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Abstract：
OBJECTIVE: The cystic fibrosis transmembrane conductance regulator (CFTR) is the most common causative gene attributed to congenital obstructive azoospermia (OA). The aim of this study was to conduct an epidemiological survey of congenital OA patients, to screen for CFTR mutations, and to follow their pregnancy outcomes in assisted reproductive technology (ART).
METHODS: This cohort study enrolled congenital OA patients undergoing ART and whole-exome sequencing from January 2018 to September 2023. Semen parameters, sex hormones, and seminal plasma biochemistry were evaluated. CFTR mutations identified in OA patients were analyzed. In addition, the laboratory outcomes, clinical outcomes, and neonatal outcomes were compared between OA patients carrying two CFTR mutations and the others after surgical sperm extraction-intracytoplasmic sperm injection (ICSI) treatment.
RESULTS: A total of 76 patients with congenital OA were enrolled. CFTR mutations were identified in 35 (46.1%) congenital OA patients. A total of 60 CFTR mutation sites of 27 types were identified, and 10 of them were novel. The average frequency was 1.71 (60/35) per person. The most common mutation was c.1210-11T > G (25%, 15/60). After ICSI treatment, there were no statistically significant differences in laboratory outcomes, clinical outcomes, and neonatal outcomes between OA patients carrying two CFTR mutations (n = 25) and other OA patients (n = 51).
CONCLUSIONS: Apart from the IVS9-5T mutation, the genetic mutation pattern of CFTR in Chinese OA patients is heterogeneous, which is significantly different from that of Caucasians. Although carrying two CFTR mutations or not had no effect on the pregnancy outcomes in OA patients after ICSI, genetic counseling is still recommended for such patients.
METHODS: This cohort study enrolled congenital OA patients undergoing ART and whole-exome sequencing from January 2018 to September 2023. Semen parameters, sex hormones, and seminal plasma biochemistry were evaluated. CFTR mutations identified in OA patients were analyzed. In addition, the laboratory outcomes, clinical outcomes, and neonatal outcomes were compared between OA patients carrying two CFTR mutations and the others after surgical sperm extraction-intracytoplasmic sperm injection (ICSI) treatment.
RESULTS: A total of 76 patients with congenital OA were enrolled. CFTR mutations were identified in 35 (46.1%) congenital OA patients. A total of 60 CFTR mutation sites of 27 types were identified, and 10 of them were novel. The average frequency was 1.71 (60/35) per person. The most common mutation was c.1210-11T > G (25%, 15/60). After ICSI treatment, there were no statistically significant differences in laboratory outcomes, clinical outcomes, and neonatal outcomes between OA patients carrying two CFTR mutations (n = 25) and other OA patients (n = 51).
CONCLUSIONS: Apart from the IVS9-5T mutation, the genetic mutation pattern of CFTR in Chinese OA patients is heterogeneous, which is significantly different from that of Caucasians. Although carrying two CFTR mutations or not had no effect on the pregnancy outcomes in OA patients after ICSI, genetic counseling is still recommended for such patients.
摘要：
目的：囊性纤维化跨膜传导调节因子（CFTR）是归因于先天性梗阻性无精子症（OA）的最常见致病基因。这项研究的目的是对先天性OA患者进行流行病学调查，来筛选CFTR突变,并跟踪他们在辅助生殖技术（ART）中的妊娠结局。
方法：这项队列研究纳入了2018年1月至2023年9月接受ART和全外显子组测序的先天性OA患者。精液参数,性激素,和精浆生化评价。分析在OA患者中鉴定的CFTR突变。此外,实验室结果,临床结果，我们比较了携带两种CFTR突变的OA患者和手术精子提取-卵胞浆内单精子注射(ICSI)治疗后的其他患者的新生儿结局.
结果：共纳入76例先天性OA患者。在35例（46.1％）先天性OA患者中发现了CFTR突变。共鉴定出27种类型的60个CFTR突变位点,其中10个是小说。平均频率为每人1.71（60/35）。最常见的突变是c.1210-11T>G(25%,15/60）。ICSI治疗后，实验室结果没有统计学上的显着差异，临床结果，携带两个CFTR突变的OA患者(n=25)和其他OA患者(n=51)之间的新生儿结局。
结论：除了IVS9-5T突变，中国OA患者CFTR的基因突变模式是异质性的，这与高加索人有很大不同。尽管携带两种CFTR突变与否对ICSI术后OA患者的妊娠结局没有影响，遗传咨询仍建议对此类患者进行。
方法：这项队列研究纳入了2018年1月至2023年9月接受ART和全外显子组测序的先天性OA患者。精液参数,性激素,和精浆生化评价。分析在OA患者中鉴定的CFTR突变。此外,实验室结果,临床结果，我们比较了携带两种CFTR突变的OA患者和手术精子提取-卵胞浆内单精子注射(ICSI)治疗后的其他患者的新生儿结局.
结果：共纳入76例先天性OA患者。在35例（46.1％）先天性OA患者中发现了CFTR突变。共鉴定出27种类型的60个CFTR突变位点,其中10个是小说。平均频率为每人1.71（60/35）。最常见的突变是c.1210-11T>G(25%,15/60）。ICSI治疗后，实验室结果没有统计学上的显着差异，临床结果，携带两个CFTR突变的OA患者(n=25)和其他OA患者(n=51)之间的新生儿结局。
结论：除了IVS9-5T突变，中国OA患者CFTR的基因突变模式是异质性的，这与高加索人有很大不同。尽管携带两种CFTR突变与否对ICSI术后OA患者的妊娠结局没有影响，遗传咨询仍建议对此类患者进行。
