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The circulating follistatin and high-sensitivity C-reactive protein (hsCRP) concentrations were significantly higher in 155 Taiwanese women with polycystic ovary syndrome (PCOS) than in 37 healthy controls. Follistatin and hsCRP levels in both the PCOS and control groups were significantly correlated with each other independent of obesity and insulin resistance. [Copyright &y& Elsevier]

Objective: To analyze the prevalence of intrauterine adhesion (IUA) formation in women undergoing transcervical resection (TCR) for submucous myomas.Design: Retrospective cohort study.Setting: Tertiary university hospital.Patient(s): One hundred fifty-three women undergoing TCR for submucous myomas were retrospectively analyzed. Among them, 132 women had a solitary myoma (group 1), 5 had two submucous myomas not in apposition to each other and who received postoperative intrauterine device (IUD) placement (group 2), 9 had two or more apposing submucous myomas and received IUD placement (group 3), and 7 had two or more apposing submucous myomas and who underwent subsequent office hysteroscopic early lysis of IUA (group 4).Intervention(s): Placement of an IUD for 1 month (groups 2 and 3) or office hysteroscopy for early lysis of IUA within 2 weeks after hysteroscopic myomectomy (group 4).Main Outcome Measure(s): Diagnostic office hysteroscopy was done 1-3 months after hysteroscopic myomectomy to evaluate whether there was permanent formation of IUA.Result(s): Two (1.5%) of 132 women in group 1 had IUA. For women receiving IUD placement; none of the 5 women in group 2 and 7 (78%) of 9 women in group 3 had IUA. For women undergoing office hysteroscopic early lysis of adhesion bands (group 4), none of 7 women had IUA.Conclusion(s): Intrauterine adhesion is a common complication after TCR for apposing submucous myomas, but not for a solitary myoma. Office hysteroscopy within 2 weeks after TCR is an easy and effective procedure in separating the newly formed IUA. [ABSTRACT FROM AUTHOR]

Objective: To examine changes in local cytokine production in the eutopic endometrium of adenomyosis after treatment with medroxyprogesterone acetate (MPA) and danazol. Design: Prospective cohort study. Setting: Tertiary university hospital. Patient(s): Twenty-four women with adenomyosis (study group) and 22 women without adenomyosis (control group). Intervention(s): Eutopic endometrium was separated into single endometrial stromal cells (ESCs), and was cultured in vitro alone, with MPA (10−7 M), or with danazol (10−7 M) for 8 days. Main Outcome Measure(s): Messenger RNA expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-α in ESCs, and their concentrations in the supernatants of ESCs. Result(s): A significant decrease of IL-6 concentration in the supernatant, measured by ELISA, was found with time of ESCs cultured with MPA and danazol in the control group, but not in adenomyosis. The IL-6 mRNA in ESCs determined by real-time quantitative polymerase chain, as well as its concentration in the supernatant, was much higher in adenomyosis than that in the control group after treatment with MPA and danazol for 8 days. Conclusion(s): Medroxyprogesterone acetate and danazol appeared to have a decreased effect on the suppression of IL-6 liberated by ESCs in adenomyosis. This aberrant secretion of IL-6 might play a role in the formation of ectopic endometrial implants in adenomyosis. [Copyright &y& Elsevier]

Objective: To study whether and how the pathogenesis of polycystic ovarian syndrome (PCOS) is related to epigenetic aberrations.Design: A case-control experimental study.Setting: Tertiary university hospital.Patient(s): Eighteen patients with PCOS and ten non-PCOS control subjects.Interventions(s): Patient-specific induced pluripotent stem cells (iPSCs) were obtained from skin fibroblasts through the application of nonviral episomal reprogramming and were differentiated into ovarian granulosa cells (GCs) with the use of a cocktail of growth factors. Primary ovarian GCs were collected during transvaginal oocyte retrieval surgery.Main Outcome Measure(s): Characterization and functional validation of iPSC-derived GCs were conducted. Whole-genomic DNA methylation profiles in women with and without PCOS in both iPSC-derived GCs and primary adult GCs were analyzed with the use of the Illumina 850K MethylationEPIC Beadchip.Result(s): The iPSC-derived GCs successfully expressed GC-associated genes and aromatase activity after differentiation. Whole-genomic DNA methylation analysis of the iPSC-derived GCs and adult GCs both revealed a hyperactive CREB signaling pathway in the PCOS group compared with the control group. The expression of CREB-binding protein (CBP) mRNA was significantly higher in the iPSC-derived GCs in the PCOS group, and the expression of CBP protein was also significantly higher in the primary GCs from women with PCOS.Conclusion(s): The combination of DNA methylomic analysis in primary adult GCs and iPSC-derived GCs showed that a preserved persistent hyperactivation of the CREB signaling pathway might be involved in the pathogenesis of PCOS. These results could have implications on the early developmental origin, inheritance nature, and environmental interaction effects of this disease. [ABSTRACT FROM AUTHOR]

Women who had stage III–IV endometriosis and who were nulliparous or who had delivered no more than two children were much more likely to develop tubo-ovarian abscesses than those without endometriosis. [Copyright &y& Elsevier]

To study the involvement of microribonucleic acids (miRNAs) in the pathogenesis of chronic anovulation and mechanism of metformin treatment in polycystic ovary syndrome (PCOS). Case-control and prospective validation cohort study. Tertiary university hospital. A total of 146 patients with PCOS and chronic anovulation and 20 non-PCOS controls were enrolled. Patients who resumed ovulation after metformin treatment (MET-OV) and remained anovulatory after metformin treatment (MET-AO) were assigned to MET-OV and MET-AO groups, respectively. All patients with PCOS received metformin treatment for 6 months. Baseline and chronological changes in the plasma levels of 14 miRNAs (miR-21, 93, 132, 193b, 221, 222, 223, 27a, 125b, 200b, 212, 320a, 429, and 483) selected by literature review, anthropometric data, and hormonal as well as metabolic profiles were measured. Predictive modeling based on baseline circulatory miRNA levels and clinical parameters was performed to predict ovulation recovery after metformin treatment. No significant differences were observed in the baseline hormonal and metabolic profiles between the MET-OV and MET-AO groups. However, the expression of miR-27a, miR-93, and miR-222 was significantly higher in the MET-OV group than that for the MET-AO and control groups. After 6 months of metformin treatment, the levels of insulin, luteinizing hormone, and 6 circulating miRNAs (miR-21, 27a, 93, 221, 222, and 223) and homeostatic model assessment for insulin resistance decreased significantly in the MET-OV group, but remained unchanged in the MET-AO group. The area under curve, sensitivity, and specificity of the adjusted prediction model, based on miRNA levels and clinical parameters using logistic regression analysis for predicting ovulatory response after metformin treatment, were 0.807, 0.892, and 0.632, respectively. The present study demonstrated a distinct pattern of baseline expression and chronological changes in the levels of several circulatory miRNAs between the MET-OV and MET-AO groups, suggesting that aberrantly overexpressed diabetogenic miRNAs are involved in the pathophysiology of chronic anovulation in PCOS, and their down-regulation might contribute toward the therapeutic effects of metformin. This could provide new insights into the mechanism of action and applicability of individualized metformin therapy in women with PCOS. [ABSTRACT FROM AUTHOR]

Objective: To analyze the impact of the diameter (myoma-φ) and the uterine cavity protruding proportion (protruding %) of the submucous myoma on serum hemoglobin (Hb) level. Design: Retrospective descriptive study. Setting: Tertiary university hospital. Patient(s): Two hundred fifty-nine women with a single submucous myoma. Intervention(s): Transvaginal ultrasound examination and office hysteroscopy. Main Outcome Measure(s): Myoma-φ and protruding % were determined with transvaginal ultrasound scan and office hysteroscopy. Menorrhagic period (months) and serum Hb were recorded within 2 weeks of these examinations. Result(s): Serum Hb negatively correlated with myoma-φ, protruding %, and menorrhagic period. The negative association between serum Hb and protruding % was even more prominent after adjusting for myoma-φ. Multivariate regression analysis revealed that myoma-φ and protruding %, after adjusting for the confounding effect of menorrhagic period, maintained a strongly negative correlation with serum Hb level. When myoma-φ was <2 cm, however, the serum Hb levels were similar regardless of the protruding %. Conclusion(s): For women with a single submucous myoma, myoma-φ and protruding % can determine the serum Hb level significantly . As myoma-φ and protruding % increased, the serum Hb level decreased accordingly. [ABSTRACT FROM AUTHOR]

Objective: To present a case of successful pregnancy after conservative bilateral gonadectomy without adjuvant chemotherapy and radiotherapy in a 46,XY gonadal dysgenetic woman with gonadoblastoma and malignant germ cell tumor. Design: Case report. Setting: Infertility center in university hospital. Patient(s): An 18-year-old female with 46,XY karyotype underwent bilateral gonadectomy, and the pathology revealed gonadoblastoma with malignant mixed germ cell tumor. Intervention(s): Chromosomal analysis, bilateral gonadectomy, donor oocyte, and IVF program. Main Outcome Measure(s): Tumor markers and pregnancy result. Result(s): The patient was free from tumor recurrence after 13 years’ follow-up. A successful twin pregnancy was achieved after oocyte donation and IVF. Conclusion(s): Gonadectomy without adjuvant therapies could be done in 46,XY gonadal dysgenetic women with gonadoblastoma in view of preservation of future fertility. [Copyright &y& Elsevier]

Objective: To investigate cell invasiveness and the production of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in endometrial stromal cells (ESCs) of adenomyosis. Design: Prospective study. Setting: Tertiary university hospital. Patient(s): Twenty-one women with adenomyosis (study group) and 25 women without adenomyosis (control group). Intervention(s): Endometrial stromal cells were purified from eutopic endometrium and were cultured in vitro. Main Outcome Measure(s): Matrigel invasion assay and measurement of MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations. Result(s): Endometrial stromal cell invasiveness of adenomyosis was not different from that of the control group (0.95 vs. 1, using the latter as the bench mark) in ESCs cultured alone. After the ESCs were cultured with IL-6, anti-IL-6, or GM6001 for 24 hours, the indices of cell invasion were not different between the two groups. MMP-2 (median 7.3 vs. 3.5 ng/mL) and TIMP-1 (median 12.1 vs. 3.9 ng/mL), but not MMP-9 and TIMP-2, secreted by ESCs in women with adenomyosis were much higher than those in women without adenomyosis. Conclusion(s): The formation of adenomyosis does not result from altered invasiveness of ESCs. The concomitant elevation of MMP-2 and TIMP-1 may partially justify why invasiveness was not increased, but other enzymes should also be considered. [Copyright &y& Elsevier]

Objective: To evaluate the association between follicular and serum nitric oxide (NO) levels and embryo development and outcome in IVF.Design: Prospective, case–control study.Setting: University hospital, tertiary medical center.Patient(s): Eighteen patients with tubal or peritoneal factor infertility and 18 female partners from couples with male factor infertility underwent controlled ovarian stimulation and IVF/intracytoplasmic sperm injection (ICSI).Intervention(s): Controlled ovarian stimulation and oocyte retrieval followed by IVF/ICSI and embryo culture.Main outcome measure(s): Degree of fragmentation of embryos and pregnancy rate.Result(s): Higher follicular NO levels were associated with advanced fragmentation of embryos. Follicular soluble Fas could not prevent embryo fragmentation. Higher serum NO levels were found among nonpregnant patients with tubal or peritoneal factor infertility. No elevated serum NO levels were found in the female partners from couples with male factor infertility.Conclusion(s): Up-regulation of serum NO is associated with implantation failure in patients with tubal or peritoneal factor infertility. [Copyright &y& Elsevier]

Objective: To determine the efficiency of a single-dose and a multiple-dose protocol for GnRH antagonist administration. Design: Randomized clinical trial. Setting: University hospital, tertiary medical center. Patient(s): Sixty-one patients undergoing controlled ovarian stimulation (COS) and IVF/ICSI. Intervention(s): COS with either a multiple-dose (MD) or a single-dose (SD) protocol for GnRH antagonist (cetrorelix) administration, or with a long protocol (LP) for GnRH agonist (buserelin) administration, followed by oocyte retrieval, IVF/ICSI, and embryo transfer. Main Outcome Measure(s): Follicular development and serum levels of E2 and LH. Result(s): The SD protocol for cetrorelix was associated with a more reduced level of follicular development, lower levels of serum estradiol on the day of HCG administration, and a more reduced number of zygotes than the LP for buserelin. The pregnancy and implantation rates did not differ significantly for the three study groups. Conclusion(s): The MD and SD GnRH antagonist protocols were effective for preventing LH surge and appear to elicit an equivalent pregnancy rate to that corresponding to a LP GnRH agonist. In terms of follicular development, the SD protocol requires further modification, including flexible scheduling or possibly a small reduction of the dosage of the administered cetrorelix. [Copyright &y& Elsevier]