| [Background]The official definition of assisted reproductive technology from the International Committee Monitoring Assisted Reproductive Technology(ICMART)is a technique for manipulating human oocytes and sperm or embryos for new life.Nowadays,assisted reproductive technology includes artificial insemination(AI),in vitro fertilization-embryo transfer(IVF)and its derivatives.What's more,IVF derivatives include intra cytoplasmic sperm injection(ICSI),frozen-thawed embryo transfer(FET),preimplantation genetic disgnosis(PGD)and so on.At present,there's one pair infertility couples in every six couples in the world.Assisted reproductive technology has been rapidly developed since the first IVF-ET baby born in England,and 14 years later in 1992,the first ICSI baby was born.It brings hope to the infertility couples worldwide.There are more than 5 million babies born after assisted repeoductive technology so far.The first ART baby was born in 1988 in China and there are more than 0.18 million cycles of treatment every year.ART may influence the composition of population in China with its booming development.The sex ratio at conception(PSR,primary sex ratio)is always calculated as male proportion and is 1.7 times higher than female under completely natural circumstances in humans.While the sex ratio at birth(SSR,secondary sex ratio)shows dramatic decrease due to the higher spontaneous abortion or other sex-selective loss during pregnancy.So the SSR in most gender-neutral countries is around 1.05,which is an ideal level for keeping a minimized overall gender imbalance.Recent evidence further clarified that the trajectory of sex ratio disproportion from conception to birth is dynamic and influenced by multiple complex factors both endogenous and exogenous.Numerous biological and environmental factors have been shown to change the secondary sex ratio naturally.Notably,as women undergoing ART received Ovulation induction treatment and the embryos cultured in vitro for some time,the key to sex ratio in IVF and/or ICSI babies were not completely similar with natural conception.Studies based on preimplantation genetic diagnosis(PGD)have revealed that the PSR of IVF embryos were significantly higher than ICSI embryos.While several large population survey using ART databases indicated that the SSR of cleavage-stage embryos transfer is remarkable lower when compared with those of blastocyst-stage.Additionally,to maximize the success rate,more than one embryo was transferred during the ART treatment,which greatly increased the incidence of twins or multi-fetus.In 2016,the International Committee Monitoring Assisted Reproductive Technology reported that the rate of twins in 2008,2009,2010 were 21.8%,20.5%and 20.4%respectively.It's much higher than the natural conception and may have huge impact in secondary sex ratio in ART.[Objective]In order to evaluate the impact of assisted reproductive technology(ART)procedure(treatment,transplant embryo type,transplant embryo stage and method of fertilization)and individual factors(age,BMI,type of infertility,cause of infertility)on the sex ratio of singletons and twins at birth after in vitro fertilization(IVF)and intra-cytoplasmic sperm injection(ICSI)treatment,We conducted a retrospective cohort study including patients undergoing their first cycle of IVF or ICSI with autologous oocytes in the Affiliated Nanjing Maternity and Child Health Hospital of Nanjing Medical University,the Affiliated Changzhou Maternity and Child Health Hospital of Nanjing Medical University and the Affiliated Wuxi Maternity and Child Health Hospital of Nanjing Medical University.[Methods]1.Secondery sex ratio:We included all the patients in these three centers since the first live birth born appears.There were 5832 patients from 2001 to 2015 after the verification.Secondaary sex ratio was stratified by assisted reproductive technology procedure(treatment,transplant embryo type,transplant embryo stage and method of fertilization),individual factors(age,BMI,type of infertility,cause of infertility),number of births and centers.2.Influencing factors:We conducted single factor and multivariate studies in singletons and twins respectively.Factors include assisted reproductive technology procedure(treatment,transplant embryo type,transplant embryo stage and method of fertilization)and individual factors(age,BMI,type of infertility,cause of infertility).The dependent variable is the sex ratio at birth in singletons and the ratio of twin boys to twin girls in twins.Pearson ?2 test was used to compare the distribution of categorical variables in different subgroups.Unconditional logistic regression was used to estimate the odds ratio(OR),95%confidence interval and P value for the association between selected characteristics and sex ratio.The models were adjusted for some individual factors including maternal age,paternal age and cause of infertility to provide adjusted odds ratio.In our analysis,potential confounders were regarded as covariates that were known associated factors for the birth outcomes and whose distribution between the singleton male and female groups were unequal at a chi-square value of P<0.10.Cause of infertility is an important related factor for assisted reproductive technology treatment and other similar researches about ART birth outcomes also adjusted it.P value<0.05 was considered to be significant.All analysis was performed with the Statistical Package for the Social Science software(Stata version 11.2).[Results]:We conducted a retrospective cohort study including patients undergoing their first cycle of IVF or ICSI with autologous oocytes from 2001 to 2015.A total of 7410 babies were born from 5832 women with 4254 live birth singletons and 1578 pairs of twins.The average age of females is 29.87 and 31.89 in males.Primary infertility patients were slightly more than secondary infertility,accounting for 53.8%.The main cause of infertility is fallopian tube factors,accounting for 40.5%.Those five kinds of protocols in these three centers,Long protocol are long term protocol,short term protocol,ultra-long term protocol,antagonist protocol and mini-stimulation protocol.Long term protocol is the most widely-used protocol,accounting for 66.1%.The SSR in singletons was significantly higher than twins(53.97%vs.50.89%,P=0.009),and the largest disparity was observed in 'thawed BE ICSI' subgroup(59.84%vs.42.45%,P=0.013).Blastocyst transfer was positively associated with elevated SSR when compared to cleavage stage embryos in singletons(Odds Ratio[OR]=1.17,P<0.001).While the decreased SSR was significantly associated with ICSI when compared to IVF(OR=0.61,P=0.046)in twins.In addition,paternal age was significantly associated with SSR(OR=0.75,P=0.014).[Conclution]:Blastocyst transfer increases SSR in comparing with cleavage stage embryos in singletons,while the use of ICSI reduces SSR in twins. |
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