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In women with PCOS receiving controlled ovarian stimulation for in vitro fertilization (IVF), follicular fluid and granulosa cells are dysfunctional, with hundreds of transcripts, proteins, lilpids and metabolites that differ significantly from controls with non-ovarian causes of infertility. However,  there is no evidence that oocytes are compromised: the proportion of metaphase II oocytes, the rate of development to blastocyst and the prevalence of aneuploid embryos are unchanged. Endometrial proteome is altered but receptivity is not affected in IVF treatments, where the implantation rates of single &#39;ideal&#39; blastocysts are similar in PCOS and controls. During ovarian stimulation for IVF, protocols that use pituitary downregulation with GnRH antagonist followed by triggering with GnRH agonist are safer (lower incidence of ovarian hyperstimulation syndrome) and equally effective (same pregnancy rates) compared with long protocols that use GnRH agonist for pituitary downregulation and hCG for ovulation triggering. FSH receptor gene polymorphisms may affect ovarian response to exogenous FSH, but the clinical usefulness of this information to plan IVF treatments of women with PCOS is still uncertain. For women with PCOS treated with IVF, frozen embryo transfer is better than fresh embryo transfer. When preparing the endometrium for frozen embryo transfer, pituitary downregulation with GnRH agonist does not increase the odds of a live birth. Progestins are better than COC to induce menses before starting an IVF cycle in women with PCOS. Insulin sensitizers or weight reduction do not seem to improve IVF outcomes.

AE-PCOS 2022

IVF and PCOS

### Welcome to the AE-PCOS Society's 20th Annual Meeting!


The AE-PCOS Society’s 20th Annual Meeting's theme will be Reflections and Directions. The meeting will aim to incorporate the perspectives of both long-time, contributing members of the Society and newer members of the Society, while highlighting the latest research findings in PCOS-related clinical and basic research.

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Please register for the AE-PCOS 2022 Conference to join the event.

The AE-PCOS Society’s 20th Annual Meeting's theme are Reflections and Directions. The meeting aims to incorporate the perspectives of both long-time, contributing members of the Society and newer members of the Society, while highlighting the latest research findings in PCOS-related clinical and basic research.

In women with PCOS receiving controlled ovarian stimulation for in vitro fertilization (IVF), follicular fluid and granulosa cells are dysfunctional, with hundreds of transcripts, proteins, lilpids and metabolites that differ significantly from controls with non-ovarian causes of infertility. However,  there is no evidence that oocytes are compromised: the proportion of metaphase II oocytes, the rate of development to blastocyst and the prevalence of aneuploid embryos are unchanged. Endometrial proteome is altered but receptivity is not affected in IVF treatments, where the implantation rates of single 'ideal' blastocysts are similar in PCOS and controls. During ovarian stimulation for IVF, protocols that use pituitary downregulation with GnRH antagonist followed by triggering with GnRH agonist are safer (lower incidence of ovarian hyperstimulation syndrome) and equally effective (same pregnancy rates) compared with long protocols that use GnRH agonist for pituitary downregulation and hCG for ovulation triggering. FSH receptor gene polymorphisms may affect ovarian response to exogenous FSH, but the clinical usefulness of this information to plan IVF treatments of women with PCOS is still uncertain. For women with PCOS treated with IVF, frozen embryo transfer is better than fresh embryo transfer. When preparing the endometrium for frozen embryo transfer, pituitary downregulation with GnRH agonist does not increase the odds of a live birth. Progestins are better than COC to induce menses before starting an IVF cycle in women with PCOS. Insulin sensitizers or weight reduction do not seem to improve IVF outcomes.

technical paper

PCOS is though to stem from prenatal exposures and seems to translate into increased comorbidity risk. The health insults, however, vary depending on the age. The presentation will go through the health risks related to PCOS over the lifespan.

PCOS over the lifespan

For the motion

Against the motion

Luteinizing hormone knockout alleviates anxiety in aged, but not in young mice

LH/CG Receptor activation protects mice from diet-induced obesity

OBJECTIVE: Polycystic ovarian syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is associated with cardiometabolic comorbidities. Information on cardiovascular disease (CVD) event risk associated with PCOS is mixed limited by sample size, diagnostic criteria, and years of follow up especially in US cohorts. Metformin, a drug traditionally used to treat patients with type 2 diabetes (T2D), is first line treatment for many women with PCOS We hypothesize that women with PCOS are at increased risk for developing cardiovascular diseases CVD and that metformin may play a protective role in disease progression.
METHODS: We leveraged the Penn Medicine electronic health record (EHR) which contains diagnosis information for 2,514,400 women. We calculated relative risk (RR) of being diagnosed with CVD or thrombotic disease (based on diagnosis codes) for women who were also diagnosed with PCOS or PCOS + T2D. For both RR calculations, our cases were women aged 15-50 who had at least one visit with PCOS diagnosis with or without T2D diagnosis. Controls were women aged 15-50 without a PCOS diagnosis but who had at least one visit for T2D. We also calculated RR of being diagnosed with CVD or thrombotic event for women aged 15-50 with at least one PCOS + T2D diagnosis who were treated with the drug metformin. Controls were women aged 15-50 with a PCOS +T2D diagnosis but were not treated with metformin.
RESULTS: Of the 945,670 women aged 15-50, 22,030 (2.3%) had at least one visit for PCOS diagnosis while 2,010 (0.2%) had PCOS and T2D. We found that the risk for CVD for women with PCOS was 1.35 times that of age matched controls (95% CI 1.29 ± 1.43, p = 1.76e-28) and the risk for thrombotic disease was 2.02 times that of age matched controls (95% CI 1.81 ± 2.26, p = 5.25e-37). We found that women with PCOS + T2D had decreased risk for CVD (RR = 0.26, 96% CI 0.23 ± 0.29, p = 6.21e-140) and thrombotic disease (RR = 0.60, 95% CI 0.47 ± 0.77, p = 3.02e-05). Because many women with T2D are prescribed metformin, we wanted to know if a metformin prescription had a protective effect on being diagnosed with CVD or thrombotic disease. By calculating RR, we found that women with PCOS + T2D who were prescribed metformin were 15% less likely of developing CVD (RR = 0.85, 95% CI 0.77 ± 0.93, p = 5.03e-05) and 4% less likely of developing TD (RR = 0.96, 95% CI 0.83 ± 1.12, NS) compared to patients that were never prescribed metformin.
CONCLUSIONS: In a large longitudinal cohort of women diagnosed with PCOS, we showed that a PCOS diagnosis was associated with an increased risk of CVD events. We also showed that PCOS patients who also had T2D diagnosis had decreased risk of CVD, which we observed was potentially associated by the protective effects of the drug metformin. Due to the high prevalence of CVD in women, longitudinal studies are needed to uncover the molecular, genetic, and pharmacogenomic pathways underlying disease progression in women with PCOS.

Cardiovascular events associated with PCOS diagnosis in large longitudinal cohort

Women with polycystic ovary syndrome (PCOS) have poorer work ability and higher disability retirement rate at midlife - A Northern Finland Birth Cohort 1966 Study

OBJECTIVE: To contrast the diagnostic accuracy of 3D ultrasonographic markers of ovarian morphology to 2D ultrasonography and serum anti-Müllerian hormone (AMH) levels for detection of polycystic ovary syndrome (PCOS). Any gains in diagnostic accuracy when combining ovarian markers was also explored.

METHODS: 30 women with PCOS based on the National Institutes of Health (NIH) criteria and 30 age- and body mass index (BMI)-matched controls were evaluated. Transvaginal ultrasound scans (GE Voluson E or S Series; 5-12 MHz) and blood draws were conducted during the early follicular phase for women with regular cycles or at a random time for women with irregular cycles. Ovarian images were analyzed for the number of 2-9mm antral follicles in the entire ovary (FNPO), number of 2-5mm antral follicles (FNPO2-5mm) and 6-9mm antral follicles (FNPO6-9mm), and ovarian volume (OV) using 3D and 2D ultrasonography by one of six trained raters. 3D versus 2D ovarian markers were compared using Bland-Altman agreement statistics for matched-pair analysis. Diagnostic accuracy of ovarian markers for PCOS was determined by Receiver Operating Characteristic (ROC) curve analysis. Stepwise logistic regression analysis determined if combinations of ultrasonographic markers or AMH yielded greater diagnostic potential than single parameters.

RESULTS: 3D measurements of FNPO, FNPO2-5mm, and OV had greater diagnostic accuracy for PCOS compared to their 2D counterparts. The most accurate markers for PCOS were 3D FNPO (AUC=0.938) and 3D FNPO2-5mm (AUC=0.933), followed by 2D FNPO (AUC=0.922) and 2D FNPO2-5mm (AUC=0.906). Despite overall agreement between 3D and 2D FNPO measures, 3D ultrasonography overcounted FNPO2-5mm (2.00 ± 3.68, P=0.006) and undercounted FNPO6-9mm (-3.00 ± 3.49, P<0.001) in women with PCOS. AMH (AUC=0.898) had greater diagnostic accuracy than 3D and 2D OV (AUC=0.854 and 0.849, respectively), but remained inferior to both 3D and 2D follicle counts. The addition of OV or AMH did not improve diagnostic accuracy for follicle counts. However, the addition of AMH did substantially improve the diagnostic accuracy of 3D OV (AUC=0.918) and 2D OV (AUC=0.911).

CONCLUSIONS: 3D ultrasonographic markers of ovarian morphology outperformed 2D markers in the diagnosis of PCOS, with 3D markers of follicle excess being the most accurate measure overall. AMH had inferior diagnostic accuracy compared to FNPO across both modalities but was superior to OV. Addition of AMH improved the predictive power of OV on 2D and 3D ultrasonography thereby offering a robust alternative when image quality prevents an accurate assessment of follicle counts.

(This study was funded by the National Institutes of Health Grant [R01HD09374, R56HD089962, UL1 TR000457-06, T32DK007158-41] and the Canadian Institute of Health Research [FRN 146182].)


3D Markers of ovarian morphology outperform 2D ultrasonography and Anti-Müllerian hormone in the diagnosis of PCOS

Comparing Rotterdam and NIH Criteria: Women with PCOS have increased risk for cardiovascular diseases regardless of diagnostic criteria used

OBJECTIVE: Polycystic Ovary Syndrome (PCOS) is associated with insulin resistance, hyperandrogenism, and dyslipidemia, but the progression of type 2 diabetes mellitus in Chinese women with PCOS have only been investigated in clinic-based study population. Therefore, a population-based longitudinal study can help establish the overall risk of diabetes progression in Chinese women with PCOS. 
METHODS: This territory-wide, retrospective cohort study evaluated data extracted from the Hong Kong Diabetes Surveillance Database (HKDSD) between year 2000 and 2019. The subjects were women with PCOS (n=3978) identified based on the ICD-9 code for PCOS diagnosis, whilst women without PCOS served as controls (n=39780). Women with PCOS were age-matched at a ratio of 1:10 to a set of non-PCOS controls. Primary outcome was the first record of incident diabetes. Crude rates for diabetes were presented, and time to diabetes was analyzed using Cox proportional hazard models. 
RESULTS: The mean follow-up was 6.3 ± 4.2 and 7.0 ± 4.3 years in women with PCOS (baseline mean age: 28.53 ± 7.39 years old) and controls (baseline mean age: 28.93 ± 7.62 years old), respectively.  In the cohort of women with PCOS, the crude incidence rate of diabetes was 21.48 per 1000 person-years (95% CI 19.56 -23.40) compared with 3.51 (95% CI 3.29-3.73) in the control cohort. The crude hazard ratio for the development of diabetes in Chinese women with PCOS was 6.25 (95% CI: 5.60-6.98, p<0.001). All participants were further stratified by age groups (≤19, 20-29, 30-39 and ≥40 years old). The incidence rate of diabetes was significantly higher in women diagnosed with PCOS than that of the age-matched control cohort, especially if PCOS was diagnosed at a younger age. Although the excess risk of developing diabetes decreased with increasing age at diagnosis, it remained significantly higher in women with PCOS across all age groups. Nevertheless, diabetes was diagnosed on average 5 years earlier in women with PCOS compared to control counterpart (mean onset of diabetes in PCOS: 34.65 ± 8.13 vs control: 39.61 ± 9.38, p<0.001). 
CONCLUSIONS: The risk of developing diabetes is markedly increased in Chinese women with PCOS compared with women without PCOS. Women diagnosed with PCOS at a younger age have the highest relative risk of developing diabetes when compared to non-PCOS women, suggesting regular glycaemic status screening might be required in order to detect diabetes at an early stage. 

Increased risk of diabetes across the reproductive age range in women with PCOS: A territory-wide retrospective analysis from the Hong Kong diabetes surveillance database

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PCOS over the lifespan

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Walter Futterweit Award in Clinical Research

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CONFERENCES

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