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Retrospective Analysis Of PGS Embryo Results By Array-based CGH Of Unexplained Recurrent Miscarriage Couples

Posted on:2016-02-24Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhangFull Text:PDF
GTID:2284330461484224Subject:Obstetrics and gynecology
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Background:Abortion, which is divided into spontaneous abortion and artificial abortion, is defined as the loss of the conceptus before 28 weeks of gestation when fetal weight is less than 1000g. Miscarriage, which is the spontaneous abortion, is divided into two types:sporadic and recurrent. Recurrent miscarriage (RM) refers to 3 or more times miscarriage with the same sexual partner and affects about 1% of couples. Etiology of RM can be divided into genetic abnormalities, uterine abnormalities, endocrine abnormalities, immune dysfunction, infection, inherited thrombophilic disorders and environmental factors. About 50% RM couples can’t explained by known reasons, called unexplained recurrent miscarriage (uRM). URM influences badly both physiological and psychological health of the couples, and becomes a significant challenge to reproductive doctors as well. As its potential reasons are sophisticated, besides maternal-fetal interface dysfunction and immune factors, embryonic chromosomal abnormity is considered as an important cause of uRM. Preimplantation genetic screening (PGS) is necessary, especially for couples who hadn’t done karyotype of abortion tissue or advanced maternal age, to diminish further pregnancy loss from embryological factor.PGS is a cytogenetic process to detect embryonic aneuploidy for subfertile couples undergoing in vitro fertilization (IVF) before embryo transfer, by aspiration polar bodies, blastomeres or trophectoderm cells, so as to increasing embryo implantation capacity and decreasing miscarriage and fetus birth associated with aneuploidy. The main indications suggested for PGS are recurrent miscarriage in patients with normal karyotypes, advanced maternal age, repeated implantation failure and severe male factor infertility. Common technique used in PGS is florescence in situ hybridization (FISH). With the development of hybridization technique, comparative genomic hybridization (CGH) becomes popular in PGS.Array-based CGH (a-CGH) technique is a molecular karyotyping technology recently developed, combining chip technique and CGH, that allows rapid high resolution cellular genome-wide DNA sequencing in one hybridization experiment. Compared to FISH, which can’t detect entire genomic 24 chromosomes in embryo cells due to technical limitation, a-CGH analyzes not only numerical but also structural abnormities, including deletion, duplication. But, it fails to recognize balanced translocation or polyploidy.Purpose:The aim of this study is to retrospective analyze embryo results of uRM couples after PGS by a-CGH and to figure out embryonic chromosomal abnormity types and rates.Methods:The study was conducted by collecting embryo results of a-CGH from Jan 2013 to Oct 2014 undergoing PGS couples who was diagnosed uRM in Reproduction Hospital Affiliated to Shandong University, amounting to 169 embryos among 47 cycles of 45 couples.Results:1. The average maternal age at biopsy was 33.62±5.21 (range 23-43) years old, and these patients had an average of 3.89±1.17 (3-7) prior losses. Among 169 embryos there are 95 (52.80%) euploid embryos and 74 (43.20%) aneuploid embryos, including numerical and structural abnormities.2. The amount of one chromosome abnormal embryos is 43. Monosomy embryo is 17 (39.53%) and trisomy embryo is 14(32.56). The ratio of monosomy/trisomy is 1.31.3.Classified the aneuploid embryos according to chromosomal number, what is figured out is that abnormal condition happens among every chromosome in genome, the most influenced ones are 16,22,8,2,6 chromosome.4. The aneuploid embryo rate is 48.78%,36.51%,71.43% respectively, in 23-29, 30-39,40-43 age group. There is a significant difference (P<0.01) between 30-39 and 40-43 age group.5. The aneuploid embryo rate is 38.93%,60.53% respectively, in 23-37,38-43 age group and the difference is significant (P<0.05).6. To Apr.2015, there are 38 embryos transferred in 35 cycles. Implantation rate is 73.68% and pregnancy rate per transfer is 71.43%. Pregnancy loss rate is 32% with ongoing pregnancy and live birth rate is 68%. Conclusions:1. Morphologic normal embryos may abnormal in chromosomes. It shows morphology should not be the unique standard to choosing embryos for transfer.2. Selecting euploid embryos though PGS by a-CGH in uRM couples could improve implantation and ongoing pregnancy.3. Among uRM couples, with increasing age of female, the embryo abnormal rate enhances. There is statistical significant difference that 38 year-old and older than 38 year-old females are more likely occurring embryo abnormity than younger females.4. Besides embryo chromosomal abnormal, etiology of uRM need further research.5. Because of limitation of sample numbers and time span of usage of a-CGH, the study still need further proceed.
Keywords/Search Tags:unexplained recurrent miscarriage, preimplantation genetic screening, array-based comparative genomic hybridization, analysis of embryo karyotype
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