used in neonates for cardiac indications from 1996 to 2000. Of the 740 neonates who were placed on extracorporeal life support for cardiac indications, 118 had hypoplastic left heart syndrome. There was no significant difference in survival between these patients and those with other defects. It is now common to use extracorporeal membrane oxygenation to support patients with a functionally univentricular circulation, and reasonable survival rates are to be expected. Although extracorporeal membrane oxygenation has become a standard of care for many paediatric centres, its use is limited to those patients who require only short-term cardiopulmonary support. Mechanical ventricular assist devices have become standard therapy for adults with cardiac failure refractory to maximal medical management. Several devices are readily available in the United States of America for adults, but there are fewer options available to children. Over the last few years, substantial progress has been made in paediatric mechanical support. Ventricular assist devices are being used with increasing frequency in children with cardiac failure refractory to medical therapy for primary treatment as a long-term bridge to recovery or transplantation. The paracorporeal, pneumatic, pulsatile “Berlin Heart” ventricular assist device is being used with increasing frequency in Europe and North America to provide univentricular and biventricular support. With this device, a patient can be maintained on mechanical circulatory support while extubated, being mobilized, and feeding by mouth. Mechanical circulatory support should be anticipated, and every attempt must be made to initiate support “urgently” rather than “emergently”, before the presence of dysfunction of end organs or circulatory collapse. In an emergency, these patients can be resuscitated with extracorporeal membrane oxygenation and subsequently transitioned to a long-term ventricular assist device after a period of stability.

ObjectiveDetermine incidence and risk factors for readmissions in early infancy.Study designSecondary analysis of data from the Cesarean Section Optimal Antibiotic Prophylaxis trial. All unplanned revisits (unplanned clinic, ER visits, and hospital readmissions) and hospital readmissions (initial discharge to 3-month follow-up) were analyzed.Results295 (15.9%) of 1850 infants had revisits with risk factors being ethnicity (adjusted odds ratio (aOR): 0.6 for Hispanic), maternal postpartum antibiotics (1.89), azithromycin treatment (1.22), small for gestational age (1.68), apnea (3.82), and hospital stay after birth >90th percentile (0.49). 71 (3.8%) of 1850 infants were readmitted with risk factors being antenatal steroids (aOR 2.49), elective repeat C/section (0.72), postpartum maternal antibiotics (2.22), O2 requirement after delivery room (2.82), and suspected/proven neonatal sepsis (0.55).Conclusion(s)Multiple risk factors were identified, suggesting potential impact on the neonatal microbiome (maternal postpartum antibiotics) or issues related to access/cost of care (Hispanic ethnicity associated with fewer revisits).

We sought to understand the multilevel syndemic factors that are concurrently contributing to the HIV epidemic among women living in the USA. We specifically examined community, network, dyadic, and individual factors to explain HIV vulnerability within a socioecological framework. We analyzed data from four diverse locations: Atlanta, New York City (the Bronx), Raleigh/Durham, and Washington, D.C. The following themes were identified at four levels including (1) exosystem (community): poverty prevalence, discrimination, gender imbalances, community violence, and housing challenges; (2) mesosystem (network): organizational social support and sexual concurrency; (3) microsystem (dyadic): sex exchange, interpersonal social support, and intimate partner violence; and (4) individual: HIV/STI awareness, risk taking, and substance use. A strong theme emerged with over 80 % of responses linked to the fundamental role of financial insecurity underlying risk-taking behavioral pathways. Multilevel syndemic factors contribute to women’s vulnerability to HIV in the USA. Financial insecurity is a predominant theme, suggesting the need for tailored programming for women to reduce HIV risk.