Mtx, a folic acid antagonist, is now used successfully in conservative treatment for unruptured tubal pregnancy 4, with lower toxic side effects and fewer complications, and it does not affect tubal patency 29,30. However, other reports have indicated the occurrence of Mtx-induced adverse effects on the fallopian tubes, such as recurrent ectopic pregnancy 4, possible tubal occlusion, and secondary infertility 15,31.
The results of the present study, revealed a reduction in the number of mucosal folds and cellular infiltration into the mucosa of the fallopian tubes at low-dose administration of Mtx for a short period. With increasing dose, cellular infiltration extended to the muscular layer and serosal layer, which was partly in agreement with previous studies in the fallopian tubes 4,15,28 and in other organs exposed to Mtx treatment 8,32.
In the chronic study at low dose, some improvement was seen to occur in the mucosal foldings and thickness of the muscle layer, together with a decrease in cellular infiltration, which was in agreement with the findings of 4,28.
Some investigators reported that normal structures in the healthy endosalpinx are essential for successfully picking up the egg and effectively transferring it to the uterine cavity 4,14. Hence, severe chronic damage to the epithelial lining and musculature of the fallopian tubes can potentially lead to tubal dysfunction and eventually result in ectopic pregnancy or infertility 1,14,33. The immunohistochemical study revealed weak positive immunoreaction for ERs in the epithelial cells of the mucosa of the fallopian tube in all groups. However, a moderately positive reaction for ERs was detected at low dose administered for 2 months. These results were in accordance with an improvement in the histological profile of the fallopian tubes by Light Microscope (LM) as seen in the present study in the form of regions of mucosal folds and normal musculature of the tube together with a decrease in cellular infiltration. These results were in agreement with those of Yang et al.28.
Some researchers stated that a balanced local hormone environment and coordination effects of estrogen and progesterone were essential for intratubal transfer of the fertilized egg into the uterine cavity 34,35. Estrogen and progesterone in the fallopian tubes played an important role in regulating the reproductive process and were essential for tubal physiology and pathology. Similar to intrauterine pregnancy, the fallopian tubes had similar mechanisms of blastocyst implantation in the endosalpinx. Uncoordinated expression of ER and PR in the endosalpinx has a close relation to tubal implantation and subsequent tubal pregnancy; declining local hormone levels will increase the risk of tubal implantation 13,27.
Some scientists further demonstrated that normal expression of ER in the endosalpinx acted in the pivotal role of the mucosal barrier against tubal implantation. Damaged steroid receptors constituted the reasons for the pathogenesis of tubal pregnancy 13. More recent studies showed simultaneous bilateral tubal pregnancies occurring after ovulation induction with clomiphene citrate 34,35; the underlying reason may be the antagonizing effects of clomiphene citrate, which acts against the role of steroid hormone receptors in regulating the reproductive function of the tubes.
From this study we have concluded that Mtx administered at a low dose for short period of time can induce reversible damage to fallopian tubes. However, in large doses (≥5▒mg/kg) it can induce long-term, irreversible damage to fallopian tubes and steroid hormone receptors (ER) in a dose-dependent manner. Therefore, Mtx should be used in a relatively small and safe range of dosage in order to avoid impairment and potential risk for subsequent tubal pregnancy or infertility.
There is no conflict of interest to declare.
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