Platelet-rich plasma infusion as an adjunct treatment for persistent thin lining in frozen embryo transfer cycles: first US experience report.

PURPOSE: To study effect of intrauterine infusion of platelet-rich plasma (PRP) on endometrial growth in the setting of thin endometrial lining in patients with prior cancelled or failed frozen embryo transfer (FET) cycles. MATERIALS AND METHODS: Single-arm cohort study of forty-six patients (51 cycles) with endometrial lining thickness (EMT) < 6 mm in prior cancelled or failed FET cycles requesting intrauterine PRP treatment in upcoming FET cycle. The primary outcomes were final EMT in FET cycle and change in EMT after PRP. The secondary outcomes were overall pregnancy rate, clinical pregnancy rate, miscarriage rate, ongoing pregnancy, and live birth rates. RESULTS: The mean pre-PRP EMT in all FET cycles was 4.0 ± 1.1 mm, and mean post-PRP EMT (final) was 7.1 ± 1.0 mm. Of 51 cycles, 33 (64.7%) reached ≥ 7 mm after PRP administration. There was a significant difference between pre-PRP EMT and post-PRP EMT in all FET cycles, with mean difference of 3.0 ± 1.5 mm. Three cycles were cancelled for failure to reach adequate lining. Total pregnancy rate was 72.9% in our cohort of 48 cycles that proceeded to transfer. Clinical pregnancy rate was 54.2% (26/48 FET cycles); clinical miscarriage rate was 14.3% (5/35 pregnancies). Twenty six women had live birth (18 with EMT ≥ 7 mm and 8 with EMT < 7 mm). Response to PRP was not correlated with any pre-cycle characteristics. CONCLUSION: We demonstrate a significant improvement in lining thickness and pregnancy rates in this challenging cohort of women after PRP infusion, with no adverse events. Cost-effectiveness of PRP with benefits and alternatives should be carefully considered.

Improved Clinical Outcomes With Dynamic, Force-Controlled, Gap-Balancing in Posterior-Stabilized Total Knee Arthroplasty.

BACKGROUND: Optimal soft-tissue management in total knee arthroplasty (TKA) may reduce symptomatic instability. We hypothesized that TKA outcomes using a computer-assisted dynamic ligament balancer that acquires medial and lateral gap sizes throughout the motion arc would show improved Knee Society Scores (KSS) compared to TKAs done with a traditional tensioner at 0 and 90°. We also sought to quantify the degree to which the planned femoral rotation chosen to optimize medio-lateral balance throughout the arc of motion deviated from the femoral rotation needed to achieve a rectangular flexion gap at 90° alone. METHODS: Baseline demographics, clinical outcomes, KSSs, and femoral rotations were compared in 100 consecutive, computer-assisted TKAs done with the balancer (balancer group) to the immediately prior 100 consecutive computer-assisted TKAs done without the balancer (control group). Minimum follow-up was 13 months and all patients had osteoarthritis. Mean knee motion did not differ preoperatively (110.1 ± 13.6° balancer, 110.4 ± 12.5° control, P = .44) or postoperatively (119.1 ± 10.3° balancer, 118.8 ± 10.9° control, P = .42). Tourniquet times did not differ (93.1 ± 13.0 minutes balancer, 90.7 ± 13.0 minutes control, P = .13). Postoperative length of stay differed (40.2 ± 20.9 hours balancer, 49.0 ± 18.3 hours control, P = .0009). There were 14 readmissions (7 balancer, 7 control), 11 adverse events (4 balancer, 7 control), and 3 manipulations (1 balancer, 2 control). The cohorts were compared using Student's t-tests, Shapiro-Wilk normalities, Wilcoxon rank-sums, and multivariable logistic regression analyses. RESULTS: Postoperative KSS improvements were higher in the balancer group (P < .0001). In multivariable regression analyses, the balancer group experienced 7 ± 2 point improvement in KSS Knee scores (P < .0001) and 4 ± 2 point improvement in KSS Function scores (P = .040) compared to the control group. CONCLUSIONS: The statistically and clinically significant improvements in postoperative KSS demonstrated in the balancer cohort are likely driven by improved stability throughout the motion arc. Further study is warranted to evaluate replicability by non-design surgeons.

Decision regret among women considering planned oocyte cryopreservation: a prospective cohort study.

PURPOSE: To (1) prospectively characterize the incidence of decision regret among women considering planned oocyte cryopreservation (planned OC), comparing those who pursued treatment vs those who did not freeze eggs, and (2) to identify baseline predictors for future decision regret. METHODS: A total of 173 women seen in consultation for planned OC were followed prospectively. Surveys were administered at (1) baseline (< 1 week after initial consultation) and (2) follow-up, 6 months after planned OC among participants who froze eggs or 6 months following consultation in the absence of further communication to pursue treatment. The primary outcome was the incidence of moderate-to-severe decision regret, indicated by a Decision Regret Scale score > 25. We also examined predictors of regret. RESULTS: The incidence of moderate-to-severe regret over the decision to freeze eggs was 9% compared to 51% over the decision not to pursue treatment. Among women who froze eggs, adequacy of information at baseline to decide about treatment (aOR 0.16, 95% CI 0.03, 0.87) and emphasis on future parenthood (aOR 0.80, 95% CI 0.66, 0.99) were associated with reduced odds of regret. Forty-six percent of women who froze eggs regretted not doing so earlier. Among women who did not freeze eggs, the primary reasons were financial and time constraints, correlating with increased odds of decision regret in an exploratory analysis. CONCLUSIONS: Among women undergoing planned OC, the incidence of decision regret is low compared to the regret confronting women seen in consultation for planned OC but who do not pursue treatment. Provider counseling is key to offset the regret risk.

Early pregnancy anxiety during the COVID-19 pandemic: preliminary findings from the UCSF ASPIRE study.

BACKGROUND: Antenatal anxiety has been linked to adverse obstetric outcomes, including miscarriage and preterm birth. However, most studies investigating anxiety during pregnancy, particularly during the COVID-19 pandemic, have focused on symptoms during the second and third trimester. This study aims to describe the prevalence of anxiety symptoms early in pregnancy and identify predictors of early pregnancy anxiety during the COVID-19 pandemic. METHODS: We assessed baseline moderate-to-severe anxiety symptoms after enrollment in the UCSF ASPIRE (Assessing the Safety of Pregnancy in the Coronavirus Pandemic) Prospective Cohort from May 2020 through February 2021. Pregnant persons < 10 weeks' gestation completed questions regarding sociodemographic characteristics, obstetric/medical history, and pandemic-related experiences. Univariate and multivariate hierarchical logistic regression analyses determined predictors of moderate or severe anxiety symptoms (Generalized Anxiety Disorder-7 questionnaire score ≥ 10). All analyses performed with Statistical Analysis Software (SAS®) version 9.4. RESULTS: A total of 4,303 persons completed the questionnaire. The mean age of this nationwide sample was 33 years of age and 25.7% of participants received care through a fertility clinic. Over twelve percent of pregnant persons reported moderate-to-severe anxiety symptoms. In univariate analysis, less than a college education (p < 0.0001), a pre-existing history of anxiety (p < 0.0001), and a history of prior miscarriage (p = 0.0143) were strong predictors of moderate-to-severe anxiety symptoms. Conversely, having received care at a fertility center was protective (26.6% vs. 25.7%, p = 0.0009). COVID-19 related stressors including job loss, reduced work hours during the pandemic, inability to pay rent, very or extreme worry about COVID-19, and perceived stress were strongly predictive of anxiety in pregnancy (p < 0.0001). In the hierarchical logistic regression model, pre-existing history of anxiety remained associated with anxiety during pregnancy, while the significance of the effect of education was attenuated. CONCLUSION(S): Pre-existing history of anxiety and socioeconomic factors likely exacerbated the impact of pandemic-related stressors on early pregnancy anxiety symptoms during the COVID-19 pandemic. Despite on-going limitations for in-person prenatal care administration, continued emotional health support should remain an important focus for providers, particularly when caring for less privileged pregnant persons or those with a pre-existing history of anxiety.

Autologous platelet-rich plasma treatment for moderate-severe Asherman syndrome: the first experience.

PURPOSE: Treatment of Asherman syndrome (AS) presents a significant clinical challenge. Based on our in vitro data showing that PRP could activate endometrial cell proliferation and migration, we hypothesized that intrauterine infusion of autologous platelet-rich plasma (PRP) may improve endometrial regeneration and fertility outcomes in patients with moderate-severe AS. MATERIALS AND METHODS: Subjects with moderate-severe AS were randomized to PRP or saline control administered following hysteroscopic adhesiolysis. Due to relative inability to randomize patients to the control group, after initial randomization of 10 subjects (6 in PRP and 4 in control groups), the remainder were prospectively enrolled in PRP group (n = 9), with 11 historic controls added to control group, for a total of 30 subjects (PRP n = 15; saline control n = 15). Right after hysteroscopy, 0.5-1 mL of PRP or saline was infused into the uterus via a Wallace catheter, followed by estrogen therapy. The primary outcomes were changes in endometrial thickness (EMT, checked in 3 weeks) and in menstrual flow; secondary outcomes were pregnancy and live birth rates. EMT and menstrual bleeding pattern were assessed before and after the intervention. Pregnancy was assessed over a 6-month period. RESULTS: There were no statistically significant differences in age, gravidity/parity, cause of AS, preoperative menses assessment, AS hysteroscopy score, and intrauterine balloon placement between the groups. There was no statistically significant difference (p = 0.79) in EMT pre-PRP infusion for control (5.7 mm, 4.0-6.0) and study arm (5.3 mm, 4.9-6.0). There was no statistically significant change (p = 0.78) in EMT after PRP infusion (1.4 mm, - 0.5-2.4) vs saline (1.0 mm, 0.0-2.5). Patients tolerated the procedure well, with no adverse effects. There was no difference in the predicted likelihood of pregnancy (p = 0.45) between the control (0.67, 0.41-0.85) and study arm (0.53, 0.29-0.76). CONCLUSIONS: PRP was well accepted and tolerated in AS patients. However, we did not observe any significant EMT increase or improved pregnancy rates after adding PRP infusion, compared to standard treatment only. The use of intrauterine PRP infusion may be a feasible option, and its potential use must be tested on a larger sample size of AS patients.

Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis.

BACKGROUND: Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD). METHODS: Retrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status. RESULTS: Among 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm2 , P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02). CONCLUSION: Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.

Decreased clinical pregnancy and live birth rates after short interval from delivery to subsequent assisted reproductive treatment cycle.

STUDY QUESTION: Does the interval from delivery to initiation of a subsequent ART treatment cycle impact clinical pregnancy or live birth rates? SUMMARY ANSWER: An interval from delivery to treatment start of <6 months or ≥24 months is associated with decreased likelihood of clinical pregnancy and live birth. WHAT IS KNOWN ALREADY: Short interpregnancy intervals are associated with poor obstetric outcomes in the naturally conceiving population prompting birth spacing recommendations of 18-24 months from international organizations. Deferring a subsequent pregnancy attempt means a woman will age in the interval with an attendant decline in her fertility. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of the Society for Assisted Reproductive Technology Clinical Outcome Reporting System (SARTCORS) cohort containing 61 686 ART cycles from 2004 to 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: The delivery-to-cycle interval (DCI) was calculated for patients from SARTCORS with a history of live birth from ART who returned to the same clinic for a first subsequent treatment cycle. Generalized linear models were fit to determine the risk of clinical pregnancy and live birth by DCI with subsequent adjustment for factors associated with outcomes of interest. Predicted probabilities of clinical pregnancy and live birth were generated from each model. MAIN RESULTS AND THE ROLE OF CHANCE: A DCI of <6 months was associated with a 5.6% reduction in probability of clinical pregnancy (40.1 ± 1.9 versus 45.7 ± 0.6%, P = 0.009) and 6.8% reduction in live birth (31.6 ± 1.7 versus 38.4 ± 0.6%, P = 0.001) per cycle start compared to a DCI of 12 to <18 months. A DCI of ≥24 months was associated with a 5.1% reduction in probability of clinical pregnancy (40.6 ± 0.5 versus 45.7 ± 0.6%, P < 0.001) and 5.7% reduction in live birth (32.7 ± 0.5 versus 38.4 ± 0.6%, P < 0.001) compared to 12 to <18 months. LIMITATIONS, REASONS FOR CAUTION: The SART database is reliant upon self-report of many variables of interest including live birth. It remains unclear whether poorer outcomes are a result of residual confounding from factors inherent to the population with a very short or long DCI or the interval itself. WIDER IMPLICATIONS OF THE FINDINGS: Birth spacing recommendations for naturally conceiving populations may not be generally applicable to patients with a history of infertility. Patients planning ART treatment should wait a minimum of 6 months, but not more than 24 months, from a live birth for optimization of clinical pregnancy and live birth rates. STUDY FUNDING/COMPETING INTEREST(S): National Center for Advancing Translational Sciences, National Institutes of Health, UCSF-CTSI Grant number UL1TR001872. The authors have no competing interests.

Association among depression, symptom experience, and quality of life in polycystic ovary syndrome.

BACKGROUND: Clinical stigmata of polycystic ovary syndrome include hirsutism, obesity, menstrual disturbances, and infertility. These symptoms impair health-related quality of life. Depression is also common. The relationship among depression, symptom self-perception, and quality of life in polycystic ovary syndrome is poorly understood. OBJECTIVE: We sought to investigate the relationship between health-related quality of life and depression in women with polycystic ovary syndrome. STUDY DESIGN: We conducted a secondary analysis of a multicenter, randomized clinical trial (Pregnancy in Polycystic Ovary Syndrome II, NCT00719186) comparing clomiphene citrate vs letrozole in the treatment of infertility. Subjects included 732 women ages 18-40 years with polycystic ovary syndrome by modified Rotterdam criteria. The validated Polycystic Ovary Syndrome Health-Related Quality of Life survey was self-administered, assessing the following domains: emotions, body hair, body weight, menstrual problems, and infertility; scores range from 1-7, with lower numbers indicating poorer quality of life. Depression was evaluated via the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire. Quality-of-life scores were compared between depressed and nondepressed women. Multivariate linear regression models analyzed the association between depression and quality-of-life scores, controlling for age, body mass index, hirsutism score, and duration of infertility. RESULTS: In all, 64 women (8.4%) met criteria for depression. Depressed women reported reduced quality of life in all domains compared to nondepressed women: mood (3.1 vs 4.6, P < .001), body hair (3.5 vs 4.2, P = .002), weight (2.0 vs 3.5, P < .001), menstrual problems (3.3 vs 4.1, P < .001), and infertility (1.9 vs 3.0, P < .001). Global quality-of-life score was reduced in depressed women (2.8 vs 3.9, P < .001). Impairments in quality of life in depressed women persisted in all domains after controlling for objective parameters including age, body mass index, hirsutism score, and infertility duration. CONCLUSION: Depression is associated with reduced quality of life related to polycystic ovary syndrome symptoms. Disturbances in health-related quality of life in depressed women are not explained by objective measures including body mass index, hirsutism scores, and duration of infertility. Depression may color the experience of polycystic ovary syndrome symptoms and should be considered when there is significant discordance between subjective and objective measures in women with polycystic ovary syndrome.

In vitro evidence that platelet-rich plasma stimulates cellular processes involved in endometrial regeneration.

PURPOSE: The study aims to test the hypothesis that platelet-rich plasma (PRP) stimulates cellular processes involved in endometrial regeneration relevant to clinical management of poor endometrial growth or intrauterine scarring. METHODS: Human endometrial stromal fibroblasts (eSF), endometrial mesenchymal stem cells (eMSC), bone marrow-derived mesenchymal stem cells (BM-MSC), and Ishikawa endometrial adenocarcinoma cells (IC) were cultured with/without 5% activated (a) PRP, non-activated (na) PRP, aPPP (platelet-poor-plasma), and naPPP. Treatment effects were evaluated with cell proliferation (WST-1), wound healing, and chemotaxis Transwell migration assays. Mesenchymal-to-epithelial transition (MET) was evaluated by cytokeratin and vimentin expression. Differential gene expression of various markers was analyzed by multiplex Q-PCR. RESULTS: Activated PRP enhanced migration of all cell types, compared to naPRP, aPPP, naPPP, and vehicle controls, in a time-dependent manner (p < 0.05). The WST-1 assay showed increased stromal and mesenchymal cell proliferation by aPRP vs. naPRP, aPPP, and naPPP (p < 0.05), while IC proliferation was enhanced by aPRP and aPPP (p < 0.05). There was no evidence of MET. Expressions of MMP1, MMP3, MMP7, and MMP26 were increased by aPRP (p < 0.05) in eMSC and eSF. Transcripts for inflammation markers/chemokines were upregulated by aPRP vs. aPPP (p < 0.05) in eMSC and eSF. No difference in estrogen or progesterone receptor mRNAs was observed. CONCLUSIONS: This is the first study evaluating the effect of PRP on different human endometrial cells involved in tissue regeneration. These data provide an initial ex vivo proof of principle for autologous PRP to promote endometrial regeneration in clinical situations with compromised endometrial growth and scarring.

Women with polycystic ovary syndrome demonstrate worsening markers of cardiovascular risk over the short-term despite declining hyperandrogenaemia: Results of a longitudinal study with community controls.

OBJECTIVE: To compare age-associated changes in cardiovascular risk markers in lean and obese reproductive-aged women with polycystic ovary syndrome (PCOS) with community controls. DESIGN: Longitudinal study at an academic medical centre PATIENTS: Patients diagnosed with PCOS by 2004 Rotterdam criteria in a multidisciplinary clinic were systematically enrolled from 2006-2014 in a PCOS cohort study and subsequently agreed to participate in a longitudinal study. The comparison controls were from the prospective, longitudinal Ovarian Aging (OVA) study, which consists of healthy women with regular menstrual cycles recruited from 2006 to 2011. MEASUREMENTS: Cardiovascular risk markers and hormone parameters at baseline and follow-up. RESULTS: Obese and lean PCOS (n = 38) and control women (n = 296) completed two study visits. The follow-up time (3.5 ± 1.5 vs 4.0 ± 0.8 years, P = .06) and magnitude of BMI gain (+0.1 kg/m2 /y [-0.11, 0.36] vs +0.26 [-0.18, 0.87] P = .19) did not differ between obese and lean PCOS and controls. In PCOS subjects, total testosterone decreased in both obese and lean, but the decrease was greater in obese subjects (-0.09 nmol/L per year; 95% CI: -0.16, -0.02 vs -0.04 nmol/L per year; 95%CI: -0.11, 0.03). Compared to their respective controls, obese and lean PCOS saw worsening triglyceride (TG) levels (P < .05) and HOMA-IR (P < .05) over time, but there was no difference in change in LDL, HDL, fasting glucose, C-reactive protein or ALT. CONCLUSIONS: In a longitudinal study, reproductive-aged women with PCOS demonstrated declines in biochemical hyperandrogenaemia over time. Despite this, PCOS subjects experienced steeper increases in cardiovascular risk factors associated with insulin resistance, including triglycerides and HOMA-IR.

Age-stratified thresholds of anti-Müllerian hormone improve prediction of polycystic ovary syndrome over a population-based threshold.

OBJECTIVE: Due to its consistent elevation in polycystic ovary syndrome (PCOS) and correlation with polycystic ovarian morphology (PCOM), anti-Mullerian hormone (AMH) has been proposed as a marker of the syndrome. However, prior studies reporting thresholds of AMH for a PCOS diagnosis have been limited by small sample size, inappropriate controls, and heterogeneous AMH assays. We sought to evaluate the suitability of a standardized AMH assay as a biomarker of PCOS. DESIGN: Cross-sectional study at academic medical centres across the United States. PATIENTS: Women with PCOS were diagnosed by Rotterdam criteria and included 282 subjects from the multisite PPCOS II trial and 109 patients from a tertiary academic centre's multidisciplinary PCOS clinic. Controls included 245 participants in the ovarian ageing (OVA) study, a community-based cohort of ovulatory women not seeking treatment for fertility. MEASUREMENTS: Determination of AMH by a central laboratory. Receiver-operating characteristic (ROC) analyses were used to investigate the accuracy of AMH thresholds for prediction of PCOS diagnosis with stratification by age. RESULTS: The optimal threshold of AMH to distinguish PCOS from controls was 55.36 pmol/L (sensitivity: 0.82, specificity: 0.78, J: 0.60). When examining the population by age groups, the optimal AMH threshold decreased with increasing age. CONCLUSIONS: AMH is an effective biomarker of PCOS. Age-stratified thresholds more accurately predicted PCOS than an overall population-based threshold.

A higher prevalence of endometriosis among Asian women does not contribute to poorer IVF outcomes.

PURPOSE: The purpose of the study was to determine whether diagnosis of endometriosis or endometriosis with endometrioma influences in vitro fertilization (IVF) outcomes in an ethnically diverse population. METHODS: Women undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31, 2009, at a university-affiliated infertility clinic, were retrospectively assessed for an endometriosis diagnosis. Differences in prevalence of endometriosis by ethnicity were determined, as well as differences in IVF success by ethnicity, with a focus on country of origin for Asian women. A multivariate model was generated to assess the relative contributions of country of origin and endometriosis to chance of clinical pregnancy with IVF. RESULTS: Endometriosis was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of endometrioma. Endometriosis prevalence in Asian women was significantly greater than in Caucasians (15.7 vs. 5.8%, p < 0.01). Women of Filipino (p < 0.01), Indian (p < 0.01), Japanese (p < 0.01), and Korean (p < 0.05) origin specifically were more likely to have endometriosis than Caucasian women, although there was no difference in endometrioma presence by race/ethnicity. Oocyte quantity, embryo quality, and fertilization rates did not relate to endometriosis. Clinical pregnancy rates were significantly lower for Asian women, specifically in Indian (p < 0.05), Japanese (p < 0.05), and Korean (p < 0.05) women, compared to Caucasian women, even after controlling for endometriosis status. CONCLUSIONS: The prevalence of endometriosis appears to be higher in Filipino, Indian, Japanese, and Korean women presenting for IVF treatment than for Caucasian women; however, the discrepancy in IVF outcomes was conditionally independent of the presence of endometriosis. Future research should focus on improving pregnancy outcomes for Asian populations whether or not they are affected by endometriosis, specifically in the form of longitudinal studies where exposures can be captured prior to endometriosis diagnoses and infertility treatment.

Metabolic and endocrine status associate with obstructive sleep apnea risk among patients with polycystic ovary syndrome.

STUDY OBJECTIVES: Risk of obstructive sleep apnea (OSA) appears to be increased among patients with polycystic ovary syndrome (PCOS), but the underlying physiology is unclear. We sought to identify predictors of OSA risk among patients with PCOS. METHODS: A cross-sectional analysis of patients evaluated for PCOS at a single tertiary center from 2017-2022 was completed. Inclusion criteria included patients 18-44 years of age who had Rotterdam criteria for PCOS and had completed a Berlin Questionnaire (BQ) for OSA risk assessment. All patients underwent standardized anthropometric, ultrasound, endocrine, and metabolic phenotyping. RESULTS: Of the 572 patients screened during the study period, 309 patients with PCOS met inclusion criteria, and 104 (33.7%) had a high-risk BQ. Those with a high-risk BQ, compared with those without, had significantly (P < .05) higher waist:hip ratio, low-density-lipoprotein cholesterol, triglycerides, fasting insulin, 2-hour insulin, fasting glucose, 2-hour glucose, homeostatic model assessment for insulin resistance, hemoglobin A1C, C-reactive protein, free testosterone, and free androgen index and had lower high-density-lipoprotein cholesterol and sex hormone binding globulin. In multivariable modeling controlling for all significantly differing variables in univariate analyses, hemoglobin A1C (ß [standard error] 1.05 [0.45], P = .02), C-reactive protein (0.09 [0.04], P = .01), and sex hormone binding globulin (-0.02 [0.01], P = .02) associated with high-risk BQ. CONCLUSIONS: Dysglycemia, inflammation, and androgen status independently associate with predicted OSA risk by BQ. Future studies are needed to comprehensively assess the impact of treatment of OSA on these outcomes among patients with PCOS to better clarify the directionality and clinical implications of these associations. CITATION: Christ JP, Shinkai K, Corley J, Pasch L, Cedars MI, Huddleston HG. Metabolic and endocrine status associate with obstructive sleep apnea risk among patients with polycystic ovary syndrome. J Clin Sleep Med. 2024;20(6):871-877.

Associations of Polycystic Ovary Syndrome With Indicators of Brain Health at Midlife in the CARDIA Cohort.

BACKGROUND AND OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with an adverse cardiometabolic profile early in life. Increasing evidence links cardiovascular risk factors, such as diabetes and hypertension, to accelerated cognitive aging. However, less is known about PCOS and its relationship to brain health, particularly at midlife. Our goal was to investigate possible associations between PCOS and midlife cognitive function and brain MRI findings in an ongoing prospective study. METHODS: We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a geographically diverse prospective cohort study of individuals who were 18-30 years at baseline (1985-1986) and followed for 30 years. We identified women with PCOS from an ancillary study (CARDIA Women's study (CWS); n = 1,163) as those with elevated androgen levels and/or hirsutism in conjunction with symptoms of oligomenorrhea. At year 30, participants completed cognitive testing, including the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test (RAVLT) (verbal learning and memory), Digit Symbol Substitution Test (processing speed and executive function), Stroop test (attention and cognitive control), and category and letter fluency tests (semantics and attention). A subset completed brain MRI to assess brain structure and white matter integrity. Multivariable linear regression models estimated the association between PCOS and outcomes, adjusting for age, race, education, and study center. RESULTS: Of the 1163 women in CWS, 907 completed cognitive testing, and of these, 66 (7.1%) met criteria for PCOS (age 54.7 years). Women with and without PCOS were similar for age, BMI, smoking/drinking status, and income. At year 30, participants with PCOS performed lower (mean z score; 95% CI) on Stroop (-0.323 (-0.69 to -7.37); p = 0.008), RAVLT (-0.254 (-0.473 to -0.034); p = 0.002), and category fluency (-0.267 (-0.480 to -0.040); p = 0.02) tests. Of the 291 participants with MRI, 25 (8.5%) met PCOS criteria and demonstrated lower total white matter fractional anisotropy, a measure of white matter integrity (coefficient (95% CI) -0.013 (-0.021 to -0.005); p = 0.002), though not abnormal white matter. DISCUSSION: Our results suggest that women with PCOS have lower cognitive performance and lower white matter integrity at midlife. Additional research is needed to confirm these findings and to determine potential mechanistic pathways including potential modifiable factors.

In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months.

Importance: Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking. Objective: To determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age. Design, Setting, and Participants: This prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely. Exposure: In utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed. Main Outcomes and Measures: Neurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay. Results: A total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07). Conclusions and Relevance: Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.

Age-related differences in the reproductive and metabolic implications of polycystic ovarian syndrome: findings in an obese, United States population.

The objective of this study was to explore age-related differences in the reproductive and metabolic manifestations of polycystic ovarian syndrome (PCOS). Using a prospective cross-sectional design, we compared metabolic and reproductive findings in women attending a multidisciplinary clinic for PCOS, stratified across the following age groups: 18-25 (n = 71), 26-35 (n = 129), and 36-45 (n = 29). The study included primarily overweight and obese women, with a mean BMI of 31.1 in the entire study group. Older women had a decreased prevalence of biochemical hyperandrogenemia (p-trend: 0.0005). Of women meeting diagnostic criteria for PCOS, older women (n = 15) had larger median waist circumference and higher median diastolic blood pressure, total cholesterol, LDL cholesterol and fasting glucose compared to younger women (p-trend: 0.03, 0.01, 0.01, 0.01 and 0.06, respectively). The odds of metabolic syndrome for women ages 36-45 are increased four-fold relative to the younger groups (OR: 4.01; 95% CI: 1.04-15.4; p = 0.04). We conclude that there are significant age-related differences in both the clinical presentation and metabolic manifestations of PCOS.

MI TKA: a risk factor for early revision surgery.

Minimal incision total knee arthroplasty (MI TKA) was developed with the potential to decrease surgical trauma, pain, and recovery time. While this procedure has increased in popularity, some surgeons have questioned its safety and long-term efficacy. In this study 58 consecutive revision total knee arthroplasties (TKAs) (57 patients) performed at one academic medical center from 2006 to 2008 are reviewed. Prospectively collected clinical and radiographic data included: incision length, gender, age, time to revision surgery, and primary diagnosis at time of revision. Of these, 34 knees involving infection and rerevision were excluded. Of the remaining 24 knees, 11 knees that met inclusion criteria had undergone MI TKA. There were no differences between the groups with regard to age, diagnosis, body mass index, and gender. Average time to revision was shorter for the MI TKA patients (29 vs. 65 months, p < 0.032, odds ratio 14.7). Reasons for revision were aseptic loosening (55%), pain/stiffness (27%), malrotation (9%), and instability (9%) in the MI TKA group and aseptic loosening (53%), instability (15%), pain/stiffness (8%), malrotation (8%), combined malrotation and instability (8%), and polyethylene wear/osteolysis (8%) in the traditional TKA group. These data suggest that MI TKA may be a risk factor for early revision.

Endophenotypic correlates of cognitive function in reproductive-age individuals with polycystic ovary syndrome.

Objective: To characterize cognitive performance in relation to hormonal and metabolic factors in women with polycystic ovary syndrome (PCOS). Design: Cross-sectional study. Setting: Tertiary university center. Patients: A total of 48 individuals, aged 21-46 years, with PCOS according to the Rotterdam criteria. Interventions: Complete history and physical examinations, endovaginal ultrasounds, dermatologic assessments, neuropsychological assessments, and metabolic and hormonal serum tests. Main Outcome Measures: Sample-based z-scores on a comprehensive cognitive test battery. Results: Subjects were defined as having an androgenic (n = 31) or a nonandrogenic (n = 17) PCOS phenotype. Compared with their nonandrogenized counterparts, subjects with hyperandrogenism demonstrated lower relative performance on the tests of executive function (ß-coefficient for the executive function composite z-score, -0.44; 95% confidence interval, -0.79 to -0.09), despite similar performance on the tests of memory, verbal reasoning, and perceptual reasoning. These differences were independent of age, years of education, and obesity. In an exploratory analysis in which subjects were stratified by the presence of insulin resistance (IR), subjects with PCOS with both IR and hyperandrogenism showed the lowest performance on a composite score of executive function, followed by those with hyperandrogenism alone. Conclusions: In this small study, subjects with hyperandrogenic PCOS demonstrated lower performance on the tests of executive function than subjects with nonandrogenic PCOS. Additional research is needed to confirm these findings in larger cohorts and investigate the role of modifiable factors, including IR, on cognitive outcomes.