Semin Reprod Med 2021; 39(05/06): 180-185
DOI: 10.1055/s-0041-1732375
Review Article

Prior Thromboembolic Disease and Assisted Reproductive Therapy

Anne Flem Jacobsen
1   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
2   Department of Obstetrics, Oslo University Hospital, Oslo, Norway
,
1   Institute of Clinical Medicine, University of Oslo, Oslo, Norway
3   Department of Hematology, Oslo University Hospital, Oslo, Norway
› Author Affiliations

Abstract

Assisted reproductive therapy (ART) increases the risk of venous thrombosis (VT) by 2- to 4-fold, whereas pregnancy increases the risk by 5- to 10-fold. Women with a history of VT undergoing ART are often suggested thromboprophylaxis. The literature is scarce and international guidelines are lacking. We made a review of the literature and base our suggestions primarily on expert opinions. We suggest women with a prior VT to use low-molecular-weight heparin as thromboprophylaxis starting from ovarian stimulation, throughout pregnancy, and 6 weeks postpartum. Assessment of VT risk should be done prior to ART. Adjustment of treatment to minimize the thrombotic risk, such as preventing ovarian hyperstimulation syndrome, single-embryo transfer, cryopreservation, and transfer of frozen embryos instead of fresh embryo in high-risk women, is suggested. Women with previous arterial thrombosis should continue aspirin during ART treatment, pregnancy, and postpartum.



Publication History

Article published online:
14 July 2021

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  • References

  • 1 Calhaz-Jorge C, De Geyter C, Kupka MS. et al; European IVF-Monitoring Consortium (EIM), European Society of Human Reproduction and Embryology (ESHRE). Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE. Hum Reprod 2017; 32 (10) 1957-1973
  • 2 Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Otterblad Olausson P. Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years. Hum Reprod 2010; 25 (04) 1026-1034
  • 3 Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium--a register-based case-control study. Am J Obstet Gynecol 2008; 198 (02) 233.e1-233.e7
  • 4 James AH, Jamison MG, Brancazio LR, Myers ER. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006; 194 (05) 1311-1315
  • 5 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
  • 6 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: e8632
  • 7 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
  • 8 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
  • 9 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
  • 10 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
  • 11 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
  • 12 Grandone E, Villani M, Colaizzo D. et al. Venous thromboembolism in women undergoing assisted reproduction: data from RIETE. Res Pract Thromb Haemost 2017; 1 (Suppl. 01) 1027
  • 13 Grandone E, Di Micco PP, Villani M. et al; RIETE Investigators. Venous thromboembolism in women undergoing assisted reproductive technologies: data from the RIETE Registry. Thromb Haemost 2018; 118 (11) 1962-1968
  • 14 Girolami A, Scandellari R, Tezza F, Paternoster D, Girolami B. Arterial thrombosis in young women after ovarian stimulation: case report and review of the literature. J Thromb Thrombolysis 2007; 24 (02) 169-174
  • 15 Chan WS, Ginsberg JS. A review of upper extremity deep vein thrombosis in pregnancy: unmasking the ‘ART’ behind the clot. J Thromb Haemost 2006; 4 (08) 1673-1677
  • 16 Nelson-Piercy C. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium: Royal College of Obstetricians and Gynaecologists. 2015 [cited November 2020]. Accessed June 30, 2021 at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/
  • 17 AORFH SFOG. Riktlinjer för trombosprofylax vid IVF, 130131. Revised 19.04. 2018 . Stockholm 2013 [cited November 2020]. Accessed June 30, 2021 at: https://www.sfog.se/start/raadriktlinjer/sfog-riktlinjer/
  • 18 Jacobsen AFSP, Damm A, Chen S, Sagberg K. Trombose, antikoagulasjon og svangerskap Den Norske Legeforening (The Medical Norwegian Association). 2020 [cited November 2020]. Accessed June 30, 2021 at: https://www.legeforeningen.no/foreningsledd/fagmed/norsk-gynekologisk-forening/veiledere/veileder-i-fodselshjelp/trombose-antikoagulasjon-og-svangerskap/
  • 19 Hellgren MLP, Rova K, Bremme K. et al. Hemostasrubbningar inom obstetrik och gynekologi Arbets - OCH Referensgrupp för Hemostasrubbningar Rapport nr 79 2018. Swedish Association of Obstetrics and Gynecology. 2018
  • 20 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
  • 21 Gurunath S, Vinekar S, Biliangady R. Assisted reproductive techniques in a patient with history of venous thromboembolism: a case report and review of literature. J Hum Reprod Sci 2018; 11 (02) 193-197
  • 22 Sachar P, Rajamani K. Young ischemic stroke in association with ovarian hyperstimulation syndrome. J Stroke Cerebrovasc Dis 2016; 25 (09) e134-e140
  • 23 Nelson SM. Prophylaxis of VTE in women - during assisted reproductive techniques. Thromb Res 2009; 123 (Suppl. 03) S8-S15
  • 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 Westerlund E, Henriksson P, Wallén H, Hovatta O, Wallberg KR, Antovic A. Detection of a procoagulable state during controlled ovarian hyperstimulation for in vitro fertilization with global assays of haemostasis. Thromb Res 2012; 130 (04) 649-653
  • 26 Nelson SM, Greer IA. Thrombophilia and the risk for venous thromboembolism during pregnancy, delivery, and puerperium. Obstet Gynecol Clin North Am 2006; 33 (03) 413-427
  • 27 Bauersachs RM, Manolopoulos K, Hoppe I, Arin MJ, Schleussner E. More on: the ‘ART’ behind the clot: solving the mystery. J Thromb Haemost 2007; 5 (02) 438-439
  • 28 Olausson N, Mobarrez F, Wallen H, Westerlund E, Hovatta O, Henriksson P. Microparticles reveal cell activation during IVF - a possible early marker of a prothrombotic state during the first trimester. Thromb Haemost 2016; 116 (03) 517-523
  • 29 Curvers J, Nienhuis SJ, Nap AW, Hamulyák K, Evers JL, Rosing J. Activated protein C resistance during in vitro fertilization treatment. Eur J Obstet Gynecol Reprod Biol 2001; 95 (02) 222-224
  • 30 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
  • 31 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
  • 32 Lindqvist PG, Bremme K, Hellgren M. Working Group on Hemostatic Disorders (Hem-ARG), Swedish Society of Obstetrics and Gynecology. Efficacy of obstetric thromboprophylaxis and long-term risk of recurrence of venous thromboembolism. Acta Obstet Gynecol Scand 2011; 90 (06) 648-653
  • 33 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
  • 34 Clark P, Greer IA. Prevention and treatment of arterial thrombosis in pregnancy. Semin Thromb Hemost 2003; 29 (02) 155-164
  • 35 Butwick AJ, Carvalho B. Neuraxial anesthesia in obstetric patients receiving anticoagulant and antithrombotic drugs. Int J Obstet Anesth 2010; 19 (02) 193-201
  • 36 Haapsamo M, Martikainen H, Tinkanen H, Heinonen S, Nuojua-Huttunen S, Räsänen J. Low-dose aspirin therapy and hypertensive pregnancy complications in unselected IVF and ICSI patients: a randomized, placebo-controlled, double-blind study. Hum Reprod 2010; 25 (12) 2972-2977
  • 37 Wang L, Huang X, Li X. et al. Efficacy evaluation of low-dose aspirin in IVF/ICSI patients evidence from 13 RCTs: a systematic review and meta-analysis. Medicine (Baltimore) 2017; 96 (37) e7720