Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center
Chromosomal abnormalities after ICSI in relation to semen parameters: results in 1114 fetuses and 1391 neonates from a single center
复制标题
DOI：
10.1093/humrep/deaa162
复制
发表时间：
2020-09-01
影响因子：
6.1
通讯作者：
Keymolen, K.
中科院分区：
文献类型：
--
作者：
Belva, F.;Bonduelle, M.;Keymolen, K.
研究问题 ICSI 怀上的胎儿和孩子的核型异常与其父亲的精液参数之间是否存在关系？ 总结答案 ICSI 后代的产前和产后核型的新发染色体异常率高于一般人群，并且与父亲的精子参数有关。已知的情况 多项研究报告了较高的新发染色体异常率ICSI 胎儿存在异常，但最近来自大型队列的数据有限。总体而言，ICSI 后受孕胎儿的非遗传性核型畸变患病率有所增加，变化范围为 1.6% 至 4.2%。只有少数研究关注 ICSI 后代的核型异常与其父亲的精液参数之间的关系。此外，ICSI 新生儿异常核型发生率有所增加，但不同研究的发生率差异很大。 研究设计、规模、持续时间 我们报告通过绒毛膜绒毛取样和羊膜穿刺术进行产前检测的核型结果，以及单中心 ICSI 受孕后代的产后血液取样结果。考虑了 2004 年 1 月至 2012 年 12 月期间取卵母细胞以及使用射精或非射精精子（新鲜或冻融）获得的新鲜 ICSI 胚胎移植后的持续妊娠。冷冻胚胎移植、卵母细胞或精子捐赠、IVF、植入前基因检测和 IVM 后的妊娠被排除在外。无论妊娠结果如何，都会报告采样后的所有异常产前结果。参与者/材料、设置、方法 在 4816 例正在进行的 ICSI 妊娠中，可获得 4267 例妊娠的妊娠结局信息。 22.3% 的妊娠进行了产前检测，对 1114 名胎儿进行了诊断。在未进行侵入性产前诊断的妊娠中，有 29.4% 的孕妇获得了产后核型，总共对 1391 名新生儿进行了采样。通过逻辑回归分析根据母亲年龄和精液质量的染色体异常患病率。对于正常精液质量的定义，采用了世界卫生组织对人类精液特征的参考值。 主要结果和机会的作用 在 29 名单胎和 12 名多胞胎中发现异常胎儿核型（41/1114；3.7%；95% CI 2.7-4.9%）： 36 例异常为新生（3.2%；95% CI） 2.3-4.4），无论是数字（n=25）、性别（n=6）还是结构（n=5），其中五个是遗传的。 Logistic 回归分析未显示母亲年龄与胎儿染色体新生异常之间存在显着相关性（比值比 (OR) 1.05；95% CI 0.96-1.15；P=0.24）。除一例外，在所有案例中，核型异常的胎儿都是通过 ICSI 使用射精精子受孕的。在 ICSI 后出生的 1391 例未进行产前检测的儿童的产后样本中，有 14 例（1.0%；95% CI 0.6-1.7）发现异常核型：12 例为新生异常，2 例为遗传性平衡核型。这14种异常核型均是在使用射精精子进行ICSI后出生的孩子中发现的。结合产前和产后数据，新发核型畸变的几率随着母亲年龄的增加而增加（OR 1.11；95% CI 1.04-1.19）。男性精子浓度较高的夫妇的胎儿和儿童中，新发染色体异常率较高
STUDY QUESTION Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father's semen parameters?SUMMARY ANSWER The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers' sperm parameters.WHAT IS KNOWN ALREADY Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies.STUDY DESIGN, SIZE, DURATION We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy.PARTICIPANTS/MATERIALS, SETTING, METHODS From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted.MAIN RESULTS AND THE ROLE OF CHANCE An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7-4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3-4.4), either numerical (n=25), sex (n=6) or structural (n=5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96-1.15; P=0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm. Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6-1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm. The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04-1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration