Effect Of Different Follicular Distribution On The Day Of Hcg Injection And The Number Of Oocytes Retrieved On The Outcome Of IVF-ET/ICSI

Background and Objectives:Ovarian stimulation is a key step in assisted reproductive technology(ART),which aims to promote the development of multiple follicles,to obtain enough quality oocytes,thereby increasing the number of transplantable embryos and the rate of pregnancy.The use of new ovulation drugs and protocols makes the average number of oocytes received 12-15,known as controlled ovarian hyperstimulation(COH).However,COH has a risk of leading ovarian hyperstimulation syndrome(DHSS),which has attracted the attention of many scholars and prompted them to explore a more rational ovarian stimulation protocol.The idea of ovarian stimulation has evolved from "COH" to modern "controlled ovarian stimulation(COS)",that is,to reduce the use of ovulation drugs,get an appropriate number of quality oocytes,and reduce OHSS or other complications.In the process of ovarian stimulation,human chorionic gonadotropin(HCG)was injected to simulate the physiological luteinizing hormone pulse and induce the discharge of the first polar body of the oocyte to promote the maturation of the oocyte and the formation of corpus luteum,called HCG trigger.HCG trigger time directly affects the acquisition of high quality oocytes,which in turn affects ART outcomes.The best time for HCG injection is not uniform at home and abroad.Some scholars believe that the standard of HCG triggering is at least two dominant follicles with an average diameter of ?18 mm[1],and some scholars believe that at least three dominant follicles with an averaged diameter of ?17 mm[2].At present,the main criteria for domestic reproductive centers is based on the diamete of dominant folliculars combined with serum estradiol(E2),luteinizing hormone(LH)and progesterone(P)levels.However,in the process of ovarian stimulation,the development of every follicle is not consistent,and often showed in a particular queue with different diameter follicles.Some scholars have suggested that according to the development of a few mature follicles to determine the HCG injection timing is not appropriate.The number of oocytes retrieved is also an important indicator of ART outcomes.At present,there is no consensus on the definition of an appropriate number of oocytes retrieved and the effect on the outcome of ART.A number of studies have shown that in the fresh cycle,the best live birth rate was obtained when the number of eggs was 15,and the uptrend of the rates of live birth when the number of eggs was 16-20 was relatively smooth[4-6],and in different age groups,this trend can be observed[7,8].At present,the use of COS to reduce ovarian stimulation,in order to get a smaller number of oocytes,and reduce the number of embryo transfer,has been gradually accepted.Most of the studies at home and abroad still calculate the pregnancy rate in each transplant cycle[9-11].In addition to leading to the pursuit of pregnancy rates,such indicators still have statistical limitations,because in different embryos transplanting strategies,we can not know if after the use of the same stimulus in different patients,the cumulative pregnancy rate is different.With the development of embryonic freezing technology and the application of single embryo transfer,the chance of freeze-thaw embryo transfer is increased,and the cumulative birth rate(CLBR)is a better indicator of ART success rate[12,13].For couples who carry out IVF/ICSI,in order to reduce complications,the CLBR per stimulus cycle is more meaningful than live birth rates per transplant cycle.However,the calculation of CLBR which included the most appropriate parameters,the views are still inconsistent.Maheshwari A[14]argue that according to different study time limits and research purposes,different molecules and denominations can be selected,such as the number of live births/n start or egg cycle,number of live cycles/n transplant cycles and number of live births/n time periods.Based on the above analysis,this study retrospectively analyzed the effect of different follicular diameter distribution on IVF/ICSI outcome at HCG injection day.The CLBR of per oocytes retrieved cycle was used as a key index to evaluate the outcome of IVF/ICSI to explore drawing up protocols based on the number of oocytes retrieved.? Effect of different follicular distribution on the day of HCG injection on the outcome of IVF-ET/ICSIMethods:The aim of the study was to analyze the effect of ?16mm/?14mm follicles ratio on the day of human chorionic gonadotropin injection on the pregnancy outcome of IVF/ICSI so as to investigate the suitable timing for HCG trigger.Of the patients who underwent in vitro fertilization-embryo transfer/intracyroplasmic sperm injection(IVF-ET/ICSI)from January 1,2014 to December 31,2015 in our reproductive center,a total of 2 391 cycles using standard pituitary down-regulation protocol with GnRH-a were included.Patients were divided into three groups according to their?16mm/?14mm follicles ratio on the day of HCG administration:High proportion(>75%),Middle proportion(50%-75%)and Low proportion(?50%).The parameters of oocyte developmental and pregnancy outcome were compared among the three groups.Results:The number of oocyte retrieved in the high proportion group(9.43±4.36)is lower than that in minddle(11.00±4.28)and low proportion(12.62±5.28)groups(P<0.05),but the fertilization rate and the high-quality embryo rate were not different in the three groups.The 'freeze-all' embryo rate was significantly higher in the low proportion group(57.88%)than in the middle proportion group(43.38%)and the high proportion group(39.73%).There was no significant difference among the three groups in clinical pregnancy rate,multiple pregnancy rate,ectopic pregnancy rate and in the incidence of OHSS(P>0.05).The rate of abortion in the low proportion group(1.61%)is the lower than the middle and high proportion groups(10.48%Vs 15.17%,P<0.05).? Cumulative live birth rates per oocytes retrieved cycle:Evaluation of Clinical Outcomes of IVF/ICSIMethods:We strongly recommend the use of cumulative live birth rate(CLBR)to assess the clinical outcomes of IVF/ICSI,and explore the effect of the number of oocytes retrieved and the age of the patients on the CLBRs of IVF/ICSI to discuss the ovulation induction based on "Target oocytes number" Of the patients who underwent in vitro fertilization-embryo transfer/intracyroplasmic sperm injection(IVF-ET/ICSI)from January 1,2014 to December 31,2015 in our reproductive center,a total of 5 901 oocytes retrieved cycles were included.To analyze the clinical and laboratory parameters of different ovulation induction programs,and to compare the effects of different number of oocytes retrieved and the age of the patients on the CLBRs of each oocytes retrieved cycle.Results:The CLBRs of cycles with GnRH-agonist protocols was slightly higher than that of cycles with GnRH-antagonist protocols(71.5%Vs 69.6%),the difference was not statistically significant.The CLBRs of mild stimulation protocols were significantly lower than that of GnRH-agonist and GnRH-antagonist protocols(P<0.05).There was a strong association between the number of oocytes retrieved and CLBR.CLBR rose significantly with an increasing number of oocytes up to 6,then the rising trend slowed down between 6 and 12 oocytes and plateaued beyond 12 oocytes in GnRH-agonist and GnRH-antagonist protocols.The plateau could be found in mild stimulation protocols when the oocytes retrieved beyond 12.1n the patients under 35 years old,the overall CLBR was higher than that of patients aged>35 years old.In patients aged>35 years old,the CLBR significantly decreased with age increased.With the increase of the number of oocytes retrieved,the incidence rates of OHSS were gradually increased in the three protocols.The incidence rate of OHSS in GnRH-agonist protocols was significantly higher than that of GnRH-antagonist protocols,and GnRH-antagonist protocols was significantly higher than that of CC mild stimulation protocols(5.4%Vs,3.8%Vs,1.5%,P<0.05).Conclusion:(1)The ?16 mm/?14 mm follicles ratio does not affect the pregnancy outcome of IVF/ICSI.(2)CLBR is an important index to assess the clinical outcomes of IVF/ICSI,and the number of oocytes retrieved and age affect CLBR obviously.(3)According to the different age and ovarian response of patients,we should design ovarian stimulation programs based on target oocytes number in order to get higher CLBR and reduce complications.