Hum. Reprod. Advance Access originally published online on October 18, 2006
Human Reproduction 2007 22(1):309; doi:10.1093/humrep/del349
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Letters to the editor |
Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage
1 Department of Obstetrics and Gynecology, University Hospital Tuebingen 2 Department of Obstetrics and Gynecology, University Hospital Luebeck and 3 Department of Gynecologic Endocrinology and Reproductive Medicine, University Hospital Heidelberg, Germany
4 To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, University Hospital Tuebingen, Calwer Strasse 7, 72076 Tuebingen, Germany. E-mail: michael.bohlmann{at}med.uni-tuebingen.de
Sir,
We read with interest the guidelines for the investigation and treatment of recurrent miscarriage (RSA) by Jauniaux and co-workers (2006). The authors should be congratulated for the comprehensive description of today’s state of knowledge.
However, several questions remain unclear, for example, why the authors state that ‘larger studies are needed to justify testing couples with recurrent miscarriages for inherited thrombophilia’. They quote Robertson et al. (2006)
, who, however, underlined in their publication that ‘universal’ screening for thrombophilia in pregnancy—not in RSA- patients—is not clinically justified.
The statement of Jauniaux and co-workers stands in contrast to two large systematic reviews (Rey et al., 2003; Robertson et al., 2006) with several thousand patients enrolled, who clearly establish links between recurrent early miscarriage and maternal hereditary thrombophilia.
The study of Carp et al. (2002)—interpreted as showing a decreased rate of miscarriage in RSA women with inherited thrombophilia—is not cited correctly either, as this Israeli group prospectively compared the live birth rate of 70 women suffering from RSA, with and without thrombophilia, in a subsequent, untreated pregnancy without significant differences in pregnancy outcome. It thus did not compare the reproductive outcome of women with thrombophilia to a healthy control group without thrombophilia, but those of patients with a history of RSA.
The study of van Dunne et al. (2005) retrospectively deals with sporadic miscarriages and is based on data of women with a history of venous thrombosis with (n = 80) or without (n = 140) the presence of a heterozygous factor V Leiden mutation. It does not show a generally reduced risk of sporadic miscarriage, as implied by the Jauniaux et al. (2006) but a reduced risk of first trimester abortions, whereas the risk of miscarriage is significantly elevated in the second trimester in those patients carrying a heterozygous factor V Leiden mutation. This study therefore cannot be a proof of a reduced risk of recurrent miscarriages in patients with a factor V Leiden mutation, nor a proof for a reduced risk of miscarriages overall.
The question today should therefore not be whether specific inherited thrombophilic disorders are risk factors for recurrent miscarriages, but how to treat patients with thrombophilia and RSA. Treatment with heparin may be beneficial (Carp et al., 2003), possibly through its interaction with the trophoblast (Hills et al., 2006), but large, prospective, randomised, placebo-controlled studies are needed to support this finding.
In addition, the knowledge of inherited thrombophilic disorders due to adequate screening after a history of recurrent pregnancy complications might have a benefit for the patient in risk situations, for example, trauma or future pregnancies, to prevent maternal thromboembolic diseases.
References
Carp H, Dolitzky M, Inbal A. (2003) Thromboprophylaxis improves the live birth rate in women with consecutive recurrent miscarriages and hereditary thrombophilia. J Thromb Haemost 1:433–438.[CrossRef][Web of Science][Medline]
Carp H, Dolitzky M, Tur-Kaspa I, Inbal A. (2002) Hereditary thrombophilias are not associated with a decreased live birth rate in women with recurrent miscarriage. Fertil Steril 78:58–62.[CrossRef][Web of Science][Medline]
van Dunne FM, Doggen CJ, Heemskerk M, Rosendaal FR, Helmerhorst FM. (2005) Factor V Leiden mutation in relation to fecundity and miscarriage in women with venous thrombosis. Hum Reprod 20:802–806.
Hills FA, Abrahams VM, Gonzalez-Timon B, Francis J, Cloke B, Hinkson L, Rai R, Mor G, Regan L, Sullivan M, et al. (2006) Heparin prevents programmed cell death in human trophoblast. Mol Hum Reprod 12:237–243.
Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. ( May 17, 2006) Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod [Epub Ahead of Print].
Rey E, Kahn SR, David M, Shrier I. (2003) Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 361:901–908.[CrossRef][Web of Science][Medline]
Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GD, Walker ID, Greaves M, Brenkel I, Regan L, et al. (2006) The Thrombosis: Risk and Economic Assessment of Thrombophila Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol 132:171–196.[CrossRef][Web of Science][Medline]
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