United States

Objective: Polycystic ovary syndrome (PCOS) is a common condition with endocrine-metabolic dysfunction, and is highly heritable. Yet, there is limited research on how offspring are affected, and the age of onset, if any. We established a cohort of women with PCOS and matched controls along with their offspring to evaluate the effects of maternal PCOS on the offspring, as well as any differential impact between boys and girls. 
Methods: Among Chinese women from our PCOS registry (diagnosed based on the 2003 Rotterdam diagnostic criteria), we invited those who have children to participate in a follow-up study, and evaluated both the mothers and their sons (PCOSs) and daughters (PCOSd). For controls, we recruited women from the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study, who did not have PCOS or GDM, together with their sons (Cs) and daughters (Cd), for comparison. All offspring aged 15-25 years were included in the current analysis, and all have undergone a detailed assessment with questionnaire, anthropometric assessment, a standardized 75g OGTT for glycemic status evaluation and biochemical tests. Difference between groups were evaluated using independent sample t-test or Mann-Whitney U test for continuous variables, while Chi-square (X2) or Fisher’s exact tests were used for categorical variables. 
Result: A total of 21 PCOSs and 18 PCOSd (mean age 19.86 ± 3.98 and 18.33 ± 2.30, respectively) as well as 26 Cs and 45 Cd (mean age 17.27 ± 0.67 and 17.58 ± 0.84, respectively) were recruited to date. We noted a high prevalence of menstrual irregularity in PCOSd when compared with Cd (PCOSd: 8/18 (44.4%) vs Cd: 7/44 (15.9%), p&lt;0.005). We also found that the frequency of elevated androgen levels was 8/18 (44.4%) and 11/33 (33.3%) in PCOSd and Cd, respectively (p=0.433). PCOSd were significantly more centrally obese than Cd (PCOSd: 5/18 (27.8%) vs Cd: 2/45 (4.4%), p=0.007). Yet, such significant difference was not observed when comparing between PCOSs and Cs. There was no significant difference in the prevalence of dyslipidemia (PCOSs: 13/21 (61.9%) vs Cs: 9/21 (42.9%), p=0.217; PCOSd: 3/18 (16.7%) vs Cd: 5/34 (14.7%), p=0.852), hypertension (none for both PCOSs and Cs; PCOSd: 1/18 (5.6%) vs Cd: 1/45 (2.2%), p=0.465) and metabolic syndrome (AHA/NHLBI) (PCOSs: 3/21 (14.3%) vs Cs: 0/26; Pd: 2/18 (11.1%) vs Cd: 0/45) in both gender between offspring of mothers with and without PCOS. There is a trend towards higher frequency of glucose abnormalities when comparing PCOSd vs Cd (PCOSs: 2/21 (9.5%) vs Cs: 1/21 (4.8%), p=0.549; PCOSd: 4/18 (22.2%) vs Cd: 2/34 (5.9%), p=0.079), although there was no significant difference.
Conclusion: PCOSd have increased risk of menstrual irregularity and central obesity compared to Cd. No difference in cardiometabolic traits were observed between PCOSs and Cs. Our preliminary results shed some light on the potential long-term cardiometabolic burden on PCOSd. 


AE-PCOS 2022

Sexual dimorphism in cardiometabolic risk in offspring of mothers with 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.

The recorded content will be available to registrants only for three months after the meeting. 


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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.

Objective: Polycystic ovary syndrome (PCOS) is a common condition with endocrine-metabolic dysfunction, and is highly heritable. Yet, there is limited research on how offspring are affected, and the age of onset, if any. We established a cohort of women with PCOS and matched controls along with their offspring to evaluate the effects of maternal PCOS on the offspring, as well as any differential impact between boys and girls. 
Methods: Among Chinese women from our PCOS registry (diagnosed based on the 2003 Rotterdam diagnostic criteria), we invited those who have children to participate in a follow-up study, and evaluated both the mothers and their sons (PCOSs) and daughters (PCOSd). For controls, we recruited women from the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study, who did not have PCOS or GDM, together with their sons (Cs) and daughters (Cd), for comparison. All offspring aged 15-25 years were included in the current analysis, and all have undergone a detailed assessment with questionnaire, anthropometric assessment, a standardized 75g OGTT for glycemic status evaluation and biochemical tests. Difference between groups were evaluated using independent sample t-test or Mann-Whitney U test for continuous variables, while Chi-square (X2) or Fisher’s exact tests were used for categorical variables. 
Result: A total of 21 PCOSs and 18 PCOSd (mean age 19.86 ± 3.98 and 18.33 ± 2.30, respectively) as well as 26 Cs and 45 Cd (mean age 17.27 ± 0.67 and 17.58 ± 0.84, respectively) were recruited to date. We noted a high prevalence of menstrual irregularity in PCOSd when compared with Cd (PCOSd: 8/18 (44.4%) vs Cd: 7/44 (15.9%), p<0.005). We also found that the frequency of elevated androgen levels was 8/18 (44.4%) and 11/33 (33.3%) in PCOSd and Cd, respectively (p=0.433). PCOSd were significantly more centrally obese than Cd (PCOSd: 5/18 (27.8%) vs Cd: 2/45 (4.4%), p=0.007). Yet, such significant difference was not observed when comparing between PCOSs and Cs. There was no significant difference in the prevalence of dyslipidemia (PCOSs: 13/21 (61.9%) vs Cs: 9/21 (42.9%), p=0.217; PCOSd: 3/18 (16.7%) vs Cd: 5/34 (14.7%), p=0.852), hypertension (none for both PCOSs and Cs; PCOSd: 1/18 (5.6%) vs Cd: 1/45 (2.2%), p=0.465) and metabolic syndrome (AHA/NHLBI) (PCOSs: 3/21 (14.3%) vs Cs: 0/26; Pd: 2/18 (11.1%) vs Cd: 0/45) in both gender between offspring of mothers with and without PCOS. There is a trend towards higher frequency of glucose abnormalities when comparing PCOSd vs Cd (PCOSs: 2/21 (9.5%) vs Cs: 1/21 (4.8%), p=0.549; PCOSd: 4/18 (22.2%) vs Cd: 2/34 (5.9%), p=0.079), although there was no significant difference.
Conclusion: PCOSd have increased risk of menstrual irregularity and central obesity compared to Cd. No difference in cardiometabolic traits were observed between PCOSs and Cs. Our preliminary results shed some light on the potential long-term cardiometabolic burden on PCOSd. 


technical paper

Natural history of PCOS

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.

IVF and PCOS

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].)


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Natural history of PCOS

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