Jianzheng Fang1, Jingjing Zhang2,3, Fuxi Zhu2,3, Xiaoyu Yang1, Yugui Cui1, Jiayin Liu1. 1. State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. 2. Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. 3. Anhui Province Key Laboratory of Reproductive Health and Genetics, Anhui Medical University, Hefei, China.
Abstract
STUDY QUESTION: Are Sad1 and UNC84 domain containing 5 (SUN5) mutations associated with the outcomes of ICSI in patients with acephalic spermatozoa syndrome (ASS)? SUMMARY ANSWER: Despite highly abnormal sperm morphology, ASS patients with SUN5 mutations have a favorable pregnancy outcome following ICSI. WHAT IS KNOWN ALREADY: ASS is a rare cause of infertility characterized by the production of a majority of headless spermatozoa, along with a small proportion of intact spermatozoa with an abnormal head-tail junction. Previous studies have demonstrated that SUN5 mutations may cause ASS. Several studies showed that ICSI could help patients with ASS father children. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 11 infertile ASS males with SUN5 mutations. Five of them underwent five ICSI cycles. Their ICSI results were compared to men with ASS without SUN5 mutations (n = 3) and to men with multiple morphological abnormalities of the sperm flagella (MMAF) (n = 9). All ICSI treatments were completed between Jan 2011 and May 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sanger DNA sequencing was used to detect mutations in SUN5. Clinical and biological data were collected from patients at the fertility center. MAIN RESULTS AND THE ROLE OF CHANCE: Sanger sequencing validated 11 patients with SUN5 mutations. Three novel mutations in SUN5 (c.829C>T [p.Q277*]; c.1067G>A [p.R356H]; c.211+1 insGT [p.S71Cfs11*]) were identified in three patients. The rates of fertilization, good-quality embryos and pregnancy for five patients with SUN5 mutations following ICSI were 81.5%, 81.8% and 100%, respectively. The rates of fertilization and good-quality embryos in patients with MMAF were significantly lower compared with ASS patients (65.6 versus 82.4%, P = 0.039 and 53.6 versus 85.2%, P = 0.031, respectively). There were no differences in ICSI results between ASS patients with and without SUN5 mutations. LIMITATIONS, REASONS FOR CAUTION: Only a small number patients with SUN5 mutations was available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS: Patients with ASS can be effectively treated with ICSI. SUN5 mutations may be one of the genetic causes of ASS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (81401251, 81370754, and 81170559), the Jiangsu Province Special Program of Medical Science (BL2012009, ZX201110, FXK201221) and a project funded by PAPD of the Priority Academic Program Development of Jiangsu High Education Institutions (JX10231802). None of the authors have any competing interests.
STUDY QUESTION: Are Sad1 and UNC84 domain containing 5 (SUN5) mutations associated with the outcomes of ICSI in patients with acephalic spermatozoa syndrome (ASS)? SUMMARY ANSWER: Despite highly abnormal sperm morphology, ASSpatients with SUN5 mutations have a favorable pregnancy outcome following ICSI. WHAT IS KNOWN ALREADY: ASS is a rare cause of infertility characterized by the production of a majority of headless spermatozoa, along with a small proportion of intact spermatozoa with an abnormal head-tail junction. Previous studies have demonstrated that SUN5 mutations may cause ASS. Several studies showed that ICSI could help patients with ASS father children. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study included 11 infertile ASS males with SUN5 mutations. Five of them underwent five ICSI cycles. Their ICSI results were compared to men with ASS without SUN5 mutations (n = 3) and to men with multiple morphological abnormalities of the sperm flagella (MMAF) (n = 9). All ICSI treatments were completed between Jan 2011 and May 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sanger DNA sequencing was used to detect mutations in SUN5. Clinical and biological data were collected from patients at the fertility center. MAIN RESULTS AND THE ROLE OF CHANCE: Sanger sequencing validated 11 patients with SUN5 mutations. Three novel mutations in SUN5 (c.829C>T [p.Q277*]; c.1067G>A [p.R356H]; c.211+1 insGT [p.S71Cfs11*]) were identified in three patients. The rates of fertilization, good-quality embryos and pregnancy for five patients with SUN5 mutations following ICSI were 81.5%, 81.8% and 100%, respectively. The rates of fertilization and good-quality embryos in patients with MMAF were significantly lower compared with ASSpatients (65.6 versus 82.4%, P = 0.039 and 53.6 versus 85.2%, P = 0.031, respectively). There were no differences in ICSI results between ASSpatients with and without SUN5 mutations. LIMITATIONS, REASONS FOR CAUTION: Only a small number patients with SUN5 mutations was available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS:Patients with ASS can be effectively treated with ICSI. SUN5 mutations may be one of the genetic causes of ASS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (81401251, 81370754, and 81170559), the Jiangsu Province Special Program of Medical Science (BL2012009, ZX201110, FXK201221) and a project funded by PAPD of the Priority Academic Program Development of Jiangsu High Education Institutions (JX10231802). None of the authors have any competing interests.
Authors: Brian J Galletta; Jacob M Ortega; Samantha L Smith; Carey J Fagerstrom; Justin M Fear; Sharvani Mahadevaraju; Brian Oliver; Nasser M Rusan Journal: Dev Cell Date: 2020-03-12 Impact factor: 12.270