• The Journal of Korean Obstetrics and Gynecology
• /
• v.23 no.2
• /
• pp.71-84
• /
• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.8975-8979
• /
• 2014

Objective: To explore the possible significance of aromatase P450 in endometrial hyperplasia with a background of polycystic ovary syndrome (PCOS). Methods: Immunohistochemistry was used to determine the expression of aromatase P450 in endometrium of PCOS patients. Semiquantitative analysis of aromatase P450 expression of mRNA and protein level wasalso carried out by real-time quantitative RT-PCR method. After endometrial cells were stimulated by testosterone and letrozole in vitro, the estradiol ($E_2$) level was determined, and the expression of cell aromatase P450 mRNA was assessed. Results: The aromatase P450 mRNA level was increased in endometria of PCOS patients. When endometrial cells were cultured with $10^{-6}M$ testosterone, the $E_2$ level in the culture medium increased. An inhibitory effect on $E_2$ generation and expression of aromatase P450 mRNA was observed when the endometrial cells were treated with $10^{-5}M$ letrozole. Conclusions: There is an increased expression of aromatase P450 in PCOS patient endometrium. Androgen stimulation could enhance the synthesis of aromatase P450 mRNA and the production of $E_2$ in endometrial cells in vitro while letrozole could do the reverse.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.7
• /
• pp.3331-3333
• /
• 2014

Background: The results of previous researches that analyzed the association between genetic polymorphisms of transcription factor-7-like 2 (TCF7L2, rs7903146) and polycystic ovary syndrome (PCOS) were conflicting. Current systematic analysis was conducted to re-explore this association using updated materials. Materials and Methods: The PubMed database was used for data collection and the final search was conducted on January 3, 2014. For TCF7L2 rs7903146, a non-signficiant slight increase in risk of PCOS development was observed under three genetic models (dominant model: OR=1.06, 95%CI: 0.93-1.21, p>0.05; recessive model: OR=1.12, 95%CI: 0.87-1.43, p> 0.05; homozygous model: OR=1.14, 95%CI: 0.87-1.47, p>0.05). In the subgroup analyses in Asian group, allele susceptibility of PCOS was calculated (allele model: OR=1.00, 95%CI: 0.74-1.35, p>0.05; dominant model: OR=0.98, 95%CI: 0.71-1.35, p>0.05; recessive model: OR=1.79, 95%CI: 0.33-9.84, p>0.05; homozygous model: OR=1.78, 95%CI: 0.32-9.80, p>0.05), the differences were again not statistically significant. Conclusions: The findings of this systemic analysis suggest that the polymorphism of TCF7L2 rs7903146 may not be associated with the susceptibility to PCOS.

• Clinical and Experimental Reproductive Medicine
• /
• v.40 no.2
• /
• pp.95-99
• /
• 2013

Objective: To evaluate the correlation between serum levels of anti-M$\ddot{u}$llerian 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 (${\geq}14mm$) 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.

• Clinical and Experimental Reproductive Medicine
• /
• v.43 no.4
• /
• pp.207-214
• /
• 2016

Objective: This study aimed to determine the threshold of $anti-M{\ddot{u}}llerian$ hormone (AMH) as predictor of follicular growth failure in polycystic ovary syndrome (PCOS) patients treated with clomiphene citrate (CC). Methods: Fifty female subjects with PCOS were recruited and divided into two groups based on successful and unsuccessful follicular growth. Related variables such as age, infertility duration, cigarette smoking, use of Moslem hijab, sunlight exposure, fiber intake, body mass index, waist circumference, AMH level, 25-hydroxy vitamin D level, and growth of dominant follicles were obtained, assessed, and statistically analyzed. Results: The AMH levels of patients with successful follicular growth were significantly lower (p= 0.001) than those with unsuccessful follicular growth ($6.10{\pm}3.52$ vs. $10.43{\pm}4.78ng/mL$). A higher volume of fiber intake was also observed in the successful follicular growth group compared to unsuccessful follicular growth group (p= 0.001). Our study found the probability of successful follicle growth was a function of AMH level and the amount of fiber intake, expressed as Y =-2.35+($-0.312{\times}AMH\;level$)+($0.464{\times}fiber\;intake$) (area under the curve, 0.88; 95% confidence interval, 0.79-0.98; p< 0.001). Conclusion: The optimal threshold of AMH level in predicting the failure of follicle growth in patients with PCOS treated with CC was 8.58 ng/mL.

• Clinical and Experimental Reproductive Medicine
• /
• v.41 no.1
• /
• pp.29-32
• /
• 2014

Objective: To investigate the causes of amenorrhea in Korean women. Methods: Medical records from 1,212 women with amenorrhea who visited the Department of Obstetrics and Gynecology, Asan Medical Center, between January 1989 and December 2011 were retrospectively reviewed. Amenorrhea was categorized as either primary or secondary. Results: Primary amenorrhea was identified in 132 of the patients (10.9%) and secondary amenorrhea in 1,080 (89.1%). The most frequent causes of primary amenorrhea were gonadal dysgenesis (28.0%, 37/132); Mayer-Rokitansky-K$\ddot{u}$ster-Hauser syndrome (20.0%, 27/132); and constitutional delay and androgen insensitivity syndrome (8.3%, 11/132; 8.3%, 11/132, respectively). Secondary amenorrhea was due to polycystic ovary syndrome (48.4%, 523/1,080); premature ovarian insufficiency (14.0%, 151/1,080); and nutrition-related hypogonadotropic hypogonadism (8.3%, 90/1,080). Conclusion: In this retrospective study, gonadal dysgenesis was the most common cause of primary amenorrhea and polycystic ovary syndrome was the most common cause of secondary amenorrhea in Korean women.

• Clinical and Experimental Reproductive Medicine
• /
• v.37 no.3
• /
• pp.261-266
• /
• 2010

Diagnosis of heterotopic pregnancy could be delayed because of insufficient clinical symptoms. Many clinician mistook the symptoms associated with ectopic pregnancy for the symptoms of complicated normal intrauterine pregnancy. The incidence of heterotopic pregnancies has been increased because of the use of various ovulation induction and assisted reproductive technologies. We experienced a case of bilateral tubal pregnancies and intrauterine twin pregnancy in polycystic ovary syndrome woman conceived after ovulation induction by clomiphene citrate. We report this case with a brief review of the literatures.

• Clinical and Experimental Reproductive Medicine
• /
• v.38 no.1
• /
• pp.42-46
• /
• 2011

Objective: This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). Methods: We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, menstrual status from 117 women with PCOS. Statistical analysis was performed with chi square and t-test, p-value<0.05 was considered as statistically significant. And receiver operating characteristic curve was used to find predictable clinical factors for endometrial disease and to decide the cuff off values. Results: In 117 women with PCOS, endometrial histologic profiles are as follows: proliferative phase in 90 women (76.9%), endometrial hyperplasia in 25 women (21.4%), and endometrial cancer in 2 women (1.7%). Of 25 women with endometrial hyperplasia, simple hyperplasia without atypia, complex hyperplasia without atypia and complex hyperplasia with atypia were diagnosed in 15 (12.8%), 6 (5.1%), 4 (3.4%) women, respectively. Age and endometrial thickness were significantly related with endometrial disease, p=0.013 and p=0.001, respectively. At the cut off level of 25.5 years in age, sensitivity and specificity predicting for endometrial disease were 70.4% and 55.6%, respectively (p=0.023). At the cut off level of 8.5 mm in endometrial thickness, sensitivity and specificity were 77.8% and 56.7%, respectively (p=0.000). Conclusion: In women with PCOS, the incidence of endometrial hyperplasia and cancer were 21.4% and 1.7%. The age and endometrial thickness may be used as clinical determining factors for endometrial biopsy.

• Clinical and Experimental Reproductive Medicine
• /
• v.38 no.2
• /
• pp.98-102
• /
• 2011

Objective: To investigate the effects of pioglitazone on controlled ovarian stimulation (COS), IVF outcomes, and follicular fluid (FF) cytokine concentrations in patients with polycystic ovary syndrome (PCOS). Methods: Eighty-six infertile patients with PCOS resistant to clomiphene citrate were randomized to receive pioglitazone (30 mg/day) or placebo on the starting day of oral contraceptive (OC) pretreatment, followed by an IVF protocol using a GnRH antagonist. Pioglitazone or placebo was administered once daily from the starting day of OC to the day of hCG injection. Results: Total dose and days of recombinant follicle-stimulating hormone administered, and the numbers of retrieved and mature oocytes, were significantly lower in the pioglitazone group than in the control group. FF tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) concentrations at oocyte retrieval were also significantly lower in the pioglitazone group. The clinical pregnancy rate was higher and the incidence of severe ovarian hyperstimulation syndrome was lower in the pioglitazone group, but the differences were not statistically significant. Conclusion: Pioglitazone reduces FF TNF-${\alpha}$ and IL-6 levels, and may improve ovarian response to COS in patients with PCOS.

• Clinical and Experimental Reproductive Medicine
• /
• v.44 no.3
• /
• pp.146-151
• /
• 2017

Objective: To identify differences in the expression of the genes for peroxisome proliferator-activated receptor $(PPAR)-{\gamma}$, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$ in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Methods: Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. Results: There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. $PPAR-{\gamma}$ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p= 0.034 and p= 0.018, respectively), but the expression of IL-6 and $TNF-{\alpha}$ mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the $PPAR-{\gamma}$, COX-2, IL-6, and $TNF-{\alpha}$ mRNA levels. Conclusion: Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of $PPAR-{\gamma}$ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.