The Application Effect Of Three Different Ovulation Induction Programs Which Are Used In Poor Ovarian Respondents In IVF Cycles And Their Impact On The Levels Of GDF-9 And BMP-15 In Serum And Follicular Fluid

Background and ObjectiveAbout nine to twenty four percent of patients who undergo in vitro fertilization-embryo transfer treatment will show poor response to controlled ovarian hyperstimulation.Poor responsders always has a lower rate of pregnancy and a higher rate of cycle cancellation.It is still a handicap about how to lower the cycle cancellation rate and improve ovarian response and pregnancy rate in poor responsders and it is the research focus in reproductive field.Researchers try different proposals to improve ovarian response of poor responsders and pregnancy rate.but there is no distinct effect.Growth differentiation factor-9(GDF-9) and growth differentiation factor-9B (GDF-9B)/bone morphogenetic protein-15(BMP-15) are two new members of transforming growth factorβ(TGF-β) superfamily discovered in recent years.They are glycoproteins synthesized and secreted by oocyte. GDF-9 and GDF-9B/BMP-15 with similar structures play an important role in boosting growth and development of early follicles.and they maintain ovarian productive and endocrine function collaboratively.Researchers pay more and more attention to the role of GDF-9 and BMP-15 in the process of in vitro fertilization-embryo transfer treatment.The main purpose of this study is to probe the application effect of three different ovulation induction programs which are used in poor ovarian responders in IVF cycles and their impact on the levels of GDF-9 and BMP-15 in serum and follicular fluid,and ultimately looking for a saving and effective controlled ovarian hyperstimulation proposal for poor responsders.Materials and methodsAll the eighty-nine objects who underwent IVF/ICSI and predicted a low response to controlled ovarian hyperstimulation in the Reproductive Center of Third Affiliated Hospital of Zhengzhou University between November 2009 and May 2010 are randomly assigned into three groups.There are thirty-three cases in group A (GnRH-a flare-up group), thirty-one in group B (GnRH antagonist group) and twenty-five in group C (Microstimulation group).Detect the levels of GDF-9 and BMP-15 in serum on HCG administration day and follicular fluid on oocyte retrieval day of all patients by enzyme-linked immunosorbent assay (ELISA) and detect endocrine levels on D2-5 of menstrual cycle and HCG administration day of all patients by chemiluminescence.Analyze the difference of Gn dose,Gn days, the number of oocytes, the rate of high quality embryos, the fertilization rate, the cleavage rate,the clinical pregnancy rate.the abortion rate and the implantation rate in the three different groups.Results1. The total dose of Gn.Gn days.the number of oocytes.the rate of high quality emb-ryos and cycle cancellation rate are 32.68±10.5vs34.50±11.6vsl7.13±4.96;10.4±2.01vs10.5±2.53vs9.7±2.09;6.06±2.05vs6.33±2.77vs4.76±2.02;45.7%vs42.4% vs43.8%;9.1%vs6.5%vs8.0%.respectively.in the patients of A.B.C three groups. There is no significant difference in Gn days, the number of oocytes,cycle canc-ellation rate and the rate of high quality embryos among the three groups of group A,B and C (P>0.05); the total dose of Gn in group A and B are significantly higher than that in group C(P<0.05);2. The fertilization rate, the cleavage rate,the clinical pregnancy rate,the abortion rate and the implantation rate are 73.7%/75.2%/72.9%;88.3%/90.2%/89.7%; 28. 6%(8/28)/23.1%(6/26)/22.7%(5/22);25%(2/8)/16.7%(1/6)/20%(1/5)and19.12%/ 18.21%/19.03%, respectively,in the patients of A, B, C three groups. There is no significant difference in the fertilization rate, the cleavage rate, the clinical pregnancy rate,the abortion rate and the implantation rate among the three groups of group A,B and C(P>0.05).3. There is no significant difference in the concentrations of GDF-9 in serum and follicular fluid among the three groups of group A,B and C (P>0.05);the concentrations of GDF-9 in serum in the three groups are significantly lower than that in follicular fluid (P<0.05); the concentrations of BMP-15 in serum and follicular fluid in group C are significantly higher than that in Group A and B;the concentrations of BMP-15 in serum among the three groups of group A,B and C are significantly lower than that in follicular fluid (P<0.05)Conclusions1. GnRH-a flare-up protocol and GnRH antagonist protocol can achieve the same clinical application result in poor ovarian responders in in vitro fertilization;2. In poor ovarian responders, the minimal stimulation protocol with Letrozole combined with little gonadotropin can achieve the same approving clinical pregnancy rate to that of GnRH-a flare-up protocol and GnRH antagonist protocol; 3. In poor ovarian responders, the minimal stimulation protocol with Letrozole combined with little gonadotropin can lower the total dose of Gn and reduce the cost and economic burden of patients,but, it has a less number of oocytes retrieved;4. The concentrations of GDF-9 and BMP-15 in serum are significantly lower than that in follicular fluid,and, GDF-9 and BMP-15 are secreted by oocytes;5. There is no significant effect on the concentrations of GDF-9 in serum and follicular fluid in the three different ovulation induction protocols;6. The minimal stimulation protocol with Letrozole combined with little gonadotropin can significantly increase the concentrations of BMP-15 in serum and follicular fluid and finally improve the quality of oocyte.