The Effect Of Exogenous Luteinizing Hormone Supplementation Timing On IVF/ICSI-ET Pregnancy Outcome

Objective:Explore the effect of exogenous luteinizing hormone（LH）supplementation timing on IVF/ICSI-ET pregnancy outcome in various superovulation protocols,to find the appropriate supplementation timing and to optimize the ovarian hyperstimulation protocols,and to provide guidance for clinical work.Methods:Retrospective analysis 458 fresh transplant cycles of IVF/ICSI-ET in our hospital from July 2015 to September 2017,which were treated with classical long protocols,modified long protocols and antagonist protocols respectively.Part of classical long protocols:Patients with serum LH≤2mIU/m L on the day of Gn startup after luteal phase down-regulation were selected as study subjects,a total of210 cases.According to whether it was added recombinant human luteinizing hormone（r-hLH）,it was divided into two groups:A group（with r-hLH）,B group（without r-hLH）,the A group and B group were divided into two subgroups according to the supplementation timing of LH:A₁ group and B₁ group（add urine derived LH（HP-HMG）on the fourth day of Gn startup）,A₂ group and B₂ group（add urine derived LH（HP-HMG）on the sixth day of Gn startup）.Compare the basic conditions of different groups of patients,hyperstimulation of ovulation,laboratory indicators and pregnancy outcomes.Part of modified long protocols:Patients aged less than 35 years old with serum LH≤2mIU/mL on the day of Gn startup after folliclllar phase down-regulation were selected as study subjects,a total of 157 cases.According to the supplementation timing of LH divided into two groups:C₁ group（add urine derived LH（HP-HMG）on the fourth day of Gn startup）and C₂ group（add urine derived LH（HP-HMG）on the sixth day of Gn startup）.Compare the basic conditions of different groups of patients,hyperstimulation of ovulation,laboratory indicators and pregnancy outcomes.Part of antagonist protocols:Patients treated with antagonist superovulation cycles were 91 cases,according to the dominant follicle diameter divided into two groups:D₁ group（add urine derived LH（HP-HMG）When 12mm<mean diameter≤14mm）,D₂ group（add urine derived LH（HP-HMG）When 14mm<mean diameter≤16mm）,Compare the basic conditions of different groups of patients,hyperstimulation of ovulation,laboratory indicators and pregnancy outcomes.Results:Part of classical long protocols:In general:The indicators of age,BMI,AFC,infertility time、type、reason,the levels of bFSH、bLH、bE₂,the level of LH on Gn starts day,Gn time、total amount,amount of FSH,the levels of E₂ and P on the HCG day,endometrial thickness,retrieved oocytes number,MII oocytes number,fertilization rate of ICSI,cleavage rate,high quality embryo rate,implantation rate,all the differences had no statistical significant（P>0.05）.The amount of HMG in group A is lower than group B（P<0.05）;The rate of IVF fertilization,2PN and clinical pregnancy and the levels of LH on the HCG day in group A are higher than group B（P<0.05）;The two groups had no statistical difference in implantation rate,but increased in the A group.Subgroup comparison:The amount of HMG in group A₁ is higher than group A₂（P<0.05）;The implantation rate and clinical pregnancy rate in group A₂ are higher than group A₁（P<0.05）;The two groups have no statistical difference in the number of MII oocytes,but increased in the group A₂;The other indicators had no statistical difference between two groups（P>0.05）.The Gn time、total amount and amount of FSH in group B₁ is lower than group B₂（P<0.05）;The rate of high quality embryo,implantation and clinical pregnancy and the levels of LH on the HCG day in group B₁are higher than group B₂（P<0.05）;Other indicators had no statistical difference between two groups（P>0.05）.Part of modified long protocols:The amount of HMG in group C₁ is higher than group C₂（P<0.05）;The rate of implantation and the levels of LH on the HCG day and retrieved oocytes number in group C₂ are higher than group C₁（P<0.05）;The two groups had no statistical difference in MII oocytes number and clinical pregnancy rate,but increased in the group C₂.Other indicators had no statistical difference between two groups（P>0.05）.Part of antagonist protocols:The Gn time、total amount and amount of HMG in group D₁ is higher than group D₂（P<0.05）;Other indicators had no statistical difference between two groups（P>0.05）.Conclusion:1.In classical long protocols,when serum LH≤2mIU/mL on the day of Gn startup,the supplementation of r-hLH can improve the fertilization rate,2PN rate and pregnancy rate,and reduce the amount of HMG.In patients with r-hLH,the supplementation of HP-HMG on the sixth day of Gn startup can increase the implantation rate and clinical pregnancy rate.In patients without r-hLH,the supplementation of HP-HMG on the fourth day of Gn startup can improve the embryo rate,implantation rate and pregnancy rate,and reduce the time and dosage of Gn.2.In the modified long protocols,aged less than 35 years with serum LH≤2mIU/mL on the day of Gn startup,the supplementation of HP-HMG on the sixth day of Gn startup can increase the number of oocytes and implantation rate,and reduce the amount of HMG.3.In the antagonist protocols,the supplementation timing of LH does not affect the outcome of pregnancy,but compared with 12mm<mean diameter≤14mm,when the dominant follicle 14mm<mean diameter≤16mm the supplementation of HP-HMG can shorten the operation time of Gn and reduce the dosage of Gn.