Systemic Methotrexate Treatment Under the Spotlight in Cervical Ectopic Pregnancies

30 06 2009

Verma and colleague recently described a safe and viable noninvasive method of managing cervical ectopic pregnancies.(1) This report takes the management of this potentially life-threatening disease a significant step forward by administering systemic methotrexate alone or in a combination with ultrasound-guided potassium chloride (KCl) into the fetal heart.

The authors investigated a relatively large number (n = 25) of early pregnant patients, where ectopic implantation was located in the cervix. Based on their results, they developed a protocol in which they managed to reduce the ratio of acute hysterectomies as a final consequence of the disease.

As a clinical doctor I am enthusiastic about new methods which are simple, easy to accomplish, cheap and have as little impact on the patient as possible, methods where the cost-benefit ratio leans to the benefit side. Cervical ectopic pregnancies occuring in the first trimester can result in severe bleeding, which can lead to blood transfusion, acute laparotomy and sometimes finally hysterectomy is also required. Despite the potentially life-threatening complications, the conservative management has its own justification. The current report highlighted the reliable and safe method of intramuscular administration of methotrexate, which is proven to be an effective way of terminating ectopic pregnancy.

Folic acid antagonist methotrexate has been used in the treatment of several serious diseases such as chorionic carcinoma (2), acute lymphoid leukemia, adjuvant treatment of breast cancers, Burkitt lymphoma, dermatomyositis and rheumatoid arthritis (3). The chronic use of this drug can cause massive side-effects, like suppression of the bone marrow or liver and kidney damage, although a single dosage is exempt from complications due to fact that methotrexate only affects those cell which are in the S-phase of the multiplication process (4).

Based on the pharmacodynamic characteristics of the drug, we described a 7-week cervical pregnancy in 1991 (5), when 2 x 50 mg of methotrexate was administered by intravenous infusion and successfully eliminated the trophoblastic tissue. Three days later the urine was negative for human chorionic gonadotroping (HCG). After dilatation of cervix with laminaria sticks, the collapsed amniotic sac left the cervix accompanied by minimal hemorrhage. According to our results since then we, and many others across Europe, have followed the same protocol to treat cervical ectopic pregnancies. We are glad that eighteen years after the publication of our data, the technique itself is still up to date.

Balint Farkas, MD
Istvan Drozgyik, MD
Jozsef Bodis, MD, PhD
Department of Obstetrics and Gynecology
University of Pecs
Pecs, Hungary

References
1. Verma U, Goharkhay N. Conservative management of cervical ectopic pregnancy. Fertil Steril. 2009 Mar;91(3):671-4.

2. Lamb EJ, Morton DG, Byron RC. Methotrexate therapy of choriocarcinoma and allied tumors. Am J Obstet Gynecol. 1964 Oct 1;90:317-27.

3. Prey S, Paul C. Br J Dermatol. Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. 2009 Mar;160(3):622-8. Epub 2008 Oct 20.

4. Park J, Franco RS, Augsburger JJ, Banerjee RK. Comparison of 2-methoxyestradiol and methotrexate effects on non-Hodgkin’s B-cell lymphoma. Curr Eye Res. 2007 Jul-Aug;32(7-8):659-67.

5. Bódis J, Csaba I, Gács E. A new method for the termination of cervical pregnancy. Orv Hetil. 1992 Jan 5;133(1):47-8.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2009.06.058

The Authors Respond:

We thank Drs. Farkas, Drozgyik and Bodis for their interest in our paper and their thoughtful comments. We agree that conservative management of cervical ectopic pregnancy is a potentially safe and cost-effective treament, in addition to preserving fertility. We acknowledge their report of successful management of a case of cervical ectopic pregnancy with methotrexate administration.

Usha Verma, MD
Department of Obstetrics and Gynecology
Miller School of Medicine
University of Miami
Miami, Florida

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2009.06.059

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