Cervical pregnancya conservative stepwise approach

Cervical pregnancy—a conservative stepwise approach Dear Sir, We wish to make some comments on a recent paper (Yitzhak et al., 1999), in which a conservative stepwise approach for the treatment of cervical pregnancy with methotrexate is presented. In their study, additional intra-arterial methotrexate administration by angiography after systemic methotrexate in a multiple dose i.m. regimen is advocated, if on follow-up evaluations serum human chorionic gonadotrophin (HCG) concentrations do not decrease or persistent fetal cardiac activity is observed. The authors prefer this approach, based on the results of a single case report (Peleg et al., 1994), to direct puncture and feticide because they fear subsequent lifethreatening haemorrhage. It is questionable, however, whether this new approach deserves a place in the treatment of cervical pregnancy. Recently, it was shown in this journal that concomitant feticide significantly enhances the therapeutic effect of methotrexate whenever fetal cardiac activity is present. The need for additional interventions was reduced (odds ratio: 0.13, 95% confidence intervals 0.02–0.68), if feticide was performed by means of direct puncture, intra© European Society of Human Reproduction and Embryology

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cardiac injection of potassium chloride or intra-amniotic installation of methotrexate (Hung et al., 1998). Furthermore, Yitzhak et al. suggest that with intra-arterial methotrexate administration by angiography a rapid local accumulation of the drug is reached, without increasing the severity of toxicity. This statement cannot be made as pharmacokinetic parameters were not studied. Two earlier studies on pharmacokinetics of systemic versus local methotrexate for tubal pregnancy have shown no differences in serum methotrexate clearance curves nor in treatment effectiveness (Schiff, 1992; Fernandez et al., 1994). Moreover, they suggested route of administration is invasive, costly, and carries inherent risks, which do not outweigh the side effects of systemic methotrexate. Therefore, in our opinion, arterial angiography should only be used for embolization whenever severe vaginal bleeding occurs in patients with cervical pregnancy treated with methotrexate (Hajenius et al., 1998). The criterion of inadequately declining serum HCG concentrations after systemic methotrexate in a multiple dose i.m. regimen for which additional treatment is necessary is not clearly defined. The authors use a decline of ,15% from baseline without specifying when this decline should be reached. Serum HCG clearance curves after systemic methotrexate in a multiple dose i.m. regimen have been well described in the literature, including the criterion for an additional course, i.e. a serum HCG concentration on day 14 of .40% of the initial value (Hajenius et al., 1996, 1997, 1998). The criterion of a 15% decline is used for the single shot methotrexate regimen, where an additional dose is given on day 7 if by then the serum HCG concentration is ,15% of that on day 4 (Stovall et al., 1993). Although the reported case was successful, we have our doubts whether yet another flowchart for the treatment of cervical pregnancy, which completely ignores the available literature, should be welcomed.

References Fernandez, H., Lelaidier, C., Bourget, P. et al. (1994) Treatment of unruptured tubal pregnancy with methotrexate: pharmacokinetic analysis of local versus intra-muscular administration. Fertil. Steril., 62, 943–947. Hajenius, P.J., Voigt, R.R., Engelsbel, S. et al. (1996) Serum human chorionic gonadotropin clearance curves in patients with interstitial pregnancy treated with systemic methotrexate. Fertil. Steril., 66, 723–728. Hajenius, P.J., Engelsbel, S., Mol, B.W.J. et al. (1997) Randomized trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy. Lancet, 350, 774–779. Hajenius, P.J., Roos, D., Ankum, W.M. and Van der Veen F. (1998) Are serum human chorionic gonadotropin clearance curves of use in monitoring methotrexate treatment in cervical pregnancy? Fertil. Steril., 70, 362–365. Hung, T.H., Shau, W.Y., Hsieh, T.T. et al. (1998) Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review. Hum. Reprod., 13, 2636–2642. Peleg, D., Bar Hava, I., Neuman-Levin, M. et al. (1994) Early diagnosis and successful non-surgical treatment of viable combined intrauterine and cervical pregnancy. Fertil. Steril., 62, 405–408. Schiff, E. (1992) Pharmacokinetics of intratubal methotrexate. Fertil. Steril., 58, 1269–1270. Stovall, T.G. and Ling, F.W. (1993) Single dose methotrexate: an expanded clinical trial. Am. J. Obstet. Gynecol., 168, 1759–1765. Yitzhak, M., Orvieto, R., Nitke, S. et al. (1999) Cervical pregnancy – a conservative stepwise approach. Hum. Reprod., 14, 847–849.

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P.J.Hajenius1 and F.Van der Veen Centre for Reproductive Medicine, Academic Medical Centre, W.M.Ankum Department of Obstetrics and Gynecology, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands 1To

whom correspondence should be addressed