Examining changes in clinical management and postpartum readmissions for hypertensive disorders of pregnancy over time.

OBJECTIVE: In response to 2013 guidelines for hypertensive disorders of pregnancy (HDP), our study examined changes in antenatal management and postpartum readmission (PPR) over time. STUDY DESIGN: This is a retrospective cohort study of individuals diagnosed antenatally with HDP who delivered at a tertiary care center from 2012 to 2017. MAIN OUTCOME MEASURES: The primary outcome was postpartum readmission for HDP in 2012-2013 vs 2014-2017. Secondary outcomes included intravenous magnesium administration and prescription for oral (PO) antihypertensive medication during delivery admission. Multivariable logistic regression models assessed differences in outcomes over time, adjusted for age, race, and payer status, for HDP with and without severe features, defined by ACOG criteria. RESULTS: Of 5,300 eligible individuals, 73.5 % had HDP without severe features and 26.5 % had severe features. The PPR frequency in this cohort was 1.1 % (N = 59). There was no difference in PPR for individuals with HDP without severe features (aOR 0.73; 95 % CI 0.28-1.88) or with severe features (aOR 1.30; 95 % CI 0.50-3.39) by epoch. Magnesium administration for HDP with severe features remained below 80 % over time. Magnesium administration for HDP without severe features and discharge prescriptions for PO medications for HDP with severe features were lower after 2013. Neither magnesium administration nor discharge prescriptions were associated with decreased odds of PPR. CONCLUSION: Although there was no difference in PPR for HDP after 2013, there were changes in antenatal management of HDP, including decreased magnesium administration for individuals with HDP without severe features and PO medication for individuals with severe features.

Fertility Preservation During the COVID-19 Pandemic: Modified But Uncompromised.

Purpose: Throughout COVID-19, our clinic remained operational for patients requiring urgent fertility preservation (FP). This study aimed to characterize changes to clinical protocols during the first wave of COVID-19 and compare outcomes to historical controls. Methods: We performed a retrospective cohort study at a university fertility center examining all patients who underwent medically indicated FP cycles during the American Society for Reproductive Medicine (ASRM) COVID-19 Task Force-recommended suspension of fertility treatment (March 17-May 11, 2020) and patients from the same time period in 2019. FP care was modified for safety during the first wave of COVID-19 with fewer monitoring visits and infection control measures. FP cycle characteristics and outcomes were compared across years. Results: The volume of cycles was nearly 30% higher in 2020 versus 2019 (27 vs. 19). Diagnoses, age, and anti-Mullerian hormone were similar between cohorts. More patients elected to pursue embryo cryopreservation over oocyte cryopreservation in 2020 versus 2019 (45.8% vs. 5.2%, p < 0.005). Patients managed during COVID-19 had fewer monitoring visits (5 ± 1 vs. 6 ± 1, p = 0.02), and 37.5% of cycles utilized a blind trigger injection. There was no difference in total days of ovarian stimulation (11 ± 1 vs. 11 ± 2, p > 0.05), but 2020 cycles utilized more gonadotropin (4770 ± 1480 vs. 3846 ± 1438, p = 0.04). There was no difference in total oocytes retrieved (19 ± 14 vs. 22 ± 12, p > 0.05) or mature oocytes vitrified (15 ± 12 vs. 17 ± 9, p > 0.05) per cycle. Conclusions: FP continued during COVID-19, and more cycles were completed in 2020 versus 2019. Despite minimized monitoring, outcomes were optimal and equivalent to historical controls, suggesting FP care can be adapted without compromising outcomes.

Guidelines informing counseling on female age-related fertility decline: a systematic review.

PURPOSE: To identify, appraise, and assess clinical practice guidelines informing patient counseling on female age-related fertility decline. METHODS: Searched electronic database records from January 1, 2006, to September 10, 2018, and professional society websites. The search terms included iterations of "guideline," "counseling," "preconception," "age-related fertility decline," and "reproductive life planning." English-language professional organization guidelines addressing patient counseling on age-specific reproductive health topics were included. Assessed the methodological quality of included guidelines using the AGREE II instrument. Guidelines were categorized as high quality or low quality based on AGREE II scores. Extracted age-specific reproductive health recommendations of high-quality guidelines. RESULTS: The search identified 2918 records. Nineteen records addressed counseling on age-related fertility decline; only 6 focused only on reproductive aging, with the remaining 13 covering related topics. Eleven met criteria for high quality. All high-quality guidelines had high "rigor of development" scores on AGREE II. Ten high-quality guidelines stated an age at which female fertility declines, ranging from 30 to "late 30s." One recommended a specific age at which patients should be counseled. Five of eleven high-quality guidelines did not discuss the obstetric and perinatal risks of advanced maternal age. CONCLUSIONS: Few high-quality guidelines address counseling on female age-related fertility decline, and existing guidance on reproductive aging counseling is inconsistent and incomplete. Greater rigor of development and incorporation of age-specific counseling recommendations into clinical practice guidelines could lead to improved patient anticipatory guidance and more informed reproductive choices.

Prognostic role of preimplantation genetic testing for aneuploidy in medically indicated fertility preservation.

OBJECTIVE: To investigate the use of preimplantation genetic testing for aneuploidy (PGT-A) among patients pursuing embryo banking (EB) for medically indicated fertility preservation (FP). DESIGN: Retrospective cohort. SETTING: University-affiliated fertility center. PATIENTS: All patients who underwent in vitro fertilization with or without PGT-A for medically indicated FP between January 2014 and April 2018. INTERVENTIONS: None MAIN OUTCOME MEASURES: EB cycle characteristics, subsequent cycle pursuit/outcomes, and frozen embryo transfer (FET) outcomes. RESULTS: A total of 58 medical EB cycles were compared; 34 cycles used PGT-A. Of the EB patients with breast cancer, 67% used PGT-A; other indications were evenly divided between PGT-A (FP/PGT-A) and no PGT-A (FP). PGT-A use increased over the study period. Groups were similar in age, days of stimulation, and days from initial FP consultation to treatment initiation. Number of oocytes (14.5 [2-63] FP vs. 17.5 [1-64] FP/PGT-A), 2PN zygotes (7 [1-38] FP vs. 9 [0-36] FP/PGT-A), and blastocysts (5.5 [0-22] FP vs. 5 [0-18] FP/PGT-A) cryopreserved were similar between groups. Equal numbers cryopreserved both oocytes and embryos (5 vs. 3). Five FP/PGT-A patients underwent a second EB cycle. Among FP/PGT-A patients, an average of 6.7 ± 5 blastocysts underwent PGT-A, with 3.5 ± 3 (48.2%) euploid embryos cryopreserved for future FET compared to an average of 7.2 ± 7 untested embryos in the FP group. CONCLUSION: PGT-A in medical EB cycles increased over time and did not limit the use of other FP methods such as oocyte cryopreservation. In some cases, poor PGT-A results informed patients to pursue a second EB cycle. When counseling patients, the prognostic benefits of PGT-A must be weighed against the financial costs and potential for "terminal" fertility diagnosis.

Posthumous assisted reproduction policies among a cohort of United States' in vitro fertilization clinics.

OBJECTIVE: To assess the presence and content of policies toward posthumous assisted reproduction (PAR) using oocytes and embryos among Society for Assisted Reproductive Technology (SART) member clinics in the United States. DESIGN: Cross-sectional questionnaire-based study. SETTING: Not applicable. PATIENTS: A total of 62 SART member clinics. INTERVENTIONS: Questionnaire including multiple choice and open-ended questions. MAIN OUTCOME MEASURES: Descriptive statistics regarding presence and content of policies regarding PAR using oocytes and embryos, consent document content regarding oocyte and embryo disposition, and eligibility of minors and those with terminal illness for fertility preservation. RESULTS: Of the 332 clinics contacted, 62 responded (response rate 18.7%). Respondents were distributed across the United States, and average volume of in vitro fertilization (IVF) cycles per year ranged from <250 to >1,500, but 71.2% (n = 42) reported a volume of <500. Nearly one-half (42.4%, n = 25) of clinics surveyed reported participating in any cases of posthumous reproduction during the past 5 years, and 6.8% (n = 4) reported participation in >5 cases. Participation in cases of posthumous reproduction was not significantly associated with practice type or IVF cycle volume among those surveyed. Only 59.6% (n = 34) of clinics surveyed had written policies regarding PAR using oocytes or embryos, whereas 36.8% (n = 21) reported they did not have a policy. Practice type, IVF cycle volume, fertility preservation volume, and prior participation in cases of PAR were not significantly associated with the presence of a policy among respondent clinics. Of those with a policy, 55.9% (n = 19) reported they had used that policy, 59.1% (n = 13) without a policy reported they had considered adopting one, and 63.6% (n = 14) reported they had received a request for PAR services. Only 47.2% (n = 25) of clinics surveyed specified that patients not expected to survive to use oocytes due to terminal illness are eligible for oocyte cryopreservation, whereas 45.3% (n = 24) did not specify. CONCLUSIONS: Respondent clinics reported receiving an increasing number of requests for PAR services, but many also lacked PAR policies. Those with policies did not always follow ASRM recommendations. Given the low response rate, these data cannot be interpreted as representative of SART clinics overall. As PAR cases become more common, however, this study highlights poor reporting of PAR and institutional policies toward PAR, suggesting that SART clinics may not be equipped to systematically manage the complexities of PAR.

Effects of adjuvant radiation therapy on survival for patients with resected primary tracheal carcinoma: an analysis of the National Cancer Database.

OBJECTIVE(S): To identify predictors for receiving adjuvant radiation therapy (RT) and investigate the impact of adjuvant RT on survival for patients with resected primary tracheal carcinoma (PTC). METHODS: The National Cancer database was queried for patients with PTC diagnosed from 2004 to 2014 undergoing resection. Patients who died within 30 days of resection were excluded to minimize immortal time bias. Kaplan-Meier methods, Cox regression modeling and propensity score weighted (PSW) log-rank tests were considered to assess the relationship between adjuvant RT and overall survival (OS). Logistic regression was performed to identify predictors associated with receiving adjuvant RT. RESULTS: A total of 549 patients were identified with 300 patients (55%) receiving adjuvant RT. Squamous cell carcinoma (SCC) was the most common histology with 234 patients (43%). Adenoid cystic carcinoma (ACC) was second most frequent with 180 patients (33%). Adjuvant RT was not associated with OS by multivariable Cox analysis or PSW log-rank test (P values > 0.05). Patients with positive surgical margins (odds ratio (OR) 1.80, confidence interval (CI) 1.06-3.07) were more likely to receive adjuvant RT than those with negative surgical margins. Patients with ACC (OR 6.53, CI 3.57-11.95) were more likely to receive adjuvant RT compared with SCC. CONCLUSIONS: Adjuvant RT was not significantly associated with OS for patients with resected PTC in this analysis. Surgical margin status and tumor histology were associated with receiving adjuvant RT. Further investigations including prospective registry studies capturing radiation technique and treatment volumes are needed to better define which patients with resected PTC may benefit from adjuvant RT.

Left-Ventricular Assist Device Impact on Aortic Valve Mechanics, Proteomics and Ultrastructure.

BACKGROUND: Aortic regurgitation is a prevalent, detrimental complication of left ventricular assist devices (LVADs). The altered hemodynamics of LVADs results in aortic valves (AVs) having distinct mechanical stimulation. Our hypothesis was that the altered AV hemodynamics modulates the valve cells and matrix, resulting in changes in valvular mechanical properties that then can lead to regurgitation. METHODS: AVs were collected from 16 LVAD and 6 non-LVAD patients at time of heart transplant. Standard demographic and preoperative data were collected and comparisons between the two groups were calculated using standard statistical methods. Samples were analyzed using biaxial mechanical tensile testing, mass spectrometry-based proteomics, and transmission electron microscopy to assess ultrastructure. RESULTS: The maximum circumferential leaflet strain in LVAD patients was less than in non-LVAD patients (0.35 ± 0.10MPa versus 0.52 ± 0.18 MPa, p = 0.03) with a trend of reduced radial strain (p = 0.06) and a tendency for the radial strain to decrease with increasing LVAD duration (p = 0.063). Numerous proteins associated with actin and myosin, immune signaling and oxidative stress, and transforming growth factor ß were increased in LVAD patients. Ultrastructural analysis showed a trend of increased fiber diameter in LVAD patients (46.2 ± 7.2 nm versus 45.1 ± 6.9 nm, p = 0.10), but no difference in fiber density. CONCLUSIONS: AVs in LVAD patients showed decreased compliance and increased expression of numerous proteins related to valve activation and injury compared to non-LVAD patients. Further knowledge of AV changes leading to regurgitation in LVAD patients and the pathways by which they occur may provide an opportunity for interventions to prevent and/or reverse this detrimental complication.

Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-ß (TGF-ß) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-ß. Here we explore whether pharmacologic inhibition of LDH activity can prevent TGF-ß-induced myofibroblast differentiation. Primary human lung fibroblasts from healthy patients and those with pulmonary fibrosis were treated with TGF-ß and or gossypol, an LDH inhibitor. Protein and RNA were analyzed for markers of myofibroblast differentiation and extracellular matrix generation. Gossypol inhibited TGF-ß-induced expression of the myofibroblast marker α-smooth muscle actin (α-SMA) in a dose-dependent manner in both healthy and fibrotic human lung fibroblasts. Gossypol also inhibited expression of collagen 1, collagen 3, and fibronectin. Gossypol inhibited LDH activity, the generation of extracellular lactic acid, and the rate of extracellular acidification in a dose-dependent manner. Furthermore, gossypol inhibited TGF-ß bioactivity in a dose-dependent manner. Concurrent treatment with an LDH siRNA increased the ability of gossypol to inhibit TGF-ß-induced myofibroblast differentiation. Gossypol inhibits TGF-ß-induced myofibroblast differentiation through inhibition of LDH, inhibition of extracellular accumulation of lactic acid, and inhibition of TGF-ß bioactivity. These data support the hypothesis that pharmacologic inhibition of LDH may play an important role in the treatment of pulmonary fibrosis.