Study Of Inhibin-B And Other Predictors Of Clinic Markers Of Ovarian Reserve And IVF Outcome

Objective:The result of Controlled Ovarian Hyperstimulation(COH) results from ovarian response in in vitro fertilization-embryo transfer(IVF-ET).So it is important to accesses the ovarian reserve.The study is to compare the basal levels of INH-B in serum and in follicular fluid,the basal levels of the follicle stimulating hormone (FSH),luteinizing hormone(LH),the ratio of the follicle stimulating hormone/ luteinizing hormone (FSH/LH) ,estradiol(E₂) in serum,serum estradiol(E₂) and endometrial thickness on the day of HCG administration in controlled ovarian hyperstimulation cycle ,the female age,the total number of antral follicles(2-9mm in diameter) by viginal ultrasound ,the total dose and the initiating dose of the gonadotropin(Gn) of the normal response group and the low response group ,the pregnant group and the nonpregnant group who had undergone IVF-ET or ICSI, to identify and quantify these kinds of predictors of ovarian response and the IVF outcome. To select the better predictors to guide therapy in IVF.Methods:Retrospective study 101 women who had undergone IVF-ET or ICSI in the reproductive medical center of Tianjin Medical University General Hospital from Mar 2008 to Nov 2008 because of fallopiantubal factors,male factors or unknown factors.The rage of the patients' age was 24-45 yers old. The patients all undergone the first COH cycle.COH Protocol:Apply Gonadotropin Releasing Hormone (GnRHa),Gonadotropin(Gonal-F,u-FSH),Human Menopausal Gonadotropin (HMG), Human Chorionic Gonadotropin(HCG).Lab Analysis: (1) INH-B assay:The INH-B levels in serum and follicular fluid were tested by Enzyme linked Immunoabsorbent Assay.(2) Hormone assay:The hormones including FSH,LH and E₂ in the serum were examined by CLIA.(3)Ultrasound measurement:The number of follicles 2-9 mm in diameter was detected before the administration of gonadotropins by transvaginal ultrasound, and endometrial thickness on the day of HCG administration in controlled ovarian hyperstimulation cycle.Result: 1)The levels of INH-B in serum and in follicular fluid were compared between the normal response group and the low response group,the pregnant group and the nonpregnant group.The levels of serum INH-B were significantly higher in the normal response group compared with the low response group (348.41±71.55pg/ml vs 266.90±33.67pg/ml, P<0.01);The levels of serum INH-B in the pregnant group were higher than that in the nonpregnant group.There were significant differences between them( 356.36±76.59pg/ml vs 306.38±64.73pg/ml, P<0.01);The levels of INH-B in follicular fluid in the normal response group and in the pregnant group were higher than that in the low response group and in the nonpregnant group (2313.06±294.45pg/ml vs 1712.70±258.53pg/ml, P <0.01 ;2303.92±360.23pg/ml vs 2041.03±384.57pg/ml, P＜0.01) ;2) The levels of FSH,LH,E₂,the ratio of FSH/LH in serum,E₂ in the serum on the day of HCG administration were compared between the normal response group and the low response group,the pregnant group and the nonpregnant group;The mean levels of FSH were significantly lower in the normal response group(5.69±2.01mIU/ml)compared with the low response group(8.05±1.01mIU/ml, P<0.01). The ratio of FSH/LH and the levels of basal E₂ in serum were lower in the normal response group compared with the low response group(1.83±0.93 vs 3.00±1.16, P<0.01; 28.27±19.24pg/ml vs 39.99±23.34pg/ml,P<0.05, respectively) ,while the levels of E₂ on the day of HCG administration in serum were higher in the normal response group compared with the low response group(2835.70±1541.98pg/ml vs 1428.20±615.11 pg/ml, P<0.01); While the levels of LH in serum were not significantly different between the normal response group and the low response group (P>0.05) ;The levels of FSH were significantly lower in the pregnant group compared with the nonpregnant group(5.62±1.76mIU/ml vs 6.81±2.12mIU/ml, P<0.05); The ratio of FSH/LH is significantantly lower compared with the nonpregnant group(1.83±0.74 vs 2.37±1.26, P＜0.01); the levels of E₂ on the day of HCG administration in serum in the pregnant group were significantly higher than the nonpregnant group (3171.99±1660.48pg/ml vs 1999.83±1191.48 pg/ml, P<0.01);While the levels of basal E₂ in serum and LH were not significantly different between the pregnant group and the nonpregnant group(P>0.05);3)The female age,the total number of antral follicles by vaginal ultrasoundand and the endometrial thickness on the day of HCG administration were compared between the normal response group and the low response group,the pregnant group and the nonpregnant group.The female age in the normal response group and in the pregnant group was younger than that in the low response group and in the nonpregnant group respectively,(32.15±4.35years vs37.90±4.78years, P＜0.01; 31.22±3.80years vs 35.32±5.28years, P<0.01);The total number of antral follicles in the normal response group were significantly higher than these in the low response group(9.56±5.30 vs 4.80±3.02, P<0.01);The total number of antral follicles had no significant difference between the pregnant group and the nonpregnant group(P>0.05). The endometrial thickness on the day of HCG administration between the normal response group and the low response group had no significant difference(P >0.05).And it also had no significant difference between the pregnant group and the nonpregnant group(l1.34±2.02mm vs 10.24±2.11mm, P>0.05)4) The initiating dose of the gonadotropin in the normal response group and in pregnant group were significantly lower than that in the lower response group and nonpregnant group(3.51±1.65 vs 5.50±1.83, P<0.05;3.42±1.65 vs 4.48±1.97, P<0.01,respectively) ; The total dose of the gonadotropin had no significant difference between the normal response group and the low response group (P>0.05).The total dose of the gonadotropin had no significant difference between the pregnant group and the nonpregnant group(P>0.05).5)The number of retrived oocytes,the rate of fertilization advanced embryos and pregnancy were compared between the normal response group and the low response group: The number of retrived oocytes in the normal response group was higher than that of the low response group(12.83±5.85 vs 2.20±0.76,P＜0.01); The rate of fertilization and pregnancy in the normal response group was significantly higher than that of the low response group(0.6609±0.18 vs 0.5667±0.24, P<0.05;42.3% vs 20.0%, P＜0.05); while the rate of advanced embryos had no significant difference between the normal response group and the low response group (P>0.05) ; The number of retrived oocytes,the rate of fertilization and advanced embryos were compared between the pregnant group and the nonpregnant group : The number of retrived oocytes and the rate of fertilization and advanced embryos were significantly higher in the pregnant group than that of the nonpregnant group respectively(12.17±6.97 vs 8.29±6.55, P<0.01;0.6798±0.13 vs 0.6070±0.23, P<0.05;0.7181±0.22 vs 0.5920±0.33, P<0.05);6) The levels of INH-B in serum was correlated positively with that in follicular fluid(r=0.764, P =0.000);the levels of serum FSH was correlated negatively with the levels of serum INH-B(r=-0.409, P=0.000); The levels of INH-B in serum was correlated negatively with the age(r=-0.507, P=0.000) ;The levels of INH-B in serum and that in follicular fluid were correlated positively with the number of retrived oocytes (r=0.532,P =0.000;r=0.577, P=0.000);The levels of serum FSH and the ratio of FSH/LH were correlated positively with the female age(r=0.652, P=0.000; r=0.530, P=0.000), Tthe antral follicles count was correlated negatively with the age(r=-0.483., P=0.000). The total dose and the initiating dose of the gonadotropin were correlated positively with the age respectively(r=0.479,P=0.000;r=0.827,P=0.000).7)To determine the value of predictors of ovarian response and IVF outcome.As an independent predictor for the ovarian response,the result of OR of the basal levels of FSH,the ratio of FSH/LH, INH-B in serum and in follicular fluid,the female age, antral follicles count have statistical significance(P<0.05).As an independent predictor , antral follicles count was the best predictor.when all factors were considered, antral follicles count and the levels of INH-B in serum have statistical significance as the predictors of ovarian response(P<0.05),and the levels of INH-B in serum was better. As an independent predictor for the IVF outcome, the result of OR of the female age, FSH,the ratio of FSH/LH,the levels of INH-B in serum and in follicular fluid, E₂ on the day of HCG administration in serum have statistical significance(P<0.05). As an indepent predictor , the levels of INH-B in follicular fluid was the best predictor. when all factors were considered, the female age and the levels of INH-B in follicular fluid and that in serum have statistical significance as the predictors of IVF outcome (P<0.05),and the levels of INH-B in serum and that in follicular fluid was better.Conclusions:1.As an independent predictor for the ovarian reserve the level of serum AFC was the best predictor. When all factors were considered,AFC and the levels of INH-B in serum have the statistical significance as predictors of ovarian reserve(P<0.05).the levels of INH-B in serum is a better predictor than AFC. 2.As an independent predictor for the outcome of IVF,the levels of INH-B in follicular fluid was the best predictor.When all factors were considered,the female age ,INH-B in serum and that in follicular fluid have statistical significance as predictors for the outcome of IVF(P＜0.05).The levels of INH-B in serum and that in follicular fluid are better than the female age.