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Background To describe the psychosocial response of the infertile population whose care was curtailed due to the COVID-19 pandemic. Methods A web-based cross-sectional survey was administered to 117 infertile patients at our center who had their infertility treatment delayed due to suspension of care at our hospital during the COVID-19 pandemic. The survey consisted of 52-question multiple-choice questions including the Life Orientation Test-Revised (LOT-R) and the Hospital Anxiety and Depression Scale (HADS) instruments. Characteristics of respondents who "agreed" (strongly agree and agree) that "delaying treatment has permanently impacted my chances at future conception" were compared with participants who "disagreed" (neutral, disagree, and strongly disagree) using Fischer's exact test. Results In total, 79.5% agreed that delaying treatment has permanently impacted their chances at future conception. There were no discernible demographic differences between patients who "agreed" versus "disagreed" with the above statement. The mean LOT-R score was 14.1 (5.1) with an optimism score of 6.8 (2.6) and a pessimism score of 7.3 (2.9). The mean HADS depression score was 5.4 (3.4) with 28.2% reporting scores in the borderline-abnormal to abnormal range. The mean HADS anxiety score was 9.0 (3.9) with 64.6% reporting scores in the borderline-abnormal to abnormal range. Nearly one third of respondents (36.8%) reported wanting to "expedite/be more aggressive with treatment," whereas only 5.1% wanted to postpone treatment. Conclusions Women undergoing ART during the COVID-19 pandemic express significant concern and signs of distress about how delays in care affect their future reproductive potential.

Background Obstructed Mullerian anomalies in adolescents can be grouped into complete outflow obstruction or unilateral outflow obstruction. The challenge with unilateral obstructions is that diagnosis can be delayed for weeks to years, as menstruation occurs normally through the patent side and thus obstruction is often not initially considered in the differential diagnosis. Cases In this case series, we present 3 unusual and challenging cases of unilateral Mullerian obstructions in adolescent female patients, along with strategies for diagnosis and management. Each case involves a unique variation of a recognized Mullerian anomaly that was initially misdiagnosed, leading to a significant delay in definitive diagnosis and treatment. Summary and Conclusion These cases highlight that even among the well-described Mullerian anomalies, there can be unusual variations. Patients who do not respond to initial management or who develop new symptoms should be further evaluated to confirm the correct diagnosis Tools that may be helpful in making the correct diagnosis include imaging studies that use contrast dye to better delineate cavities and their connections, magnetic resonance imaging with a radiologist experienced in Mullerian anomalies, and an examination under anesthesia. A definitive diagnosis is critical to the successful management of these conditions, and individualized management plans are required for each patient depending on their specific anomaly and their preferences for treatment.

STUDY QUESTION Do the length of follicular phase estradiol exposure and the total length of the follicular phase affect pregnancy and live birth outcomes in natural frozen embryo transfer (FET) cycles? SUMMARY ANSWER An estradiol level >100 pg/ml for ≤4 days including the LH surge day is associated with worse pregnancy and live birth outcomes; however, the total length of the follicular phase is not associated with pregnancy and live birth outcomes. WHAT IS KNOWN ALREADY An estradiol level that increases above 100 pg/ml and continues to increase is indicative of the selection and development of a dominant follicle. In programmed FET cycles, a limited duration of follicular phase estradiol of STUDY DESIGN, SIZE, DURATION This retrospective cohort study included infertile patients in an academic hospital setting who underwent their first natural frozen autologous Day-5 embryo transfer cycle in our IVF clinic between 01 January 2013 and 31 December 2018. Donor oocyte and gestational carrier cycles were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS The primary outcomes of this study were pregnancy and live birth rates. Patients were stratified into two groups based on the cohorts’ median number of days from the estradiol level of >100 pg/ml before the LH surge: Group 1 (≤4 days; n = 1052 patients) and Group 2 (>4 days; n = 839 patients). Additionally, patients were stratified into two groups based on the cohorts’ median cycle day of LH surge: Group 1 (follicular length ≤15 days; n = 1287 patients) and Group 2 (follicular length >15 days; n = 1071 patients). A subgroup analysis of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles was performed. Logistic regression analysis, adjusted a priori for patient age, number of embryos transferred, and use of PGT-A, was used to estimate the odds ratio (OR) with a 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE In the length of elevated estradiol analysis, the pregnancy rate per embryo transfer was statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (65.6%) compared to patients with an elevated estradiol to surge of >4 days (70.9%; OR 1.30 (95% CI 1.06–1.58)). The live birth rate per embryo transfer was also statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (46.6%) compared to patients with an elevated estradiol to surge of >4 days (52.0%; OR 1.23 (95% CI 1.02–1.48)). In the follicular phase length analysis, the pregnancy rate per embryo transfer was similar between patients with a follicular length of ≤15 days (65.4%) and patients with a follicular length of >15 days (69.0%; OR 1.12 (95% CI 0.94–1.33)): the live birth rate was also similar between groups (45.5% vs 51.5%, respectively; OR 1.14 (95% CI 0.97–1.35)). In all analyses, once a pregnancy was achieved, the length of the follicular phase or the length of elevated oestradiol >100 pg/ml no longer affected the pregnancy outcomes. LIMITATIONS, REASONS FOR CAUTION The retrospective design of this study is subject to possible selection bias in regard to which patients at our clinic were recommended to undergo a natural FET compared to a fresh embryo transfer or programmed FET. To decrease the heterogeneity of our study population, we only included patients who had blastocyst embryo transfers; therefore, it is unknown whether similar results would be observed in patients with cleavage-stage embryo transfers. The retrospective nature of the study design did not allow randomized to a specific ovarian stimulation or ovulation trigger protocol. However, all patients were managed with the standardized protocols at a single center, which strengthens the external validity of our results when compared to a study that only evaluates one specific stimulation protocol. WIDER IMPLICATIONS OF THE FINDINGS Our observations provide cycle-level characteristics that can be applied during a natural FET cycle to help optimize embryo transfer success rates. Physicians should consider the parameter of number of days that oestradiol is >100 pg/ml prior to the LH surge when determining whether to proceed with embryo transfer in a natural cycle. This cycle-specific characteristic may also help to provide an explanation for some failed transfer cycles. Importantly, our findings should not be used to determine whether to recommend a natural or a programmed FET cycle for a patient, but rather, to identify natural FET cycles that are not optimal to proceed with embryo transfer STUDY FUNDING/COMPETING INTEREST(S) No financial support, funding, or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P0.05 was considered to be statistically significant.A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

Objective To describe the incidence of first trimester clinical pregnancy loss in the infertile population during the first wave of the COVID-19 pandemic in New York City. Design Web-based cross-sectional survey. Setting New York City-based academic reproductive medicine practice. Patient(s) A total of 305 infertile patients with a confirmed intrauterine pregnancy in their first trimester between December 1, 2019, and April 1, 2020, were matched by age and treatment type to pregnant patients from the year prior. Intervention(s) None. Main Outcome Measure(s) First trimester clinical pregnancy loss rate. Result(s) In total, the first trimester pregnancy loss rate was lower in the COVID-19 era cohort compared with that in the pre-COVID-19 era cohort (11.9% vs. 20.1%). There was no difference between cohorts in the pregnancy loss rate of women conceiving via fresh embryo transfer (19.6% vs. 24.4%) or via frozen embryo transfer with preimplantation genetic testing (5.4% vs. 9.5%,). In women conceiving via frozen embryo transfer without preimplantation genetic testing, the pregnancy loss rate was statistically lower in the COVID-19 group (12.5% vs. 24.5%). There was no difference in the pregnancy loss rate by treatment type when stratifying by COVID-19 testing or symptom status. Of the 40 (13.1%) patients with a pregnancy loss, there was no difference in self-reported COVID-19 symptoms or symptom type compared with results in those who did not experience a pregnancy loss. Conclusion Despite patients expressing significant worry about COVID-19 and pregnancy, our data provides reassuring information that the first trimester pregnancy loss rate is not elevated for women conceiving via assisted reproductive technology during the global COVID-19 pandemic.

Objective To determine if the time from oocyte retrieval to frozen embryo transfer (FET) in the natural cycle affects reproductive or neonatal outcomes. Design Retrospective cohort. Setting Not applicable. Patient(s) Five hundred and seventy-six consecutive freeze-all cycles from January 2011 to December 2018 followed by natural cycle FET of a single blastocyst. Intervention(s) None. Main Outcome Measure(s) Primary outcome of live birth; secondary outcomes of preterm delivery (24–37 weeks) and small for gestational age (SGA) with a multivariable logistic regression performed with adjustment for age, infertility diagnosis, ovulatory trigger type, and preimplantation genetic testing (PGT). Result(s) Before adjustment for confounding, we found a statistically significantly different live-birth rate (57.7% vs. 48.6%) for natural cycle FET occurring in the first versus second menstrual cycle, respectively. In a multivariate analysis, performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle did not statistically significantly impact the odds of live-birth rate. After adjustment for age, diagnosis, and ovulatory trigger type, only PGT was associated with statistically significantly increased odds of live birth compared with no PGT. There were no differences in the incidence of SGA (male, 6.6% vs. 2.3%; female, 9.8% vs. 11.1%) or preterm delivery (1.6% vs. 5.6%) between both groups. Conclusion(s) Performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle after ovarian stimulation did not statistically significantly impact the odds of live birth or neonatal outcomes.

INTRODUCTION: Posthemorrhagic hydrocephalus (PHH) is a common disease process encountered in neonates. Management often includes cerebrospinal fluid (CSF) aspiration through ventricular access devices (VADs). However, a common concern surrounding serial access of implanted subcutaneous reservoirs includes introduction of infection. In addition, there is great variability in aseptic technique. Therefore, the authors sought to evaluate the incidence of VAD access-associated infections in the literature and compare them with the rate of infection found at our institution. We also highlight the use of a preassembled VAD access kit and standardized access protocol, as well as the role of provider education, in maintaining safety and sterility during serial VAD access. METHODS: A single-institution retrospective review was performed for PHH patients younger than 1 year old undergoing serial CSF aspirations via implanted VADs (2009-2019). Patients were excluded if they had a ventriculoperitoneal shunt placed as primary intervention. MEDLINE search for reports of serial VAD access in PHH was also performed. Reports were excluded if they did not include full-text articles in the English literature. RESULTS: At our institution, subcutaneous reservoirs were placed in 37 neonates with PHH for serial CSF aspiration. No infections occurred after a total of 630 taps (average, 17 taps per reservoir; range, 0-83) and 10 420 collective reservoir days (average, 282 per patient; range, 6-3700). Only 2 reservoirs required revision for malfunction. Serial VAD taps for PHH were described in 14 articles in the medical literature, with 7.9% (n = 47/592) of patients reported with tap-related infectious complications. CONCLUSION: A standardized VAD access kit, along with stringent adherence to access protocol, can significantly minimize risk of infection associated with serial VAD access. These principles can be generalized to percutaneous aspiration of CSF from subcutaneous reservoirs placed for other indications to promote safety and sterility of this common procedure.

What is the impact of low body mass index (BMI) on live birth rates and obstetric outcomes in infertile women treated with IVF and fresh embryo transfer?This was a retrospective cohort study of infertile patients in an academic hospital setting who underwent their first oocyte retrieval with planned autologous fresh embryo transfer between 1 January 2012 and 31 December 2018. The primary study outcome was live birth rate. Secondary outcomes were IVF treatment and delivery outcomes. Underweight patients were stratified into a significantly underweight group (body mass index [BMI]17.5 kg/mA total of 5229 patients were included (significantly underweight, 76; mildly underweight, 231; normal weight, 4922), resulting in 4798 embryo transfers. After oocyte retrieval, there were no significant differences between groups for total oocytes, mature oocyte yield and number of supernumerary blastocysts cryopreserved. Among women who had an embryo transfer, there were no significant differences in the live birth rates in significantly (31.0%, odds ratio [OR] 0.67, confidence interval [0.95, CI] 0.40-1.13) and mildly (37.7%, OR 0.95, CI 0.73-1.33) underweight patients compared with normal-weight patients (35.9%). Additionally, there were no statistically significant increased risks of preterm delivery, Caesarean delivery or a low birthweight (2500 g) neonate.Mildly and significantly underweight infertile women have similar pregnancy and live birth rates to normal-weight patients after IVF treatment. In addition, underweight patients do not have an increased risk of preterm delivery (37 weeks), Caesarean delivery or a low birthweight neonate.

We present a case of a tubal ectopic pregnancy (EP) in a patient with an initially undetectable serum β-human chorionic gonadotropin (β-hCG) level. A 33-year-old woman in a same-sex relationship underwent timed donor intrauterine insemination. Her serum β-hCG level was

OBJECTIVE: Assess the effect of class III (body mass index [BMI, kg/m(2)] 40–49.9) and class IV obesity (≥ 50) on clinical pregnancy and live birth outcomes after first oocyte retrieval and fresh embryo transfer cycle. DESIGN: Cohort study SETTING: Academic center PATIENTS: Patients undergoing their first oocyte retrieval with planned fresh embryo transfer in our clinic between 01/01/2012 and 12/31/2018. Patients were stratified by BMI: 18.5–24.9 (n = 4913), 25–29.9 (n = 1566) 30–34.9 (n = 559), 35–39.9 (n = 218), and ≥ 40 (n = 114). INTERVENTION: None MAIN OUTCOME MEASURE: Live birth rate RESULTS: Following embryo transfer, there were no differences in pregnancy rates across all BMI groups (p value, linear trend = 0.86). However among pregnant patients, as BMI increased, a significant trend of a decreased live birth rate was observed (p value, test for linear trend = 0.004). Additionally, as BMI increased, a significant trend of an increased miscarriage rate was observed (p value, linear trend = < 0.001). Compared to the normal-weight cohort, women with a BMI ≥ 40 had a significantly higher rate of cancelled fresh transfers after retrieval (18.4% vs. 8.2%, OR 2.51; 95%CI 1.55–4.08). Among singleton deliveries, a significant trend of an increased c-section rate was identified as the BMI increased (p value, linear trend = 40 have worse IVF treatment outcomes compared to normal-weight patients. After embryo transfer, their pregnancy rate is comparable to normal-weight women; however, their miscarriage rate is higher, leading to a lower live birth rate for pregnant women in this population. Patients with a BMI > 40 have a c-section rate that is 50% higher than normal-weight patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02011-1.

STUDY QUESTIONWill a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve?SUMMARY ANSWERA delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation.WHAT IS KNOWN ALREADYIn clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes.STUDY DESIGN, SIZE, DURATIONA retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018.PARTICIPANTS/MATERIALS, SETTING, METHODSDiminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) 40 years old with an AMH MAIN RESULTS AND THE ROLE OF CHANCEThe mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85–1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH 40 years old with an AMH LIMITATIONS, REASONS FOR CAUTIONThere is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91–180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles.WIDER IMPLICATIONS OF THE FINDINGSA delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected.STUDY FUNDING/COMPETING INTEREST(S)No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest.TRIAL REGISTRATION NUMBERNot applicable.

Introduction Immune-related hepatitis (ir-hepatitis) is a common side-effect of checkpoint inhibitors (CPIs). Here, we characterise ir-hepatitis in a large cohort of patients with metastatic melanoma (MM) treated with CPIs and describe potential risk factors and efficacy of medical management. Methods The retrospective study included a large cohort of patients with MM treated with CPIs between 2010 and 2019. Patients were retrieved from the national Danish Metastatic Melanoma Database. Results Five hundred twenty one patients were included. Ir-hepatitis was found in 6.8% of patients. Combination therapy was associated with a significantly greater risk than monotherapy. Of all patients, 34.9% with hepatitis had a different hepatitis grading, when based on either alanine transaminase (ALT) or aspartate transaminase (AST) levels. Of all patients, 72.1% with hepatitis received steroid treatment, and two patients received additional second-line immunosuppressants. Of all patients, 35.5% experienced hepatitis relapse during steroid tapering. Of all patients, 18.6% and 25% of patients with grade ≥2 and ≥ III3, respectively, developed hepatitis within 7 days after finishing an antibiotic treatment for infection. Patients (62.5%) who received a cumulative dose of >4000 mg steroid experienced cancer progression, compared with 22.7% of patients treated with Conclusion Several observations of clinical importance were made. Infection and antibiotic treatment during CPIs could be a possible risk factor for developing ir-hepatitis. Severity of ir-hepatitis is potentially underestimated in a significant number of patients, if only one liver enzyme is measured. The role of second-line immunosuppressants needs to be further investigated because of the high risk of hepatitis relapse during steroid tapering and the potential negative impact of cumulative steroid dose on response to CPIs.

The aim of this paper was to determine the optimal follicle size at trigger in clomiphene citrate-based in vitro fertilization (IVF) protocols.This is a retrospective cohort study performed in at a single academic institution that included first IVF cycles with clomiphene citrate-based protocols at our center between 01/01/2013 and 03/31/2019. Patients were dichotomized by whether they had ≥2 follicles20 mm on trigger day. Group A consisted of patients with2 follicles20 mm on trigger day and Group B consisted of patients with ≥2 follicles20 mm on trigger day. The primary outcome was the number of mature oocytes retrieved. Secondary outcomes included pregnancy and live birth rates.A total of 635 patients were included: (Group A=399 patients and Group B=236 patients). The median (IQR) diameter of the largest follicle was 20.0 mm (19.0-21.0) in Group A and 22.7 mm (21.8-24.0) in Group B (P0.001). Among the entire cohort, mean number of oocytes retrieved was significantly higher in Group B (9.9±6.5; RR 1.08 [95% CI 1.03-1.14]) compared to Group A (9.2±6.3). In a subgroup analysis of patients in the upper quartile for age (≥41.7 years), Group B had significantly more oocytes retrieved (8.1±5.9 vs. 6.7±4.5; RR 1.23 (95% CI 1.10-1.38]), more mature oocytes retrieved (6.0±4.0 vs. 5.2±3.4; RR 1.16 [95% CI 1.02-1.33]), and more zygotes (4.7±3.5 vs. 3.6±2.8; RR 1.32 [95% CI 1.13-1.55]). In the secondary analysis, pregnancy and live birth rates after fresh transfer were similar between groups.In clomiphene citrate-based IVF protocols, administering the ovulatory trigger at larger follicle sizes yielded more total oocytes retrieved without a significant difference in mature oocyte number. In older patients, larger follicle sizes at trigger yielded more mature oocytes and zygotes per retrieval. Based on these results, in older patients it may be advantageous to administer the ovulatory trigger in clomiphene-based IVF cycles when two or more follicles measures20 mm. However, this benefit was not observed when assessed among all ages combined.

OBJECTIVE: To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred. DESIGN: Retrospective cohort study. SETTING: A University based Reproductive Endocrinology and Infertility Clinic. PATIENT (S): Retrospective review of 1957 IUI cycles performed on 660 patients between July 2007 and May 2012. INTERVENTION (S): None MAIN OUTCOME MEASURE (S): The primary outcome was live birth. Secondary outcomes were positive serum pregnancy result and clinical pregnancy. Risk ratios (RR) and 95% confidence intervals (CI) were calculated using a cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. RESULTS: Live birth rates were similar in IUI cycles with and without regurgitation (6.3% vs 6.8%, respectively, RR=0.82, 95% CI [0.53–1.26]). Clinical pregnancy rates in the presence or absence of regurgitation were 10.5% versus 10.0%, RR=0.99, 95% CI [0.73–1.35]. Positive serum pregnancy tests following IUI did not differ by regurgitation status (15.0% versus 15.4%, RR=0.97, 95% CI [0.75–1.24]). Results were unchanged when adjusted for covariates (age, race/ethnicity, BMI, duration of infertility, medication, infertility diagnosis, total motile count, and method of sperm preparation). CONCLUSION: The presence of regurgitation during IUI procedure is not related to pregnancy outcome.

PURPOSE: To assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes. METHODS: This single-center retrospective cohort study included blastocyst single embryo transfers (SET) performed between 1/2012–2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality. Among cycles resulting in live birth, associations with preterm birth, small for gestational age (SGA) and large for gestational age (LGA), were evaluated using logistic regression. RESULTS: A total of 1023 fresh and 1222 CET cycles were included, of which 465 (45.1%) fresh and 600 (48.5%) CET cycles resulted in singleton live birth. Clinical pregnancy rates increased with increasing expansion among fresh transfers (p for trend = 0.001) but not CET (p = 0.221), and with TE quality for both fresh and CET cycles (p = 0.005 and

Continuous monitoring of blood glucose (BG) levels is a key aspect of diabetes management. Patients with Type-1 diabetes (T1D) require an effective tool to monitor these levels in order to make appropriate decisions regarding insulin administration and food intake to keep BG levels in target range. Effectively and accurately predicting future BG levels at multi-time steps ahead benefits a patient with diabetes by helping them decrease the risks of extremes in BG including hypo- and hyperglycemia. In this study, we present a novel multi-component deep learning model that predicts the BG levels in a multi-step look ahead fashion. The model is evaluated both quantitatively and qualitatively on actual blood glucose data for 97 patients. For the prediction horizon (PH) of 30 mins, the average values for root mean squared error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and normalized mean squared error (NRMSE) are $$23.22 \pm 6.39$$ 23.22 ± 6.39 mg/dL, 16.77 ± 4.87 mg/dL, $$12.84 \pm 3.68$$ 12.84 ± 3.68 and $$0.08 \pm 0.01$$ 0.08 ± 0.01 respectively. When Clarke and Parkes error grid analyses were performed comparing predicted BG with actual BG, the results showed average percentage of points in Zone A of $$80.17 \pm 9.20$$ 80.17 ± 9.20 and $$84.81 \pm 6.11,$$ 84.81 ± 6.11 , respectively. We offer this tool as a mechanism to enhance the predictive capabilities of algorithms for patients with T1D.

Background Awake craniotomy (AC) and direct electric stimulation emerged together with epilepsy surgery >80 years ago. The goal of our study was to evaluate the benefits of awake surgery in patients with drug-resistant epilepsy caused by focal cortical dysplasia (FCD) affecting eloquent areas. Methods Our material included 95 patients with drug-resistant epilepsy and FCD, who were operated on between January 2009 and December 2018. These 95 patients were assigned into 3 groups: AC; general anesthesia (GA) with intraoperative neuromonitoring; and GA without intraoperative neuromonitoring. We investigated the following variables: age at surgery, lesion side, eloquent cortex involvement, brain mapping success rate, epilepsy surgery success rate, intraoperative complications, postoperative complications, and intraoperative changes of the preoperative resection plan according to results of the brain mapping by direct electric stimulation. Results We found statistically significant differences between the AC and GA groups in the mean age at operation, lesion side, eloquent localization, and postoperative transient neurologic deficit. Seizure outcome in the AC was satisfactory (71% complete seizure control) and comparable to the seizure outcome in the GA groups. Our preoperative plan was changed because of functional constraints in 6 patients (43%) operated on during AC. Conclusions AC during epilepsy surgery for FCD in eloquent areas may change the preoperative plan. The good rate of postoperative seizure control and the absence of permanent postoperative neurologic deficit in our series is the main proof that AC is a useful tool in patients with FCD involving the eloquent cortex.

Background A number of studies have looked at dual triggers with hCG and GnRH agonist (GnRHa) in varying doses, but the question remains: what is the optimal dose of hCG to minimize ovarian hyperstimulation syndrome (OHSS) and still offer adequate pregnancy rates? The purpose of this study was to compare pregnancy and OHSS rates following dual trigger for oocyte maturation with GnRHa and a low-dose hCG versus hCG alone. A secondary objective was the assess pregnancy outcomes in subsequent frozen cycles for the same population. Methods A total of 963 women 2 and an AMH > 2 ng/mL who underwent fresh autologous in vitro fertilization (IVF) with GnRH antagonist protocol at a University-based fertility center were included in this retrospective cohort study. Those who received a low dose dual trigger with hCG (1000u) and GnRHa (2 mg) were compared to those who received hCG alone (10,000u hCG/250-500 μg Ovidrel). Differences in implantation rates, pregnancy, live birth, and OHSS were investigated. Results The dual trigger group was younger (mean 33.6 vs 34.1 years), had a higher AMH (6.3 vs 4.9 ng/mL,) more oocytes retrieved (18.1 vs 14.9) and a higher fertilized oocyte rate (80% vs 77%) compared with the hCG only group. Yet, the dual trigger group had a lower probability of clinical pregnancy (gestational sac, 43.4% vs 52.8%) and live birth (33.4% vs 45.8%), all of which were statistically significant. There were 3 cases of OHSS, all in the hCG-only trigger group. In subsequent frozen cycles, pregnancy rates were comparable between the two groups. Conclusions The dual trigger group had a better prognosis based on age and AMH levels and had better stimulation outcomes, but significantly worse pregnancy outcomes, suggesting the low dose hCG (1000u) in the dual trigger may not have provided adequate luteal support, compared to an hCG-only trigger (10,000u hCG/250-500 μg Ovidrel). Interestingly, the pregnancy rates were comparable in subsequent frozen cycles, further supporting the hypothesis that the issue lies in inadequate luteal phase support, rather than embryo quality. Based on these findings, our program has changed the protocol to 1500u of hCG in a dual trigger.

We demonstrate tests of a flow-based router enhanced with the additional mechanisms: Emergency Connections, Efficient Congestion Control, Global Protected Flow List and Per-User Fairness. The tests were conducted in the Click environment. The analyzed mechanisms allow for immediate acceptance of high priority traffic, protection of streaming flows in congestion, and ensure high reliability and fairness. In this paper, we show that these mechanisms work successfully in a laboratory network. Moreover, they all work at the same time providing high-level coordinated performance. Test results show significant advantages of the cross-protect router architecture over standard IP routers in several areas.

Objective To assess the association between body mass index (BMI) and embryo aneuploidy and mosaicism in a cohort of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing technology. Design Retrospective cohort study. Setting Academic center. Patients Patients undergoing their first IVF cycle with trophectoderm biopsy and PGT-A at our center between January 1, 2017, and August 31, 2020. Patients classified as underweight on the basis of BMI (BMI Intervention None. Main Outcome Measures Number and proportion of aneuploid, mosaic, and euploid embryos. Results The patients were stratified according to the World Health Organization’s BMI classification: normal weight (18.5–24.9 kg/m2, n = 1,254), overweight (25–29.9 kg/m2, n = 351), and obese (≥30 kg/m2, n = 145). Age-adjusted regression models showed no relationship between BMI classification and the number or proportion of aneuploid embryos. There were no statistically significant associations between BMI classifications and the number or proportion of mosaic or euploid embryos. A subgroup analysis of patients classified into age groups of 40 years similarly showed no relationships between BMI and embryo ploidy outcomes. Conclusion Body mass index was not associated with the number or proportion of aneuploid, mosaic, or euploid embryos in this large cohort of patients undergoing IVF with PGT-A, suggesting that the negative effect of excess weight on reproductive outcomes was independent of the ploidy status of the embryo cohort.

Simple Summary Microsatellite instability (MSI) has been detected in multiple types of gynecologic cancers. MSI is linked to mutations in mismatch repair (MMR) genes that cause mismatch repair deficit (dMMR) in human cells. Discovery of new therapeutic approaches are needed especially for treatment of advanced endometrial and other gynecological cancers with dMMR/MSI. In addition, there is a need to identify markers for reliable detection of dMMR/MSI gynecological cancers. Determination of the mechanism leading to these malignancies would help in diagnosis and therapeutic intervention. In this review, we summarize the MMR defects and MSI observed in gynecological cancers, and new therapeutic strategies to treat these cancers. Abstract Mutations in mismatch repair genes leading to mismatch repair (MMR) deficiency (dMMR) and microsatellite instability (MSI) have been implicated in multiple types of gynecologic malignancies. Endometrial carcinoma represents the largest group, with approximately 30% of these cancers caused by dMMR/MSI. Thus, testing for dMMR is now routine for endometrial cancer. Somatic mutations leading to dMMR account for approximately 90% of these cancers. However, in 5–10% of cases, MMR protein deficiency is due to a germline mutation in the mismatch repair genes MLH1, MSH2, MSH6, PMS2, or EPCAM. These germline mutations, known as Lynch syndrome, are associated with an increased risk of both endometrial and ovarian cancer, in addition to colorectal, gastric, urinary tract, and brain malignancies. So far, gynecological cancers with dMMR/MSI are not well characterized and markers for detection of MSI in gynecological cancers are not well defined. In addition, currently advanced endometrial cancers have a poor prognosis and are treated without regard to MSI status. Elucidation of the mechanism causing dMMR/MSI gynecological cancers would aid in diagnosis and therapeutic intervention. Recently, a new immunotherapy was approved for the treatment of solid tumors with MSI that have recurred or progressed after failing traditional treatment strategies. In this review, we summarize the MMR defects and MSI observed in gynecological cancers, their prognostic value, and advances in therapeutic strategies to treat these cancers.

Purpose: Increasing evidence suggests that circulating biomarkers may serve diagnostic and longitudinal monitoring purposes in pediatric neuro-oncology. Mutant tumor DNA is detectable in the cerebrospinal fluid (CSF) of pediatric diffuse midline glioma (DMG) patients and quantity can reflect disease burden. CSF sampling ("liquid biopsy") via a CSF access device could therefore play a role in DMG management. Therefore, we set to evaluate the incidence of hydrocephalus (HCP) in DMG patients, and to characterize ventricular reservoir placement and access practices. Methods: A single institution retrospective review of DMG patients ≤21-years-old was performed (1984-2019). MEDLINE searches for reports of ventricular reservoir or shunt placement in DMG, and reservoir access for intraventricular chemotherapy (IVC) were performed. Results: At our institution, 62.6% of DMG patients (67/108) required intervention for HCP: 19.4% provided transient CSF access (ETV alone n = 3, EVD n = 8, unspecified n = 2), and 80.6% permanent CSF access (ETV + reservoir n = 13, shunt n = 41). Further, 22/34 patients with initially transient CSF devices required conversion to a permanent device. Five devices were revised for malfunction, one for infection. Seventeen articles cited HCP in 22 to 100% of DMG patients. IVC administration was described in 632 patients (seven articles), with 42 infectious and 63 non-infectious complications. Conclusions: Management of HCP is often necessary in children with DMG. Given the low rate of clinical risk associated with VAD placement and access, and the potential utility of longitudinal disease monitoring via CSF analysis, VAD placement could be considered in future clinical trials to guide DMG treatment.

Objective: To describe the patient and cycle characteristics of women who undergo intrauterine insemination (IUI) immediately after an unsuccessful oocyte retrieval. Design: Retrospective case series. Setting: University-affiliated center. Patient(s): Women who underwent an oocyte retrieval procedure in which no oocytes were retrieved followed by an IUI on the same morning. Intervention(s): None. Main Outcome Measure(s): Live birth rate, subsequent live birth rate. Result(s): From 2011 to 2019, 63 cycles in 57 patients were identified. The mean (SD) age was 39.6 (4.6) years, and diminished ovarian reserve (94.7%) was the most common diagnosis. The median (IQR) number of previous IVF cycles in this cohort was 3 (1–7), with 56.1% having had at least one previous canceled IVF cycle. The majority of patients had undergone either controlled ovarian hyperstimulation (COH) (64.9%) or modified natural cycles (21.1%). The mean (SD) number of follicles >14 mm at the time of trigger was 1.9 (1.4), with 38.9% of patients manifesting a drop in their estradiol levels after the trigger. One pregnancy resulting in a live birth was identified (1.8%). For patients who underwent subsequent IVF cycles, 60.7% had at least one subsequent cancelled cycle. Three patients went on to achieve a live birth using autologous oocytes (6.5%). Conclusion(s): Same-day IUI for patients who have no oocytes retrieved is associated with a

PURPOSE: To test whether an electronic whiteboard in the IVF laboratory increases the likelihood that critical evaluation procedures are performed within optimum pre-set time ranges. METHODS: A retrospective cohort study of oocyte retrievals in our IVF clinic between 06/01/2012 and 05/31/2018 was included. The electronic whiteboard was introduced on 04/06/2014. Prior to implementation, embryologists strived to adhere to the set evaluation times without a formal guide. The primary outcomes were the proportion of embryologist evaluations performed in optimum time ranges and the proportion of usable embryos per patient. RESULTS: A total of 4645 retrievals met inclusion criteria. Implementation of the whiteboard was associated with (1) an increase in the proportion of fertilization checks performed within the optimum time range for ICSI cycles (+ 5.1%, RR = 1.06, CI = 1.02–1.10); (2) an increase in the proportion of day 3 evaluations performed within the optimum time range, whether assisted hatching was performed (+ 23.6%, RR = 1.48, CI = 1.36–1.60) or not (+ 13.8%, RR = 1.23, CI = 1.12–1.35); and (3) an increase in the proportion of day 5 evaluations within the optimum time range (+ 15.5%, RR = 1.23, CI = 1.12–1.35). Additionally, the mean number of usable embryos per patient increased from 2.8 to 4.5 after the whiteboard was implemented (RR = 1.25, CI = 1.19–1.31). CONCLUSION: The use of an electronic whiteboard that posts optimum times for performing critical procedures significantly increases the proportion of evaluations that occur within these ranges. Such improved standardization led to positive downstream effects on the number of usable embryos per patient. We suggest that electronic whiteboard implementation driven by real-time data collection should be considered in all IVF laboratories. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02007-x.

STUDY QUESTION Do women ≥40 years old without a male partner who utilize donor sperm have the same reproductive outcomes as those who utilize their partner’s sperm? SUMMARY ANSWER After controlling for relevant confounders, women ≥40 years old using donor sperm for IVF have significantly higher odds of having a live birth compared to those utilizing their partner’s sperm. WHAT IS KNOWN ALREADY Women who are unpartnered or in same-sex relationships are by definition not infertile, but may choose to conceive using donor sperm. It is not known how IVF outcomes are affected with the use of donor sperm compared to women utilizing their partner’s sperm, particularly at very advanced maternal ages. STUDY DESIGN, SIZE, DURATION This is a retrospective cohort study conducted at a university-affiliated center of women undergoing IVF with fresh embryo transfer between 2008 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were divided into two groups based on the ejaculated sperm source utilized: donor or partner sperm. Live birth rate was the primary outcome. Pregnancy rate was the secondary outcome. Multivariable logistic regression was performed and adjusted for age, the developmental stage of the embryo, and the number of embryos transferred. Unadjusted odds ratio (OR) and adjusted OR (aOR) with 95% CI for pregnancy and live birth were estimated. Statistical significance was denoted by P MAIN RESULTS AND THE ROLE OF CHANCE A total of 3910 cycles in women ≥40 years old were analyzed, of which 307 utilized donor sperm and 3603 utilized their partner’s sperm to conceive. In the univariate analysis, patients utilizing donor sperm were found to have similar pregnancy rates as those utilizing partner sperm (41.0 vs 39.8%, OR: 0.95, 95% CI: 0.75–1.20). After adjusting for age, the number of embryos transferred and the developmental stage of the embryos, the model estimates did not vary (aOR: 1.22, 95% CI: 0.95–1.56). Similarly, the univariate analysis for live birth did not demonstrate a difference between groups (19.2 vs 17.8%, OR: 0.91, 95% CI: 0.67–1.22). However, after a similar adjustment was made for confounders, the use of donor sperm was associated with statistically significant increased odds of live birth (aOR: 1.38, 95% CI: 1.01–1.88). LIMITATIONS, REASONS FOR CAUTION As with any retrospective study, the potential for residual confounding exists, despite attempts to control for this with regression modeling. WIDER IMPLICATIONS OF THE FINDINGS Women ≥40 years old who are unpartnered or in same-sex relationships can be counseled that their odds of a live birth are slightly better than women in heterosexual relationships utilizing their partner’s sperm. These findings serve to further refine and individualize counseling on the expected IVF outcomes for women in this population. STUDY FUNDING/COMPETING INTEREST(S) No funding was sought for this study. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.

Objective To describe how to create an inflatable vaginal stent for use in McIndoe vaginoplasty that can be constructed using standard operating room supplies. Design Step-by-step video instructions that demonstrate how to construct and use an inflatable vaginal stent. (This video article was exempt from institutional review board approval.) Setting Academic hospital. Patient(s) A woman presenting with vaginal agenesis requiring a McIndoe vaginoplasty for the creation of a neovagina. Intervention(s) A novel inflatable vaginal stent compliant with operating room procedures that is radio-opaque, functional, and can be used for patients with or without a functional uterus. The device is modeled after the effective inflatable vaginal stent that was previously commercially available but is no longer produced. Although a vaginal stent may be created in the operating room by placing surgical sponges inside a sterilized condom, many operating rooms have restrictions on equipment that can be brought into the operating room and special criteria for how to sterilize this equipment, and there are also restrictions against leaving non–radio-opaque objects “inside” the patient. The novel inflatable vaginal stent we have developed has multiple advantages compared with a rigid dilator: it is deflatable, so it does not cause trauma or interrupt the delicate tissue graft during insertion, removal, or repositioning; it is firm enough to conform and circumferentially press the tissue graft against the dissected vaginal space but is soft enough to decrease the risk of pressure necrosis or damage to the urethra; and it has a drainage port to prevent the buildup of a fluid pocket that could interfere with graft adherence. Our stent incorporates all these unique properties and can be easily constructed using sterile operating room supplies. The construction of this device requires a silicone Foley catheter, sterile foam sponges from a vaginal prep kit, a sterile radio-opaque sponge, a sterile vaginal ultrasound probe cover, a long Kelly, a 60-cc catheter tip syringe, a ruler, scissors, 0-vicryl suture, and sterile gloves. Main Outcome Measure(s) Effectiveness of a self-made inflatable vaginal stent using standard operating room supplies that meets operating room protocol standards. Result(s) A standard dose of prophylactic antibiotics should be administered preoperatively to prevent surgical site infection. After placement of the tissue graft in the dissected neovagina cavity, the vaginal stent is placed and slowly inflated to circumferentially apply the tissue graft against the dissected vaginal space. The stent remains in place for 7 days and then should be removed in the operating room to allow for an examination under anesthesia, which provides the ideal setting to best evaluate the initial graft adherence. After careful inspection of the neovagina and tissue graft, a standard silicone vaginal mold is placed to maintain vaginal patency and prevent stricture of the tissue graft. The silicone mold should remain in place continuously until complete graft adherence occurs (approximately 4 to 6 weeks), and then it can be worn nightly until the patient is regularly sexually active. If at any point the patient discontinues nightly use of the silicone mold before regular sexual activity, vaginal stricture and a decrease in vaginal caliber will occur. Conclusion(s) Our novel inflatable vaginal stent is useful to surgeons performing a McIndoe vaginoplasty for vaginal agenesis with or without a uterus. It is compliant with operating room protocols and restrictions, as it is constructed from operating room supplies and is radio-opaque. Moreover, it is adjustable in size and effective in applying circumferential pressure for graft adherence. When used for segmental vaginal agenesis, the Foley catheter may be advanced through the cervix, then the balloon can be inflated, to stabilize the position of the stent during the first week postoperatively. The main limitation of this device is that it must be constructed by the surgeon, but the advantage of self-constructing the stent is that the size and shape can be tailored to conform to each individual patient. We prefer this inflatable vaginal stent to a rigid vaginal dilator in the first week of tissue healing to allow for easy insertion and removal of the stent without disrupting the tissue graft, to help prevent tissue necrosis, and to provide a fluid drainage port during graft adherence. We recommend this device as an ideal option for surgeons to consider when performing a McIndoe vaginoplasty.

To improve the total knee arthroplasty (TKA) prosthesis design, it is essential to study the kinematics of the tibiofemoral joint. Many studies have been conducted in this area; however, conflicting results and incomparable testing methods make it difficult to draw definitive conclusions or compare research from studies. The goal of this article is to introduce what is known about both healthy and prosthetic tibiofemoral joint kinematics.Healthy tibiofemoral joint kinematics are reviewed in vivo by different activities, and the kinematics of existing knee prosthetic design features are considered separately. These features include but are not limited to cruciate retaining, posterior cruciate substituting, mobile-bearing, and high flexion.The type of activity that is being performed has a great influence on the kinematics of healthy knees, and the influences of different TKA prosthetic design features on the kinematics are complex and varied. Moreover, the TKA postoperative functional performance is influenced by many factors, and prosthetic design is among them, but not the only one that defines the performance.

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)

Tert-butyl hydroquinone (TBHQ) is an aromatic compound that is commonly used as a preservative in processed food to prevent rancidity and lengthen shelf life. TBHQ is known to act as an antioxidant by protecting cells from radical oxygen species and thus preventing DNA damage. Although previous studies have found TBHQ to cause cancer cell death at high concentrations, they have also contrastingly found TBHQ, when studied in animal models, to enhance carcinogenic effects. However, the effect of TBHQ on breast cancer has not been thoroughly explored. With the prevalence of breast cancer and the wide use of TBHQ in processed food items, it is imperative that we explore their possible relationship. This study examined the effects of TBHQ, alone and in combination with hormones and anti-hormones, on ERα and p53 expression in both MCF-7 and T-47D breast cancer cell lines. To ensure treatment conditions without the presence of endogenous steroids or growth factors, the cells were cultured with a 5% charcoal-stripped fetal bovine serum (FBS) for six days. Western blot analysis revealed alterations in the expression of ERα and p53 protein levels after 24 hours of treatment with varying concentrations of TBHQ (0.005 to 1 mM). A concentration-dependent decrease of ERα protein levels was observed in both cell lines, with a 49% reduction occurring with 100 µM TBHQ as compared to the control. P53 levels portray a continued increase of expression through concentrations of TBHQ (0.005 to 1 mM), found similarly in both cell lines. To gain further insight into possible similarities between BPS and other known effectors of ERα, the optimal concentration of TBHQ (100 μM) was used in combination with hormones and anti-hormones. Down-regulation of ERα protein levels was observed after 24-hour co-treatment of T-47D & MCF-7 cells with a combination of TBHQ and E2. Antiestrogen ICI with TBHQ showed a significant down-regulation as compared to TBHQ alone, and TBHQ with TAM portrayed no significant differences. A similar trend in the effects on p53 expression was depicted in T-47D and MCF-7 cells. Image cytometric analysis with propidium iodide staining was utilized to quantify cell values and viability changes to further portray the effects of TBHQ on T-47D and MCF-7 cellular growth. The viability assay shows a biphasic effect with increasing concentrations of TBHQ, with a maximum decrease in proliferation seen at a concentration of 100 uM TBHQ. TBHQ alone and in combination with E2 and antiestrogens showed a decreased proliferation compared to the control in T-47D cells. However, cytolocalization of ERα upon treatment with estradiol and TBHQ remained unaltered. Our studies offer a unique perspective on the effects of TBHQ on two different breast cancer cell lines, and provide valuable insight for further exploration of the mechanism of action of TBHQ on tumor suppressor gene and steroid receptors.

To demonstrate safe and efficient techniques for hysteroscopic partial and complete uterine septum incisions with radiofrequency electrosurgery. Review of these techniques may be particularly helpful for a surgical trainee or a less experienced hysteroscopic surgeon.Video instruction of the hysteroscopic uterine septum incision techniques.Academic hospital setting.One patient with a partial uterine septum and 1 patient with a complete uterine septum and a duplicated cervix (2 distinct external cervices) (1).Hysteroscopic partial and complete uterine septum incisions with a 7-mm unipolar knife electrode. Importantly, the demonstrated techniques can be performed using any hysteroscopic cutting instrument with which the surgeon is comfortable.Surgical techniques that can be used to safely and efficiently incise a uterine septum and determine when the incision is complete.For a partial uterine septum, surgical techniques include uterine septum shortening, uterine septum thinning, and measurement of the residual septum length with the operating instrument to determine when the incision is complete. Visualization of the tubal ostia should be used throughout the procedure to maintain a horizontal incision plane. For a complete uterine septum with a duplicated cervix, we additionally demonstrate how to make a window through the septum at the level of the internal os to incise the uterine body portion while preserving the tissue wall inferiorly that separates the duplicated cervices.Uterine septum incision is typically a short procedure that can be successfully performed with operative hysteroscopy. However, if a systematic approach is not followed, the surgeon can quickly and unknowingly become disoriented, resulting in inadvertent uterine perforation, incomplete septum incision, or excessive septum incision causing myometrial thinning, which has been shown to increase the risk of uterine rupture during pregnancy. In practice, the choice of technique used for septum incision should be made intraoperatively and will depend on the septum size and shape. Often, septum shortening, thinning, and residual measurement are best used in combination to achieve a successful result. Surgeons will find the use of these techniques helpful to maintain intraoperative orientation and provide a framework to guide adequate removal of either a partial or complete uterine septum.

OBJECTIVE To demonstrate the advantage of using aqueous vaginal contrast and scheduled hematocolpos with magnetic resonance imaging (MRI) to improve the delineation of gynecologic anatomy and to recommend that this modality be considered in patients with complex mullerian anomalies. DESIGN Video demonstration of MRI adjuncts to improve visualization of gynecologic anatomy. SETTING Academic Hospital. PATIENT(S) A patient with obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) who presented for definitive surgical management. INTERVENTION(S) OHVIRA is a unilateral obstructed mullerian anomaly that presents typically after menarche with progressively worsening dysmenorrhea caused by progressive distension of the obstructed hemivagina and uterine horn. The definitive treatment for this anomaly is resection of the unilateral obstruction. When the obstructed hemivagina is within close proximity to the patent hemivagina, vaginal septum resection should be performed to relieve the obstruction successfully. However, when the obstructed hemivagina and uterine horn are not adjacent to the patent hemivagina, a simple septum resection is not feasible and there is a high rate of restenosis if anastomosis is attempted. In this case, laparoscopic removal of the obstructed uterine horn, fallopian tube, cervix, and vagina should be considered as an alternative approach to resolving the obstruction. A surgical approach can be recommended only once the surgeon has a clear understanding of the patient's pelvic anatomy and the magnitude of the obstruction. In the presented case, a 17-year-old patient with OHVIRA presented for definitive surgical management. While on hormonal suppression, a pelvic MRI was performed that identified a uterus didelphys with a left hemiuterus and cervix communicating with a patent vagina. The right hemiuterus and cervix were measured 2.5 cm from the patent vagina. However, because of hormonal suppression, the vaginal cavity was decompressed, making it very difficult to discern the relationship between the two uteri and vaginas. To better determine whether vaginal septum resection to relieve the obstruction was feasible, norethindrone was discontinued to allow menstrual blood to fill the obstructed hemivagina followed by a subsequent pelvic MRI with aqueous vaginal contrast to fill the patent vagina with contrast gel to improve the visualization of the decompressed vaginal cavities. MAIN OUTCOME MEASURE(S) Advantage of aqueous vaginal contrast and scheduled hematocolpos with MRI to image pelvic anatomy in a patient with a complex mullerian anomaly to guide surgical decision-making. RESULT(S) The addition of vaginal aqueous contrast clearly delineated the course and caliber of the patent vagina and its relationship to the obstructed hemivagina, now filled with blood. The inferior margin was in closer proximity to the patent vagina, but with only a very narrow segment (

Ovarian torsion is a surgical emergency that can be clinically challenging to diagnose. Patients who have received assisted reproductive technologies (ART) are a subset of women with an increased risk for torsion. As the ART population continues to increase, there is a need to delineate risk factors for the development of ovarian torsion in this unique population. A pilot study was performed to determine the proportion of patients with suspected ovarian torsion who have received ART and to identify possible diagnostic biomarkers for ovarian torsion among these patients.A single institution retrospective cohort study of patients taken to surgery for suspected ovarian torsion over a 5-year period.During the study period, 171 patients were taken to surgery for suspected ovarian torsion. Patients receiving ART constituted 19 (11%) of these patients. Among the 19 fertility treatment patients, 16 had received treatment with gonadotropins, 10 of which had surgically confirmed ovarian torsion. These ten patients had higher preoperative peak estradiol levels (3122 versus 1875 pg/mL, p = 0.05) and a larger ovarian diameter (9.7 versus 7.6 cm, p = 0.05) than the six patients receiving gonadotropins found to not have ovarian torsion.These results suggest infertility treatment using gonadotropins for ovarian hyperstimulation may be an independent risk factor for ovarian torsion as suggested by the disproportionate number of such individuals represented in the study population (9% of all patients, 84% of fertility patients). Additionally, among women taking gonadotropins, an association exists between peak estradiol levels, ovarian diameter, and risk for ovarian torsion.