Human Reproduction, Vol. 17, No. 9, 2482,
September 2002
© 2002 European Society of Human Reproduction and Embryology
Factor V Leiden and recurrent miscarriage
Department of Gynecologic Endocrinology and Reproductive Medicine, Women's Hospital, University Hospital Heidelberg, Voss-Str. 9, 69115 Heidelberg, Germany E-mail: michael.bohlmann{at}med.uni-heidelberg.de
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Dear Sir,
We read with interest the article by Rai and colleagues concerning the prospective outcome of untreated pregnancies in patients with factor V Leiden mutation and recurrent miscarriages (Rai et al., 2002
). Rai and colleagues should be congratulated for their skilful evaluation of their data, showing a significantly lower live birth rate amongst women carrying the factor V allele (37.5%) compared with those of a normal genotype (69.3%).
However, a few questions have to be put forward. As the authors state that the women in the control group, `Did not receive pharmacological treatment except for folic acid' during pregnancy, it would have been of interest to know what the underlying pathologies (if any) had been causing more than two recurrent miscarriages before this observed pregnancy. Otherwise these patients have to be considered as idiopathic recurrent aborters.
Some authors have linked endocrine disorders such as hyperprolactinaemia (Hirahara et al., 1998), hypothyroidism (Abalovich et al., 2002) and a status of hyperandrogenaemia (Bussen et al., 1999) to pregnancy complications or recurrent miscarriages. It would have been of interest if there were any significant differences with regard to these pathologies between both groups of patients.
Furthermore, it remains to be elucidated if any other thrombophilic changes, also carrying a risk for abortions, such as decreased factor XII activity (Braulke et al., 1993; Ogasawara et al., 2001; Iinuma et al., 2002) or hyperhomocysteinaemia (Nelen et al., 2000) have been detected in patients of either group. The prevalence of combined thrombophilic defects (Sarig et al., 2002) would be of interest in the group of patients who carry the factor V Leiden allele. Since, for example, Martinelli et al. described an increased risk for thrombosis in pregnant patients with double heterozygous factor V and prothrombin gene mutations (Martinelli et al., 2001), one might assume that such a double mutation might also have an impact on the occurrence of placental malperfusion.
In addition, the numbers in the Abstract do not match: early miscarriage: n = 19, late miscarriage: n = 9, total number 28, compared with 25 as stated by the authors.
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Abalovich, M., Gutierrez, S., Alcaraz, G., Maccallini, G., Garcia, A. and Levalle, O. (2002) Overt and subclinical hypothyroidism complicating pregnancy. Thyroid, 12, 63–68.[Web of Science][Medline]
Braulke, I., Pruggmayer, M., Melloh, P., Hinney, B., Kostering, H. and Gunther, E. (1993) Factor XII (Hageman) deficiency in women with habitual abortion: new subpopulation of recurrent aborters? Fertil. Steril., 59, 98–101.[Web of Science][Medline]
Bussen, S., Sutterlin, M. and Steck, T. (1999) Endocrine abnormalities during the follicular phase in women with recurrent spontaneous abortion. Hum. Reprod., 14, 18–20.
Hirahara, F., Andoh, N., Sawai, K., Hirabuki, T., Uemura , T. and Minaguchi, H. (1998) Hyperprolactinemic recurrent miscarriage and results of randomized bromocriptine treatment trials. Fertil. Steril., 70, 246–252.[Medline]
Iinuma, Y., Sugiura-Ogasawara, M., Makino, A., Ozaki, Y., Suzumori, N. and Suzumori, K. (2002) Coagulation factor XII activity, but not an associated common genetic polymorphism (46C/T), is linked to recurrent miscarriage. Fertil. Steril., 77, 353–356.[Web of Science][Medline]
Martinelli, I., Legnani, C., Bucciarelli, P., Grandone, E., de Stefano, V. and Mannucci, P.M. (2001) Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia. Thromb. Haemost., 86, 800–803.[Web of Science][Medline]
Nelen, W.L., Blom, H.J., Steegers, E.A., den Heijer, M. and Eskes, T.K. (2000) Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil. Steril., 74, 1196–1199.[Web of Science][Medline]
Ogasawara, M.S., Aoki, K., Katano, K., Ozaki, Y. and Suzumori, K. (2001) Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage. Fertil. Steril., 75, 916–919.[Web of Science][Medline]
Rai, R., Backos, M., Elgaddal, S., Shlebak, A. and Regan, L. (2002) Factor V Leiden and recurrent miscarriage-prospective outcome of untreated pregnancies. Hum. Reprod., 17, 442–445.
Sarig, G., Younis, J.S., Hoffman, R. Ianir, N., Blumenfeld, Z. and Brenner, B. (2002) Thrombophilia is common in women with idiopathic pregnancy loss and is associated with late pregnancy wastage. Fertil. Steril., 77, 342–347.[Web of Science][Medline]
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