[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.目的： 分析基于二代测序（NGS）技术的胚胎植入前非整倍体遗传学检测（PGT-A）中嵌合体胚胎检出率的相关因素，以及嵌合体胚胎移植的妊娠结局。 方法： 通过回顾性观察研究收集重庆市妇幼保健院生殖医学中心2019年1月至2023年5月期间的745个PGT-A周期2 850个囊胚患者的临床资料。使用NGS技术对活检细胞进行检测，根据检测结果将胚胎分为整倍体胚胎、非整倍体胚胎及嵌合体胚胎，比较患者的临床特征及实验室相关参数对嵌合体胚胎检出率的影响。分析比较同期98个嵌合体胚胎移植周期和486个整倍体胚胎移植周期的妊娠结局，包括临床妊娠率和活产率。 结果： 在2 850个囊胚中，1 489个囊胚为整倍体（52.2%，1 489/2 850），917个（32.2%，917/2 850）为非整倍体，444个（15.6%，444/2 850）为嵌合体；嵌合体中，有245个（55.2%，245/444）胚胎为染色体片段嵌合，118个（26.6%，118/444）为整条染色体嵌合，81个（18.2%，81/444）为复杂嵌合。不同遗传检测机构的嵌合体检出率波动范围为13.5%~27.0%。女方年龄、抗苗勒管激素水平、PGT-A指征、促排卵方案、促性腺激素（Gn）用量、Gn天数、内细胞团分级、滋养外胚层细胞分级、遗传检测机构和胚胎活检时间在整倍体、非整倍体和嵌合体胚胎间分布均有显著差异（P均<0.05）。多因素分析显示，滋养外胚层细胞分级和遗传检测机构与嵌合体检出率明显相关，与滋养外胚层细胞分级为A级相比，分级为B-级者（OR=1.59，95%CI为1.04~2.44，P=0.033）嵌合体检出率明显升高；与检测机构a相比，c机构的嵌合体检出率明显升高（OR=2.89，95%CI为2.10~3.98，P<0.001）。嵌合体胚胎移植的临床妊娠率（分别为51.0%、65.2%，P=0.008）和活产率（分别为39.4%、53.2%，P=0.017）明显低于整倍体胚胎移植者；在校正了女方年龄、PGT-A指征、滋养外胚层细胞分级和胚胎体外培养天数后，嵌合体胚胎移植者的临床妊娠率（OR=0.52，95%CI为0.32~0.83，P=0.007）和活产率（OR=0.50，95%CI为0.31~0.83，P=0.007）均明显低于整倍体胚胎移植者。 结论： 滋养外胚层细胞分级和遗传检测机构与嵌合体胚胎检出率有关。与整倍体胚胎移植相比，嵌合体胚胎移植的临床妊娠率和活产率均明显降低。对于无整倍体胚胎可移植的夫妇，在遗传咨询中可根据嵌合比例和嵌合类型等适当推荐移植嵌合体胚胎，以期获得最优妊娠结局。.