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Purpose: Although some reproductive and metabolic characteristics of polycystic ovary syndrome (PCOS) are known risk factors for breast cancer, the evidence regarding a potential association between PCOS and breast cancer is scarce. In this population-based cohort study including all 1,719,452 women born in Denmark between 1940 and 1993, we investigated the association between PCOS and breast cancer., Methods: PCOS diagnoses, cancer diagnoses, covariates, migrations, and vital status were all obtained from national population and health registers. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer overall and for histological subtypes separately were calculated based on adjusted cox proportional hazards models., Results: During a median follow-up of 26 years, 63,078 women were diagnosed with breast cancer. We found an increased risk of breast cancer overall among women with PCOS compared with women without PCOS (HR: 1.21, 95% CI 1.02-1.44). In analyses stratified for menopausal status, the increased risk was restricted to postmenopausal women (HR: 1.63, 95% CI 1.23-2.15). The results for ductal and lobular histological subtypes analyses separately resembled those observed for breast cancer overall., Conclusion: This is the first study to report an increased risk of breast cancer among women with a history of PCOS. The increased risk was seemingly confined to postmenopausal women. Our results therefore contribute to an increased knowledge of the etiology of breast cancer, but our findings should be further confirmed in other large cohort studies with an appropriately long follow-up period., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Most previous studies found an elevated risk of endometrial cancer among women with polycystic ovary syndrome (PCOS). However, these had highly varying methods for ascertainment of PCOS diagnoses and limitations such as few exposed women and short follow-up. In this cohort study, we investigated the association between PCOS and endometrial cancer among women born in Denmark between January 1, 1940, and December 31, 1993 (n = 1 719 121). Data in this study, including PCOS and endometrial cancer diagnoses and covariates, were derived from nationwide registers. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% CIs. A total of 7862 endometrial cancer cases were identified during 23.7 years of follow-up (IQR, 37.7-61.9). We found an increased risk of endometrial cancer among women with PCOS compared with women without PCOS (HR = 3.02; 95% CI, 2.03-4.49). The risk was increased for premenopausal women (HR = 5.82; 95% CI, 3.64-9.30), whereas no marked association was seen for postmenopausal women. However, for postmenopausal women, results were limited by few cases and young age at the end of follow-up. Mounting evidence of an increased risk for endometrial cancer among women with PCOS reinforces the need for prevention and early detection. This article is part of a Special Collection on Gynecological Cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Is there an association between the length of in vitro culture, mode of ART and the initial endogenous hCG rise, in cycles with a foetal heartbeat after single embryo transfer (ET) and implantation?, Summary Answer: Both the length of in vitro culture and the mode of ART have an impact on the initial endogenous rise in hCG in singleton pregnancies., What Is Known Already: Different factors have been identified to alter the kinetics of hCG in pregnancies. Current studies show conflicting results regarding the kinetics of hCG after different types of ART (fresh vs frozen ET (FET)), the inclusion or not of preimplantation genetic testing (PGT), and the length of time in in vitro culture., Study Design, Size, Duration: This was a multicentre cohort study, using prospectively collected data derived from 4938 women (5524 treatment cycles) undergoing IUI (cycles, n = 608) or ART (cycles, n = 4916) treatments, resulting a in singleton ongoing pregnancy verified by first-trimester ultrasound scan. Data were collected from the Danish Medical Data Centre, used by the three participating Danish public fertility clinics at Copenhagen University hospitals: Herlev Hospital, Hvidovre Hospital, and Rigshospitalet, from January 2014 to December 2021., Participants/materials, Setting, Methods: The fresh ET cycles included cleavage-stage (2 or 3 days in vitro) and blastocyst (5 days in vitro) transfers. FET cycles included cleavage-stage (3 days in vitro before cryopreservation) or blastocyst (5 or 6 days in vitro before cryopreservation) transfers. The IUI cycles represented no time in vitro. To attain a comparable interval for serum-hCG (s-hCG), the ovulation induction time was identical: 35-37 h before oocyte retrieval or IUI. The conception day was considered as: the insemination day for pregnancies conceived after IUI, the oocyte retrieval day for fresh ET, or the transfer day minus 3 or 5 as appropriate for FET of Day 3 or 5 embryos. Multiple linear regression analysis was used, including days post-conception for the hCG measurement as a covariate, and was adjusted for the women's age, the cause of infertility, and the centre. For FET, a sensitivity analysis was used to adjust for endometrial preparation., Main Results and the Role of Chance: The study totally includes 5524 cycles: 2395 FET cycles, 2521 fresh ET cycles, and 608 IUI cycles. Regarding the length of in vitro culture, with IUI as reference (for no time in in vitro culture), we found a significantly lower s-hCG in pregnancies achieved after fresh ET (cleavage-stage ET or blastocyst transfer). S-hCG was 18% (95% CI: 13-23%, P < 0.001) lower after fresh cleavage-stage ET, and 23% (95% CI: 18-28%, P < 0.001) lower after fresh blastocyst transfer compared to IUI. In FET cycles, s-hCG was significantly higher after blastocyst transfers compared to cleavage-stage FET, respectively, 26% (95% CI: 13-40%, P < 0.001) higher when cryopreserved on in vitro Day 5, and 14% (95% CI: 2-26%, P = 0.02) higher when cryopreserved on in vitro Day 6 as compared to Day 3. Regarding the ART treatment type, s-hCG after FET blastocyst transfer (Day 5 blastocysts) cycles was significantly higher, 33% (95% CI: 27-45%, P < 0.001), compared to fresh ET (Day 5 blastocyst), while there was no difference between cleavage-stage FET (Days 2 + 3) and fresh ET (Days 2 + 3). S-hCG was 12% (95% CI: 4-19%, 0.005) lower in PGT FET (Day 5 blastocysts) cycles as compared to FET cycles without PGT (Day 5 blastocysts)., Limitations, Reasons for Caution: The retrospective design is a limitation which introduces the risk of possible bias and confounders such as embryo score, parity, and ovarian stimulation., Wider Implications of the Findings: This study elucidates how practices in medically assisted reproduction treatment are associated with the hCG kinetics, underlining a potential impact of in vitro culture length and mode of ART on the very early embryo development and implantation. The study provides clinicians knowledge that the type of ART used may be relevant to take into account when evaluating s-hCG for the prognosis of the pregnancy., Study Funding/competing Interest(s): No funding was received for this study. AP has received consulting fees, research grants, or honoraria from the following companies: Preglem, Novo Nordisk, Ferring Pharmaceuticals, Gedeon Richter, Cryos, Merck A/S, and Organon. AZ has received grants and honoraria from Gedeon Richter. NLF has received grants from Gedeon Richter, Merck A/S, and Cryos. MLG has received honoraria fees or research grants from Gedeon Richter, Merck A/S, and Cooper Surgical. CB has received honoraria from Merck A/S. MB has received research grants and honoraria from IBSA. MPR, KM, and PVS all report no conflicts of interest., Trial Registration Number: The study was registered and approved by the Danish Protection Agency, Capital Region, Denmark (Journal-nr.: 21019857). No approval was required from the regional ethics committee according to Danish law., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

An association between polycystic ovary syndrome (PCOS) and epithelial ovarian tumors is biologically plausible as conditions inherent to PCOS such as excessive androgenic hormones, reproductive factors and obesity are also risk factors for these hormone-sensitive tumors. However, previous studies have showed conflicting results and have various methodological limitations. This population-based cohort study investigates the association between PCOS and epithelial ovarian tumors and includes all women born in Denmark between January 1, 1940 and December 31, 1993 (n = 1 719 304). PCOS diagnoses, ovarian cancer and borderline ovarian tumor diagnoses, covariates, migration and vital status were obtained from the Danish national registers. Adjusted cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for epithelial ovarian cancer and for borderline ovarian tumors overall as well as for histological subtypes separately. During median 26 years of follow-up we identified 6490 women with ovarian cancer and 2990 women with borderline ovarian tumors. Overall, we observed no marked associations between a diagnosis of PCOS and overall epithelial ovarian cancer or overall epithelial borderline ovarian tumors, irrespective of time since diagnosis. However, we found an increased risk of ovarian cancer among postmenopausal women with PCOS (HR 2.28 95% CI 1.02-5.09) and an increased risk of serous borderline ovarian tumors (HR 2.34 95% CI 1.21-4.53) in women with PCOS compared with women without PCOS. Importantly, low statistical precision is a crucial limitation of our study and in previous studies and larger studies with longer follow-up are therefore warranted., (© 2023 UICC.)

Introduction: Polycystic ovary syndrome is a condition characterized by hormonal and metabolic disturbances that may affect bone health. The purpose of this study was to investigate the effect of polycystic ovary syndrome on bone mineral density and to examine which clinical characteristics of the syndrome could influence bone mineral density., Materials and Methods: We examined 183 premenopausal women: 158 women with polycystic ovary syndrome and 25 healthy age- and body mass index matched controls. Bone mineral density and body composition were investigated by whole-body dual energy X-ray absorption. Total and free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, estradiol, fasting insulin and glucose, parathyroid hormone, calcium and 25-OH-cholecalciferol were measured. The effect of polycystic ovary syndrome on bone mineral density was analyzed by statistical two-way analysis of variance tests and multiple linear regressions for investigating the connection between bone mineral density and selected clinical parameters., Results: Women with polycystic ovary syndrome had significantly lower bone density in the lumbar vertebrae L1-L4 compared to healthy controls, independently of body mass index. We found that total lean body mass was the most important associating factor for bone mineral density and these were strongly correlated throughout all regression analyzes. We found no connection between lumbar bone density and androgen status, hyperinsulinemia, estradiol or calcium homeostasis., Conclusions: Premenopausal women with polycystic ovary syndrome have lower bone mineral density in the lumbar vertebrae L1-L4 compared to healthy controls. Total lean body mass and polycystic ovary syndrome are significantly associated to this finding.