Polymorphisms in period genes and bone response to hormone therapy in postmenopausal Korean women.

OBJECTIVE: In this study, we aimed to explore the association between polymorphisms in the period (PER) gene and bone response to hormone therapy (HT) in postmenopausal Korean women. METHODS: The PER1 c.2284C > G, c.2247C > T, PER2 c.3731G > A, PER3 c.2592G > A, c.3083T > C polymorphisms, and PER3 54bp variable number of tandem repeats (VNTR) were analyzed in 509 postmenopausal Korean women who received HT. Bone mineral density (BMD) at the lumbar spine and femoral neck before and after 1 year of HT and serum levels of osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-κB ligand (sRANKL) and bone turnover markers were measured after 6 months of HT. RESULTS: The PER1 c.2884 C > G polymorphism and PER3 54bp VNTR were associated with annual percent changes in BMD of the femoral neck after 1 year of HT (p < 0.05). Changes in BMD at the femoral neck in the non-CC genotype of the PER1 c.2884C > G polymorphism and in the 4-repeat homozygote of PER3 54bp VNTR were significantly lower than those in CC genotype and non-4-repeat homozygote, respectively. The PER1 c.2884C > G polymorphism was associated with the non-response (>3% BMD loss/year after HT) of HT. The non-CC genotype of the PER1 c.2884C > G polymorphism showed a 1.92-times higher risk of non-response at the lumbar spine and/or femoral neck (p = 0.01) compared with the CC genotype. No significant changes in bone markers after 6 months of HT were noted according to the PER1 c.2884C > G polymorphism. CONCLUSIONS: The PER1 c.2884C > G polymorphism may be associated with risk of non-response to HT in postmenopausal Korean women.

Increased risk for post-operative corneal injuries in patients who undergo laparoscopic gynecologic surgery.

BACKGROUND: The objective of this study was to verify whether or not the incidence of post-operative corneal injuries (PCIs) in patients who undergo laparoscopic gynecologic surgery is higher than patients who undergo non-laparoscopic gynecologic surgery. METHODS: The peri-operative variables were extracted from the medical records of patients who underwent gynecologic surgery under general anesthesia at our institute between January 2004 and June 2010. The extracted variables were age, day of week of surgery, type of surgery (laparoscopy vs. non-laparoscopy), surgical scheduling (elective vs. emergent), pre-operative hemoglobin, surgery time, peri-operative transfusions, and PCIs. The association of peri-operative variables with PCIs was examined using univariate and multivariate analyses. RESULTS: A total of 6992 consecutive patients were included in this study. PCIs occurred in 23 patients (0.3%). Based on univariate analysis, the type of surgery and surgery times were associated with PCIs. Based on multivariate analysis, laparoscopy and lengthy surgery times significantly increased the risk for PCIs. The median duration of PCI symptoms was 3 days (range, 1-11 days); no patient had long-term sequalae. CONCLUSION: Laparoscopic gynecologic surgery increases the incidence of PCI compared with non-laparoscopic gynecologic surgery.

The effects of hormone therapy on metabolic risk factors in postmenopausal Korean women.

OBJECTIVE: We sought to assess the prevalence of metabolic syndrome (MetS) among Korean postmenopausal women and to investigate the effect of hormone therapy status and reproductive characteristics on body composition and MetS risk factors. STUDY DESIGN: We performed a cross-sectional study involving a cohort of 2005 postmenopausal Korean women. We defined MetS using the modified National Cholesterol Education Program (NCEP) criteria proposed by the American Heart Association/National Heart, Lung, and Blood Institute guidelines. The criteria for abdominal obesity were adopted from the cut-offs suggested by the Korean Society for the Study of Obesity. Participants with three or more of the following conditions were classified as having MetS: waist circumference ≥ 85 cm; blood pressure ≥ 130/85 mmHg; fasting plasma triglycerides ≥ 150 mg/dl; high density lipoprotein cholesterol < 50 mg/dl; glucose ≥ 100 mg/dl and/or receiving treatment for their condition. RESULTS: The prevalence of MetS was 22.1% in the study population and increased with age. After adjusting for age and related reproductive characteristics, it was found that ever-use of hormone therapy (prior or current) was associated with decreased risk of postmenopausal MetS. Among individual risk factors for MetS, current hormone therapy seemed to be associated with decreased prevalence of abdominal obesity and better glucose metabolism and prior use of hormone therapy were associated with lower risk of abdominal obesity and high blood pressure. CONCLUSION: Postmenopausal hormone therapy is associated with decreased risk of MetS in postmenopausal Korean women.

Polycystic ovary syndrome with hyperandrogenism as a risk factor for non-obese non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with polycystic ovary syndrome (PCOS). However, most studies investigated the prevalence of NAFLD in obese PCOS patients. AIM: To compare the prevalence of non-obese NAFLD in women with or without PCOS, and to assess an independent association between PCOS and NAFLD in a non-obese Asian cohort. METHODS: This was a case-control study using a prospective PCOS cohort. After subjects with other potential causes of chronic liver disease were excluded, 275 non-obese women with PCOS and 892 non-obese controls were enrolled. NAFLD was determined by hepatic ultrasonography. Main outcomes were the prevalence of NAFLD on hepatic ultrasonography between non-obese women with or without PCOS, and an independent association between non-obese NAFLD and PCOS. RESULTS: Non-obese women with PCOS had a significantly higher prevalence of NAFLD than those without PCOS (5.5% vs. 2.8%, P = 0.027). PCOS was associated with non-obese NAFLD (odds ratio: 2.62, 95% confidence intervals: 1.25-5.48) after adjustment for age and body mass index (BMI). In women with PCOS, the level of androgenicity represented by free testosterone or free androgen index was associated with NAFLD after adjustment for age, BMI, lipid profile, insulin resistance or glycaemic status. CONCLUSIONS: Non-obese NAFLD is more prevalent in women with polycystic ovary syndrome than in those without. In non-obese patients with polycystic ovary syndrome, hyperandrogenemia may be an independent risk factor for non-obese NAFLD.

Effects of Anesthetic Agent Propofol on Postoperative Sex Hormone Levels.

Introduction: Several studies have found anesthetic agents including propofol in ovarian follicular fluid. However, little is known about the effect of anesthetic agents on ovarian function. We aimed to investigate whether there were differences in the postoperative levels of sex hormones when propofol was used as the anesthetic agent. Methods: A retrospective review was done of 80 patients who underwent ovarian surgery, with 72 infertile women serving as controls. Patients were included in the study if their serum estradiol (E2) and follicle stimulating hormone (FSH) levels were measured during their first postoperative menstrual cycle. Results: Patients were grouped according to the use or non-use of propofol as follows: propofol group (n = 39) and non-propofol group (n = 41). The control group did not undergo surgery. Postoperative E2 levels did not differ between the three groups, but FSH levels were significantly higher in the patients who had undergone surgery compared to controls (p < 0.05). Post-hoc analysis of E2 and FSH levels in the propofol and non-propofol groups did not show any significant differences. Conclusions: The use of propofol did not result in any differences compared to other anesthetic agents in terms of postoperative sex hormone levels after gynecologic surgery. The type of anesthetic agent does not seem to affect the postoperative levels of female sex hormones.

MicroRNA Profile of Granulosa Cells after Ovarian Stimulation Differs According to Maturity of Retrieved Oocytes.

Background: Recent animal studies demonstrated that regulating the microRNA (miRNA) in granulosa cells (GCs) modulates the meiotic competence of oocytes. However, the difference in expression profiles of miRNAs in human GCs according to the maturity of the oocyte still remains to be elucidated. Objective: This observational study investigated whether the miRNA profile of human GCs differs according to the maturity of the retrieved oocyte after controlled ovarian stimulation for in vitro fertilization (IVF). Methods: Ten women who underwent ovarian stimulation cycles with GnRH agonist long protocols were recruited. The follicular fluid (FF) from dominant follicles was individually aspirated at oocyte retrieval. Oocytes were divided into two groups according to oocyte maturity ("mature group" vs. "immature group"). GCs were collected from the FF and miRNA was analyzed using real-time PCR. Results: Mean number of MII oocytes in the mature group was 1.6 ± 0.9 with none in the immature group (p = 0.008). Mean number of MI oocytes was 5.6 ± 2.1 in the mature group and 1.0 ± 0.0 in the immature group (p = 0.008). The total number of retrieved oocytes was 8.8 ± 1.9 in the mature group and 2.0 ± 1.2 in the immature group (p = 0.008). The GCs of the mature group showed a significantly lower expression of hsa-let-7b compared to the GCs of the immature group (p < 0.001). Conclusion: Taken together, the miRNA expression profiles of human GCs obtained from dominant follicles are associated with maturity of the adjacent oocyte and may be useful as a prognosticator of IVF outcome.

Hepatosplenic T-cell lymphoma: prolymphocytic transformation 18 months after splenectomy.

We report a young woman with pancytopenia and huge splenomegaly who was also found to have peripheral T-cell lymphoma with massive infiltration of T-cell evident in the liver and spleen. A liver biopsy showed predominant sinusoidal infiltration of pan-T cell antibody-stained T-lymphoid cells. Histologic examination of the spleen revealed numerous tumor cells predominantly infiltrated in the cords and sinuses of the red pulp, which were identical to those described in the liver. Several clusters of small round abnormal cells were observed in marrow cytology. Although the patient felt well during 18 months after the splenectomy was done, the patient eventually manifested a huge hepatomegaly, showed increasing white blood cell count to 42 x 10(9)/l, and numerous prolymphocytes (66.9%) in the bone marrow. This change represented a prolymphocytic transformation of the patient's original hepatosplenic T-cell lymphoma.

Insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), and IGFBP-3 protease activity in the peritoneal fluid of patients with and without endometriosis.

OBJECTIVE: To compare levels of insulin-like growth factor (IGF) components in the peritoneal fluid of patients with and without endometriosis. DESIGN: Patients with endometriosis were compared with control patients. SETTING: Seoul National University Hospital, Korea. PATIENT(S): Forty-three patients with endometriosis and 20 patients without endometriosis. INTERVENTION(S): Peritoneal fluid specimens were collected. MAIN OUTCOME MEASURE(S): Insulin-like growth factors, IGF binding protein (IGFBP) profiles and IGFBP-3 protease activity. RESULT(S): The IGF-I levels in peritoneal fluid were significantly higher in patients with endometriosis than in control patients, while the IGFBP-3 levels and the relative proportion of IGFBP-2 in peritoneal fluid were significantly lower in patients with endometriosis than in control patients. However, IGF-II levels, IGFBP-4 profiles, and IGFBP-3 protease activity did not differ significantly between the two groups. No correlation between these IGF components in peritoneal fluid and the stage of endometriosis was noted. CONCLUSION(S): The profiles of IGF components in peritoneal fluid of patients with pelvic endometriosis may play an important role in the growth of ectopic endometrium and endometriosis-induced infertility.

Human amnion-derived mesenchymal stem cells are a potential source for uterine stem cell therapy.

OBJECTIVES: Human amnion is an easy-to-obtain novel source of human mesenchymal stem cells, which poses little or no ethical dilemmas. We have previously shown that human amnion-derived mesenchymal (HAM) cells exhibit certain mesenchymal stem cell-like characteristics with respect to expression of stem cell markers and differentiation potentials. MATERIALS AND METHODS: In this study, we further characterized HAM cells' potential for in vivo therapeutic application. RESULTS: Flow cytometric analyses of HAM cells show that they express several stem cell-related cell surface markers, including CD90, CD105, CD59, CD49d, CD44 and HLA-ABC, but not CD45, CD34, CD31, CD106 or HLA-DR. HAM cells at the 10th passage showed normal karyotype. More interestingly, the AbdB-like HOXA genes HOXA9, HOXA10 and HOXA11 that are expressed in the mesenchyme of the developing female reproductive tract and pregnant uteri are also expressed in HAM cells, suggesting similarities between these two mesenchymal cell types. Progesterone receptor is also highly expressed in HAM cells and expression of genes or proteins in HAM cells could be manipulated with the aid of lentivirus technology or cell-permeable peptides. To test potentials of HAM cells for in vivo application, we introduced enhanced green fluorescence protein (EGFP)-expressing HAM cells to mice by intrauterine infusion (into uteri) or by intravenous injection (into the circulation). Presence of EGFP-expressing cells within the uterine mesenchyme after intrauterine infusion or in lungs after intravenous injection was noted within 1-4 weeks. CONCLUSIONS: Collectively, these results suggest that HAM cells are a potential source of mesenchymal stem cells with therapeutic potential.

Simultaneous program of natural-cycle in vitro fertilization and cryopreserved-thawed embryo transfer.

PURPOSE: This clinical study was designed to identify and compare the pregnancy rates of simultaneous program of natural-cycle IVF and cryopreserved-thawed ET (NICE) with those of natural-cycle IVF and cryopreserved-thawed ET. METHODS: All three groups comprised spontaneously ovulating infertile women under the age of 40 and without any male factor present. The NICE program was performed in 36 patients (47 cycles) who had previously undergone IVF-ET resulting in cryopreserved embryos. As control groups, the natural-cycle IVF was performed in 45 patients (80 cycles), and the cryopreserved-thawed ET alone in 29 patients (40 cycles). RESULTS: The cancellation rate of the initiated cycles prior to ET was 19.1% (9/47) in the NICE group, 23.8% (19/80) in the natural-cycle IVF group, and 2.5% (1/40) in the cryopreserved-thawed ET group. The mean number of embryos transferred was 4.0 +/- 1.1 (2-5) in the NICE group, 1.0 in the natural-cycle IVF group, and 4.2 +/- 1.8 (1-5) in the cryopreserved-thawed ET group. The clinical pregnancy rates per aspiration cycle (32.5%) and per ET cycle (34.2%) in the NICE group were significantly higher than those (14.9, 16.4%) in the natural-cycle IVF group. The clinical and delivered pregnancy rates per ET (34.2, 26.3%) in the NICE group were higher than those (20.5, 15.4%) in the cryopreserved-thawed ET group, without statistical significance. CONCLUSIONS: Since the NICE program results in saving the fresh oocyte for patients participating in cryopreserved-thawed ET, more favorable pregnancy rates may be obtained from NICE cycles in women ovulating normally who had previously undergone IVF-ET with embryo cryopreservation.

Influence of female age on pregnancy outcome in in vitro fertilization and embryo transfer patients undergoing intracytoplasmic sperm injection.

PURPOSE: To determine the influence of female age on the outcomes of ICSI in IVF-ET patients. METHODS: One hundred and seventy-five couples underwent 352 cycles of ICSI. The quality of oocytes and embryos, fertilization rate, and pregnancy outcomes were retrospectively evaluated according to female age; < 30 years in Group A (49 cycles), 30-34 in Group B (177 cycles), 35-39 in Group C (97 cycles), and > or = 40 in Group D (29 cycles). RESULTS: The fertilization rates were not significantly different among the age groups. Significant negative linear correlations were observed between female age and the numbers of oocytes retrieved and embryos transferred, and cumulative embryo score. Clinical pregnancy rates were significantly decreased and spontaneous abortion rate increased with advancing age. CONCLUSIONS: Female age may be a prognostic indicator in ICSI program.

The outcome of sperm retrieval and intracytoplasmic sperm injection in patients with obstructive azoospermia: impact of previous tuberculous epididymitis.

PURPOSE: Our purpose was to investigate the influence of previous tuberculous epididymitis in patients with obstructive azoospermia on the outcome of sperm retrieval and intracytoplasmic sperm injection (ICSI). METHODS: Eighty-eight cycles of ICSI were performed in 44 patients with obstructive azoospermia; 16 cycles (7 patients) with tuberculous obstructive azoospermia and 72 cycles (37 patients) with nontuberculous obstructive azoospermia. RESULTS: The rates of fertilization and embryo cleavage were comparable, and there was no significant difference in the clinical pregnancy rate per fresh transfer between the two groups. The rates of embryo implantation and clinical miscarriage were also comparable. CONCLUSIONS: Embryo quality and pregnancy outcome in sperm retrieval and ICSI were comparable in both the tuberculous and the nontuberculous obstructive azoospermia patients. Although there was a preponderance of testicular sperm used in the tuberculous obstructive azoospermia group, our results suggest that previous tuberculous epididymitis in patients with obstructive azoospermia does not affect the outcome of sperm retrieval and ICSI.