Search

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism., Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant., Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001)., Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

Letrozole, an aromatase inhibitor, has recently been introduced as a favorable medical treatment for ectopic pregnancy. We aimed at evaluating the effects of different doses of letrozole for termination of ectopic pregnancy and study their effects on villous trophoblastic tissue. Sixty patients with undisturbed ectopic pregnancy were classified into three equal groups. Group I: the control group that contained women who underwent laparoscopic salpingectomy, Group II: patients who received letrozole (5 mg day -1 ) for 10 days, and Group III: patients who received letrozole (10 mg day -1 ) for 10 days. Subsequently, the β-hCG levels were determined on the first day and after 11 days of treatment. Group IV consisted of patients of GII and GIII; their β-hCG did not drop below 100 mIU/ml within 11 days, and underwent salpingectomy. Placental tissues from patients undergoing salpingectomy either from the control group or GIV were processed for the evaluation of estrogen (ER) and progesterone (PR) receptors, vascular endothelial growth factor (VEGF), and cleaved caspase 3 (CC-3) expression. Cases exposed to high dose letrozole 10 mg day -1 resulted in a higher ectopic pregnancy resolution rate of 85% (17/20), while the resolution rate of the low dose letrozole-treated group (5 mg day -1 ) was 65% (13/20), and also showed a significant reduction in β-hCG levels on the 11th day, 25.63 ± 4.29 compared to the low dose letrozole group 37.91 ± 7.18 (P < 0.001), Meanwhile, the letrozole-treated group GIV showed markedly reduced expression of ER, PR, and VEGF and a significant increase in the apoptotic index cleaved caspase-3 compared to the control group (P < 0.001). The utilization of letrozole at a dose of 10 mg day -1 for medical treatment of ectopic pregnancy results in a high-successful rate without any severe side effects. Letrozole depriving the placenta of estrogen that had vascular supporting signals resulted in destroying the vascular network with marked apoptosis., (© 2022. The Author(s).)