Increased sperm count may account for high population frequency of factor V Leiden

Abstract

To cite this article: Cohn DM, Repping S, Bü ller HR, Meijers JCM, Middeldorp S. Increased sperm count may account for high population frequency of factor V Leiden. J Thromb Haemost 2010; 8: 513-6. Summary. Background: Factor V Leiden (FVL) increases the risk of venous thrombosis and pregnancy loss in carriers. Nevertheless, this relatively old mutation is prevalent in Caucasion populations, which could be explained by positive selection pressure. Men with FVL have previously been found to have higher fecundity (the time between marriage and first pregnancy). Whether this is caused by increased sperm counts in men with FVL is unknown. Objectives: To assess whether men with factor V Leiden have increased sperm counts. Patients/ methods: We performed a prospective cohort study among 1139 consecutively included male partners of subfertile couples presenting at our university hospital for fertility workup between January 2000 and July 2007. All potential candidates who gave informed consent were included, irrespective of their fertility workup. In this retrospective analysis, we excluded participants with known causes of spermatogenic function or azoospermia. Subsequently, we genotyped all participants and compared sperm counts between FVL carriers and noncarriers. Results: We identified 37 FVL carriers and 921 noncarriers. FVL carriers had higher total sperm counts and total motile sperm counts than non-carriers: 236 · 10 6 (95% CI 158-292 · 10 ), respectively. Conclusions: To our knowledge, this is the first study that indicates that an increased incidence of a genotype may be controlled by increased sperm counts. However, the finding that men with FVL had higher total (motile) sperm counts was not statistically significant and needs confirmation in other studies.

Mutations of Two Major Coagulation Factors Are Not Associated with Male Infertility

“…There was only one other study conducted in male partners of subfertile couples regardless of their spermatogenesis status, which reported that factor V Leiden carriers had higher total sperm counts and total motile sperm counts than noncarriers. However, these findings were not statistically significant (21).…”

Evolution of Factor V Leiden

“…Possibly contributing to the aforementioned high fecundity in FVL males is a statistically non-significant elevation in sperm count. In a cohort of men of subfertile couples, total sperm count was 236 • 10 6 (95%CI 158 -292 • 10 6 ) in FVL carriers versus 163 • 10 6 (95%CI 147 -178• 10 6 ) in controls (11).…”

“…Survival benefits mainly relate to haemorrhage and inflammation although data are conflicting, especially on inflammation. Nevertheless FVL might be associated with: less acute blood loss, less menstrual blood loss, decreased risk of intracranial haemorrhage, milder phenotypes of haemophilia, higher survival in and lower susceptibility to severe sepsis, higher survival in acute respiratory distress syndrome (ARDS), decreased diabetic nephropathy, improved embryo implantation, a higher sperm count and higher fecundity in both men and women (see ▶ Table 1) (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25).…”

Inherited thrombophilia: a double-edged sword

“…These findings inspired us to investigate male fertility by means of sperm counts in a pilot study among 19 male carriers identified in our previous family study. 56 Next, we identified 37 factor V Leiden carriers and 921 noncarriers in a prospective cohort study of male partners of subfertile couples in whom an established diagnosis of abnormal spermatogenic function was ruled out. 56 The total sperm count appeared higher in factor V Leiden carriers than in noncarriers, but the difference was not statistically significant.…”

“…56 Next, we identified 37 factor V Leiden carriers and 921 noncarriers in a prospective cohort study of male partners of subfertile couples in whom an established diagnosis of abnormal spermatogenic function was ruled out. 56 The total sperm count appeared higher in factor V Leiden carriers than in noncarriers, but the difference was not statistically significant. Although the results drew some attention on conference presentations, it took a long time before the manuscript was accepted in a peer-reviewed journal, which may have been because of an absence of a biological explanation.…”