Abstract
Acquired resistance to the anticoagulant action of activated protein C (APC) has been
proposed to explain the increased risk of venous thrombosis associated with pregnancy,
hormone replacement therapy and the use of oral contraceptives. In this study, we
have investigated whether the hormonal changes induced during in vitro fertilization
(IVF) treatment are also associated with acquired APC resistance. Twenty-nine women,
who were planned for an IVF cycle, donated blood at four time points during treatment,
i.e. at baseline, down-regulation, hyperstimulation and luteal support. In the plasma
samples, APC sensitivity ratios (APCsr) and the levels of progesteron and estradiol
were measured. The changes in plasma concentrations of hormones were in accordance
with literature. The APCsr increased significantly during hyperstimulation and remained
high during luteal support. The extent of APC resistance occurring during IVF treatment
was comparable to that observed during the use of second generation OC and was less
pronounced than that occurring during pregnancy. The change in estradiol between baseline
and hyperstimulation correlated with the change in APCsr. Although this suggests that
plasma estrogen levels are an important determinant for acquired APC resistance, it
remains to be established which plasma proteins are responsible for estrogen-induced
APC resistance.
Keywords
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References
- Venous thromboembolism during pregnancy.N. Engl. J. Med. 1996; 335: 108-114
- Risk of venous thrombosis with hormone-replacement therapy.Lancet. 1996; 348: 972
- Risk of venous thromboembolism in users of hormone replacement therapy.Lancet. 1996; 348: 977-980
- Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The heart and estrogen/progestin replacement study.Ann. Int. Med. 2000; 132: 689-696
- Oral contraceptives and cardiovascular disease (first of two parts).N. Engl. J. Med. 1981; 305: 612-618
WHO. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World health organization collaborative study of cardiovascular disease and steroid hormone contraception. Lancet 1995;346:1582–8.
- Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components.Lancet. 1995; 346: 1589-1593
- Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational research group on oral contraceptives and the health of young women.Br. Med. J. 1996; 312: 83-88
- Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing third-generation progestagen.Lancet. 1995; 346: 1593-1596
- Coagulation effects of oral contraception.Am. J. Obstet. Gynecol. 1987; 157: 1042-1048
- Effects of oral contraceptives on haemostasis variables.Thromb. Haemost. 1997; 78: 315-326
- Effects on hemostatic variables of desogestrel- and gestodene-containing oral contraceptives in comparison with levonorgestrel-containing oral contraceptives: a review.Am. J. Obstet. Gynecol. 1998; 179: S51-S61
- APC resistance and other haemostatic variables during pregnancy and puerperium.Thromb. Haemost. 1999; 81: 527-531
- Thrombosis in pregnancy: maternal and fetal issues.Lancet. 1999; 353: 1258-1265
- Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45–64 years. Relationships to hormone replacement therapy.Thromb. Haemost. 2000; 83: 530-535
- Acquired APC resistance related to oral contraceptives and pregnancy and its possible implications for clinical practice.Blood Coagul. Fibrinolysis. 1997; 8: 152-154
- Detection of decreased response to activated protein C during pregnancy by an endogenous thrombin potential-based assay.Semin Thromb. Hemost. 1999; 25: 497-502
- Influence of hormone replacement therapy, oral contraceptives and pregnancy on APC resistance.Thromb. Haemost. 1999; 82 (Suppl): 770-771
- Resistance to activated protein C in healthy women taking oral contraceptives.Br J. Haematol. 1995; 91: 465-470
- Sensitivity to activated protein C: influence of oral contraceptives and sex.Thromb. Haemost. 1995; 73: 402-404
- Oral contraceptives and venous thrombosis: different sensitivities to activated protein C in women using second- and third-generation oral contraceptives.Br J. Haematol. 1997; 97: 233-238
- End of the line for third-generation-pill controversy?.Lancet. 1997; 349: 1113-1114
- Third-generation oral contraceptive and deep venous thrombosis: from epidemiologic controversy to new insight in coagulation.Am. J. Obstet. Gynecol. 1997; 177: 887-891
- Effects of oral contraceptives on hemostasis and thrombosis.Am. J. Obstet. Gynecol. 1999; 180: S375-382
- Thromboembolic disease associated with ovarian stimulation and assisted conception techniques.Hum. Reprod. 1997; 12: 2167-2173
- Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports.Hum. Reprod. 1995; 10: 94-97
- The influence of hyperestrogenism during in vitro fertilization on the fibrinolytic mechanism.Int. J. Fertil. Women Med. 1998; 43: 34-39
- Hyperestrogenism induced by menotropins alone or in conjunction with luprolide acetate in in vitro fertilization cycles: the impact on hemostasis.Fertil. Steril. 1995; 63: 566-570
- Do lowered factor VII levels at extremely high endogenous oestradiol levels protect against thrombin formation?.Blood Coagul. Fibrinolysis. 1994; 5: 205-210
- Effect of activated protein C on thrombin generation and on the thrombin potential in plasma of normal and APC-resistant individuals.Blood Coagul. Fibrinolysis. 1997; 8: 28-38
- Changes induced in serum protein profiles by ovarian stimulation during in-vitro fertilization — embryo transfer treatment: a comparison between conception and non-conception cycles.Hum. Reprod. 1992; 7: 585-591
- APC resistance determined with the endogenous thrombin potential is associated with venous thrombosis: a blinded clinical evaluation.Thromb. Haemost. 1999; 82: 202-203
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© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
