Subscribe to RSS
DOI: 10.1055/s-0042-1760255
Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis
Abstract
Background Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined.
Methods We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART.
Results Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07–0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60–4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86–255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41–2.23 to 4.99, 95% CI: 1.24–20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0–115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7–13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41–137.45).
Conclusion Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.
Keywords
assisted reproductive technology - ovarian hyperstimulation syndrome - venous thromboembolism - pulmonary embolism - deep vein thrombosisPublication History
Received: 01 July 2022
Accepted: 18 October 2022
Article published online:
31 December 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 De Geyter C, Calhaz-Jorge C, Kupka MS. et al; European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2014: results generated from European registries by ESHRE: the European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Hum Reprod 2018; 33 (09) 1586-1601
- 2 Sanchez O, Benhamou Y, Bertoletti L. et al. Recommandations de bonne pratique pour la prise en charge de la maladie veineuse thromboembolique chez l'adulte. Version courte. Rev Mal Respir 2019; 36 (02) 249-283
- 3 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
- 4 Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (02) (2, Suppl): e691S-e736S
- 5 Bates SM, Rajasekhar A, Middeldorp S. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv 2018; 2 (22) 3317-3359
- 6 Al-Sabbak M. Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium. Green-Top Guideline No. 37a. RCOG Green Top Guideline. Published online April 2015
- 7 Royal College of Obstetricians and Gynaecologists. The Management of Ovarian Hyperstimulation Syndrome. Green-top Guideline No. 5 February 2016. RCOG Green Top Guideline. Published online February 26, 2016; London: RCOG; 2016.
- 8 Conard J. Thromboses artérielles et veineuses dans le cadre de l'Assistance Médicale à la Procréation (AMP): prévention et prise en charge. Recommandation de bonne pratique. Agence de biomédecine. Published July 15, 2013. Accessed December 6, 2022 at: https://www.agence-biomedecine.fr/IMG/pdf/recommandations_amp_thromboses_vdef.pdf
- 9 Page MJ, McKenzie JE, Bossuyt PM. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372 (71) n71
- 10 Abramov Y, Elchalal U, Schenker JG. Febrile morbidity in severe and critical ovarian hyperstimulation syndrome: a multicentre study. Hum Reprod 1998; 13 (11) 3128-3131
- 11 Abramov Y, Elchalal U, Schenker JG. Pulmonary manifestations of severe ovarian hyperstimulation syndrome: a multicenter study. Fertil Steril 1999; 71 (04) 645-651
- 12 Filipovic-Pierucci A, Gabet A, Deneux-Tharaux C, Plu-Bureau G, Olié V. Arterial and venous complications after fertility treatment: a French nationwide cohort study. Eur J Obstet Gynecol Reprod Biol 2019; 237: 57-63
- 13 Grandone E, Colaizzo D, Vergura P. et al. Age and homocysteine plasma levels are risk factors for thrombotic complications after ovarian stimulation. Hum Reprod 2004; 19 (08) 1796-1799
- 14 Hansen AT, Kesmodel US, Juul S, Hvas AM. No evidence that assisted reproduction increases the risk of thrombosis: a Danish national cohort study. Hum Reprod 2012; 27 (05) 1499-1503
- 15 Hansen AT, Kesmodel US, Juul S, Hvas AM. Increased venous thrombosis incidence in pregnancies after in vitro fertilization. Hum Reprod 2014; 29 (03) 611-617
- 16 Hansen AT, Juul S, Knudsen UB, Hvas AM. Low risk of venous thromboembolism following early pregnancy loss in pregnancies conceived by IVF. Hum Reprod 2018; 33 (10) 1968-1972
- 17 Henriksson P, Westerlund E, Wallén H, Brandt L, Hovatta O, Ekbom A. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study. BMJ 2013; 346 (jan15 3): e8632-e8632
- 18 Jacobsen AF, Skjeldestad FE, Sandset PM. Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. J Thromb Haemost 2008; 6 (06) 905-912
- 19 Michalas S, Loutradis D, Drakakis P. et al. Oocyte donation to women over 40 years of age: pregnancy complications. Eur J Obstet Gynecol Reprod Biol 1996; 64 (02) 175-178
- 20 Murugappan G, Li S, Lathi RB, Baker VL, Luke B, Eisenberg ML. Increased risk of severe maternal morbidity among infertile women: analysis of US claims data. Am J Obstet Gynecol 2020; 223 (03) 404.e1-404.e20
- 21 Olausson N, Discacciati A, Nyman AI. et al. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilization with fresh respectively frozen-thawed embryo transfer: nationwide cohort study. J Thromb Haemost 2020; 18 (08) 1965-1973
- 22 Rova K, Passmark H, Lindqvist PG. Venous thromboembolism in relation to in vitro fertilization: an approach to determining the incidence and increase in risk in successful cycles. Fertil Steril 2012; 97 (01) 95-100
- 23 Selter J, Wen T, Palmerola KL, Friedman AM, Williams Z, Forman EJ. Life-threatening complications among women with severe ovarian hyperstimulation syndrome. Am J Obstet Gynecol 2019; 220 (06) 575.e1-575.e11
- 24 Villani M, Dentali F, Colaizzo D. et al. Pregnancy-related venous thrombosis: comparison between spontaneous and ART conception in an Italian cohort. BMJ Open 2015; 5 (10) e008213
- 25 Villani M, Favuzzi G, Totaro P. et al. Venous thromboembolism in assisted reproductive technologies: comparison between unsuccessful versus successful cycles in an Italian cohort. J Thromb Thrombolysis 2018; 45 (02) 234-239
- 26 Won HS, Kim DY, Yang MS, Lee SJ, Shin HH, Park JB. Pregnancy-induced hypertension, but not gestational diabetes mellitus, is a risk factor for venous thromboembolism in pregnancy. Korean Circ J 2011; 41 (01) 23-27
- 27 Yinon Y, Pauzner R, Dulitzky M, Elizur SE, Dor J, Shulman A. Safety of IVF under anticoagulant therapy in patients at risk for thrombo-embolic events. Reprod Biomed Online 2006; 12 (03) 354-358
- 28 Sennström M, Rova K, Hellgren M. et al. Thromboembolism and in vitro fertilization - a systematic review. Acta Obstet Gynecol Scand 2017; 96 (09) 1045-1052
- 29 Chan WS, Dixon ME. The “ART” of thromboembolism: a review of assisted reproductive technology and thromboembolic complications. Thromb Res 2008; 121 (06) 713-726
- 30 Chen CD, Wu MY, Chao KH, Lien YR, Chen SU, Yang YS. Update on management of ovarian hyperstimulation syndrome. Taiwan J Obstet Gynecol 2011; 50 (01) 2-10
- 31 Chauleur C, Gris JC, Laporte S. et al; STRATHEGE Group. Use of the Delphi method to facilitate antithrombotics prescription during pregnancy. Thromb Res 2010; 126 (02) 88-92
- 32 Chauleur C, Gris JC, Laporte S. et al; STRATHEGE Investigators and The STRATHEGE Group. Benefit of risk score-guided prophylaxis in pregnant women at risk of thrombotic events: a controlled before-and-after implementation study. Thromb Haemost 2018; 118 (09) 1564-1571
- 33 Dargaud Y, Rugeri L, Vergnes MC. et al. A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study. Br J Haematol 2009; 145 (06) 825-835
- 34 Delluc A, De Moreuil C, Kerspern H. et al. Body mass index, a major confounder to insulin resistance association with unprovoked venous thromboembolism. Results from the EDITH case-control study. Thromb Haemost 2013; 110 (03) 593-597
- 35 Tromeur C, Le Mao R, Leven C, Couturaud F, Théreaux J, Lacut K. Prise en charge diagnostique et thérapeutique de la maladie veineuse thromboembolique chez le patient obèse. Rev Mal Respir 2020; 37 (04) 328-340
- 36 Couturaud F, Leroyer C, Tromeur C. et al. Factors that predict thrombosis in relatives of patients with venous thromboembolism. Blood 2014; 124 (13) 2124-2130
- 37 Chan WS. The ‘ART’ of thrombosis: a review of arterial and venous thrombosis in assisted reproductive technology. Curr Opin Obstet Gynecol 2009; 21 (03) 207-218