鑲嵌型胚胎和單一整倍體胚胎植入的產前及產後結果比較

Compared of prenatal and postnatal outcomes between mosaic embryo transfer and single euploid embryo transfer

李孟儒(Meng-Ju Lee)

指導教授 ： 李妮鍾

國立臺灣大學/醫學院/分子醫學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202102302

摘要

背景
2020年，美國生殖醫學會委員會建議，如果鑲嵌型胚胎移植後有懷孕的話，應提供產前遺傳諮詢與討論產前診斷檢測，如絨毛膜絨毛取樣術和羊膜穿刺術。然而，不只鑲嵌型胚胎移植，連整倍體胚胎移植的產前診斷檢測數據都很稀少。因此，我們收集了鑲嵌型胚胎移植和整倍體胚胎移植的產前（包括產前篩檢和產前診斷檢測）和產後結果（包括先天性異常），以釐清鑲嵌型或整倍體胚胎移植是否能發育成正常的胎兒。
目的
比較鑲嵌型胚胎移植和單一整倍體胚胎移植的產前及產後結果
方法
我們回顧收集單一診所內2156個整倍體單胚胎移植、69個鑲嵌型單胚胎移植和 26個鑲嵌型雙胚胎移植的著床前基因檢測-非整倍體週期，利用次世代定序的方法分析，時間從2016年1月到2020年8月。
結果
鑲嵌型雙胚胎移植組和整倍體單胚胎移植組的非侵入型產前篩檢率顯著更高（53.8% 對 26.1%，p=0.024）。分別與鑲嵌型單胚胎移植和鑲嵌型雙胚胎移植組相比，整倍體單胚胎移植組的羊膜穿刺率顯著較低（7.5%對33.3%，p<0.00001；7.5% 對 23.1%，p=0.035）。整倍體胚胎移植有8個產前檢查結果異常和18個先天性異常。然而，我們的研究在121個鑲嵌型胚胎移植中沒有發現異常的產前和產後檢查結果。鑲嵌型雙胚胎移植組的出生體重顯著降低 (p=0.0119)。與整倍體單胚胎移植組相比，鑲嵌型雙胚胎移植組的早產率和雙胞胎妊娠率顯著升高（26.7% vs 7.4%，p=0.004871；33.3% vs.0.6%，p<0.00001）。單條染色體嵌合與兩條染色體嵌合體與>2條染色體嵌合體、嵌合水平20~49%與50~80%、節段染色體與整條染色體、單染色體與三染色體的懷孕率、持續妊娠率和活產率的比較皆無顯著差異。
結論
整倍體胚胎移植產前結果異常的原因是鑲嵌型胚胎的切片限制、著床前基因檢測-非整倍體的平衡和微缺失的限制、母體細胞污染。鑲嵌型胚胎可以通過非整倍體細胞的減少和自我校正機制發育成正常胎兒。不論植入整倍體胚胎或是鑲嵌胚胎，都可能發生異常的產前和產後臨床結果。因此，無論移植的胚胎是整倍體還是嵌合體，都應提供完整的植入前遺傳諮詢和產前產後檢查。

關鍵字

單胚胎移植 ； 雙胚胎移植 ； 著床前基因檢測-非整倍體 ； 次世代定序 ； 產前結果 ； 產後結果

並列摘要

Background
In 2020, the ASRM (American Society of Reproductive Medicine) Committee suggested that prenatal genetic counseling and discussion of prenatal diagnostic testing such as chorionic villus sampling (CVS) and amniocentesis should be provided if the pregnancy continues due to mosaic embryo transfer. However, the prenatal diagnostic testing data is scarce not only in mosaic embryo transfer, but also in euploid embryo transfer. Therefore, we collected prenatal (including prenatal screening and prenatal diagnostic testing) and postnatal outcomes (including congenital abnormalities) of mosaic embryo transfer and euploid embryo transfer to clarify whether mosaic or euploid embryo transfer will produce normal fetal development results.
Purpose
To compare the prenatal and postnatal outcomes between mosaic embryo transfer and single euploid embryo transfer.
Methods
Retrospectively, we collected 2156 euploid single embryo transfers (SET), 69 mosaic SET and 26 mosaic double embryo transfers (DET) preimplantation genetic testing for aneuploidy (PGT-A) cycles analyzed by next generation sequencing(NGS) in single clinic from January in 2016 and August in 2020.
Results
The noninvasive prenatal screening (NIPS) rate was significantly higher between the group of mosaic DET and euploid SET (53.8% vs. 26.1%, p=0.024). A significantly lower amniocentesis rate in the group of euploid SET compared with the group of mosaic SET and mosaic DET, respectively (7.5% vs. 33.3%, p<0.00001;7.5% vs. 23.1%, p=0.035). There are 8 abnormal prenatal examination results and 18 congenital anomalies in euploid embryo transfer. However, our study found no abnormal prenatal and postnatal examination result in the 121 mosaic embryos transfer. The birth weight was significant lower in the group of mosaic DET (p=0.048). The preterm birth rate and twin pregnancy rate were significant higher in the group of mosaic DET compared with the group of euploid SET (26.7% vs 7.4%, p=0.004871; 33.3% vs.0.6%, p<0.00001). The pregnancy rate, ongoing pregnancy rate and live birth rate did not differ significantly between mosaicism in one chromosome vs. two chromosomes vs. >2 chromosome, mosaic level 20~49% vs. 50~80%, segmental chromosome vs. whole chromosome and monosomy vs. trisomy.
Conclusions
The reasons for the abnormal prenatal results of euploid embryo transfer are biopsy limitation for mosaic embryos, PGT-A limitation for balanced and microdeletion, maternal cell contamination. Mosaic embryos can develop to normal fetuses through clone depletion of aneuploidy cells and self-correction mechanism. Irrespective of the euploid embryos or mosaic embryos transfer, abnormal prenatal and postnatal clinical outcomes may occur. Therefore, preimplantation genetic counseling, prenatal and postnatal examinations should be provided completely whether the transferred embryo is euploidy or mosaicism.

並列關鍵字

single embryo transfer ； double embryo transfer ； preimplantation genetic testing for aneuploidy ； next generation sequencing ； prenatal outcome ； postnatal outcome

參考文獻

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