Italian Journal of Medicine (2012) 6, 116–118
Authors: Ida Strina, Giuseppe De Placido, Maristella D’Uva, Ilaria Jane Romano, Pierpaolo Di Micco
Affiliations:
a. Department of Obstetrics and Gynecology and Human Reproduction, “Federico II” University of Naples, Italy
b. Cardiology Unit, AO Monaldi, Naples, Italy
c. Internal Medicine Division, Buonconsiglio Fatebenefratelli Hospital, Naples; Thrombosis Center, Istituto Clinico Humanitas, Milan, Italy
Corresponding author: Pierpaolo Di Micco (pdimicco@libero.it)
DOI: 10.1016/j.itjm.2011.09.007
Summary
Introduction: Women receiving hormone therapy for assisted reproduction are at increased risk for thrombosis. Controlled ovarian stimulation may contribute to thrombotic events, particularly in thrombophilic patients.
Materials and methods: A case of arterial thrombosis of the iliac-femoro-popliteal axis is described in a young woman with Factor V Leiden-related thrombophilia during recombinant FSH and leuprorelin therapy for IVF-ET, despite pharmacological prophylaxis with enoxaparin.
Results: The thrombosis caused critical limb ischemia; clinical course and management are reported.
Discussion: Further studies are needed to define optimal prevention strategies and to determine whether thrombophilic women undergoing ovarian stimulation should receive prophylactic anticoagulation.
Introduction
Thrombophilia is associated with pregnancy loss and infertility. Its relationship with unexplained female sterility and repeated IVF-ET failures remains debated. Controlled ovarian stimulation with gonadotropins induces haemostatic changes that can increase thrombotic risk. While venous events are more common, arterial thromboses—though rare—have been documented.
Case history
A 38-year-old woman (smoker, 64 kg) developed leg pain with mild cyanosis during hormonal stimulation for ICSI (alpha-follitropin 300 U daily + leuprorelin 3.75 mg). On day 9, estradiol reached 1,800 pg/mL and nine follicles were present without ascites.
She was heterozygous for Factor V Leiden (FVL) and had a history of pulmonary embolism at 18 years plus superficial venous thromboses (Table 1). Family history included maternal pulmonary embolism and thrombosis (Table 2). She had undergone three prior ART cycles with enoxaparin prophylaxis (6,000 U daily) without complications.
After 2 days of persistent pain unrelieved by NSAIDs, Doppler ultrasound showed complete thrombosis of the iliac-femoro-popliteal arterial axis. Angiography confirmed occlusion; angioplasty or surgery was not feasible. The patient was treated with IV unfractionated heparin (35,000 U/day, aPTT 1.5–2.5) and iloprost (2 ng/kg/min), leading to modest flow recovery and residual claudication. Oocyte retrieval was cancelled.
Discussion
Arterial thrombosis can complicate ovarian stimulation even without hyperstimulation syndrome. This case demonstrates that standard enoxaparin prophylaxis may not prevent arterial events in high-risk women. Thrombophilia testing is not routinely recommended before ART, and anticoagulant prophylaxis lacks consensus in guidelines.
However, women with prior thrombotic episodes or known thrombophilia may benefit from individualized risk assessment and preventive therapy. The potential for life-threatening vascular complications raises ethical concerns about proceeding with ART in such patients.
Conflict of interest
The authors declare no conflicts of interest.
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