pill, or where additional risk factors are present, pharmacologic prophylaxis should be considered. This is illustrated in the Case History.
Box 8.1 Clinical and laboratory criteria for the diagnosis of antiphospholipid syndrome.
Clinical criteria
Vascular thrombosis: one or more clinical episodes of arterial, venous or small vessel thrombosis, in any tissue or organ. Thrombosis must be confirmed by objective validated criteria (i.e. unequivocal findings of appropriate imaging studies or histopathology). For histopathologic confirmation, thrombosis should be present without significant evidence of inflammation in the vessel wall.
Pregnancy morbidity:
one or more unexplained deaths of a morphologically normal fetus at or beyond 10 weeks’ gestation, with normal fetal morphology documented by ultrasound or by direct examination of the fetus; or
one or more premature births of a morphologically normal neonate before 34 weeks’ gestation because of: (i) eclampsia or severe preeclampsia defined according to standard definitions; or (ii) recognized features of placental insufficiency; or
three or more unexplained consecutive spontaneous abortions before 10 weeks’ gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded.
Laboratory criteria
Lupus anticoagulant present in plasma, on two or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Haemostasis (scientific subcommittee on lupus anticoagulants/phospholipid‐dependent antibodies).
Anticardiolipin antibody of immunoglobulin G (IgG) and/or IgM isotype in serum or plasma, present in medium or high titer (i.e. >40 GPL units or MPL units, or >99th centile), on two or more occasions, at least 12 weeks apart, measured by a standardized enzyme‐linked immunosorbent assay (ELISA).
Anti‐β2 glycoprotein‐I antibody of IgG and/or IgM isotype in serum or plasma (in titer >99th centile), present on two or more occasions, at least 12 weeks apart, measured by a standardized ELISA, according to recommended procedures.
Prophylactic therapy is probably not necessary during controlled ovarian stimulation, when the risk of thrombosis is minimal [14]. Given the rarity of occurrence of VTE prior to hCG, and the potential for increased risk of significant intra‐abdominal bleeding, which may occur following oocyte retrieval, medical thromboprophylaxis should be delayed until after oocyte retrieval. A suggested approach is provided in Figure 8.1. If thromboprophylaxis is commenced with ovarian stimulation, a good approach would be to withhold LMWH for 24 hours prior to oocyte retrieval and recommence it 12 hours after the procedure [15].
All patients diagnosed with moderate to severe OHSS, even those being managed on an outpatient basis, should receive thromboprophylaxis. The duration of treatment should be individualized, taking into account risk factors and whether or not conception occurs [8].
Post IVF follow‐up
Clinical reports of DVT occurring following IVF treatment indicate that it most frequently presents in early pregnancy [16] between 5 and 10 weeks after hCG administration [17]. This has implications for both the duration for which prophylaxis should be administered in high risk patients, and for the duration for which clinical surveillance should be maintained in order ensure early detection and treatment. It is apparent from literature that thrombophilic tendencies associated with OHSS persist and VTE can present weeks after resolution of the clinical syndrome. Therefore, a prolonged duration of prophylaxis and extended vigilance might be necessary [18]. A 2009 review suggests “thromboprophylaxis should be considered for patients who develop moderate‐to‐severe OHSS for an extended period of 1–2 months beyond the resolution of clinical OHSS” [19]. This approach was not only deemed safe but also shown to be cost effective [20]. In patients who conceive, it may be necessary to continue thromboprophylaxis throughout the antenatal period.
Figure 8.1 A suggested approach to thromboprophylaxis in a patient undergoing IVF.
Additionally, focus should also be placed on the judicious use of methods for preventing ovarian hyperstimulation as it is a major risk factor in developing IVF related VTE, especially in high risk patients. Techniques that can be employed include use of an antagonist cycle [21], milder stimulation protocols and use of gonadotropin releasing hormone (GnRH) agonist trigger instead of hCG. Additionally, cryopreservation of all embryos and natural cycle (if possible) frozen embryo transfer avoids the use of exogenous hCG completely [22].
Many reported cases of DVT following IVF are in sites other than the 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:
