Christian De Geyter1,2, Ursula Gobrecht-Keller3, Astrid Ahler3, Manuel Fischer3. 1. Reproductive Medicine and Gynecological Endocrinology (RME), University Hospital, University of Basel, Vogesenstrasse 134, CH-4031, Basel, Switzerland. christian.degeyter@usb.ch. 2. Reproductive Medicine and Gyn. Endocrinology (RME), Vogesenstrasse 134, CH-4031, Basel, Switzerland. christian.degeyter@usb.ch. 3. Reproductive Medicine and Gynecological Endocrinology (RME), University Hospital, University of Basel, Vogesenstrasse 134, CH-4031, Basel, Switzerland.
Abstract
PURPOSE: The DNA fragmentation in sperm is associated with reduced outcome in assisted reproduction. Using YoPro1 as the staining dye and flow cytometry and sorting (FACS), the number of spermatozoa with DNA fragmentation can be lowered to 5%. Can the cumulative outcome of ICSI be improved using FACS? METHODS: A prospective, randomized, double-blind clinical trial was conducted in 104 infertile couples with male infertility based on abnormal conventional semen analysis results. Cumulative ongoing pregnancy rate was the primary outcome parameter. In 52 cases, semen was processed for ICSI using swim-up. In another 52 cases, spermatozoa with fragmented DNA were removed with FACS. RESULTS: The cumulative pregnancy rate at 12 weeks of gestation (51.9% versus 46.2%) and live birth rate (42.3% versus 34.6%) were higher and the miscarriage rate was lower (27.8% versus 35.3%) after FACS-sorting as compared with swim-up. An interim analysis scheduled before initiation of the study after 100 cases demonstrated that the aim of a 20% gain in pregnancy rate could not be achieved. For that reason, the prospective study was stopped prematurely. CONCLUSIONS: A trend towards consistently better results was achieved by removing spermatozoa with fragmented DNA. The fragmentation of the DNA in sperm is the end stage of apoptosis. Sorting of spermatozoa may be improved by selecting parameters of processes active more upstream of apoptosis, such as chromatin decondensation. TRIAL REGISTRATION: NCT02166567 . June 14, 2014.
RCT Entities:
PURPOSE: The DNA fragmentation in sperm is associated with reduced outcome in assisted reproduction. Using YoPro1 as the staining dye and flow cytometry and sorting (FACS), the number of spermatozoa with DNA fragmentation can be lowered to 5%. Can the cumulative outcome of ICSI be improved using FACS? METHODS: A prospective, randomized, double-blind clinical trial was conducted in 104 infertile couples with male infertility based on abnormal conventional semen analysis results. Cumulative ongoing pregnancy rate was the primary outcome parameter. In 52 cases, semen was processed for ICSI using swim-up. In another 52 cases, spermatozoa with fragmented DNA were removed with FACS. RESULTS: The cumulative pregnancy rate at 12 weeks of gestation (51.9% versus 46.2%) and live birth rate (42.3% versus 34.6%) were higher and the miscarriage rate was lower (27.8% versus 35.3%) after FACS-sorting as compared with swim-up. An interim analysis scheduled before initiation of the study after 100 cases demonstrated that the aim of a 20% gain in pregnancy rate could not be achieved. For that reason, the prospective study was stopped prematurely. CONCLUSIONS: A trend towards consistently better results was achieved by removing spermatozoa with fragmented DNA. The fragmentation of the DNA in sperm is the end stage of apoptosis. Sorting of spermatozoa may be improved by selecting parameters of processes active more upstream of apoptosis, such as chromatin decondensation. TRIAL REGISTRATION: NCT02166567 . June 14, 2014.
Entities:
Keywords:
Apoptosis; Chromatin remodeling; DNA fragmentation; Flow cytometry; ICSI
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