成人型多囊肾并发男性不育症行胚胎植入前遗传学诊断的结局分析

Preimplantation genetic diagnosis for infertile males with autosomal dominant polycystic kidney disease

目的:成人型多囊肾(ADPKD)是最常见的遗传性肾脏疾病,ADPKD可引起少弱精子症和无精子症,从而导致男性不育症。本文回顾性分析了ADPKD并发男性不育症行胚胎植入前遗传学诊断(PGD)的治疗结局。方法:回顾性分析了2015年4月至2017年2月行PGD治疗的7例ADPKD并发男性不育症夫妇的临床资料,6例为少弱精子症,1例为梗阻性无精子症。7例患者均为PKD1基因杂合突变。ICSI后培养囊胚至第5或6天行卵裂球活检,采用Sureplex扩增试剂盒进行单细胞全基因组扩增,首先进行单体型连锁分析和Sanger测序,未致病的胚胎再进行全基因组低覆盖度测序行染色体拷贝数分析。选择非致病且整倍体的囊胚进行移植。结果:7例患者共行7个PGD周期,26枚囊胚中,12枚为未致病的整倍体囊胚。7例患者冻胚移植后6例临床妊娠,其中5例顺产(4例单胎,1例双胎),自然流产1例。结论:ADPKD并发男性不育症经PGD后可以实现较高的妊娠率与活产率,又可以避免子代再患ADPKD。本结论对于可以自然妊娠的ADPKD患者也有一定的借鉴意义。

Objective： Autosomal dominant polycystic kidney disease(ADPKD） is one of the most common genetic renal diseases,which may cause oligoasthenospermia and azoospermia and result in male infertility. This study aimed to analyze the outcomes of preimplantation genetic diagnosis(PGD） in male patients with ADPKD-induced infertility. Methods： We retrospectively analyzed the clinical data on 7 male patients with ADPKD-induced infertility undergoing PGD from April 2015 to February 2017,including 6 cases of oligoasthenospermia and 1 case of obstructive azoospermia,all with the PKD1 gene heterozygous mutations. Following intracytoplasmic sperm injection(ICSI）,we performed blastomere biopsy after 5 or 6 days of embryo culture and subjected the blastomeres to Sureplex whole-genome amplification, followed by haplotype linkage analysis, Sanger sequencing, array-based comparative genomic hybridization to assess the chromosomal ploidy of the unaffected embryos,and identification of the unaffected euploid embryos for transfer. Results： One PGD cycle was completed for each of the 7 patients. Totally,26 blastocysts were developed,of which 12 were unaffected and diploid. Clinical pregnancies were achieved in 6 cases following 7 cycles of frozen embryo transplantation,which included5 live births and 1 spontaneous abortion. Conclusion： For males with ADPKD-induced infertility,PGD may contribute to high rates of clinical pregnancy and live birth and prevent ADPKD in the offspring as well. This finding is also meaningful for the ADPKD patients with normal fertility.