Clinical Analysis Of Assisted Reproductive Technology With Müllerian Duct Abnormalities Of Assisted Reproductive Technology And Gene Mutation Study

Part 1 Obstetric outcomes of Müllerian duct anomalies with assisted reproductive technologyObjective: The Müllerian duct anomalies seriously affected the females’ reproductive health.This study is to evaluate the effect of Müllerian duct anomalies（MDAs）on obstetric outcomes of assisted reproductive technology.Materials and methods: During the period from April 2011 to June 2016,144 women with MDAs complained of infertility at the Reproductive Medicine Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Anhui Medical University were collected as the study group.Their uterine anomalies were diagnosed using transvaginal ultrasonography（US）and hysteroscopy or laparoscopy,or three-dimensional US or hysterosalpinography（HSG）.The diagnosed anomalies were grouped according to the classification proposed by a subcommittee of the American Fertility Society,which includes 20 with didelphic uterus,35 with unicornuate uterus,57 with septate uterus,16 with bicornuate uterus,and 16 with arcuate uterus.The control group consisted of group consisted of 1089 infertility patients without documented uterine anomalies who only had tubal factors during the same period.Patients in both case and control groups had normal chromosomal karyotype（46,XX）.Patients with other potential uterine anomalies（e.g.,cervical stenosis,submucous myomas,endometrial polyps,intrauterine adhesions,other intracavitary filling defects）were excluded from both groups.Results: There were no differences in the age,duration of infertility,days of stimulation,fertilization rate,and some other items between the patients with anomalies and normal controls（Table 1）.The implantation rate per embryo transfer（19.4% vs.34.1%,P=0.002）,pregnancy rate（29.6% vs.46.5%,P=0.019）,and delivery rate（50% vs.82.9%,P=0.004）of the patients with anomalies were all lower than those of the normal controls.The first trimester spontaneous abortion rate（48.8%vs.10.4%,P= 0.001）and miscarriage rate（50% vs.17.1%,P=0.004）of the patients with anomalies were all higher than those of the normal controls.Patients with bicornuate uterus was associated with the highest rate of first trimester spontaneous abortions（3/8,37.5%）and the highest preterm delivery rate（2/8,25.0%）.The multiple pregnancy rate was 7.7%（5/65）for the combined unicornuate,septate,and arcuate uteri,which is lower than that for the didelphic and bicornuate uteri（5/17,29.4%）.Conclusion: Women with uterine anomalies undergoing IVF/ICSI-ET have relatively poor pregnancy outcomes compared with normal controls.The results had been improved for the septate uteri that underwent metroplasty.Arcuate uteri had better obstetric outcomes with IVF/ICSI-ET.Whole Exome Sequencing in Müllerian duct anomalies and Gene study of CASKIN2Objective: the purpose of this study was to identify new causative genes of the Müllerian duct anomalies using the next generation sequencing.Materials and methods:Five congenital absence of the uterus and vagina（CAUV）patients were used for the whole-exome sequencing.Simultaneously,a larger cohort of ¹20 müllerian duct anomalies and ²50 normal controls were selected for replication of some candidate genes or variants which found in the above sequencing.Results: Two novel heterozygous missense variant of the CASKIN2 gene（NM₀20753: c.969C>A,p.H323Q;c.1228G>A,p.V410M）was detected in 2unrelated CAUV patients by performing whole exome sequencing and was not found in the inner public database.Sequencing all 21 coding exons of CASKIN2 in ¹20patients and ²00 controls showed that only three missense variants(c.1128G>A,p.V410M;c.2815C>T,p.T939M;c.3377G>A,p.R1126 H were identified in the patients.Normal controls had none missense and nonsense mutations of the CASKIN2.Conclusions: The results indicate that mutations in the coding sequence of CASKIN2 may be an causative gene for müllerian duct anomalies in the Chinese Han population.