Estradiol to progesterone ratio is not a predictor of oocyte maturity at time of ovulation trigger.

PURPOSE: To evaluate the relationship between progesterone and oocyte maturity rate via estradiol to progesterone ratio (E/P) at the time of ovulatory trigger. METHODS: This is a retrospective cohort study of first autologous IVF cycles from January to December 2018 from a private practice fertility center. Serum estradiol and progesterone levels were measured on the day of ovulatory trigger. E/P was calculated to control for degree of response. Embryos were cultured to the blastocyst stage for trophectoderm biopsy. Preimplantation genetic testing for aneuploidy (PGT-A) was performed using next-generation sequencing (NGS). Oocyte retrieval rate (oocytes retrieved/follicles ≥ 13 mm), maturity rate (MII/oocytes retrieved), and euploid rate (euploid/total biopsied embryos) were calculated. Clinical pregnancy, ongoing pregnancy (> 10 weeks), and live births following frozen embryo transfer (FET) were examined in relation to E/P. Regression analyses were performed to analyze E/P as a categorical value (defined by quartile) on oocyte maturity. RESULTS: Two hundred eleven women underwent controlled ovarian hyperstimulation and had steroid levels at trigger available. Mean E at trigger was 3449 ± 2040 pg/mL while mean P was 1.13 ± 0.58 ng/mL, with mean E/P of 3.36 + 2.04. There were no differences between quartiles of E/P with respect to retrieval, maturity rate, or euploid rate. Two hundred eleven IVF cycles resulted in 138 euploid frozen embryo transfers. There were no differences between quartiles of E/P with respect to clinical pregnancy, ongoing pregnancy, or live birth rate. CONCLUSION: E/P ratio at the time of trigger does not impact oocyte retrieval rate, maturity rate, or euploid rate. Pregnancy and live birth outcomes were also not impacted.

Euploid rates among oocyte donors: is there an optimal age for donation?

PURPOSE: To examine cycle blastocyst euploid rates among age subgroups of oocyte donors. METHODS: Retrospective cohort analysis of ova donation in vitro fertilization cycles (OD-IVF) for which trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A) by array comparative genomic hybridization (aCGH) or next generation gene sequencing (NGS) was employed between January 2015 and December 2018 in a single high-volume fertility center. RESULTS: Compared to oocyte donors age 26-30, oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates (80 [66.7, 87.5]%, vs. 75 [62.5, 87.5]%, median [IQR], p = 0.07), blastocyst formation rates (66.7 [50, 75]%, vs. 62.5 [52, 75]%, p = 0.55), and number of retrieved oocytes (29 [23, 37] vs. 27 [20, 35], p = 0.18). Age of oocyte donor from 18 to 34 was not correlated with cycle blastocyst euploid rate. CONCLUSION: Oocyte donors age ≤ 25 had similar cycle blastocyst euploid rates, blastocyst formation rates, and number of retrieved oocytes compared to donors age 26-30. There was no correlation between cycle blastocyst euploid rates and age of the oocyte donor from 18 to 34 years. Given the lack of significant age-related change in cycle blastocyst euploid rates, our data support existing practices which do not favor a specific age subgroup of young oocyte donors.

Earlier day of blastocyst development is predictive of embryonic euploidy across all ages: essential data for physician decision-making and counseling patients.

PURPOSE: The purpose of this study is to evaluate whether day of blastocyst development is associated with embryo chromosomal status as determined by high-density oligonucleotide microarray comparative genomic hybridization (aCGH). METHODS: This is a retrospective cohort analysis, including women who underwent in vitro fertilization (IVF) with trophectoderm biopsy at a single private fertility center from January 2014 to December 2014. Repeat cycles were excluded. Cycles were assessed for percentage of blastocysts biopsied on days 5, 6, or 7 and rate of euploid embryos per cycle. Cycles were stratified by Society for Assisted Reproductive Technology (SART) age groups (< 35, 35-37, 38-40, 41-42, > 42) and by donor status. RESULTS: A total of 388 IVF cycles and 2132 biopsied blastocysts were evaluated. The percentages of blastocysts biopsied on days 5, 6, and 7 were 62.5, 35.8, and 1.7%, respectively. Blastocyst euploid rates on days 5, 6, and 7 were 49.5, 36.5, and 32.9%, respectively. Earlier blastocyst development was associated with a significantly increased euploid rate (p < 0.0001). Younger maternal age (p < 0.0001) and higher number of blastocysts biopsied per patient (p = 0.0063) were both independently associated with greater percentage of euploidy. CONCLUSIONS: Earlier blastocyst development is independently associated with a higher likelihood of embryonic euploidy in both autologous and donor embryos. In non-biopsied embryos, these data support selection of day 5 blastocysts for transfer over later-developing embryos. These results can assist with patient counseling regarding expectations and outcomes. To our knowledge, this is the first study to examine embryonic euploidy as stratified by both day of blastocyst development and SART age group.

Economic Burden of Endometrial Cancer Associated With Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged females, and women with PCOS are at increased risk for endometrial cancer (EndoCA), the most common gynecological malignancy. Our study sought to assess the economic burden associated with EndoCA in PCOS. METHOD: Using PRISMA systematic review guidelines, we evaluated studies on EndoCA rates in patients with PCOS. Excluded studies were reviews and case reports, non-human subjects, without controls, without full text available, or reporting solely on other conditions. Selected studies were assessed for quality using the Newcastle-Ottawa Scale (NOS). Meta-analysis used DerSimonian-Laird random effects model to assess pooled risk ratio (RR). Excess cost was assessed in U.S. dollars (USD). RESULT: Of 98 studies screened, nine were included. Pooled RR for EndoCA in PCOS was 3.46 (95% CI 2.28-5.23), p=<0.001. In the US, prevalence of EndoCA in patients with PCOS in 2020 was 1.712%, compared with a baseline estimated prevalence in all women of 0.489%. The excess prevalence of EndoCA attributable to PCOS was 1.223%, approximately 98,348 affected women. A population-attributable fraction of EndoCA for PCOS was 24.4%. Given estimated cost of EndoCA exceeds $1.9 billion (in 2023 USD), the economic burden of EndoCA attributable to PCOS exceeds $467 million/year. CONCLUSION: The excess annual healthcare cost for EndoCA attributable to PCOS exceeds $467 million/year (2023 USD) for the US. Although a concerning morbidity of PCOS, it is notable that the economic burden of EndoCA attributable to the disorder represents only a small fraction of its total healthcare burden.

The Association Between Obesity and Polycystic Ovary Syndrome: An Epidemiologic Study of Observational Data.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female cardiometabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence. OBJECTIVE: To determine the association between the prevalence of PCOS and obesity. MATERIALS AND METHODS: A systematic review was conducted to identify population studies on PCOS prevalence globally through July 2023. Linear regression and random-effect models were applied to examine the association of mean body mass index (BMI) or obesity prevalence with the prevalence of PCOS diagnosed by 1990 National Institutes of Health (NIH), 2003 Rotterdam (Rotterdam), and 2006 Androgen Excess-PCOS (AE-PCOS) criteria. Subgroup analyses were also conducted for recruitment methods and study quality. RESULTS: Fifty-eight studies with 85 956 adults from 24 countries were included. Considering all available data, a borderline association was observed between PCOS and obesity prevalence when using the AE-PCOS but not the NIH or Rotterdam criteria. Alternatively, subgroup analysis of studies with better recruitment methods demonstrated a significant positive association of population mean BMI or obesity prevalence with PCOS prevalence when using the Rotterdam or AE-PCOS criteria, while using only high-quality studies revealed an association using NIH as well as Rotterdam and AE-PCOS criteria. Overall, we observed that a 1% increase in obesity prevalence resulted in an approximately 0.4% increase in PCOS prevalence by the Rotterdam criteria. CONCLUSION: The prevalences of PCOS and obesity appear to be modestly associated, although our data cannot establish causality. This study also emphasizes the need to undertake only high-quality studies in assessing PCOS epidemiology.

Alterations in nonesterified free fatty acid trafficking rather than hyperandrogenism contribute to metabolic health in obese women with polycystic ovary syndrome.

OBJECTIVE: To determine whether alterations in nonesterified fatty acid (NEFA) dynamics or degree of hyperandrogenism (HA) contribute to the difference in insulin sensitivity between women with metabolically healthy obese polycystic ovary syndrome (PCOS) (MHO-PCOS) and women with metabolically unhealthy obese PCOS (MUO-PCOS). DESIGN: Prospective cross-sectional study. SETTING: Tertiary-care academic center. PATIENTS: One hundred twenty-five obese women with PCOS. INTERVENTION: Consecutive obese (body mass index [BMI] ≥ 30 kg/m2) oligo-ovulatory women (n = 125) with PCOS underwent an oral glucose tolerance test and a subgroup of 16 participants underwent a modified frequently sampled intravenous glucose tolerance test to determine insulin-glucose and -NEFA dynamics. MAIN OUTCOME MEASURES: Degree of insulin resistance (IR) in adipose tissue (AT) basally (Adipo-IR) and dynamically (the nadir in NEFA levels observed [NEFAnadir], the time it took for NEFA levels to reach nadir [TIMEnadir], and the percent suppression in plasma NEFA levels from baseline to nadir [%NEFAsupp]); peak lipolysis rate (SNEFA) and peak rate of NEFA disposal from plasma pool (KNEFA); whole-body insulin-glucose interaction (acute response of insulin to glucose [AIRg], insulin sensitivity index [Si], glucose effectiveness [Sg], and disposition index [Di]); and HA (hirsutism score, total and free testosterone levels, and dehydroepiandrosterone sulfate levels). RESULTS: A total of 85 (68%) women were MUO-PCOS and 40 (32%) were MHO-PCOS using the homeostasis model of assessment of IR. Subjects with MUO-PCOS and MHO-PCOS did not differ in mean age, BMI, waist-to-hip ratio, HA, and lipoprotein levels. By a modified frequently sampled intravenous glucose tolerance test, eight women with MUO-PCOS had lesser Si, KNEFA, and the percent suppression in plasma NEFA levels from baseline to nadir (%NEFAsupp) and greater TIMEnadir, NEFAnadir, and baseline adipose tissue IR index (Adipo-IR) than eight subjects with MHO-PCOS, but similar fasting NEFA levels and SNEFA. Women with MUO-PCOS had a higher homeostasis model of assessment-ß% and fasting insulin levels than women with MHO-PCOS. In bivalent analysis, Si correlated strongly and negatively with Adipo-IR and NEFAnadir, weakly and negatively with TIMEnadir, and positively with KNEFA and %NEFAsupp, in women with MUO-PCOS only. CONCLUSION: Independent of age and BMI, women with MUO-PCOS have reduced NEFA uptake and altered insulin-mediated NEFA suppression, but no difference in HA, compared with women with MHO-PCOS. Altered insulin-mediated NEFA suppression, rather than HA or lipolysis rate, contributes to variations in insulin sensitivity among obese women with PCOS.

Direct economic burden of mental health disorders associated with polycystic ovary syndrome: Systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is the most common hormone disorder affecting about one in seven reproductive-aged women worldwide and approximately 6 million women in the United States (U.S.). PCOS can be a significant burden to those affected and is associated with an increased prevalence of mental health (MH) disorders such as depression, anxiety, eating disorders, and postpartum depression. We undertook this study to determine the excess economic burden associated with MH disorders in women with PCOS in order to allow for a more accurate prioritization of the disorder as a public health priority. Methods: Following PRISMA reporting guidelines for systematic review, we searched PubMed, Web of Science, EBSCO, Medline, Scopus, and PsycINFO through July 16, 2021, for studies on MH disorders in PCOS. Excluded were studies not in humans, without controls, without original data, or not peer reviewed. As anxiety, depression, eating disorders, and postpartum depression were by far the most common MH disorders assessed by the studies, we performed our meta-analysis on these disorders. Meta-analyses were performed using the DerSimonian-Laird random effects model to compute pooled estimates of prevalence ratios (PRs) for the associations between PCOS and these MH disorders and then calculated the excess direct costs related to these disorders in U.S. dollars (USD) for women suffering from PCOS in the U.S. alone. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results: We screened 78 articles by title/abstract, assessed 43 articles in full text, and included 25 articles. Pooled PRs were 1.42 (95% confidence interval [CI]: 1.32-1.52) for anxiety, 1.65 (95% CI: 1.44-1.89) for depression, 1.48 (95% CI: PR: 1.06-2.05) for eating disorders, and 1.20 (95% CI: 0.96-1.50) for postpartum depression, for PCOS relative to controls. In the U.S., the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $1.939 billion/yr, $1.678 billion/yr, and $0.644 billion/yr in 2021 USD, respectively. Postpartum depression was excluded from the cost analyses due to the non-significant meta-analysis result. Taken together, the additional direct healthcare costs associated with anxiety, depression, and eating disorders in PCOS were estimated to be $4.261 billion/yr in 2021 USD. Conclusions: Overall, the direct healthcare annual costs for the most common MH disorders in PCOS, namely anxiety, depression, and eating disorders, exceeds $4 billion in 2021 USD for the U.S. population alone. Taken together with our prior work, these data suggest that the healthcare-related economic burden of PCOS exceeds $15 billion yearly, considering the costs of PCOS diagnosis, and costs related to PCOS-associated MH, reproductive, vascular, and metabolic disorders. As PCOS has much the same prevalence across the world, the excess economic burden attributable to PCOS globally is enormous, mandating that the scientific and policy community increase its focus on this important disorder. Funding: The study was supported, in part, by PCOS Challenge: The National Polycystic Ovary Syndrome Association and by the Foundation for Research and Education Excellence.

Polycystic Ovary Syndrome (PCOS) affects one in seven reproductive-age women worldwide. PCOS impacts women's physical and mental health, and it may also have detrimental effects on their social lives, academic achievement and careers. Studies show women with PCOS have higher rates of depression, anxiety, eating disorders, infertility and postpartum depression compared with women without the condition. The economic burden of PCOS is enormous. Previous studies show PCOS-related economic costs totals billions of dollars. But few studies have examined the costs associated with PCOS-associated mental health care. Learning more about these costs may help policymakers and clinicians allocate resources for mental health care for women with PCOS. Yadav et al. analyzed the results of 25 studies to assess the mental health impact of PCOS and its costs. The analysis found that women with PCOS are 60% more likely to have depression or anxiety compared to women without the condition. They were also twice as likely to have eating disorders. Caring for these mental health issues in PCOS patients increases US healthcare costs by approximately $4.2 billion yearly. These costs raise the healthcare-related economic burden of treating PCOS and associated conditions to $15 billion in the United States each year. The analysis suggests that earlier recognition and better treatment of PCOS could reduce associated healthcare costs and improve the quality of life for women with PCOS. The results may help policymakers and clinicians understand the condition's impact and prioritize resources for PCOS care. More research on the condition is necessary to reduce the enormous economic and personal burden caused by it.

Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences.

CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5% to 20% of women of reproductive age. The economic burden of PCOS was previously estimated at approximately $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, without considering the costs of pregnancy-related and long-term morbidities. OBJECTIVE: This study aimed to estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS. METHODS: PubMed, EmBase, and Cochrane Library were searched, and studies were selected in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health, or Androgen Excess and PCOS Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index were included. Two investigators working independently extracted data on study characteristics and outcomes. Data were pooled using random effects meta-analysis. The I2 statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. RESULTS: The additional total healthcare-related economic burden of PCOS due to pregnancy-related and long-term morbidities in the United States is estimated to be $4.3 billion annually in 2020 USD. CONCLUSION: Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.

Transfer of embryos with segmental mosaicism is associated with a significant reduction in live-birth rate.

OBJECTIVE: To evaluate the impact of segmental mosaicism on pregnancy outcomes from the transfer of embryos previously designated as euploid. DESIGN: Retrospective cohort analysis. SETTING: Single, private, high-volume fertility center. PATIENT(S): Three hundred and twenty-seven women who underwent 377 frozen single euploid embryo transfers. INTERVENTION(S): Trophectoderm biopsy of embryos cultured to the blastocyst stage, where all transferred embryos were designated euploid by high-density oligonucleotide array comparative genomic hybridization (aCGH); after ascertaining all outcomes, revaluation of aCGH results for evidence of segmental mosaicism (defined as mosaicism on a portion of a chromosome). MAIN OUTCOME MEASURE(S): Live-birth rate and spontaneous abortion rate. RESULT(S): Of the 377 embryos transferred, 357 were euploid with no mosaicism, and 20 embryos had segmental mosaicism. Segmental mosaics had a statistically significantly lower live-birth rate compared with euploid controls (30.0% vs. 53.8%). When controlling for age and day of Trophectoderm biopsy, the odds for live birth after transfer of segmental mosaics were reduced by 66% compared with euploid controls (0.34; 95% confidence interval, 0.13-0.92). The spontaneous abortion rate was statistically significantly higher after transfer of segmental mosaics compared with euploid controls (40.0% vs. 18.2%). CONCLUSION(S): Blastocysts with segmental mosaicism have reduced reproductive potential but retain the ability to result in live birth. These results support reporting segmental mosaicism to optimize selection of a single embryo for transfer that will maximize the chance of life birth.

A short study in the treatment of hot flashes with buccal administration of 17-beta estradiol.

OBJECTIVE: To assess the efficacy and safety of 17-beta estradiol buccal tablets in reducing hot flush frequency (HFF) in postmenopausal women. METHODS: Estradiol buccal tablets containing 0.05, 0.1, 0.2, or 0.4 mg or placebo were administered for 28 days to 99 postmenopausal women in a randomized, double-blind study; 19 premenopausal women were studied concurrently for comparison of laboratory data. Objective and subjective assessments of HFF were obtained along with measures of estradiol, estrone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH). RESULTS: Measurements of HFF revealed significant decreases from baseline in all estradiol groups (P < 0.01). In the 0.4 mg group, HFF decreased significantly compared to placebo (P < 0.01). All estradiol doses produced similar improvement in the vaginal maturation index. Mean serum estradiol levels increased as doses increased but were lower than in the premenopausal subjects. Mean serum FSH and LH levels decreased in all estradiol groups but not to the levels of the premenopausal subjects; the greatest decrease occurred at the two highest estradiol doses. CONCLUSION: A numerical dose-response relationship with hot flushes was seen in this pilot study comparing 0.05, 0.1, 0.2, and 0.4 mg buccal estradiol. Only 0.4 mg 17-beta estradiol significantly reduced the occurrence of hot flushes compared to placebo.