Purpose This study is intended to investigate the candidate pathogenic gene in a patient with primary infertility but without the defect in routine semen parameters from a consanguineous family and explore the potential impacts of mutations on assisted reproductive technology outcome. Methods Whole‐exome sequencing (WES) was carried out. A variant in his family found by WES was verified by Sanger sequencing. Intracytoplasmic sperm injection (ICSI) was applied to obtain a successful outcome. Results A Cation Channel of Sperm 3(CATSPER3) homozygous variant (NM_ 178019.3:exon5:c.707T>A, p.L236*) was identified for the first time. The anti‐CD46 immunofluorescence analysis revealed the failure of sperm acrosome reaction (AR) caused by the mutation. ICSI treatment was successful. Conclusion This is the first report of a homozygous pathogenic CATSPER3 mutation. This mutation may cause male infertility with the failure of AR but without the defect in routine semen parameters. ICSI was supposed to be the most appropriate therapy.

BackgroundTo develop a novel preimplantation genetic screening (PGS) test using next generation sequencing(NGS) as a alternative to current array comparative genomic hybridization (array CGH) method for detection of small segmental translocations in two patients with repeated implantation failure (RIF) and recurrent miscarriage (RM). Inconsistent results were resolved by validation with fluorescence in situ hybridization (FISH).Case PresentationOne couple with normal cytogenetic and array CGH result suffered from implantation failure. Later NGS analysis showed 46,XY.ngs[GRCh37/hg19] 9p24.3-9p24.1(10,291-8,680,890×1),13q33.1-13q34(103,046,327-114,785,444×3). The other couple with normal cytogenetic and array CGH result also received NGS analysis. Due to the detected abnormal finding, which was 46,XY.ngs 4q34.3-4q35.2(179,673,982-191,016,503×3),6p25.3-6p22.3 (146,672-17,829,693×1), the couple decided against the corresponding embryo transfer.ConclusionsThe NGS approach is a reliable alternative to array CGH for the discovery of small segmental translocations in patients with RIF and RM.

Sperm carries male genetic information, and flagella help move the sperm to reach oocytes. When the ultrastructure of the flagella is abnormal, the sperm is unable to reach the oocyte and achieve insemination. Multiple morphological abnormalities of sperm flagella (MMAF) is a relatively rare idiopathic condition that is mainly characterized by multiple defects in sperm flagella. In the last decade, with the development of high-throughput DNA sequencing approaches, many genes have been revealed to be related to MMAF. However, the differences in sperm phenotypes and reproductive outcomes in many cases are attributed to different pathogenic genes or different pathogenic mutations in the same gene. Here, we will review information about the various phenotypes resulting from different pathogenic genes, including sperm ultrastructure and encoding proteins with their location and functions as well as assisted reproductive technology (ART) outcomes. We will share our clinical detection and diagnosis experience to provide additional clinical views and broaden the understanding of this disease.

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