Marcello Di Nisio a,b,*, Adalisa Ponzano b,c, Gian Mario Tiboni b,c, Maria Domenica Guglielmi d, Anne Wilhelmina Saskia Rutjes e,f, Ettore Porreca g
a Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
b Department of Medicine and Ageing Sciences, University G. D’Annunzio, Chieti-Pescara, Italy
c Unit of Assisted Reproductive Technology, Ortona General Hospital, Ortona, Chieti, Italy
d Department of Internal Medicine, Ospedale SS.ma Annunziata, Chieti, Italy
e Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
f Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
g Department of Medical, Oral and Biotechnological Sciences, Gabriele D’Annunzio University, Chieti, Italy
ABSTRACT:
Introduction: The effects of multiple inherited and acquired thrombophilic defects on the outcome of in-vitro
fertilization (IVF) remain unexplored. The aim of this study was to evaluate the association between multiple
thrombophilia and clinical outcomes in a large prospective cohort of women undergoing IVF.
Materials and methods: Consecutive women scheduled for IVF were eligible. The primary study outcome was live
birth. Secondary outcomes included spontaneous abortion, clinical pregnancy, and symptomatic venous
thromboembolism.
Results: 687 women with a mean age of 34.6 (±3.2) years were included. Overall, 22 women (3.2%) had two or
more thrombophilic defects. The probability of live birth was not statistically significantly different between
women with ≥2 thrombophilia (odds ratio [OR] 0.62; 95% confidence interval [CI], 0.18 to 2.11) or ≥1
thrombophilia (OR 0.67;95% CI, 0.41 to 1.09) and women without any thrombophilia. None of the individual
inherited thrombophilia nor positivity to antiphospholipid antibodies or lupus anticoagulant were associated
with live birth. Single positivity for lupus anticoagulant carried a more than threefold higher risk of abortion (OR
3.74; 95% CI, 1.30 to 10.75). There were no statistically significant associations between individual or multiple
thrombophilic defects and clinical pregnancy or pregnancy test results. No woman had a history of venous
thromboembolism and none developed a thrombotic event during the study.
Conclusions: In women undergoing IVF, the presence of two or more thrombophilic defects was rare and showed
no statistically significant associations with IVF outcomes.