Correlation Of Serum Anti-M(u|¨)llerian Hormone Concentrations With Assisted Reproduction Outcome In Polycystic Ovary Syndrome Patients And Altered AMH MRNA Expression On Granulosa Cells In Different Ovarian Reserve Status

Chaper1Correlation of serum Anti-Mullerian hormone concentrations on day3of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patientsObjective:To investigate whether serum Anti-Mullerian hormone (AMH) on day3could predict controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome.Methods:A total of164PCOS patients undergoing their first IVF treatment cycle were prospectively included. On cycle day3before the start of GnRH analog medication, serum levels of estradiol, FSH, LH, testosterone and insulin was determined. AMH was determined on the day in which pituitary desensitization was confirmed, before starting gonadotrophins treatment (day3). The controlled ovarian stimulation and clinical outcomes for the study population were divided according to the <25th,25to75th, or>75th percentile of serum day-3AMH.Results:Estradiol levels on hCG day and the number of retrieved oocytes significantly increased with increasing serum AMH levels, while total consumption of gonadotropin dose showed a significant decrease(P <0.05). Fertilization rate and the number of good quality embryos were comparable among the low, average and high groups(P>0.05). embryo implantation rates in the high AMH group was significantly inferior to those with low and average AMH concentration (27versus48.8and50%, P<0.01). Clinical pregnancy rates was lower in the high AMH group than that of the low and average group (45.9versus65and66.7%, P=0.09), but this difference was only close to statistical significance. In addition, ordinal regression analysis indicated that LH level was the only independent predictor of embryo implantation rates (P=0.017).Conclusions:In PCOS women, AMH levels on day3of the IVF stimulation cycle positively predict ovarian response to gonadotrophins. However, the women with high AMH levels had a significantly decreased IR, which may be due to remarkably increased LH concentrations. Chaper2The use of Anti-Mullerian Hormone in predicting ovary response to CC+HMG ovulation induction treatment in women with polycystic ovary syndromeObjective:1. To evaluate whether the baseline serum Anti-Mullerian hormone (AMH) has a role to predict ovulation induction by clomiphene citrate (CC) and human menopausal gonadotropin (HMG) in PCOS patients.2. To describe changes of Anti-Miillerian hormone plasma levels during CC+HMG ovulation induction treatment in women with PCOS.Method:A total of52women with PCOS received01using CC and HMG were subdivided into responsive and non-responsive groups, to compare differences in daseline serum AMH between the two groups. No follicle reached a diameter of≥10mm on day21of the menstrual cycle was considered non-responsive to OI. In addition, serum levels of FSH, AMH, LH and E2were assessed on day3and21(no response group) or the day administrated of HCG (response group). Meanwhile, the number of2-5mm antral follicles were estimated using ultrasound.Results:1. Serum AMH levels were significantly lower in women with PCOS who responded to CC+HMG than those who did not (8.19±2.91VS12.09±5.06, P<0.01). A value of9.44ng/ml AMH could be used to predict response to CC+HMG in women with PCOS (sensitivity66.7%, specificity74.4%).2. Mean AMH values decreased from8.19±2.91ng/ml to3.25±1.36ng/ml from D3to HCG day in responsive groups, and dreased from12.09±5.06ng/ml to7.52±1.23ng/ml from D3to21in non-responsive groups. The signitcant positive correlation were found between the decline in AMH and the increase in FSH plasma levels and the decrease in number of2-5mm antrol follicles both in response and non-response groups. The decrease in AMH was positively associated with increased estradiol levels in responsive group, but not in non-responsive cases.Conclusions:Serum AMH can be used to predict ovary response to OI in PCOS patients. The present study demonstrated that AMH plasma levels declined during OI treatment. The dreased AMH may be associated with reduced small antrol follicles and increasd FSH. Chaper3Comparison of hormonal and metabolic characteristics and ovary response to ovulation induction in amenorrheic and oligomenorrheic women with PCOSObjective:To compare differences in endocrine and metabolic characteristics and response to ovulation induction (0I) treatment between oligomenorrheic and amenorrheic women with polycystic ovary syndrome (PCOS).Methods:154infertile PCOS patients presenting with oligomenorrhea or amenorrhea were retrospectively analysed, the differences in endocrine and metabolic characteristics and01outcome parameters between oligomenorrheic and amenorrheic women were compared.Results:Total follicle count, serum levels of total testosterone (T) and luteotropic hormone (LH) and insulin resistant index (HOMA-IR) were significantly higher in amenorrheic patients compared with oligomenorrheic women(P<0.05). There were no differences in age, body mass index (BMI), follicle stimulating hormone (FSH), glucose and insulin levels and lipid level between groups. During clomiphene citrate and HMG OI, The ovulation rate in amenorrheic group was significantly inferior to oligomenorrheic group (84.62VS96.8%, P<0.01). The duration to reach a dominant follicle, the cycles need to add HMG and the total dose of HMG were higher in amenorrheic patients compared with oligomenorrheic women. No significant differences were found between the two groups in the total number of mature follicles, estradiol level and endometrial thickness on day of HCG administration and pregnancy rate.Conclusion:The degree of cycle irregularity might be a simple and effective clinical parameter to estimate the degree of metabolic and endocrine disorders and response to01. Chaper4Ovarian reserve status is associated with altered AMH mRNA expression in granulosa cellsObjective:To compare whether the synthesis of anti-Mullerian hormone (AMH) by granulose cells was different among patients with polycystic ovary (PCO), normal ovarian reserve (NOR) and diminished ovarian reserve (DOR).Methods:Patients with PCO (n=30), NOR (n=20) and DOR (n=17) undergoing controlled ovarian hyperstimulation during a cycle with in vitro fertilization were included in this study. Granulosa cells were obtained from follicular aspirates during oocyte retrieval. The quantitative real-time PCR was undertaken to evaluate the expression of AMH and AMHR-II mRNA among PCO, NOR and DOR groups. AMH levels in follicle fluid among the three groups were measured by ELISA. Women with PCO including16anovulatory (anov) PCO and14ovulatory PCO, we further compared the genetic difference among anov PCO, ovulatory PCO and NOR patients.Results:The AMH and AMHR-Ⅱ mRNA were all expressed on the granulosa cells of the three groups. AMH mRNA levels in granulose cells of PCO, NOR and DOR were0.82±0.44,0.57±0.25and0.26±0.13respecticely, the difference was statistically significant (P<0.001). The expression of AMH mRNA level was significantly higher in PCO than in NOR groups (P<0.01), which was higher in NOR group than this in DOR (P<0.05).AMH mRNA levels in anov PCO was1.01±0.52, significantly higher than ovulatory PCO0.62±0.19(P<0.05) and NOR group0.57±0.25(P<0.01). The expression of AMH mRNA in ovulatory PCO was higher than this in NOR, but this difference was no statistical significance. There was no difference in the expression of AMHR-II mRNA between the groups.Conclusion:The expression of the AMH mRNA on granulose cells among patients with PCO, NOR and DOR was different. When compared with NOR group, the expression of AMH mRNA level was significantly decreased in patients with DOR, AMH levels in follicle fluid were also declind. Whereas the expression of AMH mRNA is relative higher in anov PCO than in those with ovulatory PCO and NOR, which may be associated with follicle arrest in women with anov PCO.