Objective To explore the effect of progestin-primed ovarian stimulation in combination with clomiphene citrate on the clinical outcome of normalovulatory women in controlled ovarian stimulation(COS)for IVF/ICSI cycle.Methods1.A prospective randomized controlled trial was performed in 242 patients with normal ovarian reserve from June 2015 to October 2015.They were allocated into two groups by simple randomization: group A(HMG+MPA+CC,n=121)or group B(HMG+MPA,n=121).In group A,clomiphene citrate(50mg/d)in combination with h MG(150IU)and MPA(10mg/d)were applied simultaneously from cycle day 3.Equal starting doses of h MG and MPA were administered for group B.Compare and analysis the endocrine characteristic of progestin-primed ovarian stimulation in combination with clomiphene citrate and progestin-primed ovarian stimulation by dynamicly Monitoring the changes of hormones during ovarian stimulations.The number of oocytes retrieved,the doses and durations of Gn administered,the number of mature oocytes,the number of fertilization and cleavage,and pregnancy outcomes from FETs were compared between the two groups.2.A comparation in subgroups based on the serum LH values,serum P values on the trigger day in order to evaluate the effect of LH,P levels on treatment outcomes.In the control group,correlated and regression analysis was done between LH and E2 levels on the trigger day,and compared between subgroups based on the serum E2 values on the trigger day in order to explain the differences between LH subgroups in the control group3.Both groups were divided into three subgroups according to the number of oocytes retrieved,Lower ovarian response(No.of oocytes retrieved≤5);Normal ovarian response(No.of oocytes retrieved: 6-20);Higher ovarian response(No.of oocytes retrieved≥20).Compare proportions of different ovarian response and then evaluate the the effect of two protocol.Results1.No statistically difference was found in the number of oocytes retrieved(9.1±5.8 vs.9.8±8.1,p>0.05)and viable embryos(3.6±2.7 vs.3.6±3.4,p>0.05)between the two groups.Group A received significantly lower Gn dose(1349.4±189.4IU vs.1463.4±364.6 IU,p<0.01),and shorter Gn duration(8.9±1.0 days vs.9.3±1.9 days,p<0.05).In group A,LH values on menstruation 9-10 days and on the trigger day during the stimulation were no significant differences compared with the basic level(p>0.05).While in group B,LH values decline progressively,and LH value on the trigger day was significantly lower compared with the basic level(p<0.05).LH value in group A was higher than in group B throughout the process of ovulation(P<0.01).P value and E2 value on the trigger day were higher in group A than group B.Other parameters such as the number of mature oocyte,fertilization,cleavage were similar(p>0.05).During the following up of FET,from June 2015 to March 2016,a total of 174 women completed 189 FET cycles,no significant difference was found in the clinical pregnancy rate(62.63%(62/99)vs.61.11%(55/90),p>0.05)and implantation rate(47.22%(85/180)vs.46.84%(74/158),p>0.05)between the two groups.2.No statistically difference was found in the number of oocytes retrieved,viable embryos,Gn dose and duration among three subgroups devided by LH values on the trigger day from group A;In group B,Except no statistically difference was found in the number of viable embryos,lower LH subgroup tend to retrieve more oocytes and need more Gn dose and duration than higher LH subgroup.Three subgroups were devided by P values on the trigger day from both groups.Higher P subgroup tend to retrieve more oocytes,need more Gn dose and duration and have more viable embryos than lower P subgroup in both groups.In the control group,there was a negative correlation between LH and E2 levels on the trigger day,the correlation coefficient was-0.31,and the regression coefficient was 0.09.The changing trend among E2 subgroups were similar to P subgroups.3.The proportion of normal ovarian response was significantly higher in group A than group B(65%(79/121)vs.50%(60/121),P<0.05)Conclusion1.Clomiphene citrate does not damage Progesterone’s anti-positive feedback,ppos in combination with clomiphene citrate can effectively prevent premature LH surge;LH values of ppos in combination with clomiphene citrate change smoothly during ovarian stimulation.2.PPOS in combination with clomiphene citrate decrease Gn dosage as well as its duration compared with ppos.3.PPOS in combination with clomiphene citrate can improve ovarian response.4.We were able to get viable embryos from ppos in combination with clomiphene citrate and obtain satisfactory clinical pregnancy rate and embryos implantation rate in the subsequent FET cycles. |