Context: Polycystic ovary syndrome (PCOS) represents the most common endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality.Objective: The objective of the study was to test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development.Design: Granulosa cells were prepared from follicular fluid aspirated from 4-to 8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles. Setting:The study was conducted at a university hospital.Patients: Fourteen women with anovulatory PCOS and nine women with regular ovulatory cycles participated in the study. Main Outcome Measures:Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators, was measured.Results: Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS, compared with women with regular ovulatory cycles (P ϭ 0.004). Lower apoptotic rates were associated with decreased levels of the apoptotic effector caspase-3 (P ϭ 0.001) and increased levels of the anti-apoptotic survival factor cellular inhibitor of apoptosis proteins-2 in the PCOS group that were coupled to higher proliferation rates (P ϭ 0.032). Gene expression profiling confirmed the immunocytochemical findings. Conclusions:Our findings indicate that there are significant differences in the rate of cell death and proliferation in granulosa cell populations in PCOS patients. These are associated with decreased expression of apoptotic effectors and increased expression of a cell survival factor. These results provide new insights that may be useful in developing specific therapeutic intervention strategies in PCOS. (J Clin Endocrinol Metab 93: 881-887, 2008) P olycystic ovary syndrome (PCOS) is a common endocrine abnormality in women of reproductive age, affecting 6.6 -8% of women in this age group (1). It is the main cause of anovulatory infertility and is characterized by chronic anovulation, hyperandrogenemia, and polycystic ovaries on ultrasound scan (2). Abbreviations: Bcl, B-cell lymphoma; BMI, body mass index; cIAP, cellular IAP; DHEAS, dehydroepiandrosterone sulfate; IAP, inhibitor of apoptosis proteins; Mcl, myeloid leukemia cell differentiation protein; PCOS, polycystic ovary syndrome; TUNEL, terminal deoxynucleotidyl transferase biotin-deoxyuridine 5-triphosphate nick end labeling; XIAP, X-linked inhibitor of apoptosis protein.

An estimated 5000 to 6000 hysterectomies are performed each year in Denmark. A nationwide survey disclosed a complication rate of 18%, a median hospital stay of 4 days, and readmission of 8% of patients within 30 days. The Danish Hysterectomy Database (DHD) was established in 2003 to provide a national basis for improving the outcome of hysterectomy. The study population included all women having elective hysterectomy on benign indications in the years [2004][2005][2006]. Structured data are registered prospectively by the surgeons providing treatment, and feedback is provided as clinical indicators with defined goals. Annual plenary meetings, elaboration of national clinical guidelines, and parallel causal studies all are elements of the DHD.Hysterectomies carried out in Denmark from 2004 to 2006 numbered 13,425. In 2005, all 31 gynecological departments in Denmark participated in database collaboration; the national response rate was 99%. Data validity was, in general, good, with agreement rates of 82% to 100%. High data completeness of 92% to 100% was documented. Two clinical guidelines, dealing with antibiotic prophylaxis and when to initiate anticoagulant therapy, were implemented during the period under review. The median patient age was 47 years. Participants were healthy or had no more than mild systemic disease with no functional limitations. The median postoperative hospital stay was stable at 2 days. The rate of postoperative surgical infection declined from 4% to 2%; bleeding complications from 8% to 6%; the reoperation rate from 5% to 4%; and the readmission rate from 7% to 5%.Experience with the DHD demonstrates that clinical performance indicators and nationwide collaboration are helpful in monitoring and improving the outcome of hysterectomy.