The dissertation presents a novel solution to a relevant scientific problem conveying an experimental confirmation of the protective role of calcium folinate as an effective adjuvant to a methotrexate therapy for the treatment of progressing tubal pregnancy, improving comprehensive pre-pregnancy preparation of women with ectopic pregnancy, and preserving reproductive health.
The study included the experimental part and the clinical part (retrospective and prospective stages) of the work.
In experimental animals use of different doses of methotrexate leads to a significant dose-dependent deviations of indicators of the functional status of liver: the level of ALT, AST, acid phosphatase activities, alkaline phosphatase has increased; erythrocyte intoxication index has increased; medium molecular weight peptides has increased. Toxicity of methotrexate was manifested by the presence of oxidative stress, as well as impaired antioxidant protection, glucose, creatinine and bilirubin levels did not change significantly. Furthermore, cytotoxic action of methotrexate was accompanied by significant changes of the humoral immune system (level of Ig A, Ig М, Ig G, TNF-α, CICs has increased), greater number of apoptotic and necrotic neutrophils in the blood, as well as dose-dependent morpho-functional structural alterations of the uterus and liver in response to a single and double injection of methotrexate.
Targeted therapy with calcium folinate promotes normalization of biochemical parameters and manifestations of cytolytic syndrome; reduced oxidative stress, activated antioxidant protection, normalization of imune state, improved morphological structural organization of liver and uterus of experimental animals treated with different doses of methotrexate.
The most influential chances of ectopic pregnancy risk has identified at retrospective stage: early sex life; high infectious index in childhood; intrauterine spirals; medical abortion in history; smoking habits; inflammatory diseases of the female genital organs (adnexitis, colpitis).
The effect of cytostatic methotrexate on the women body is dose-dependent. Double administration of methotrexate on days 3 and 7 causes a significant increase in the enzymes AST, ALT, acetic and alkaline phosphatases, creatinine, whereas, single use of methotrexate has no cytolytic effect on liver, does not affect blood levels of total bilirubin, glucose, but significantly raises levels of homocysteine, a decreases levels of vitamin D, folic acid in the plasma. Even after 30 days after treatment of ectopic pregnancy with cytostatic, concentrations of folic acid, homocysteine and vitamin D remain significantly different from control.
The administration of calcium folinate with single and double dose of methotrexate completely attenuates manifestations of cytolytic and cholestatic syndromes while reducing the toxic effect on plasma levels of folate, homocysteine and vitamine. The early and late apoptosis of neutrophils does not depend on the localization of pregnancy and is significantly higher after use of methotrexate in a dose-dependent manner.
The side effect of methotrexate was also dose-dependent and manifested by an increased risk of early and late complications. The toxic effects of cytostatics eliminates by adjuvant therapy with calcium folinate (three times reduces the percentage of patients with anemia and leukopenia.
The conservative treatment of ectopic pregnancy with methotrexate in comparison with surgery allows 2.5 times more effective to maintain patency of the fallopian tubes. The calcium folinate as a accompany therapy to conservative treatment of ectopic pregnancy and a complex rehabilitation of pre-pregnancy preparation allows us to eliminate the toxic effects of cytostatics: reduce the level of patients with anemia and leukopenia by three times, normalize folic acid, homocysteine and vitamin D, reduce the percentage of miscarriages by 2 times, increase the absolute values of clinical pregnancies to 37.5 %, and live births to 30.0 %, which is 10 % more than in the group of patients treated only methotrexate.
