Analysis Of The Effectiveness Of Down Syndrome Screening And Exploration Of The Reason Of Abnormal Screening Marker In ART Pregnancies

Objective: The aim of this study was to assess the efficiency of Down syndrome (DS)screening in pregnancies achieved by assisted reproduction techniques (ART), andexplore the cause of abnormal screening serum markers in ART pregnancies byanalyzing DS screening data base and endocrine hormone levels in the process of ART.Finally, provide important experimental basis for genetic counseling of ART pregnancy.Methods: The object of this study were pregnant women who underwent DS screeningbetween October2012and January2014in prenatal diagnosis center, the First Hospitalof Jilin University. Including1867cases of the first-trimester screening (FTS) and29591cases of the second-trimester screening (STS). In FTS and STS, respectively,617and15404natural pregnancies, and96and225ART pregnancies were recruited in ourpreliminary study. Exclusion of pregnancy with twin, DS screening applicationinformation fill in incomplete, not follow-up yet or lost follow-up and duplex serummarkers screening in FTS. And then, according to research the rule and reason of alteredDS screening marker in ART pregnancy, we exclude pregnancy with history of adversepregnancy outcomes. In FTS and STS, finally,544and14280natural pregnancies withnormal outcomes were included in control group,and96and219ART pregnancies withnormal outcomes were included in study group respectively. Maternal serum markerlevels were measured using time-resolved fluoroimmunoassay, include pregnancy-associated plasma protein-A (PAPP-A)、 free beta-human chorionic gonadotropin (f-βhCG)、 alpha-fetoprotein (AFP) and unconjugated estriol (uE3). Fetal nuchaltranslucency (NT) was measured by ultrasound. Electrochemiluminescence immunoassaywas used to analyze endocrine hormone levels, include follicle-stimulating hormone (FSH)、 luteinizing hormone (LH)、 estradiol (E2)、 progesterone (P) and humanchorionic gonadotropin (HCG). SPSS17.0software for statistical analysis.Results are as follows:1. There are617natural pregnancies who underwent first-trimester combined DSscreening. Screening positive rate、false positive rate (FPR) and detection rate (DR),respectively, was3.57%(22/617)、3.4%(21/617) and100%(1/1).2. There are15404natural pregnancies who underwent second-trimester triple DSscreening. Screening positive rate、false positive rate (FPR) and detection rate (DR),respectively, was5.75%(886/15404)、5.68%(875/15404) and78.57%(11/14).3. In FTS,617natural pregnancies included544pregnancies who had normal outcomes.FPR was3.13%(17/544). The median MoM of PAPP-A、 f-βhCG and NT,respectively, was1.09MoM、0.96MoM and1.16MoM.4. In STS,15404natural pregnancies included14280pregnancies who had normaloutcomes. FPR was5.41%(773/14280). The median MoM of AFP、f-βhCG and uE3,respectively, was1.09MoM、0.96MoM and1.16MoM.5. There are96ART pregnancies, who underwent first-trimester combined DSscreening, with normal outcomes.FPR was2.10%(2/96). The median MoM of PAPP-A、f-βhCG and NT, respectively, was1.0MoM、1.14MoM and1.15MoM.6. There are219ART pregnancies, who underwent second-trimester triple DS screening,with normal outcomes.FPR was7.76%(17/219). The median MoM of PAPP-A、f-βhCG and NT, respectively, was0.90MoM、0.92MoM and0.92MoM.7. We found a statistically significant increased in the mean of maternal age and weightin ART pregnancies compared with control group (p﹤0.01).8. There was significant difference in the MoM of f-βhCG, in FTS, but no difference inthe size of screening FPR in ART pregnancies (1.45MoM VS1.20MoM, p﹤0.05).However, there were no difference in the MoM of FTS marker and size of screeningFPR between each ART group and control group. 9. MoM of uE3in ART pregnancies was significant decreased(0.95MoM VS1.06MoM, p﹤0.01), but FPR was no difference compared with control group. There weresignificant difference in the MoM of AFP and uE3between IVF pregnancies andnatural pregnancies, leading to a higher FPR (10%VS5.41%, p﹤0.05). MoM of uE3in ICSI pregnancies was significant decreased(0.78MoM VS1.06MoM, p﹤0.01),but FPR was no difference compared with control group.MoM of AFP in FETpregnancies was significant increased (1.09MoM VS0.96MoM, p﹤0.05), but FPRwas no difference compared with control group.MoM of all serum marker and FPR inIUI pregnancies were no significant difference compared with control group.10. There was a positive correlation between the levels of serum P at the time of HCGadministration and the MoM of AFP in IVF pregnancies. There was also a positivecorrelation between the levels of LH at the time of HCG administration orgonadotrophin (Gn) starting and the MoM of uE3in IVF pregnancies.Conclusions:1. First-trimester combined screening and second-trimester triple screening caneffectively reduce the number of newborn infant with DS because of the higher DR.2. There was no difference in the size of FPR in FTS between ART pregnancies andnatural pregnancies. This results prompt that first-trimester combined screening canbe more used in ART pregnancies.3. MoM of AFP and uE3were significant decreased in IVF pregnancies, and thisresults leading to a higher FPR. Altered second-trimester screening markers may berelated to endocrine hormone levels at the time of HCG administration or Gn starting.