| Objective:About 12.5%of couples are affected by infertility all over the world.In China,about 15-20%of women and 10-12%of men suffered from infertility,and this proportion is also on the rise.Assisted reproductive technology is the most important method for treating infertility currently.So far,more than 6 million offspring have been born all over the world.In China,the total number of cycles in various categories carried out every year in recent years has exceeded 1 million,and the number of births has exceeded300,000 annually.Since the invention of assisted reproductive technology for more than 40years,it has gradually developed the technology based on intrauterine insemination(IUI),in vitro fertilization-embryo transfer(IVF-ET)and its derivative technology,which has also made more and more infertility patients have the opportunity to conceive their children.However,there are still a large number of couples who cannot receive pregnancy or obtain live births even after receiving ART treatment.Therefore,a comprehensive and in-depth evaluation of the effect of assisted reproductive therapy and its influencing factors is required.Successfully conceiving and obtaining live births is the only and the most important purpose of couples seeking assisted reproductive therapy.Therefore,the live birth rate has become the most original and intuitive evaluation method,and has gradually become one of the most widely used evaluation indicators of the effect of assisted reproductive technology.Live birth rate can be further divided into different types according to different calculation methods,such as single-cycle live birth rate,cumulative live birth rate,etc.The single-cycle live birth rate is the proportion of the number of live births in a specific cycle.It has been favored by clinical researchers because of its simple calculation and good evaluation function.With the development of embryo freezing/thawing technology,one-time ovulation for multiple embryo transfers has gradually become the mainstream,and the previous single-cycle live birth rate is no longer suitable for evaluating the dynamic relationship between multiple transfers at this time.Therefore,the concept of cumulative live birth rate has been gradually promoted,that is,to comprehensively consider the relationship between the patient’s baseline situation and multiple transplantation cycles,and then evaluate the probability that the patient will receive at least one live birth after multiple transplantation.However,at this stage,research on various types of live births,especially cumulative live births,is mainly concentrated in western countries.For China,although the researches on single-cycle live birth rate are more extensive,researches on the cumulative live birth rate have not been widely carried out,and there is a lack of multi-center comparison of large sample population data.In addition,although China’s assisted reproductive treatment started late,it has developed rapidly.The number of approved centers and sperm banks that are allowed to carry out assisted reproductive treatment has shown an increasing trend year by year,which may objectively cause regional imbalances in the infertility diagnoses,treatment plan and treatment level.Therefore,studies on the effects of different assisted reproductive treatments and live birth rates in different centers are urgently needed.The study is based on multi-center assisted reproductive therapy data.First,single-cycle live birth rate and the conservative and optimal estimates of cumulative live birth rate are calculated,and then the potential influencing factors of live birth rate are extensively discussed.Methods:This article was a retrospective cohort study including patients treated at three assisted reproductive centers in China from January 2013 to December 2016,consisting of 5,995 patients(7,195 transfer cycles)in the First Affiliated Hospital with Nanjing Medical University,2515 patients(3110 transfer cycles)of the Affiliated Nanjing Maternity and Child Health Hospital of Nanjing Medical University,5801 patients(7010transfer cycles)of the Shengjing Hospital Affiliated to China Medical University,a total of14311 patients(with 17315 transfer cycles).After sorting and summarizing the relevant evidence in the published literature,two types of potential research factors are finally included for analysis.One is non-medical factors,such as the patient’s age,height,weight,and duration of infertility.The other is medical factors,such as the patient’s types of infertility,infertility diagnosis,insemination method,endometrial thickness on the HCG day,etc.The main evaluation(outcome)indicators are three different types of live birth rates(single-cycle birth rate,conservative and optimal estimates of cumulative cycle live birth rate).This article divided the research factors into different groups,and drew different complex bar charts or line charts according to the transfer cycle or research factors,and discusses the impact of the transfer cycle and the research factors on live birth rate.For the comparison between the conservative estimates of the single-cycle live birth rate and conservative estimate of the cumulative live birth rate,theχ~2 test is used(the trend test uses the Cochran-Armitage test),the optimal estimate of the cumulative live birth rate is calculated by the product limit method.The log-rank test was used for comparison.For the remaining comparisons between groups,continuous variables are usually tested by t test,one-way ANOVA or Kruskal-Wallis test,and categorical variables are tested byχ~2 test.All the test level was 0.05(two-tailed)Results:A total of 14311 subjects were included in this study,totaling 17315 transfer cycles.The average age of the study population was 30.95±4.65 years old,the average pre-pregnancy BMI was 22.7±3.31 kg/m~2,the average duration of infertility was 4.04±3.13years,the endometrial thickness was 10.37±2.38 mm,and the tubal factor was the majority of the infertility diagnosis(62.48%).The results of the single-cycle-live-birth-rate study showed that:as the number of transfer cycles increases,the single-cycle live birth rate shows a downward trend,from40.54%in the first cycle to 11.46%in the fourth cycle.The comparative analysis of the basic information of the live birth population in the first three cycles found that the number of people who received live births in the second/third cycle was older(P<0.001)than those in the first cycle.The duration of infertility is longer(P=0.04),and the endometrial thickness on the HCG day is thinner(P<0.001).In addition,after grouping according to the research factors,it was found that with the increasing of age,the single-cycle live birth rate decreased significantly(P<0.01),and the decline was more obvious in the group older than37 years old;meanwhile,the duration of infertility and single-cycle live birth rate also had negative correlation.With the increasing of infertility years,the single-cycle live birth rate showed a downward trend(P<0.001);the endometrial thickness on the HCG day and live birth rate showed a significant positive correlation,and the women whose endometrial thickness on the HCG day was greater than or equal to 7mm had significant higher single-cycle live birth rate than the control group.The results of the study on cumulative live birth rate showed that the cumulative live birth rate was on the rise with the increasing of transfer cycles.After four transfer cycles,the conservative and optimal estimates of the cumulative live birth rate can be increased to44.24%and 63.21%,respectively.However,under the influence of related factors,the changes among the subgroups are not completely consistent.There was a significant negative correlation between age and cumulative live birth rate.With increasing age,the cumulative live birth rate decreased significantly(P<0.05).Compared with the population whose age between 30 and 34 years old,after four transfer cycles,the conservative and optimal estimates of cumulative live birth rate for those over the age of 37 have dropped from 52.95%and 77.30%to 18.17%and 26.51%,respectively;and when the age exceeded37 years old,the conservative estimate of cumulative live birth rate changes slowly with the increase of the transfer cycles and had no statistical significance(P>0.05);The effect of BMI on cumulative birth rate was not significant,we can only find the difference between the obese group(BMI>28kg/m~2)and other groups(P<0.01),and no statistical significance was found among the groups whose BMI<28kg/m~2(P>0.05);the conservative estimate and optimal estimate of cumulative live birth rate of those with an endometrial thickness less than 7 mm decreased by 17.60%and 30.93%,compared with those greater than or equal to 7mm;for the infertility type,the cumulative live birth rate of primary infertility is significantly higher than the population of secondary infertility(P<0.01).In addition,the study found that male factor-induced infertility had the highest cumulative live birth rate(61.79%and 75.55%),while tubal factor-induced infertility cumulative live birth rate was at the lowest level(50.53%and 58.92%).Conclusions:The results of this study show that in the whole population,with the increasing of the number of transplantation cycles,the single-cycle live birth rate is in a downward trend,from 40.54%in the first cycle to 11.46%in the fourth cycle;After four transfer cycles,the conservative and optimal estimates of cumulative live birth rate can be increased to 44.24%and 63.21%,respectively.In addition,this study also found that:the woman’s age,duration of infertility and BMI were negatively correlated with assisted reproductive treatment live birth rate,and endometrial thickness on the HCG day was positively correlated with it.This suggests that couples undergoing infertility treatment should be treated as soon as possible while adjusting their own conditions to actively prepare for pregnancy.In addition,the cumulative live birth rate is more advantageous than the traditional single-cycle live birth rate in evaluating the outcome of assisted reproductive therapy.It directly assesses the chance of obtaining live births throughout the treatment process,which is more meaningful to clinicians and patients.The results of the study also suggest that clinicians need to conduct personalized evaluation and treatment based on the basic situation of couples undergoing infertility treatment to avoid inappropriate selection.Under normal circumstances,as long as the patient adhere to the treatment and go through multiple transplantation cycles,they can get a more ideal success rate.However,due to the limitations of the research center and time,we should be cautious about the extrapolation and application of relevant conclusions. |
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