Abstract
BackgroundRecurrent 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.MethodsA 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.ResultsWe 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.ConclusionsThis 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.
Highlights
Recurrent pregnancy loss (RPL) is defined as the loss of at least three pregnancies in the first trimester
Population (Table 1) A total of 33 volunteers were included in the unexplained recurrent pregnancy loss (URPL) group and 27 in the control group
The median age of the men did not differ between the URPL and control groups (34 [30–36] and 33 [29–35] years, respectively) but male body mass index (BMI) was significantly higher in the URPL group than in controls (25 [23,24,25] versus 24 [22,23,24,25], P = .025)
Summary
Recurrent pregnancy loss (RPL) is defined as the loss of at least three pregnancies in the first trimester. 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. Pregnancy loss is defined as a miscarriage occurring before 12 weeks of gestation. The most common cause of these losses is embryo aneuploidy. Recurrent pregnancy loss (RPL) is defined as three or more consecutive early pregnancy losses in the first trimester of gestation. The total number of motile spermatozoa has been found to be significantly decreased in RPL compared with fertile men [2, 3] and morphological sperm alterations are more numerous [4,5,6,7,8,9,10,11]
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