Thromboembolism and in-vitro fertilization: a systematic review Maria Sennström1, Karin Rova2, Margareta Hellgren3, Ragnhild Hjertberg 4 , Eva Nord1, Lars Thurn2 ,5 & Pelle G Lindqvist2,6 1Dept. of Women’s and Children’s Health, Div of Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, 2CLINTEC, Karolinska Institute, Stockholm IVF, Stockholm, 3Dept. of Obstetrics and Gynecology, Institute for Clinical Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 4Ultragyn, Stockholm, 5Dept of Obstetrics and Gynecology, Skåne University Hospital, Lund, 6Karolinska University Hospital Huddinge, Stockholm, Sweden ACTA Obstetricia et Gynecologica Scandinavica Journal Club -Gynecology- September 2017 Edited by Francesco D’Antonio

Background Severe complications in in vitro fertilization (IVF) are rare . Ovarian hyper stimulation syndrome (OHSS) is the most common and serious of these complications. In its severe forms, it is associated with an increase in the risk of thromboembolism (TE). Data on the incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) related to OHSS are limited, and are dominated by case reports in the literature. IVF is reported to double the risk of TE in pregnancy, but the absolute risk is presumed to be low. The literature provides scarce data concerning the true incidence of TE and IVF and there is no generally accepted consensus on thromboprophylaxis in relation to IVF.

Aim of the study To assess the frequency of thromboembolism and to assess thromboprophylaxis in relation to IVF.

Methodology Study design: Systematic review. Medical databases: MEDLINE and the Cochrane Library (1966-2016). Inclusion criteria: All study designs were accepted except single case reports. Exclusion criteria: animal studies, biochemical studies, articles not addressing the subject, articles without patient data and reviews consisting of already included articles

Results (1)

Results (2) The frequency of TE during pregnancy in patients after IVF, with or without OHSS varies between 0.8-25 per 1000, compared to 0.17- 2.5 /1000 in the background pregnant population. In studies assessing the risk of antepartum VTE, the reported risk was approximately doubled, OR 2.2 (95% CI; 1.62.9) ( and the reported risk of first-trimester VTE was increased 5-10-fold (OR 6.4, 95%CI; 4.0-10.1). The risk of VTE after IVF failing to lead to conception was not increased, compared to a reference population.

Limitations Small number of included studies. Large heterogeneity in study design and inclusion criteria. Different outcomes measures reported. Lack of stratification according to maternal characteristics, co-morbidity and type of IVF.

Conclusion The antepartum risk of VTE after IVF is doubled, compared to the background pregnant population and is related to a very high risk of VTE after OHSS in the first trimester.