1 Department of Gynecology-Fertility, and 2 Department of Gastroenterology, C.A.Z.K.Groeninghe Campus Sint-Niklaas,Houtmarkt 33, Kortrijk, Belgium
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Abstract |
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Key words: jugular vein/thrombosis/ovulation induction
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Introduction |
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Case report |
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In October 1999, she began a long schedule for IVF and intracytoplasmic sperm injection (ICSI). She started with buserelin puffs (Suprefact; Aventis, Brussels, Belgium) and on the fourth day of the next cycle, ovarian stimulation was initiated with gonadotrophins (Humegon; Organon; Brussels, Belgium; two ampoules/day). After 12 days of stimulation, the patient developed 11 follicles with a diameter of 1522 mm. The concentration of oestradiol was 2069 pg/ml.
Follicle aspiration was carried out 36 h after administration of 10 000 IU of human chorionic gonadotrophin (HCG) and eight oocytes were recovered. Six of these oocytes were used for ICSI and five were fertilized. Two embryos were transferred 3 days later and the patient received 1500 IU of HCG every 3 days for luteal phase support. At 11 days after embryo transfer, the patient presented with mild abdominal distension due to enlarged ovaries (86x60 and 60x80 mm) and a small amount of ascites.
A blood sample showed an oestradiol concentration of 1107 pg/ml, and a progesterone concentration of >60 000 ng/ml, HCG = 102 IU/l, haemoglobin = 13.1 g/dl; haematocrit = 40%; Na = 132 mmol/l; and total albumin = 56 g/l.
HCG (Pregnyl) was stopped and progestagens (Utrogestan; Piette, Drogenbos, Belgium) 3x2 compr./day vaginally were continued, because of a risk for OHSS. HCG concentrations rose quickly, reaching 9413 IU/l after 12 days. One month after embryo transfer, the patient presented with neck swelling and pain. Echography and Doppler ultrasound demonstrated an occlusive thrombus involving the left internal jugular vein. Echography from the uterus showed a twin pregnancy, di-amniotic with positive heart activity and this twin pregancy is still ongoing. Both ovaries were polycystic and enlarged (8x5 and 6x5 cm). See Table I for follow-up blood results. There was no evidence of haemoconcentration.
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Discussion |
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Prevention of OHSS is important to reduce the risk of thrombosis. Risk factors are young, thin women with polycystic ovarian syndrome (PCOS), a rapid increase in oestradiol concentration during stimulation (>3500 pg/ml), multifollicular growth (>15 immature follicles) and the use of GnRH agonists.
Preventive measures include: (i) no HCG for ovulation induction or for luteal phase support in the group at risk; (ii) stimulation using a low dose of gonadotrophins for a longer period; (iii) early timed follicular aspiration; and (iv) i.v. albumin therapy at the time of follicular aspiration (Delbeke et al., 1998). Despite prophylactic albumin therapy, cases of severe OHSS and thrombosis have been reported (Moutos et al., 1997
).
The increased risk of thrombosis during ovarian stimulation without OHSS (as in our case), is due to endogenous hyper-oestrogenism. The multifollicular growth in the ovaries with a high oestradiol concentration is responsible for an increased rate of thrombosis. Here, the thrombosis occurred several weeks after resolution of a mild degree of hyperstimulation. The activation of coagulation can thus persist several weeks after resolution of symptoms.
Another risk for thrombosis is a hereditary hypercoagulable state. APC resistance or factor V Leiden mutation was reported in a case of jugular vein thrombosis after ovarian hyperstimulation (Horstkamp et al., 1996). A 35% frequency of this thrombophilic disorder has been found in the Dutch population (Koster et al., 1993
). This risk is 10-fold higher than the risk for ATIII, protein C and S deficiencies. Cases of internal jugular vein thrombosis and these thrombophilic disorders were also described (Kligman et al., 1995
). An unusually located venous thrombosis should prompt an evaluation of a hypercoagulable state; in our patient, the screening was negative.
Pregnancy and ovarian hyperstimulation creates a hypercoagulable state (Ellis et al., 1998); a twin pregnancy is ongoing in our patient. Additional risk factors for internal jugular vein thrombosis are iatrogenic thrombosis after venous catherisation, i.v. drug abuse, tumour compression and paraneoplastic phenomena. Here, we can rule out such factors.
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Conclusions |
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Low molecular weight heparins have been used succesfully in pregnancy and are particularly suited for use in this setting because they do not cross the placenta, appear to cause less osteoporosis during long-term use than standard heparin, and do not require routine laboratory monitoring.
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Acknowledgments |
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Notes |
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References |
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Submitted on April 5, 2000; accepted on December 7, 2000.