lower limb, but this may simply reflect publication bias [23]. The jugular vein appears to be a relatively frequent site, with the majority of thromboses occurring here being associated with hormonal ovarian stimulation [16]. It should be emphasized that clinical diagnosis for DVT is highly unreliable [24]. Early recourse to objective diagnosis of DVT is advised, particularly in the at‐risk patient. Compression and duplex Doppler ultrasound techniques have been demonstrated to be reliable noninvasive means of diagnosing or excluding DVT, including those affecting upper extremities and neck veins, and are readily available [25].
Key points
Challenge: The patient with thrombosis risk or thrombophilia.
Background:
DVT occurring after IVF is a rare but potentially life‐threatening complication of IVF.
Considerable changes in the coagulation and fibrinolytic systems are observed following hCG administration.
OHSS is a major risk factor in developing VTE in all patients undergoing ART.
Management:
All patients beginning IVF should be subject to an individual risk assessment prior to commencing treatment.
Screening for thrombophilias should be considered in women who have had a previous thrombotic event or a family history of thrombosis, and maybe in women who have developed OHSS.
Thromboprophylaxis should be considered in women with a previous DVT, women who develop moderate to severe OHSS and in women with a thrombophilia. In addition, women who develop serious infections or immobilization should receive thromboprophylaxis.
Compression stockings and low‐molecular weight heparin constitute first line thromboprophylaxis.
Thromboprophylaxis should normally commence 24 hours after oocyte retrieval to reduce the risk of hemorrhagic complications. This should be extended throughout the first trimester. In cases where thrombophilia has been detected, consideration should be given to extending prophylaxis throughout pregnancy.
Prevention: Judicious employment of methods to prevent OHSS, especially in high‐risk patients.
Answers to questions patients ask
1 Q1 If I am at “high risk” of venous thromboembolism (VTE) during IVF, what is the treatment that will be recommended to me? A1. Low‐molecular weight heparin administered subcutaneously is the treatment of choice for VTE prophylaxis. The dose is calculated according to body weight and is taken daily. An example of a dosing regimen using a commonly used LMWH is shown in Table 8.2.Table 8.2 Enoxaparin dosing regimen for VTE prophylaxis [8].WeightEnoxaparin<50 kg20 mg daily50–90 kg40 mg daily91–130 kg60 mg daily*131–170 kg80 mg daily*>170kg0.6 mg/ kg/ day** can be given in 2 divided doses
2 Q2. When will I be expected to commence this treatment? A2. This will depend on the local protocol of your fertility unit. Treatment can commence soon after egg collection or even earlier during the stimulation process. If it is commenced prior to egg collection, it should be withheld for 24 hours before the procedure.
3 Q3 If I develop deep vein thrombosis during my IVF cycle, how will it be treated? A3. It will be treated with low‐molecular weight heparin administered subcutaneously, but at a higher dose than for prophylaxis. Again, it will be calculated according to body weight.
4 Q4 What are the risks of this treatment? A4. Administration of low‐molecular weight heparin is largely safe. It carries a small risk of heparin induced thrombocytopenia (low platelets) or heparin induced osteoporosis (bone thinning). Patients can also develop allergic skin reactions, but again this risk is very small [8].
References
1 1 Grandone E, Colaizzo D, Vergura P, Cappucci F, Vecchione G, Lo BA, et al. Age and homocysteine plasma levels are risk factors for thrombotic complications after ovarian stimulation. Hum Reprod. 2004; 19(8):1796–9.
2 2 Stewart JA, Hamilton PJ, Murdoch AP. (1997) Thromboembolic disease associated with ovarian stimulation and assisted conception techniques. Hum Reprod. 1997; 12(10):2167–73.
3 3 Sennstrom M, Rova K, Hellgren M, Hjertberg R, Nord E, Thurn L, et al. Thromboembolism and in vitro fertilization—a systematic review. Acta Obstet Gynecol Scand. 2017; 96:1045–52.
4 4 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(1):95–100.
5 5 Lox C, Canez M, DeLeon F, Dorsett J, Prien S. Hyperestrogenism induced by menotropins alone or in conjunction with luprolide acetate in in vitro fertilization cycles: the impact on hemostasis. Fertil Steril. 1995; 63(3):566–70.
6 6 Lox C, Canez M, Prien S. The influence of hyperestrogenism during in vitro fertilization on the fibrinolytic mechanism. Int J Fertil Womens Med. 1998; 43(1): 34–9.
7 7 Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. Status of the coagulation and fibrinolytic systems in ovarian hyperstimulation syndrome. Fertil Steril. 1996; 66(3):417–24.
8 8 Royal College of Obstetricians and Gynaecologists. Reducing the risk of venous thromboembolism during pregnancy and the puerperium. Green‐top Guideline No. 37a. London;2015.
9 9Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4(2): 295–306.
10 10 Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet. 1999; 353(9160):1258–65.
11 11 Dulitzky M, Cohen SB, Inbal A, Seidman DS, Soriano D, Lidor A, et al. Increased prevalence of thrombophilia among women with severe ovarian hyperstimulation syndrome. Fertil Steril. 2002; 77(3):463–7.
12 12 Fábregues F, Tàssies D, Reverter JC, Carmona F, Ordinas A, Balasch J. Prevalence of thrombophilia in women with severe ovarian hyperstimulation syndrome and cost‐effectiveness of screening. Fertil Steril. 2004; 81:989–95.
13 13 Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet. 1999; 353(9160):1258–65.
14 14 Ludwig M, Felberbaum RE, Diedrich K. Deep vein thrombosis during administration of HMG for ovarian stimulation. Arch Gynecol Obstet. 2000; 263(3): 139–41.
15 15 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: 354–8.
16 16 Arya R, Shehata HA, Patel RK, Sahu S, Rajasingam D, Harrington KF, et al. Internal jugular vein thrombosis after assisted conception therapy. Br J Haematol. 2001; 115(1):153–5.
17 17 Stewart JA, Hamilton PJ, Murdoch AP. Thromboembolic disease associated with ovarian stimulation and assisted conception techniques. Hum Reprod. 1997; 12(10):2167–73.
18 18 Rao AK, Chitkara U, Milki AA. A subclavian vein thrombosis following IVF and ovarian hyperstimulation syndrome: a case report. Hum Reprod. 2005; 20:3307–12.
19 19 Chan WS. The “ART” of thrombosis: a review of arterial and venous thrombosis in assisted reproductive technology. Curr opin Obstet Gynecol. 2009; 21:207–18.
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