High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

The details matter: personalized prediction of live birth after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To derive and internally validate a clinical prediction model for live birth (LB) in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Four academic reproductive endocrinology clinics. PATIENTS: A total of 207 women with PCOS confirmed using Rotterdam criteria undergoing their first fresh IVF cycle. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was cumulative LB per IVF cycle start. This included any LB that resulted from either fresh embryo transfer or any subsequent frozen embryo transfer from embryos obtained at the index oocyte retrieval. A prediction model was derived using multivariable logistic regression. Covariates considered for inclusion in the prediction model included demographic characteristics, medical history, and prior fertility treatment. Predicted probabilities for LB were calculated using the prediction model which included the 90% shrinkage factor for each adjusted odds ratio. RESULTS: The final model, on the basis of maximization of the area under the receiver operating characteristic curve, included age < 35 years, White race, presence of polycystic ovaries on ultrasound (polycystic ovary morphology), normal body mass index (<25 kg/m2), being metabolically healthy (no metabolic risk factors), and being a nonresponder to ovulation induction agents including letrozole and clomiphene citrate. The area under the receiver operating characteristic curve score for the model was 0.68 (95% confidence interval [CI]: 0.60, 0.77). Predicted probabilities of LB ranged from 8.1% (95% CI: 2.8, 21.5) for a woman who had no favorable predictors to 74.2% (95% CI: 59.5, 84.9) for a woman who had all favorable predictors. CONCLUSION: Our study demonstrated that, in addition to anovulation, the underlying pathophysiology and associated comorbidities alter the likelihood of a successful pregnancy in women with PCOS undergoing IVF. Further validation of this model is needed before it can serve as a tool to personalize prediction estimates for the probability of LB in women with PCOS.

Depressed, stressed, and inflamed: C-reactive protein linked with depression symptoms in midlife women with both childhood and current life stress.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

A Latent Variable Analysis of Psychomotor and Neurocognitive Performance After Acute Cannabis Smoking.

Objective: This paper evaluated a novel, tablet-based neurocognitive and psychomotor test battery for detecting impairment from acute cannabis smoking using advanced quantitative methods. The study was conducted in a state with legal, recreational cannabis use and included participants who use cannabis occasionally or daily, and a no use comparison group. Methods: Participants completed a tablet-based test assessing reaction time, decision making, working memory and spatial-motor performance. The test was completed before and after participants smoked cannabis (or after a rest period in the case of controls). An Exploratory Factor Analysis approach was implemented to reduce dimensionality and evaluate correlations across the four assessed domains. Linear regression models were utilized to quantify associations between factor scores and cannabis use groups (daily vs. occasional vs. no use). Results: Seven factors were identified explaining 56.7% of the variance among the 18 measures. Regression models of the change in factors after cannabis smoking indicated those who use cannabis daily demonstrated poorer performance on a latent factor termed Displaced and Delayed (standardized coefficient 0.567, 95% CI: 0.178, 0.955; P = 0.005) compared to those with no use. Those who use cannabis occasionally exhibited a decline in performance on a latent factor termed Recall and Reaction (standardized coefficient 0.714, 95% CI: 0.092, 1.336; P = 0.025) compared to no use. Conclusions: This analysis demonstrates an innovative, quantitative approach to study how cannabis consumption affects neurocognitive and psychomotor performance. Results demonstrated that acute cannabis use is associated with changes in neurocognitive and psychomotor performance, with differences based on the pattern of occasional or daily use.

Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone.

BACKGROUND: Progesterone administration has therapeutic effects in tobacco use disorder (TUD), with females benefiting more than males. Conversion of progesterone to the neurosteroid allopregnanolone is hypothesized to partly underlie the therapeutic effects of progesterone; however, this has not been investigated clinically. METHODS: Smokers (n = 18 males, n = 21 females) participated in a randomized, double-blind, placebo-controlled crossover study of 200 mg progesterone daily across 4 days of abstinence. The ratio of allopregnanolone:progesterone was analyzed in relationship to nicotine withdrawal, smoking urges, mood states, subjective nicotine effects, and neural response to smoking cues. RESULTS: Allopregnanolone:progesterone ratio interacted with sex to predict withdrawal symptoms (p = 0.047), such that females with higher allopregnanolone:progesterone ratios reported lower withdrawal severity (b = - 0.98 [- 1.95, - 0.01]; p = 0.048). In addition, allopregnanolone:progesterone ratio interacted with sex to predict confusion (p = 0.014) and fatigue (p = 0.034), such that females with higher allopregnanolone:progesterone ratios reported less confusion (b = - 0.45 [- 0.78, - 0.12]; p = 0.008) and marginally lower fatigue (b = - 0.50 [- 1.03, 0.02]; p = 0.062. Irrespective of sex, higher ratios of allopregnanolone:progesterone were associated with stronger "good effects" of nicotine (b = 8.39 [2.58, 14.20]); p = 0.005) and weaker "bad effects" of nicotine (b = - 7.13 [- 13.53, - 0.73]; p = 0.029). CONCLUSIONS: Conversion of progesterone to allopregnanolone correlated with smoking-related outcomes in both sex-dependent and sex-independent ways. Sex-dependent effects suggest that conversion of progesterone to allopregnanolone may contribute to greater therapeutic benefits in females but not males with TUD. Trial registration Clinicaltrials.gov registration, retrospectively registered: NCT01954966; https://clinicaltrials.gov/ct2/show/NCT01954966 \.

Progesterone Increases Nicotine Withdrawal and Anxiety in Male but Not Female Smokers During Brief Abstinence.

INTRODUCTION: Although exogenous progesterone may hold promise as a treatment for nicotine use disorders, it is unclear whether it is similarly effective in males and females. This study examined the effects of progesterone on nicotine use disorder comprehensively using behavioral, psychological, and neural measures in male and female smokers exposed to brief abstinence. AIMS AND METHODS: Thirty-three male and 33 female non-treatment-seeking smokers participated in a double-blind, randomized, placebo-controlled crossover study of 200 mg of progesterone or placebo daily over a four-day abstinence period. Smoking behavior and subjective effects of nicotine were assessed at baseline and after final drug administration. Nicotine withdrawal, smoking urges, mood states, and neural response to smoking cues were measured at baseline, after the first drug administration, and after the final drug administration. RESULTS: No main effect of drug (progesterone vs. placebo) emerged for any outcome. Significant sex by drug interactions emerged for nicotine withdrawal (p = .020), perceived strength of nicotine (p = .040), and perceived bad effects of nicotine (p = .029). Males receiving progesterone reported worse nicotine withdrawal (p = .046) and a trend towards decreased bad effects of nicotine (p = .070). Males on progesterone also reported greater tension and anxiety relative to placebo (p = .021). Females on progesterone perceived nicotine's effects as being stronger relative to placebo (p = .046). CONCLUSIONS: Progesterone causes sex-dependent effects on smoking-related outcomes during brief abstinence. Specifically, progesterone in males may increase rather than decrease nicotine withdrawal and negative affect during abstinence, potentially hindering efforts to quit smoking. IMPLICATIONS: In male and female smokers undergoing a brief period of abstinence, we examined the effects of progesterone on smoking outcomes. While progesterone had limited effects in female smokers, in males, it worsened nicotine withdrawal and negative affect. Our findings emphasize the importance of analyzing sex differences in future studies examining progesterone as a potential treatment and suggest that progesterone in males could potentially exacerbate aspects of nicotine dependence. CLINICALTRIALS.GOV REGISTRATION: NCT01954966. https://clinicaltrials.gov/ct2/show/NCT01954966.

Impact of mode of conception on early pregnancy human chorionic gonadotropin rise and birth weight.

Objective: To assess whether the mode of conception and embryo biopsy impact first-trimester human chorionic gonadotropin (hCG) dynamics and subsequent risk of small for gestational age (SGA) or large for gestational age (LGA). Design: Retrospective cohort study. Setting: University fertility center. Patients: Six hundred-two pregnant patients with singleton live births. Interventions: Serial serum hCG measurements were obtained between 10 and 28 days postconception to determine the within-woman rate of change in hCG (slope) by mode of conception (unassisted pregnancy, fresh embryo transfer (ET), frozen ET, and frozen ET following preimplantation genetic testing for aneuploidy (PGT-A). Main Outcome Measures: Primary outcomes included birth weight, SGA, and LGA. Results: Mode of conception is not independently associated with birth weight, SGA, or LGA. Mediation analysis revealed an expected one-day increase in log-transformed hCG varied by mode of conception: unassisted (0.41), fresh ET (0.39), frozen ET (0.42), PGT-A (0.44). Human chorionic gonadotropin rise has a positive effect on birth weight (55 g per SD increase in hCG slope) and is associated with SGA (odds ratio, 0.65), but not with LGA (odds ratio, 1.18). Conclusions: Human chorionic gonadotropin rise is an important mediator of the mode of conception/birth weight relationship. Preimplantation genetic testing for aneuploidy has the highest rate of hCG rise, followed by frozen ET, unassisted, and fresh ET. Faster rise is associated with higher birth weight and lower risk of SGA but does not impact LGA risk. Importantly, PGT-A does not increase the risk of extreme birth weight relative to other modes of conception evaluated.

Adverse childhood experiences interact with inflammation and menopause transition stage to predict verbal memory in women.

OBJECTIVE: Women with more adverse childhood experiences (ACEs) may face a triple threat of risk factors for cognitive concerns during the menopause transition: reduced estradiol, increased inflammation, and early life stress sequelae. Our objective was to determine the extent to which ACEs and peripheral basal inflammatory markers associate with verbal memory across the menopause transition. METHODS: Penn Ovarian Aging cohort participants (n â€‹= â€‹167) were assessed for ACEs (low (0-1) or high (≥2)) and had remaining stored blood samples at study end assayed for interleukin (IL)-6, IL-1-beta (IL-1ß), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α). Annual assessment included a verbal memory test (the Buschke Selective Reminding Test) and menopause stage determination. To estimate the effects of menopause stage, ACEs, and cytokines on verbal memory, repeated cognitive outcome measures were modeled in generalized estimating equations. Covariates included body mass index, smoking, race, education, age at baseline, and baseline verbal memory performance. Cytokine levels were log-transformed. RESULTS: Advancing menopause stage was associated with worse performance on immediate verbal recall and delayed verbal recall (ps â€‹< â€‹0.001). During perimenopause, higher ACE exposure was associated with worse immediate verbal recall at higher levels of TNF-α (slope difference p â€‹= â€‹0.041). CONCLUSIONS: Inflammation may mechanistically link ACEs and verbal memory for high ACE women during perimenopause. Reducing inflammation for these individuals may have positive impact on verbal memory across the menopause transition.

A comprehensive survey of collaborative biostatistics units in academic health centers.

The organizational structures of collaborative biostatistics units in academic health centers (AHCs) in the United States and their important contributions to research are an evolving and active area of discussion and inquiry. Collaborative biostatistics units may serve as a centralized resource to investigators across various disciplines or as shared infrastructure for investigators within a discipline (e.g., cancer), or a combination of both. The characteristics of such units vary greatly, and there has been no comprehensive review of their organizational structures described in the literature to date. This manuscript summarizes the current infrastructure of such units using responses from 129 leaders. Most leaders were over 45 years old, held doctoral degrees, and were on a 12-month appointment. Over half were tenured or on a tenure track and held primary appointments in a school of medicine. Career advancement metrics most important included being funded as co-investigator on NIH grants and being either first or second author on peer-reviewed publications. Team composition was diverse in terms of expertise and training, and funding sources were typically hybrid. These results provide a benchmark for collaboration models and evaluation and may be used by institutional administrators as they build, evaluate, or restructure current collaborative quantitative support infrastructure.

Influences of the menopause transition and adverse childhood experiences on peripheral basal inflammatory markers.

OBJECTIVE: To characterize the influence of early life stress on peripheral basal inflammatory markers across the menopause transition. METHODS: Participants from the longitudinal Penn Ovarian Aging study were assessed for childhood adversity at study end (14 years) using the Adverse Childhood Experiences (ACE) questionnaire. Responses were categorized as low (0-1) or high (≥2) ACE exposure. The stored blood sample catalogue was reviewed to exclude those samples collected during use of medications that could impact immune status or medications suggestive of infection or allergies. Remaining blood samples (n â€‹= â€‹640) from 167 participants were assayed for interleukin-6 (IL-6), interleukin 1-beta (IL-1ß), high sensitivity C-reactive protein (hsCRP), and tumor necrosis factor alpha (TNF-α). Menopause staging (premenopause, early transition, late transition, and postmenopause) was determined by questionnaire and menstrual diaries at yearly assessments. Generalized linear models for repeated measures were used to quantify the association between outcomes of interest (i.e., IL-6, IL-1ß, hsCRP, and TNF-α) and exposures (i.e., menopause stage, ACE status, their interaction) while controlling for relevant covariates (i.e., BMI, smoking, age at first blood sample, and race). Inflammatory marker levels were log-transformed for modeling. RESULTS: Log IL-6 levels were higher in the late perimenopause versus premenopause (p â€‹= â€‹0.035). Menopause stage â€‹× â€‹ACE interaction was observed for log IL-6, IL-1ß, and TNF-α (p â€‹= â€‹0.042, p â€‹= â€‹0.054, p â€‹= â€‹0.053, respectively); for individuals with high (≥2) ACE exposure, IL-6 was higher in the late perimenopause (p â€‹= â€‹0.015) while IL-1ß and TNF-α were lower in the postmenopause versus premenopause (p â€‹= â€‹0.019 and p â€‹= â€‹0.020). CONCLUSIONS: Results from this investigation indicate that the late perimenopause stage may be a window of risk for inflammation, particularly for individuals with greater childhood adversity. Prospective studies designed to address childhood stress and inflammation across the menopause transition are needed to confirm these findings. Heightened inflammation, even if transitory, may have negative impact on healthy aging.

Risk factors for atypical hyperplasia and endometrial cancer in the infertility population: a case-control study.

OBJECTIVE: To estimate the incidence and identify risk factors for atypical endometrial hyperplasia (AH) and endometrial cancer (EC) in American women undergoing infertility evaluation. DESIGN: Case-control study. SETTING: Academic reproductive endocrinology and infertility practice. PATIENTS: Female patients (18-50 years) seeking infertility evaluation from January 1, 2009 to December 1, 2018. Patients with known genetic predisposition to cancer or prior cancer diagnosis were excluded. Cases were defined as patients diagnosed with AH or EC during infertility workup (n = 22). Controls without AH or EC were randomly selected in a 10:1 ratio (n = 220) from all women undergoing infertility evaluation in the same year. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Incidence of AH or EC and odds of AH or EC accounting for age, race, body mass index (BMI), and ovulatory dysfunction. RESULTS: Twenty-two cases of AH or EC were identified among 11,569 women undergoing infertility evaluation (incidence 2 per 1,000 women, 95% confidence interval [CI] 1.2-2.9 per 1,000). Of these women, 68% had a BMI ≥30 kg/m2 compared with 25% of controls. In multivariable analyses, women with a BMI ≥30 kg/m2 were 5.9 times more likely to be diagnosed with AH or EC (adjusted odds ratio 5.9, 95% CI 2.0-17.2). Women with ovulatory dysfunction were 3.4 times more likely to be diagnosed with AH or EC (adjusted odds ratio 3.4, 95% CI 1.1-10.1). CONCLUSIONS: The incidence of AH and EC in a population of women undergoing infertility evaluation is 10 times that in the general population of premenopausal women. Obesity is the strongest independent risk factor for AH and EC in women with infertility.

A predictive model for chemotherapy-related diminished ovarian reserve in reproductive-age women.

OBJECTIVE: To develop and internally validate a clinical predictive tool to assess the likelihood that a young cancer patient will experience diminished ovarian reserve (DOR) after chemotherapy. DESIGN: Prospective cohort study. SETTING: University hospitals. PATIENT(S): Postpubertal adolescent and young adult women with a new diagnosis of cancer requiring chemotherapy. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Diminished ovarian reserve after completion of and recovery from chemotherapy, defined as serum antimüllerian hormone (AMH) <1 ng/mL at 8-24 months after completion of chemotherapy. RESULT(S): A multivariable logistic regression model which includes age, cancer type, exposure to an alkylating agent, and baseline AMH value accurately predicts the diagnosis of DOR after chemotherapy with an area under the receiver operating characteristic curve of 0.89. CONCLUSION(S): Pretreatment information on age, cancer type, use of an alkylating agent, and baseline AMH levels make up a clinically useful predictive tool to identify which women are most at risk for DOR caused by chemotherapy.

Postpartum complications increased in women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome are at a higher risk of cardiometabolic and psychiatric comorbidities and preconception and antepartum complications, but the impact of polycystic ovary syndrome during the postpartum period is unknown. OBJECTIVE: This study aimed to investigate the risk of postpartum cardiovascular disease complications and perinatal and postpartum depression. STUDY DESIGN: This was a retrospective cohort study conducted using a United States insurance claims database. Women with and without polycystic ovary syndrome aged 18 to 50 years enrolled continuously in a single health plan during the preconception, antepartum, and postpartum periods between 2000 and 2016 were included. The primary outcome was postpartum cardiovascular disease and depression (perinatal and postpartum). Multivariable logistic regression was used to adjust for covariates including age, geographic location, preterm delivery, assisted reproductive technology use, multiple births, prepregnancy depression, prepregnancy diabetes, prepregnancy hypertension, gestational diabetes, gestational hypertension, obesity, history of hyperlipidemia, smoking, and race. RESULTS: We identified 42,391 unique women with polycystic ovary syndrome and 795,480 women without polycystic ovary syndrome. In multivariable models, women with polycystic ovary syndrome had significantly higher odds of cardiovascular disease complications, including postpartum preeclampsia (adjusted odds ratio, 1.30; 95% confidence interval, 1.17-1.45), eclampsia (adjusted odds ratio, 1.45; 95% confidence interval, 1.14-1.86) cardiomyopathy (adjusted odds ratio, 1.26; 95% confidence interval, 1.03-1.54), hypertensive heart disease (adjusted odds ratio, 1.32: 95% confidence interval, 1.07-1.64), thrombotic disease (adjusted odds ratio, 1.50; 95% confidence interval, 1.20-1.87), congestive heart failure (adjusted odds ratio, 1.35; 95% confidence interval, 1.13-1.61), and cerebrovascular accidents (adjusted odds ratio, 1.21; 95% confidence interval, 1.14-1.29), than those without polycystic ovary syndrome, as well as both perinatal (adjusted odds ratio, 1.27; 95% confidence interval, 1.22-1.33) and postpartum depression (adjusted odds ratio, 1.46; 95% confidence interval, 1.36-1.57). Nonobese women with polycystic ovary syndrome had higher odds of postpartum eclampsia (adjusted odds ratio 1.72; 95% confidence interval, 1.31-2.26), peripartum cardiomyopathy (adjusted odds ratio, 1.43; 95% confidence interval, 1.14-1.79), and cerebrovascular accidents (adjusted odds ratio, 1.28; 95% confidence interval, 1.19-1.38) than nonobese women without polycystic ovary syndrome. In the group of women without prepregnancy depression, the odds of perinatal depression (adjusted odds ratio, 1.32; 95% confidence interval, 1.26-1.39) and postpartum depression (adjusted odds ratio, 1.50; 95% confidence interval, 1.39-1.62) were higher in women with polycystic ovary syndrome than those without polycystic ovary syndrome. CONCLUSION: In a large United States cohort, our study found that women with polycystic ovary syndrome are at increased risk of both cardiovascular and psychiatric complications during the postpartum period. Polycystic ovary syndrome should be recognized as an at-risk condition; our findings underscore the need for routine screening and early interventions for these major comorbidities.

Return to Baseline Functional Status in Older Women Undergoing Surgery for Pelvic Organ Prolapse.

OBJECTIVE: The aim of the study was to determine the rate of return to baseline functional status 3 months after surgery for pelvic organ prolapse (POP) in women 65 years or older. METHODS: This is a multicenter prospective cohort study of women older than 65 years undergoing POP surgery. Functional status was determined by the Activities Assessment Scale at the preoperative visit and 3 months after surgery. We compared a variety of clinical variables and preoperative functional status scores for women who worsened, improved, or returned to baseline functional status after surgery using univariable and multivariable analysis. RESULTS: A total of 192 women were enrolled in the study. Of 176 women who completed both sets of questionnaires, 59% improved, 35% returned, and 6% worsened from their baseline functional status. Variables significantly associated with postoperative functional status score were depression (P < 0.002) and preoperative functional status score (P < 0.001). The group that improved from baseline had the lowest (worst) preoperative functional status score (78.7 ± 16.4), whereas the group that worsened after surgery had the highest (best) preoperative functional status score (98.6 ± 2.2). After adjusting for age and depression, higher preoperative functional status score was predictive of failure to return to baseline functional status. CONCLUSIONS: Most older women undergoing surgery for POP, including those with low preoperative functional status, return to or improve from their baseline functional status within 3 months of surgery. Women with higher functional status before surgery are less likely to report improvement in physical functioning after surgery.

Beyond Premature Ovarian Insufficiency: Staging Reproductive Aging in Adolescent and Young Adult Cancer Survivors.

CONTEXT: Although stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors). OBJECTIVE: This work aimed to evaluate applying STRAW + 10 criteria in AYA survivors using bleeding patterns with and without endocrine biomarkers, and to assess how cancer treatment gonadotoxicity is related to reproductive aging stage. DESIGN: The sample (n = 338) included AYA survivors from the Reproductive Window Study cohort. Menstrual bleeding data and dried-blood spots for antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) measurements (Ansh DBS enzyme-linked immunosorbent assays) were used for reproductive aging stage assessment. Cancer treatment data were abstracted from medical records. RESULTS: Among participants, mean age 34.0 ±â€…4.5 years and at a mean of 6.9 ±â€…4.6 years since cancer treatment, the most common cancers were lymphomas (31%), breast (23%), and thyroid (17%). Twenty-nine percent were unclassifiable by STRAW + 10 criteria, occurring more frequently in the first 2 years from treatment. Most unclassifiable survivors exhibited bleeding patterns consistent with the menopausal transition, but had reproductive phase AMH and/or FSH levels. For classifiable survivors (48% peak reproductive, 30% late reproductive, 12% early transition, 3% late transition, and 7% postmenopause), endocrine biomarkers distinguished among peak, early, and late stages within the reproductive and transition phases. Gonadotoxic treatments were associated with more advanced stages. CONCLUSIONS: We demonstrate a novel association between gonadotoxic treatments and advanced stages of reproductive aging. Without endocrine biomarkers, bleeding pattern alone can misclassify AYA survivors into more or less advanced stages. Moreover, a large proportion of AYA survivors exhibited combinations of endocrine biomarkers and bleeding patterns that do not fit the STRAW + 10 criteria, suggesting the need for modified staging for this population.

Impact of Surgical Wait Time to Hysterectomy for Benign Gynecologic Disease.

STUDY OBJECTIVE: To determine the impact of surgical wait time on healthcare use and surgical outcomes for patients undergoing hysterectomy for benign gynecologic indications. DESIGN: Retrospective cohort study. SETTING: Urban, academic tertiary care center. PATIENTS: Patients who underwent hysterectomy for benign disease between 2012 and 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into 2 groups, dichotomized by surgical wait times >30 days or ≤30 days. Healthcare use was measured by the number of discrete patient interactions with the healthcare system through phone calls, secure electronic messaging, and office and emergency room visits. Univariate and multivariable logistic regression models were performed to assess the association between surgical wait time and healthcare use and perioperative outcomes while controlling for confounders. A total of 277 patients were included in our analysis: 106 (38.3%) had surgical wait times >30 days (median 47 days, range 24-68 days), and 171 (67.1%) had surgical wait times ≤30 days (median 19 days; range 12-26 days). The groups did not differ by age, insurance status, substance use, or comorbid conditions. Patients in the group with surgical wait times >30 days were more likely to have increased healthcare use (69 of 106, 65% vs 43 of 171, 25%; odds ratio 5.55; 95% confidence interval, 3.27-9.41). There were no differences in intraoperative complications (9 of 106, 8% vs 19 of 171, 11%; p = .482) or postoperative complications (28 of 106, 26% vs 32 of 171, 19%; p = .13) between the groups; however, after controlling for potential confounders, patients with surgical wait times >30 days were 3.22 times more likely to be readmitted than patients with surgical wait times ≤30 days (95% confidence interval, 1.27-8.19). CONCLUSION: A surgical wait time >30 days in patients undergoing a hysterectomy for benign disease is associated with increased healthcare use in the interim. Although patients who experience longer surgical wait times do not experience worse surgical outcomes, they may be at higher risk for readmission after surgery. Targeted interventions to optimize perioperative coordination of care for patients undergoing a hysterectomy for benign disease, especially those within vulnerable populations, are needed to improve quality of care, decrease any redundant or inefficient healthcare use, and reduce any unnecessary delays.

Soluble Flt1 levels are associated with cardiac dysfunction in Black women with and without severe preeclampsia.

Background: We evaluate soluble fms-like tyrosine kinase-1 (sFlt-1) levels and cardiac function during pregnancy and postpartum among Black women with and without preeclampsia. Study design: Prospective longitudinal cohort study from 2015 to 2017 of Black women with preterm severe preeclampsia and normotensive pregnant controls.We obtained echocardiograms and sFlt-1 levels during pregnancy and postpartum. Results: 93 Black women were included (43 cases, 50 controls). Higher sFlt1 levels were correlated with worse longitudinal strain, diastolic dysfunction, decreased ventricular-arterial coupling, and increased chamber and arterial elastance at the time of preeclampsia diagnosis and postpartum. Conclusions: Higher sFlt1 levels are associated with cardiovascular dysfunction during pregnancy and postpartum.

Enduring impact of childhood adversity on lower urinary tract symptoms in adult women.

AIMS: To determine whether childhood adversity is associated with self-reported lower urinary tract symptoms (LUTS) among older adult women. METHODS: A convenience sample of women (≥55 years old) who presented to an academic urology practice or who had participated in a previous bladder health prevention study completed questionnaires including the LUTS Tool (on frequency and bother of LUTS), the Adverse Childhood Experiences (ACEs) Questionnaire, the Spielberger State-Trait Anxiety Inventory, and the Center for Epidemiologic Studies Depression Scale. RESULTS: The average age (SD) of participants (N = 151) was 64.7 (6.9) years. The total number of ACEs predicted the total number of LUTS, ß = .39 (95% confidence interval [CI] = 0.14, 0.64), P = .003, as well as LUTS frequency, ß = .09 (95% CI = 0.04, 0.13), P < .001. ACEs predicted bother for nocturia, ß = 0.12 (95% CI = 0.03, 0.22), P = .008. Negative affect symptoms did not mediate the relationship between the total number of ACEs and the total number of LUTS. Rather, ACEs predicted LUTS and negative affect symptoms through (at least partially) independent pathways. Analyses controlled for tobacco use, number of vaginal deliveries, hypertension, overactive bladder medication use, body mass index, income, and race because these variables were significantly associated with the total number of ACEs or total number of LUTS. CONCLUSIONS: Childhood adversity has an enduring impact on risk for LUTS in adulthood even when controlling for potential confounds and this relationship cannot be explained by negative affect symptoms.

Management of early pregnancy loss with mifepristone and misoprostol: clinical predictors of treatment success from a randomized trial.

BACKGROUND: Early pregnancy loss is a common event in the first trimester, occurring in 15%-20% of confirmed pregnancies. A common evidence-based medical regimen for early pregnancy loss uses misoprostol, a prostaglandin E1 analog, with a dosage of 800 µg, self-administered vaginally. The clinical utility of this regimen is limited by suboptimal effectiveness in patients with a closed cervical os, with 29% of patients experiencing early pregnancy loss requiring a second dose after 3 days and 16% of patients eventually requiring a uterine aspiration procedure. OBJECTIVE: This study aimed to evaluate clinical predictors associated with treatment success in patients receiving medical management with mifepristone-misoprostol or misoprostol alone for early pregnancy loss. STUDY DESIGN: We performed a planned secondary analysis of a randomized trial comparing mifepristone-misoprostol with misoprostol alone for management of early pregnancy loss. The published prediction model for treatment success of single-dose misoprostol administered vaginally included the following variables: active bleeding, type of early pregnancy loss (anembryonic pregnancy or embryonic and/or fetal demise), parity, gestational age, and treatment site; previous significant predictors were vaginal bleeding within the past 24 hours and parity of 0 or 1 vs >1. To determine if these characteristics predicted differential proportions of patients with treatment success or failure, we performed bivariate analyses; given the small proportion of treatment failures in the combined treatment arm, both arms were combined for analysis. Thereafter, we performed a logistic regression analysis to assess the effect of these predictors collectively in each of the 2 treatment groups separately as well as in the full cohort as a proxy for the combined treatment arm. Finally, by using receiver operating characteristic curves, we tested the ability of these predictors in association with misoprostol treatment success to discriminate between treatment success and treatment failure. To quantify the ability of the score to discriminate between treatment success and treatment failure in each treatment arm as well as in the entire cohort, we calculated the area under the curve. Using multivariable logistic regression, we then assessed our study population for other predictors of treatment success in both treatment groups, with and without mifepristone pretreatment. RESULTS: Overall, 297 evaluable participants were included in the primary study, with 148 in the mifepristone-misoprostol combined treatment group and 149 in the misoprostol-alone treatment group. Among patients who had vaginal bleeding at the time of treatment, 15 of 17 (88%) in the mifepristone-misoprostol combined treatment group and 12 of 17 (71%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. Among patients with a parity of 0 or 1, 94 of 108 (87%) in the mifepristone-misoprostol treatment group and 66 of 95 (69%) in the misoprostol-alone treatment group experienced expulsion of pregnancy tissue. These clinical characteristics did not predict treatment success in the combined cohort alone (area under the curve=0.56; 95% confidence interval, 0.48-0.64). No other baseline clinical factors predicted treatment success in the misoprostol-alone treatment arm or mifepristone pretreatment arm. In the full cohort, the significant predictors of treatment success were pretreatment with mifepristone (adjusted odds ratio=2.51; 95% confidence interval, 1.43-4.43) and smoking (adjusted odds ratio=2.15; 95% confidence interval, 1.03-4.49). CONCLUSION: No baseline clinical factors predicted treatment success in women receiving medical management with misoprostol for early pregnancy loss. Adding mifepristone to the medical management regimen of early pregnancy loss improved treatment success; thus, mifepristone treatment should be considered for management of early pregnancy loss regardless of baseline clinical factors.

Modeling Variation in the Reproductive Lifespan of Female Adolescent and Young Adult Cancer Survivors Using AMH.

CONTEXT: Many female survivors of adolescent and young adult cancers (AYA survivors) have shortened reproductive lifespans. However, the timing and duration of ovarian function after cancer treatment are largely unknown. OBJECTIVE: To model the trajectory of ovarian function over two decades following cancer treatment and evaluate how trajectories vary by treatment gonadotoxicity and age. DESIGN: In a prospective cohort, AYA survivors aged 18-39 at variable times since cancer treatment completion provided dried blood spots (DBS) every 6 months for up to 18 months. Anti-Müllerian hormone (AMH) levels were measured using the Ansh DBS AMH enzyme-linked immunosorbent assay. The mean AMH trajectory was modeled for the entire cohort and separately by treatment gonadotoxicity and age using functional principal components analysis. RESULTS: 763 participants, mean (standard deviation) enrollment age 33.3 (4.7) and age at cancer diagnosis 25.9 (5.7) years, contributed 1905 DBS samples. The most common cancers were breast (26.9%), lymphoma (24.8%), and thyroid (18.0%). AMH trajectories differed among survivors by treatment gonadotoxicity (low, moderate, or high) (P < 0.001). Following low or moderately gonadotoxic treatments, AMH levels increased over 2-3 years and plateaued over 10-15 years before declining. In contrast, following highly gonadotoxic treatment, AMH levels were lower overall and declined shortly after peak at 2-3 years. Younger age at treatment was associated with higher trajectories, but a protective effect of younger age was not observed in survivors exposed to highly gonadotoxic treatments (Pinteraction < 0.001). CONCLUSIONS: In this large AYA survivor cohort, timing and duration of ovarian function strongly depended on treatment gonadotoxicity and age at treatment. The findings provide novel, more precise information to guide reproductive decision-making.