Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients’ platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) (p < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) (p < 0.05), strong alteration in the membrane Young modulus, increased production of platelets’ microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia (FVL, FII20210A, PLA1/A2, MTHFR C677T or 4G/5G PAI-1) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes.

Summary: The present study aimed to evaluate the impact of factor V Leiden (FVL) polymorphism within the reproductive problems encountered by patients with polycystic ovary syndrome (PCOS). A total of 92 female patients with PCOS and 101 healthy controls were included in the study. Clinical and laboratory parameters were examined. The full history of each patient was taken. Single nucleotide polymorphism rs6025 in F5 was genotyped in PCOS patients and compared to the genotype frequency of the healthy controls. The data were analysed for correlation with infertility and pregnancy loss in PCOS patients. The prevalence of FVL polymorphism was higher, however not significantly, in PCOS patients compared to that of the control group (respectively OR=2.238, 95 % CI 0.777±6.449, p=0.104). The carriers of FVL polymorphism showed a higher rate of primary infertility (30.0% versus 12.5%, OR=3.143, 9 % CI 0.686±14.388, p=0.047) and their total reproductive failure rate was higher (60.5% versus 47.2%, OR=1.819, 95% CI 0.632±9.259, p=0.117). Carriage of FVL polymorphism in PCOS patients is associated with primary infertility and a presumed cause of the further investigations needed to understand the impact of FVL on PCOS. Carriage of FVL polymorphism in PCOS patients is associated with a higher rate of primary infertility, which draws attention to the role of this factor in the aetiology of the PCOS-related subfertility. Further investigations are needed to understand the impact of FVL on PCOS.