PMID- 29619224 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220316 IS - 2051-4190 (Print) IS - 2051-4190 (Electronic) IS - 2051-4190 (Linking) VI - 28 DP - 2018 TI - Sperm aneuploidy and DNA fragmentation in unexplained recurrent pregnancy loss: a multicenter case-control study. PG - 4 LID - 10.1186/s12610-018-0070-6 [doi] LID - 4 AB - BACKGROUND: Recurrent pregnancy loss (RPL) is defined as the loss of at least three pregnancies in the first trimester. Although the most common cause is embryo aneuploidy, and despite female checkup and couple karyotyping, in about 50% of cases RPL remain unexplained. Male implication has little been investigated and results are discordant. In this context, we conducted a multi-center prospective case-control study to investigate male gamete implication in unexplained RPL. METHODS: A total of 33 cases and 27 controls were included from three university hospitals. We investigated environmental and family factors with a detailed questionnaire and andrological examination, sperm characteristics, sperm DNA/chromatin status using the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and sperm aneuploidy using fluorescence in situ hybridization (FISH). The Mann-Whitney test and the Wilcoxon or Fisher exact tests were used. A non-parametric Spearman correlation was performed in order to analyze the relationship between various sperm parameters and FISH and sperm DNA fragmentation results. RESULTS: We found significant differences between cases and controls in time to conceive, body mass index (BMI), family history of infertility and living environment. In cases, total sperm motility and the percentage of morphologically normal spermatozoa were significantly decreased. No difference was found between cases and controls in sperm DNA fragmentation or chromatin integrity. In cases, spermatozoa with aneuploidy, hyperhaploidy and chromosome 18 disomy were significantly increased. CONCLUSIONS: This prospective case-control study is one of the largest to examine environmental factors, sperm characteristics, sperm DNA fragmentation and chromatin, and chromosome anomalies in spermatozoa in relation to unexplained recurrent pregnancy loss. The originality of our study lies in the comprehensive andrological examination and search for risk factors and fertility history. Further studies are needed to confirm the links between unexplained RPL and a male family history of infertility or miscarriages. The increased sperm aneuploidy observed in unexplained RPL supports a male etiology. These data pave the way for further studies to demonstrate the value of preimplantation genetic screening in men with increased sperm aneuploidy whose partners experience unexplained RPL. FAU - Esquerre-Lamare, Camille AU - Esquerre-Lamare C AD - 1Research Group on Human Fertility EA 3694, University Paul Sabatier Toulouse III, 330 av Grande Bretagne, 31059 Toulouse, France. ISNI: 0000 0001 0723 035X. GRID: grid.15781.3a AD - 2CECOS Groupe d'Activite de Medecine de la Reproduction, CHU Toulouse, Toulouse, France. ISNI: 0000 0001 1457 2980. GRID: grid.411175.7 FAU - Walschaerts, Marie AU - Walschaerts M AD - 1Research Group on Human Fertility EA 3694, University Paul Sabatier Toulouse III, 330 av Grande Bretagne, 31059 Toulouse, France. ISNI: 0000 0001 0723 035X. GRID: grid.15781.3a AD - 2CECOS Groupe d'Activite de Medecine de la Reproduction, CHU Toulouse, Toulouse, France. ISNI: 0000 0001 1457 2980. GRID: grid.411175.7 FAU - Chansel Debordeaux, Lucie AU - Chansel Debordeaux L AD - 3CECOS Service Biologie de la Reproduction, CHU Bordeaux, Bordeaux, France. ISNI: 0000 0004 0593 7118. GRID: grid.42399.35 FAU - Moreau, Jessika AU - Moreau J AD - 1Research Group on Human Fertility EA 3694, University Paul Sabatier Toulouse III, 330 av Grande Bretagne, 31059 Toulouse, France. ISNI: 0000 0001 0723 035X. GRID: grid.15781.3a AD - 2CECOS Groupe d'Activite de Medecine de la Reproduction, CHU Toulouse, Toulouse, France. ISNI: 0000 0001 1457 2980. GRID: grid.411175.7 FAU - Bretelle, Florence AU - Bretelle F AD - 4Service de Gynecologie-Obstetrique, AP-HM Hopital Nord Marseille, Marseille, France. ISNI: 0000 0001 0407 1584. GRID: grid.414336.7 FAU - Isus, Francois AU - Isus F AD - 1Research Group on Human Fertility EA 3694, University Paul Sabatier Toulouse III, 330 av Grande Bretagne, 31059 Toulouse, France. ISNI: 0000 0001 0723 035X. GRID: grid.15781.3a AD - 5Andrologie, Groupe d'Activite de Medecine de la Reproduction, CHU Toulouse, Toulouse, France. ISNI: 0000 0001 1457 2980. GRID: grid.411175.7 FAU - Karsenty, Gilles AU - Karsenty G AD - 6Service d'Urologie et Transplantation Renale, AP-HM La Conception, Marseille, France. ISNI: 0000 0001 0407 1584. GRID: grid.414336.7 FAU - Monteil, Laetitia AU - Monteil L AD - 7Service de Genetique Medicale, CHU Toulouse, Toulouse, France. ISNI: 0000 0001 1457 2980. GRID: grid.411175.7 FAU - Perrin, Jeanne AU - Perrin J AD - 8CECOS Laboratoire de Biologie de la Reproduction, AP-HM La Conception, Marseille, France. ISNI: 0000 0001 0407 1584. GRID: grid.414336.7 AD - 9Mediterranean Institute for Biodiversity and Ecology (IMBE), Aix-Marseille Universite, CNRS, IRD, Avignon University, Marseille, France. ISNI: 0000 0001 2190 2394. GRID: grid.7310.5 FAU - Papaxanthos-Roche, Aline AU - Papaxanthos-Roche A AD - 3CECOS Service Biologie de la Reproduction, CHU Bordeaux, Bordeaux, France. ISNI: 0000 0004 0593 7118. GRID: grid.42399.35 FAU - Bujan, Louis AU - Bujan L AD - 1Research Group on Human Fertility EA 3694, University Paul Sabatier Toulouse III, 330 av Grande Bretagne, 31059 Toulouse, France. ISNI: 0000 0001 0723 035X. GRID: grid.15781.3a AD - 2CECOS Groupe d'Activite de Medecine de la Reproduction, CHU Toulouse, Toulouse, France. ISNI: 0000 0001 1457 2980. GRID: grid.411175.7 LA - eng PT - Journal Article DEP - 20180402 PL - England TA - Basic Clin Androl JT - Basic and clinical andrology JID - 101640161 PMC - PMC5879915 OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Sperm DNA fragmentation OT - Sperm aneuploidy OT - Unexplained recurrent pregnancy loss COIS- Done in the manuscript (Methods section).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/04/06 06:00 MHDA- 2018/04/06 06:01 PMCR- 2018/04/02 CRDT- 2018/04/06 06:00 PHST- 2018/01/18 00:00 [received] PHST- 2018/03/08 00:00 [accepted] PHST- 2018/04/06 06:00 [entrez] PHST- 2018/04/06 06:00 [pubmed] PHST- 2018/04/06 06:01 [medline] PHST- 2018/04/02 00:00 [pmc-release] AID - 70 [pii] AID - 10.1186/s12610-018-0070-6 [doi] PST - epublish SO - Basic Clin Androl. 2018 Apr 2;28:4. doi: 10.1186/s12610-018-0070-6. eCollection 2018.