Semin Thromb Hemost 2023; 49(04): 330-336
DOI: 10.1055/s-0042-1758062
Review Article

The ART of Thromboprophylaxis in the Prevention of Gestational Venous Thromboembolism

Elvira Grandone
1   Department of Obstetrics and Gynecology, University of Foggia, Foggia, Italy
2   Thrombosis and Haemostasis Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza,” Foggia, Italy
3   Department of Obstetrics and Gynecology, The First I.M. Sechenov Moscow State Medical University, Moscow, Russia
,
Doris Barcellona
4   Thrombosis and Haemostasis Unit, Department of Medical Science and Public Health, University of Cagliari, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy
,
Mariano Intrieri
5   Department of Medicine and Health Science “V. Tiberio,” University of Molise, Campobasso, Italy
,
Giovanni Tiscia
2   Thrombosis and Haemostasis Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza,” Foggia, Italy
,
Luigi Nappi
1   Department of Obstetrics and Gynecology, University of Foggia, Foggia, Italy
,
Maha Othman
6   Department of Biomedical and Molecular Sciences, School of Medicine, Queen's University, Kingston, Ontario, Canada
7   School of Baccalaureate Nursing, St Lawrence College, Kingston, Ontario, Canada
8   Department of Clinical Pathology, School of Medicine, Mansoura University, Mansoura, Egypt
› Author Affiliations

Abstract

Assisted reproductive techniques (ART) allow infertile couples to conceive. Use of hormones to obtain a controlled ovarian stimulation and an adequate growth of the endometrium preparatory for embryo implantation are not riskless. Among others, thrombotic events can occur during the ovulation induction or pregnancy following ART. As the number of women approaching ART to conceive is steadily increasing, the issue of thrombotic risk in this setting is relevant. Data on the weight of each risk factor and on potential benefit of thromboprophylaxis are largely lacking. In this review, we discuss risk of venous thromboembolism during pregnancy following ART, with a focus on general (i.e.: age, body mass index, thrombophilia, bed rest, transfusions) and ART-specific (i.e., polycystic ovarian syndrome, ovarian hyperstimulation syndrome) risk factors. We also attempt to provide some suggestions to guide clinical practice, based on available data and studies performed outside ART.



Publication History

Article published online:
11 November 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Brenner B, Grandone E, Makatsariya A, Khizroeva J, Bitsadze V, Tretyakova M. Approach to the evaluation and treatment of venous thromboembolism in pregnancy. Semin Reprod Med 2021; 39 (5-06): 186-193
  • 2 Machin N, Ragni MV. Hormones and thrombosis: risk across the reproductive years and beyond. Transl Res 2020; 225: 9-19
  • 3 Wasserloos A, Thomassen MCLGD, Costa SD. et al. Effect of blood loss during caesarean section on coagulation parameters. Thromb Res 2021; 202: 84-89
  • 4 Grandone E, Colaizzo D, Mastroianno M. et al. Pulmonary embolism associated with transfusion after severe post-partum haemorrhage: is less more?. Blood Transfus 2020; 18 (01) 13-19
  • 5 ART Fact Sheet. Accessed August 29, 2022 at: https://www.eshre.eu/-/media/sitecore-files/Press-room/ESHRE_ARTFactSheet_2022.pdf?la=en&hash=223AAF16CEC0EC6510EB371B52BE10384892AF49
  • 6 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
  • 7 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
  • 8 Nelson SM. Prophylaxis of VTE in women - during assisted reproductive techniques. Thromb Res 2009; 123 (Suppl. 03) S8-S15
  • 9 Nelson SM. Venous thrombosis during assisted reproduction: novel risk reduction strategies. Thromb Res 2013; 131 (Suppl. 01) S1-S3
  • 10 Villani M, Ageno W, Grandone E, Dentali F. The prevention and treatment of venous thromboembolism in pregnancy. Expert Rev Cardiovasc Ther 2017; 15 (05) 397-402
  • 11 Virkus RA, Løkkegaard EC, Bergholt T, Mogensen U, Langhoff-Roos J, Lidegaard Ø. Venous thromboembolism in pregnant and puerperal women in Denmark 1995-2005. A national cohort study. Thromb Haemost 2011; 106 (02) 304-309
  • 12 Friederich PW, Sanson BJ, Simioni P. et al. Frequency of pregnancy-related venous thromboembolism in anticoagulant factor-deficient women: implications for prophylaxis. Ann Intern Med 1996; 125 (12) 955-960
  • 13 Grandone E, De Stefano V, Rossi E, Cappucci F, Colaizzo D, Margaglione M. Antithrombotic prophylaxis during pregnancy in women with deficiency of natural anticoagulants. Blood Coagul Fibrinolysis 2008; 19 (03) 226-230
  • 14 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
  • 15 Mor YS, Schenker JG. Ovarian hyperstimulation syndrome and thrombotic events. Am J Reprod Immunol 2014; 72 (06) 541-548
  • 16 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
  • 17 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
  • 18 James AH, Tapson VF, Goldhaber SZ. Thrombosis during pregnancy and the postpartum period. Am J Obstet Gynecol 2005; 193 (01) 216-219
  • 19 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
  • 20 James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol 2009; 29 (03) 326-331
  • 21 Knight M. UKOSS. Antenatal pulmonary embolism: risk factors, management and outcomes. BJOG 2008; 115 (04) 453-461
  • 22 Simpson EL, Lawrenson RA, Nightingale AL, Farmer RD. Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database. BJOG 2001; 108 (01) 56-60
  • 23 Larsen TB, Sørensen HT, Gislum M, Johnsen SP. Maternal smoking, obesity, and risk of venous thromboembolism during pregnancy and the puerperium: a population-based nested case-control study. Thromb Res 2007; 120 (04) 505-509
  • 24 Liu S, Rouleau J, Joseph KS. et al; Maternal Health Study Group of the Canadian Perinatal Surveillance System. Epidemiology of pregnancy-associated venous thromboembolism: a population-based study in Canada. J Obstet Gynaecol Can 2009; 31 (07) 611-620
  • 25 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
  • 26 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
  • 27 Skeith L. Prevention and management of venous thromboembolism in pregnancy: cutting through the practice variation. Hematology (Am Soc Hematol Educ Program) 2021; 2021 (01) 559-569
  • 28 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
  • 29 Piazza G. Oh heavy burden: recognizing the risk of venous thromboembolism in women undergoing assisted reproduction. Thromb Haemost 2018; 118 (12) 2011-2013
  • 30 National Institute for Health and Care Excellence. Venous Thromboembolic Diseases: Diagnosis, Management and Thrombophilia Testing. NICE Guideline No. 158, March 26, 2020. London: NICE; 2020. Accessed March 21, 2022 at: https://www.ncbi.nlm.nih.gov/books/NBK556698/
  • 31 Zore T, Joshi NV, Lizneva D, Azziz R. Polycystic ovarian syndrome: long-term health consequences. Semin Reprod Med 2017; 35 (03) 271-281
  • 32 Levi-Setti PE, Di Segni N, Gargasole C, Ronchetti C, Cirillo F. Ovarian hyperstimulation: diagnosis, prevention, and management. Semin Reprod Med 2021; 39 (5-06): 170-179
  • 33 Timmons D, Montrief T, Koyfman A, Long B. Ovarian hyperstimulation syndrome: a review for emergency clinicians. Am J Emerg Med 2019; 37 (08) 1577-1584
  • 34 Fernández-Sánchez M, Visnova H, Yuzpe A, Klein BM, Mannaerts B, Arce JC. ESTHER-1 and ESTHER-2 Study Group. Individualization of the starting dose of follitropin delta reduces the overall OHSS risk and/or the need for additional preventive interventions: cumulative data over three stimulation cycles. Reprod Biomed Online 2019; 38 (04) 528-537
  • 35 Vlaisavljevic V, Apter S, Capalbo A. et al; ESHRE Clinic PI Working Group. The Maribor consensus: report of an expert meeting on the development of performance indicators for clinical practice in ART. Hum Reprod Open 2021; 2021 (03) hoab022
  • 36 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 (2, Suppl): e691S-e736S
  • 37 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
  • 38 Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. 2015. Accessed June 3, 2022 at: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg37a/
  • 39 Al-Inany HG, Youssef MA, Aboulghar M. et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev 2011; (05) CD001750
  • 40 Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J. et al; ESC Scientific Document Group. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018; 39 (34) 3165-3241
  • 41 Turrini M, Bourgain C. Appraising screening, making risk in/visible. The medical debate over non-rare thrombophilia (NRT) testing before prescribing the pill. Sociol Health Illn 2021; 43 (07) 1627-1642
  • 42 Grandone E, Piazza G. Thrombophilia, inflammation, and recurrent pregnancy loss: a case-based review. Semin Reprod Med 2021; 39 (1-02): 62-68
  • 43 Petrilli CM, Heidemann L, Mack M, Durance P, Chopra V. Inpatient inherited thrombophilia testing. J Hosp Med 2016; 11 (11) 801-804
  • 44 Papadimitriou E, Boutzios G, Mathioudakis AG, Vlahos NF, Vlachoyiannopoulos P, Mastorakos G. Presence of antiphospholipid antibodies is associated with increased implantation failure following in vitro fertilization technique and embryo transfer: a systematic review and meta-analysis. PLoS One 2022; 17 (07) e0260759
  • 45 Jarne-Borràs M, Miró-Mur F, Anunciación-Llunell A, Alijotas-Reig J. Antiphospholipid antibodies in women with recurrent embryo implantation failure: a systematic review and meta-analysis. Autoimmun Rev 2022; 21 (06) 103101
  • 46 Grandone E, Vecchione G, Colaizzo D, Cappucci F, Margaglione M. Homocysteine and antiphospholipid antibodies in a woman undergoing ovarian follicular stimulation: prospective clinical and laboratory evaluation. Am J Obstet Gynecol 2004; 191 (01) 370-371
  • 47 Orquevaux P, Masseau A, Le Guern V. et al. In vitro fertilization in 37 women with systemic lupus erythematosus or antiphospholipid syndrome: a series of 97 procedures. J Rheumatol 2017; 44 (05) 613-618
  • 48 Ricci G, Bogatti P, Fischer-Tamaro L. et al. Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization: prospective cohort study. Hum Reprod 2011; 26 (11) 3068-3077
  • 49 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
  • 50 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
  • 51 James A. Committee on practice bulletins—obstetrics practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol 2011; 118: 718-729
  • 52 Branch DW, Holmgren C, Goldberg JD. Committee on practice bulletins-obstetrics practice bulletin no 132: antiphospholipid antibody syndrome. Obstet Gynecol 2012; 20: 1514-1521
  • 53 Chan WS, Rey E, Kent NE. et al; VTE in Pregnancy Guideline Working Group, Society of Obstetricians and Gynecologists of Canada. Venous thromboembolism and antithrombotic therapy in pregnancy. J Obstet Gynaecol Can 2014; 36 (06) 527-553