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.

Surgical sperm extraction with intracytoplasmic sperm injection has become widespread worldwide and is regarded as the sole option for patients with azoospermia. However, the sperm retrieval rate remains unsatisfactorily low, particularly for men with non-obstructive azoospermia (NOA). Therefore, the technical challenges associated with improving the sperm retrieval rate for men with NOA are being addressed. The most successful method developed to date is microdissection testicular sperm extraction (micro-TESE), which is rapidly becoming recognized as a useful technique due to its relatively high sperm retrieval rate and low complication rate. However, even with micro-TESE, the sperm retrieval rate for men with NOA remains at 30-60 %, with an even lower birth rate. The technical challenges associated with improving the outcomes of surgical sperm extraction are being approached through the use of ultrasound and optimal surgical devices such as narrow band imaging, multiphoton microscopy, and optical coherent tomography. In addition to the difficulties related to searching for sperm, medical treatments that induce spermatogenesis remain controversial. For example, varicocele repair prior to surgical sperm extraction and hormonal therapy before and after TESE have been extensively examined. We herein briefly summarized the development process in surgical sperm extraction up to the present and technical challenges to improve the outcomes of surgical sperm extraction.