Comparative Study Of Various Ovulation Protocol In IVF/ICSI Patients With Poor Ovarian Response

Ovarian hyporesponsiveness(POR)is a pathological condition in which the response of exogenous gonadotropin(Gn)to ovarian stimulation is poor.It often occurs in older people with poor ovarian reserve and past response to conventional ovarian stimulation.The main manifestations are the high rate of cancellation of the cycle,the number of oocytes retrieved from the oocyte retrieval cycle,the poor oocyte quality,and the small number of transplantable embryos[1].Some literatures have shown that [2],the incidence of POR in the process of assisted reproduction and ovulation induction accounts for about 9%~24%,and it is increasing year by year with the passage of time.In China,with the liberalization of national fertility policies,more and more women of childbearing age are seeking assisted reproductive technology(ART)to help pregnant women.This group of people also shows POR in ART treatment.ART treatment of POR patients has become a severe challenge in the field of reproductive medicine.This study reviewed retrospectively 1717 cycles of POR patients undergoing in vitro fertilization-embryo transfer(IVF-ET)using different ovulation-promoting programs in our hospital to compare the clinical,laboratory,and pregnancy outcomes of different ovulation-promoting programs.,Provides evidence for in vitro fertilization(IVF)/intravesicular intracytoplasmic sperm injection(ICSI)selection for ovulation induction in POR patients.Objective This study retrospectively analyzed 1743 cycles of POR patients undergoing in vitro fertilization-embryo transfer(IVF-ET)using different ovulation-promoting protocols in our hospital and was divided into two parts.The first part includes three ovulation-promoting protocols: clomiphene(CC)+ letrozole(LE)micro-stimulation,mesenteric progesterone(MPA)micro-stimulation and Gn RH antagonist protocols;part two includes two ovulation-promoting protocols,natural cycles,Luteal-phase ovarian stimulation protocol after natural cycle oviposition or ovulation.A comparison of the clinical,laboratory and pregnancy outcomes of the two components was performed to provide the basis for the selection of appropriate ovulation-promoting regimens for IVF/ICSI.Materials and Methods1 Patient(s)1.1 The first part: clomiphene + letrozole micro-stimulation,mesenteric progesterone micro-stimulation and antagonists protocolsThe clinical data of 1453 cycles of POR with IVF / ICSI in our hospital from October 2015 to December 2016 were analyzed retrospectively.The patients in the clomiphene(CC)+ letrozole(LE)micro-stimulation protocol(group CC+LE,683cycles),mesenteric progesterone(MPA)micro-stimulation protocol(group MPA,503cycles),and Gn RH antagonist protocol(group Gn RHA 267 cycles).Ovulation was routinely performed with IVF / ICSI.1.2 The second part: natural cycles,Luteal-phase ovarian stimulation protocol after natural cycle oviposition or ovulationThe clinical data of 290 cycles of POR with IVF / ICSI in our hospital from June2016 to October 2017 were analyzed retrospectively.The patients in the natural cycle protocol(162 cycles),Luteal-phase ovarian stimulation protocol after natural cycle oviposition or ovulation(group Luteal-phase ovarian stimulation,128 cycles).Ovulation was routinely performed with IVF / ICSI.1.3 Inclusion criteria:(1)The POR criteria are based on the diagnostic criteria of ESHRE 2011 in Bologna[3]:(1)age ? 40 years or Other risk of presence of POR(eg chromosomal abnormalities,pelvic infections,history of ovarian cancer surgery and chemotherapy);(2)previous POR history: conventional ovarian hyperstimulation oocyte number ?3;(3)ovarian reserve abnormalities: such as antral follicles <5-7 or anti-Mullerian hormone(AMH)<0.5-1.1 ng / ml.Meet the conditions of three of the two or meet the conditions(2)twice can be diagnosed as POR;(2)causes of infertility mainly fallopian tube and / or male factors to meet the line IVF / ICSI-ET Pregnancy indications;(3)Egg-collecting cycles are all frozen.1.4 Exclusion criteria:(1)patients with IVF / ICSI contraindications;(2)endocrine and metabolic diseases;(3)affect the outcome of IVF pregnancy related diseases,such as: untreated tubal hydronephrosis,uterine fibroids ?4cm,severe adenomyosis,?,?endometriosis,untreated endometrial lesions,etc.2 Design The age,infertility,body mass index(BMI),and AFC of the enrolled patients were collected.The basal endocrine levels of all enrolled patients and serum LH and serum E2 levels on the trigger day were measured by chemiluminescence.The patients were analyzed statistically.The amount of Gn used,days of Gn,number of oocytes retrieved,number of embryos available,rate of good embryos,rate of non-obtained eggs,advance ovulation rate,thickness of the intima of transplanted day,number of transplanted embryos,rate of embryo implantation,clinical pregnancy rate,early abortion rate,Cumulative pregnancy rate,live birth rate,etc.3 Statistical method SPSS21.0 software package was used for statistical analysis.In the comparison between the three groups,the measurement data that meet the normal distribution are expressed as mean±standard deviation(x±s),and analysis of the variance of the row-wise factor.For the comparison between the three groups,if there is a homogeneity of variance,use the LSD method.If the variance is not uniform,use the Tamhanes,s T2 method.Count data is expressed in terms of rate(%),using the row x column c2 test.For the comparison between the two groups,the measurement data that meet the normal distribution are expressed as mean±standard deviation(x±s).Two independent sample t-tests are used,and the count data are expressed in terms of percentage(%).The four-tabulation c2 test is used.Measured data with non-normal distribution are expressed in median(interquartile range),using non-parametric Mann-Whitney U test and Kruskal-Wallis H test.P<0.05 was considered statistically significant.Results The first part:(1)There was no significant difference in age,infertility years,BMI,AFC,basal FSH,basal LH,basal E2 and AMH between the CC + LE protocol?MPA protocol?Gn RHA protocol(P > 0.05).(2)The Gn consumption [(2586.05±740.36)IU] and Gn days [(9.28±2.25)d] in the CC+LE group were lower than those in the MPA group [(2741.25±857.53)IU,(9.84±2.91)d](P=0.003,P =0.001)and Gn RHA group [(2769.78±710.49)IU,(9.91±2.77)d](P=0.001,P=0.004);The number of retrieved eggs in CC+LE group[(3.56±2.68)n] is higher than MPA Group [(3.05±2.56)n](P=0.001).(3)The LH value of the trigger day in the CC+LE group [(7.83±2.42)m IU/L] was higher than that of the MPA group [(3.76±1.5)m IU/L](P<0.001)and the Gn RHA group [(2.68±1.12)m IU/L].(P<0.001),but there was no significant difference in the rate of premature ovulation between the CC+LE group and the other two groups(P>0.05).The unobtained rate in the CC+LE group [4.4(30/683)] was lower than in the MPA group [7.8(39/503)](P=0.008)and the Gn RHA group [9.4(25/267)](P=0.015,P=0.003).(4)The trigger day estrogen level in the Gn RHA group [(1679.55±8363.71)ng/L],the number of retrieved eggs [(4.33±2.71)n],and the number of embryos available[2(1,3)n] were higher than CC+LE Group [(1215.81±885.07)ng/L,(3.56±2.68)n,1(1,2.25)n](P<0.001)and MPA group [(1182.37±817.23)ng/L,(3.05±2.56)n,1(0,2)n](P<0.001).(5)In the CC+LE group,MPA group,Gn RHA group,There was no significant difference in endometrial thickness,number of embryos transplanted,embryo implantation rate,and early miscarriage rate in the three groups of frozen embryo transfer(P>0.05).The clinical pregnancy rates of CC+LE,MPA,and Gn RHA were27.6%,24.8%,and 30.6%,respectively.The cumulative pregnancy rates were 35.6%,30.8%,and 38.4%,and the live birth rate was 23.0% and 20.6%,respectively.26.8%,there was no statistical difference between the groups(P>0.05).The second part:(1)There was no significant difference in age,infertility years,BMI,AFC,basal FSH,basal LH,basal E2 and AMH between the natural cycle?Luteal-phase ovarian stimulation groups(P > 0.05).(2)Luteal-phase ovarian stimulation group trigger day E2 [(1046.84±725.70)ng/L],number of retrieved eggs [(2.6±1.1)n],number of embryos available [1(0,2)n)is higher than that of group natural cycle [(351.94±179.75)ng/L,(0.8±0.3)n,0(0,1)n](P<0.001).The rate of high quality embryos in group Luteal-phase ovarian stimulation [47.9(90/188)] was higher than that in group natural cycle [31.5(23/73)](P=0.017).(3)There was no significant difference in the rate of unobtained eggs between the two groups(P>0.05);the trigger day LH in group Luteal-phase ovarian stimulation[(3.39±1.04)m IU/L] and the rate of advance ovulation [0.8(1/128)] were lower than those in group natural cycle [(14.45)±4.23)m IU/L,16.0(26/162)](P<0.001).(4)The clinical pregnancy rates in group Luteal-phase ovarian stimulation and group natural cycle were 26.8% and 20.0%,respectively.The early abortion rates were 13.3% and 16.7%,and the cumulative pregnancy rates were 28.3% and 20.0%,respectively.There was no significant difference between the groups(P>0.05).Conclusions(1)The effect of Gn RHA,CC,MPA are similar,There was no significant difference in the rate of early ovulation between the three groups,illustrate CC,MPA and Gn RHA both had significant down-regulation effect.(2)For POR patients,the number of oocytes retrieved and the number of available embryos of the Gn RH antagonist protocol may higher than the micro-stimulation protocol.(3)For patients with POR,Luteal-phase ovarian stimulation protocol may have better eggs retrieved,the number of available embryos and the quality embryo rate.(4)The Luteal-phase ovarian stimulation protocol after natural cycle oviposition or ovulation is feasible.