Treatment of ectopic pregnancy (EP) with drug therapy is a relatively new decision since a surgical operation was considered the only way to eliminate the anomaly of the fetus. The preferred method of administering methotrexate in the treatment of EP is an intramuscular injection (Cecchino, Júnior, & Júnior, 2014). There are several different regimens for the use of methotrexate. Among the most common treatment regimens, there are single-dose, double-dose, and multiple-dose injections. The single-dose administration suggests 50 mg / m2, while multiple dosages are injected on the first, third, fifth, and seventh days of treatment (Cecchino et al., 2014). Compared to multiple-dose methotrexate, single doses are much more effective and safer for the reproductive health of a woman (Uyar et al., 2013). Because the effect of the given treatment varies in different cases, its administration should be considered in a long-term perspective.
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Speaking of the effect of the medication, one should note that methotrexate is an antagonist of folic acid and its derivatives, which are essential for the synthesis of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Methotrexate also promotes the growth of cells of the outer layer of the embryo, through which all the substances enter to maintain its vital activity. The effect of inhibition of the dihydrofolate reductase synthesis, which converts folic acid into tetrahydrofolic that is involved in the creation of DNA and RNA, is rather pronounced (Cecchino et al., 2014). The blockade of synthesis leads to a change in metabolism and a weakening of the production of significant proteins. In other words, the mechanism of work is the inactivation of dihydrofolate reductase, which leads to a decrease in the level of tetrahydrofolate, thereby interrupting the division of trophoblast cells. The advantages of drug therapy include the preservation of the tube, the absence of complications after surgery and anesthesia, and relatively low cost of treatment. The drug prescription occurs with the confirmation of EP, depending on its term.
The use of methotrexate is possible only in the absence of bleeding and after detecting ectopic pregnancy with ultrasound. At this point, a fetal egg size should be no less than four cm (Practice Committee of the American Society for Reproductive Medicine, 2013). The mandatory conditions for drug treatment also include the possibility of outpatient monitoring, the absence of a painful syndrome in the pelvic area, less than 5000 mIU / ml, and the cessation of fetal cardiac activity. As for laboratory tests, it is necessary to quantify the level of β-subunit of hCG gonadotropin (β-hCG) in blood serum and assess liver and kidney function, including farnesyl diphosphate (FPP) along with creatinine level (Song et al., 2015). Among other required tests, one may state hysterosalpingography (HSG) and contrast Doppler scanning.
The period of observation from the moment of methotrexate administration depends on the dynamics of β-hCG level reduction in blood serum and averages from three to seven weeks, yet can take up to 109 days. It is important to note that the level of β-hCG in the treatment of methotrexate does not, as a rule, decrease as rapidly as during surgery (Chong et al., 2015). If β-hCG does not fall or even grows, likely, pregnancy has not been interrupted, and the embryo continues to grow. In this case, treatment should be continued. While selecting the specified method of treatment, a weekly outpatient visit is compulsory until the level of β-hCG reaches the norm to exclude chorion persistence.
Cecchino, G. N., Júnior, E. A., & Júnior, J. E. (2014). Methotrexate for ectopic pregnancy: When and how. Archives of Gynecology and Obstetrics, 290(3), 417-423.
Chong, W., Fridman, D., Rotenberg, O., Hawkins, E., Mehta, S., Chudnoff, S., & Levie, M. (2015). Factors predicting the success rate of a single dose of systemic methotrexate for the treatment of ectopic pregnancy. Journal of Minimally Invasive Gynecology, 22(6), 89-90.
Practice Committee of the American Society for Reproductive Medicine. (2013). Medical treatment of ectopic pregnancy: A committee opinion. Fertility and Sterility, 100(3), 638-644.
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Song, T., Kim, M. K., Kim, M. L., Jung, Y. W., Yun, B. S., & Seong, S. J. (2015). Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: A randomized controlled trial. Human Reproduction, 31(2), 332-338.
Uyar, I., Yucel, O. U., Gezer, C., Gulhan, I., Karis, B., Hanhan, H. M., & Ozeren, M. (2013). Effect of single-dose methotrexate on ovarian reserve in women with ectopic pregnancy. Fertility and Sterility, 100(5), 1310-1313.