Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study.

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.

A novel triad for the diagnosis of endometriosis, the short anogenital distance combines with high endometrial BCL2 and low endometrial FASL.

OBJECTIVE: To investigate the anogenital distance from the upper verge of the anus to the posterior fourchette (AGDAF ), FASL, and BCL2 combination as a reliable and non-invasive tool for the diagnosis of endometriosis. METHODS: This study included 100 women with endometriosis and 50 women without endometriosis as the control group. All cases underwent history taking, body mass index (BMI) measurement, AGD measurement, and FASL and BCL2 immunohistochemical staining of the eutopic endometrial tissue. RESULTS: This study included 150 women divided into endometriosis and control groups. Endometriosis cases significantly had shorter AGDAF , 22.9 ± 2.6 mm, compared with the control group, 27.3 ± 3.5 mm (P < 0.001). Lower FASL and higher BCL2 expression were associated with endometriosis (P < 0.001). The combined measurement of AGDAF (cut-off point 24.55 mm) with FASL and BCL2 was associated with endometriosis (P < 0.001). The combined diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of AGDAF , FASL, and BCL2 were 83%, 78%, 87.3%, and 69.6%, respectively. The area under the curve was greater for AGDAF , FASL, and BCL2 in combination than for individual measurements. CONCLUSION: Combining short AGDAF with high BCL2 and low FASL is a highly sensitive, non-invasive diagnostic tool for endometriosis.

Transient ovarian torsion in a pregnant woman after vitrified-warmed embryo transfer: a case report.

Assisted reproduction is a risk factor for adnexal torsion due to ovarian hyperstimulation and increased incidence of twin pregnancy. Both risk factors can be eliminated in frozen embryo transfers, but in our case ovarian torsion occurred after the use of an aromatase inhibitor (Femara) in endometrium preparation due to the presence of corpus luteum. Case presentation: G2P1+0 presented at 7 weeks gestation after vitrified-warmed embryo transfer with right loin pain and mild right iliac pain and tenderness. Ultrasound examination revealed transient or incomplete ovarian torsion. The presentation of the case was somewhat misleading and the transient nature of the torsion provided an opportunity for the conservative management of the case. In conclusion, ovarian torsion is still an undesired event, even after single embryo transfers and in vitrified-warmed cycles. Clinical and ultrasound follow-up precluded the need for surgery in our case.

Prophylactic common iliac artery temporary clamping versus balloon occlusion for management of placenta accreta spectrum disorders: A prospective clinical trial.

OBJECTIVE: The present study aims to compare prophylactic common iliac artery (CIA) temporary clamping and preoperative balloon occlusion for managing placenta accreta spectrum (PAS) disorders. STUDY DESIGN: Between January 2019 and June 2020, 46 patients with PAS disorders were included. Of them, 26 patients were offered CIA balloon occlusion (Group A), while temporary CIA clamping was done for the other 20 patients (Group B). Primary outcomes were procedure-related complications, and secondary outcomes included intraoperative and postoperative complications, reoperation rates, total procedure time, blood loss, and amount of blood transfusion. RESULTS: Blood loss was statistically non-significant higher in group B than in group A (p-value = 0.143). Only one patient in group A and three in group B needed reoperation. The bleeding continued for a mean of 1.6 days in group A and 1.7 days in group B, with non-significant statistical differences between both groups p value = 0.71. Nine patients in group A (34.6%) and four in group B (20%) required ICU admission. The mean Apgar score was 7 and 6.6 in babies of group A and group B patients, respectively. The median number of allogeneic blood transfusions performed was two in patients in group A and 1 in group B (p-value = 0.001). CONCLUSION: Both techniques offer good choices for patients with PAS to decrease mortality and morbidity rates. The selection of a better technique depends on institutional references and physicians' experience.

Evaluation of Different Doses of the Aromatase Inhibitor Letrozole for the Treatment of Ectopic Pregnancy and Its Effect on Villous Trophoblastic Tissue.

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 ß-hCG levels were determined on the first day and after 11 days of treatment. Group IV consisted of patients of GII and GIII; their ß-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 ß-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.