Angela Q Leung1,2,3, Avery Davis Bell4,5,6, Curtis J Mello4,5, Alan S Penzias7,8,9, Steven A McCarroll4,5, Denny Sakkas7. 1. Boston IVF, Boston, MA, USA. angela.q.leung@gmail.com. 2. Division of Reproductive Endocrinology and Infertility, Department of Ob/Gyn, Beth Israel Deaconess Medical Center, Boston, MA, USA. angela.q.leung@gmail.com. 3. Harvard Medical School, Boston, MA, USA. angela.q.leung@gmail.com. 4. Department of Genetics, Harvard Medical School, Boston, MA, USA. 5. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. 6. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA. 7. Boston IVF, Boston, MA, USA. 8. Division of Reproductive Endocrinology and Infertility, Department of Ob/Gyn, Beth Israel Deaconess Medical Center, Boston, MA, USA. 9. Harvard Medical School, Boston, MA, USA.
Abstract
PURPOSE: This pilot study sought to (1) validate the use of a novel technology for single-sperm-cell genome sequencing (Sperm-seq) in infertile men who may not have optimal quantity or quality of sperm for genomic analysis and (2) compare these results to fertile donors. METHODS: Infertile men undergoing IVF with female partners with a previous history of failed fertilization with ICSI (FF) or poor blastulation of embryos (PB) were recruited from a large IVF center. Sperm-seq was used to analyze thousands of individual sperm and was carried out at an affiliated university research institute. Global aneuploidy rate, crossover locations, and crossover frequencies were assessed in the infertile population, and compared with a control group of 20 fertile donors, which were analyzed previously at the same laboratory. RESULTS: Eight patients were initially included, but 3 samples did not yield high-quality genomic data for analysis. A total of 10,042 sperm were analyzed from 5 patients, 2 in the FF group, and 3 in the PB group. The global aneuploidy rate among the samples was 2-4%, similar to the control group. Likewise, crossover locations and frequencies were similar. CONCLUSION: Sperm-seq provides a robust analysis but may not be applicable to all male infertility cases due to technical limitations. This group of male infertility patients did not have higher rates of aneuploidy or abnormal crossover patterns compared to a fertile donor population. Our data may suggest that FF and PB phenotypes may not be related to sperm aneuploidy or meiotic errors but rather to other intrinsic nuclear anomalies.
PURPOSE: This pilot study sought to (1) validate the use of a novel technology for single-sperm-cell genome sequencing (Sperm-seq) in infertile men who may not have optimal quantity or quality of sperm for genomic analysis and (2) compare these results to fertile donors. METHODS: Infertile men undergoing IVF with female partners with a previous history of failed fertilization with ICSI (FF) or poor blastulation of embryos (PB) were recruited from a large IVF center. Sperm-seq was used to analyze thousands of individual sperm and was carried out at an affiliated university research institute. Global aneuploidy rate, crossover locations, and crossover frequencies were assessed in the infertile population, and compared with a control group of 20 fertile donors, which were analyzed previously at the same laboratory. RESULTS: Eight patients were initially included, but 3 samples did not yield high-quality genomic data for analysis. A total of 10,042 sperm were analyzed from 5 patients, 2 in the FF group, and 3 in the PB group. The global aneuploidy rate among the samples was 2-4%, similar to the control group. Likewise, crossover locations and frequencies were similar. CONCLUSION: Sperm-seq provides a robust analysis but may not be applicable to all male infertility cases due to technical limitations. This group of male infertility patients did not have higher rates of aneuploidy or abnormal crossover patterns compared to a fertile donor population. Our data may suggest that FF and PB phenotypes may not be related to sperm aneuploidy or meiotic errors but rather to other intrinsic nuclear anomalies.
Authors: Maartje Cissen; Madelon van Wely; Irma Scholten; Steven Mansell; Jan Peter de Bruin; Ben Willem Mol; Didi Braat; Sjoerd Repping; Geert Hamer Journal: PLoS One Date: 2016-11-10 Impact factor: 3.240
Authors: Christopher L R Barratt; Lars Björndahl; Christopher J De Jonge; Dolores J Lamb; Francisco Osorio Martini; Robert McLachlan; Robert D Oates; Sheryl van der Poel; Bianca St John; Mark Sigman; Rebecca Sokol; Herman Tournaye Journal: Hum Reprod Update Date: 2017-11-01 Impact factor: 15.610