OBJECTIVE: The aim of this study was to investigate the effect of insulin sensitizing agents on hormonal and metabolic parameters as well as menstrual patterns in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and twenty-three patients with PCOS were included. Metformin was administered to patients at 1,500 mg or 1,700 mg daily for 3 months. If the patients had no improvement of the menstrual cycle or metformin-related adverse effects developed, the patients changed medication to a daily dose of either 15 mg pioglitazone or up to 45 mg. Then resumption of a regular menstrual cycle or recovery of ovulation was evaluated. Hormonal and metabolic profiles were compared between the response and non-response group to insulin sensitizing agents. RESULTS: One hundred and five patients with PCOS were treated with metformin for 3 months. Forty-eight patients (45.7%) showed improvement of menstrual cycle regularity after 3 months of metformin use, whereas 57 patients (54.3%) had no change. The mean free testosterone measured after 3 months of treatment was significantly lower in metformin responders than in non-responders. The other parameters did not differ between the groups. Of the 23 patients who used pioglitazone for 3 to 6 months, 19 patients (82.6%) showed improvement in their menstrual cycles. CONCLUSION: Metformin treatment seems to be effective for the improvement of menstrual cyclicity irrespective of insulin resistance in women with PCOS. When metformin related adverse effect occurred, pioglitazone would be effective for aiding the resumption of the menstrual cycle.
Female ; Humans ; Insulin ; Insulin Resistance ; Menstrual Cycle ; Metabolome ; Metformin ; Ovulation ; Periodicity ; Polycystic Ovary Syndrome ; Testosterone ; Thiazolidinediones

OBJECTIVE: To evaluate the correlation between serum levels of anti-Mullerian hormone (AMH) and ovarian response to mild stimulation in normoovulatory women and anovulatory women with polycystic ovary syndrome (PCOS). METHODS: Seventy-four cycles of mild stimulation (clomiphene citrate+gonadotropin followed by timed intercourse or intrauterine insemination) performed in normoovulatory women (57 cycles) and anovulatory women with PCOS (17 cycles). Ovarian sensitivity was defined by the number of mature follicles (> or =14 mm) on triggering day per 100 IU of gonadotropin. A correlation between ovarian sensitivity and the baseline serum AMH level (absolute or multiples of the median [MoM] value for each corresponding age) was calculated. Correlation between ovarian response and serum AMH level was evaluated. RESULTS: Ovarian sensitivity to mild stimulation was positively correlated with absolute serum AMH (r=0.535, p<0.001) or AMH-MoM value (r=0.390, p=0.003) in normoovulatory women, but this correlation was not observed in anovulatory women with PCOS (r=0.105, p>0.05, r=-0.265, p>0.05, respectively). CONCLUSION: Ovarian response to mild stimulation is possibly predicted by the serum AMH level in normoovulatory women, but not in anovulatory women with PCOS.
Anti-Mullerian Hormone ; Female ; Gonadotropins ; Humans ; Ovulation Induction ; Polycystic Ovary Syndrome

OBJECTIVE: To evaluate the efficacy of earlier oocyte retrieval in IVF patients with a premature LH surge on hCG day. METHODS: One hundred forty IVF patients (164 cycles) with premature LH surge on hCG day were included, retrospectively. We divided them into 2 study groups: LH surge with timed ovum pick-up (OPU) 36 hours after hCG injection (group B, 129 premature cycles), and LH surge with earlier OPU within 36 hours after hCG injection (group C, 35 cycles). Control groups were tubal factor infertility without premature LH surge (group A, 143 cycles). RESULTS: The mean age (year) was statistically higher in group C than in groups A or B (38.2+/-5.4 vs. 36.2+/-4.2 vs. 36.8+/-4.9, respectively; p=0.012). The serum LH levels (mIU/mL) on hCG day were significantly higher in group B and C than in group A (22.7+/-14.9 vs. 30.3+/-15.9 vs. 3.2+/-2.9, respectively; p>0.001). Among groups A, B, and C, 4.9%, 31.7%, and 51.4% of the cycles, respectively, had no oocytes, and the overall rates of cycle cancellation (OPU cancellation, no oocyte, or no embryos transferrable) were 15.4%, 65.9%, and 74.3%, respectively. The fertilization rate (%) was significantly higher in group B than in group C (73.2+/-38.9 vs. 47.8+/-42.9, p=0.024). The clinical pregnancy rate was significantly higher in group C than in groups A and B (44.4% vs. 27.3% vs. 9.1%, respectively, p=0.021). However, the miscarriage rate was also higher in group C than in group B (22% vs. 0%, respectively, p=0.026). CONCLUSION: Earlier OPU may not be effective in reducing the risk of cycle cancellation in patients with premature LH surge on hCG day. A larger scale study will be required to reveal the effectiveness of earlier ovum retrieval with premature LH surge.
Abortion, Spontaneous ; Embryonic Structures ; Female ; Fertilization ; Fertilization in Vitro ; Humans ; Infertility ; Lutein ; Luteinizing Hormone ; Oocyte Retrieval ; Oocytes ; Ovum ; Pregnancy ; Pregnancy Rate ; Retrospective Studies

OBJECTIVE: To investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day. METHODS: A total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated. RESULTS: The duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A (2.5+/-0.9 vs. 3.2+/-0.8 ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates. CONCLUSION: Our prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.
Embryonic Structures ; Estradiol ; Female ; Fertilization ; Fertilization in Vitro ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Lutein ; Luteinization ; Oocytes ; Ovulation ; Ovulation Induction ; Pregnancy ; Pregnancy Rate ; Prospective Studies

OBJECTIVE: To compare the blood glucose levels, insulin concentrations, and insulin resistance during the two phases of the menstrual cycle between healthy women and patients with premenstrual syndrome (PMS). METHODS: From January of 2011 to the August of 2012, a descriptive cross-sectional study was performed among students in the School of Medicine of Jahrom University of Medical Sciences. We included 30 students with the most severe symptoms of PMS and 30 age frequency-matched healthy controls. We analyzed the serum concentrations of glucose, insulin, and insulin resistance by using the glucose oxidase method, radioimmunometric assay, and homeostasis model assessment of insulin resistance equation, respectively. RESULTS: No significant differences between the demographic data of the control and PMS groups were observed. The mean concentrations of glucose of the two study groups were significantly different during the follicular and luteal phases (p=0.011 vs. p<0.0001, respectively). The amounts of homeostasis model assessment of insulin resistance of the two study groups were significantly different in the luteal phase (p=0.0005). CONCLUSION: The level of blood glucose and insulin resistance was lower during the two phases of the menstrual cycle of the PMS group than that of the controls.
Blood Glucose ; Cross-Sectional Studies ; Female ; Glucose ; Glucose Oxidase ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Luteal Phase ; Menstrual Cycle ; Premenstrual Syndrome

OBJECTIVE: To investigate the effect of peroxisome proliferator activated receptor gamma (PPARgamma) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. METHODS: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPARgamma agonist). RESULTS: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPARgamma agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin E2 production in the ESCs of endometriosis. CONCLUSION: This study suggests that PPARgamma agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.
Aromatase ; Biopsy ; Biphenyl Compounds ; Blotting, Western ; Cell Proliferation ; Dinoprostone ; Down-Regulation ; Endometriosis ; Endometrium ; Female ; Humans ; Peroxisomes ; PPAR gamma ; Prostaglandin-Endoperoxide Synthases ; Stromal Cells ; Telomerase ; Thiazolidinediones

OBJECTIVE: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. METHODS: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. RESULTS: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. CONCLUSION: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.
Animals ; Atrophy ; Busulfan ; Estrogens ; Fertility ; Genistein ; Gonadotropin-Releasing Hormone ; Humans ; Phytoestrogens ; Rats ; Receptors, Estrogen ; Seminiferous Tubules ; Soybeans ; Spermatogenesis ; Testis ; Testosterone

Endometriosis is defined as the presence of functional endometrial tissue outside the uterus, causing diverse progressive symptoms such as infertility, pelvic pain, and dysmenorrhea. Although endometriosis has been described since the 1800s, the mechanisms responsible for its pathogenesis and progression remain poorly understood. It is well established that endometriosis grows and regresses in an estrogen-dependent fashion and the disease can be effectively cured by definitive surgery. However, prolonged medical therapy may be needed in most of the cases since conservative surgery is usually performed especially in young women. This treatment modality is often associated with only partial relief and/or recurrence of the disease. In the present review, up-to-date findings on the treatment of endometriosis will be briefly summarized. The outcomes of surgery in patients with endometriosis will be reviewed in terms of pelvic pain relief as well as infertility treatment largely based on recent Cochrane reviews and clinical reports. The efficacy of newer drugs including aromatase inhibitor, anti-tumor necrosis factor-alpha, and dienogest will be also reviewed based on recent clinical studies.
Aromatase ; Dysmenorrhea ; Endometriosis ; Female ; Humans ; Infertility ; Nandrolone ; Necrosis ; Pelvic Pain ; Recurrence ; Uterus

To overcome the difficulty of controlling stem cell fate and function in applications to regenerative medicine, a number of alternative approaches have been made. Recent reports demonstrate that a non-cellular niche modulating the biophysical microenvironment with chemical factors can support stem cell self-renewal. In our previous studies, early establishment was executed to optimize biophysical factors and it was subsequently found that the microgeometry of the extracellular matrix made huge differences in stem cell behavior and phenotype. We review here a three-dimensional, non-cellular niche designed to support stem cell self-renewal. The characteristics of stem cells under the designed system are further discussed.
Extracellular Matrix ; Phenotype ; Regenerative Medicine ; Stem Cells

Recently, a significant understanding of the molecular mechanisms regulating spermatogenesis has been achieved utilizing small RNA molecules (small RNAs), including small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs) which emerged as important regulators of gene expression at the post-transcriptional or translation level. piRNAs are only present in pachytene spermatocytes and round spermatids, whereas miRNAs are expressed abundantly in male germ cells throughout spermatogenesis. This review is aimed at providing a glimpse of piRNAs and their interacting family proteins such as PIWIL1, PIWIL2, and PIWIL4 in spermatogenesis.
Animals ; Gene Expression ; Germ Cells ; Humans ; Infertility ; Male ; Mice ; MicroRNAs ; Proteins ; RNA ; RNA, Small Interfering ; Spermatids ; Spermatocytes ; Spermatogenesis