The role of toll-like receptors (TLRs) and their therapeutic applications in endometrial cancer

Endometrial cancer (EC) is developed nations' most prevalent form of gynecologic cancer. Patients are frequently diagnosed with EC when the tumor is still limited to the uterus. Patients without tumor metastasis have a 5-year survival rate ranging from 80 to 90%; however, almost 16.8% of EC patients develop a metastatic form of the tumor. In the early stages of tumorigenesis, the immune system is able to identify aberrant cells as non-self, therefore providing the optimal pro-inflammatory microenvironment for the elimination of cancer cells. Although, chronic inflammation can be a crucial aspect of tumor development. Toll-like receptors (TLRs), as the main pattern recognition receptors (PRRs) in innate immunity, may stimulate an inflammatory response and provide cell survival in the tumor microenvironment (TME). TLRs are vital immunomodulators that may significantly impact the development of gynecologic malignancies. Therefore, TLR inhibitors are being researched for their possible benefits in treating gynecologic cancers. The aim of this study is to review the current knowledge in this field and provide some insight into the therapeutic potential of TLR inhibitors in EC (AU)

The role of toll-like receptors (TLRs) and their therapeutic applications in endometrial cancer.

Endometrial cancer (EC) is developed nations' most prevalent form of gynecologic cancer. Patients are frequently diagnosed with EC when the tumor is still limited to the uterus. Patients without tumor metastasis have a 5-year survival rate ranging from 80 to 90%; however, almost 16.8% of EC patients develop a metastatic form of the tumor. In the early stages of tumorigenesis, the immune system is able to identify aberrant cells as non-self, therefore providing the optimal pro-inflammatory microenvironment for the elimination of cancer cells. Although, chronic inflammation can be a crucial aspect of tumor development. Toll-like receptors (TLRs), as the main pattern recognition receptors (PRRs) in innate immunity, may stimulate an inflammatory response and provide cell survival in the tumor microenvironment (TME). TLRs are vital immunomodulators that may significantly impact the development of gynecologic malignancies. Therefore, TLR inhibitors are being researched for their possible benefits in treating gynecologic cancers. The aim of this study is to review the current knowledge in this field and provide some insight into the therapeutic potential of TLR inhibitors in EC.

Letrozole and ovarian hyperstimulation syndrome: Retrospective cross-sectional study.

Background: Recently, letrozole has been used to prevent moderate to severe ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology cycles due to its estrogen-reducing and androgen-increasing effects on the ovaries, affecting granulosa cells, and reducing vascular endothelial growth factor production. Objective: This study aimed to investigate the impact of letrozole consumption in preventing OHSS in infertile women with polycystic ovarian syndrome undergoing in vitro fertilization. Materials and Methods: In this cross-sectional study, among 1743 medical records of infertile women who were scheduled for oocyte retrieval at Research and Clinical Center for Infertility, Yazd, Iran. Data of 343 women with polycystic ovarian syndrome diagnosis and at risk of OHSS was extracted from March 2022-2023. The stimulation was carried out using a flexible gonadotropin releasing hormone (GnRH) antagonist protocol. Women were divided into 2 groups based on whether they received letrozole or not. In the letrozole group, 2.5 mg letrozole twice daily was continued from the trigger day, while in the control group, women did not receive letrozole. The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription were analyzed. Results: 89 women in the letrozole and 254 women in the control group were examined. There was no statistically significant difference between groups in terms of age and body mass index; however, anti-Mullerian hormone was significantly higher than control group (7.53 ± 4.61 vs. 5.47 ± 3.63, p < 0.001). The parameters of OHSS severity, hospitalization rates, and the need for albumin prescription showed no significant differences between the groups. Conclusion: Recent study indicates that incorporating letrozole into the treatment of GnRH antagonists and cabergoline does not reduce the OHSS severity.

Effect of serum vitamin D level on endometrial thickness and parameters of follicle growth in infertile women undergoing induction of ovulation.

In this paper, 153 infertile women undergoing induction of ovulation at an academic tertiary care centre were included in a cross-sectional study. Serum Vitamin D level was measured and the rate of clinical pregnancy (defined as a sonographic presence of FHR of an intrauterine gestational sac) and patient and cycle parameters were determined. The results showed that a correlation exists between endometrial thickness as well as the number of antral follicles and replete level of Vitamin D. Interestingly, the median level of these two parameters was of upmost level in the most replete tertile of serum Vitamin D level. There was no correlation between the serum level of Vitamin D and pregnancy rate. Vitamin D status was associated with endometrial thickness and number of antral follicles, but this study did not find a pivotal effect of serum Vitamin D level on pregnancy rate. Impact statement What is already known on this subject? Literature reviews have indicated that a Vitamin D deficiency is directly responsible for a reduced fertility and reproduction capacity. Women with higher level of Vitamin D in serum and follicular fluid are more likely to become pregnant. What do the results of this study add? This study, assessing the effect of serum level of Vitamin D on endometrial thickness and parameters of follicle growth in infertile women undergoing induction of ovulation showed that a correlation exists between endometrial thickness as well as the number of antral follicles and replete level of Vitamin D. It can be concluded that a replete Vitamin D status is associated with a better state of endometrial thickness and a number of antral follicles, but this study did not find a pivotal effect of serum Vitamin D level on the pregnancy rate. What are the implications of these findings for clinical practice and further research? If a relationship would be proved between Vitamin D deficiency and endometrial thickness and parameters of follicle growth it is possible that with prescribing supplemental Vitamin D as a relatively inexpensive and safe way along with the other more complex and costly infertility treatments, achieving the pregnancy would be easier.

The relationship between serum vitamin D level and premenstrual syndrome in Iranian women.

BACKGROUND: Premenstrual syndrome (PMS) is among the most unfavorable problems in women in reproductive age; however its pathophysiology is still not fully confirmed. Vitamin D as an immunomodulator could prevent inflammatory state before and during menstruation. OBJECTIVE: The aim was to investigate whether there is any relationship between serum vitamin D levels and PMS. MATERIALS AND METHODS: In total, 82 women participate in this case-control study which was conducted in Shahid Akbar-abadi hospital from November 2013 to March 2015. Categorization was based on an Iranian version of the premenstrual symptoms screening tool (PSST). Levels of 25 hydroxy-vitamin D3 (25OHD) were determined by using 25-OH Vitamin D ELISA kit in luteal phase. Characteristics of participants and vitamin D levels were compared between two groups by using independent sample t-test. RESULTS: Menarche age of women with PMS was significantly lower than normal women (p=0.04). Body mass index was not statistically different between groups. We observed a high rate of vitamin D deficiency and also its severe deficiency in both PMS and non-PMS groups. However, our study demonstrated no significant difference in the levels of serum 25OHD between the two groups. CONCLUSION: It seems there is no association between PMS and serum levels of vitamin D3; however, the high rate of vitamin D deficiency among young Iranian women emerges special health care considerations in this group.

Endoureterotomy for treatment of primary obstructive megaureter in children.

PURPOSE: To describe a new approach to the treatment of primary obstructive megaureter (POMU) using endoscopic endoureterotomy. The results obtained with this technique are reviewed with long-term follow-up. PATIENTS AND METHODS: A total of 47 children (mean age 3.7 years) with 52 POMU units and a history of failed conservative management underwent endoureterotomy of obstructed juxtavesical and intramural ureter. A 3F Double-J ureteral stent was introduced up to the obstructed segment of ureter. Then a zebra catheter was inserted into the affected ureter beside the stent, followed by a neonatal-size ureteroscope. Following delineation of the length of the narrowed portion of the ureter, a guidewire with a plastic sheath replaced the zebra catheter. A longitudinal incision was made through the detrusor muscle at the 6 o'clock position, leaving the bladder adventitia untouched. The Double-J stent was left in place, while its distal tip was fixed by long nylon suture and single knot to the external genitalia to permit easy removal 1 week after the procedure. RESULTS: With a mean follow-up of 39 months (range 14-62 months), no leakage, ureteral-orifice obstruction, or reflux was observed. The postoperative success rate was 90% (47 of 52 ureters), defined as resolution or decrease in hydroureteronephrosis and improvement or stability of renal function determined by renal scan. In 37 ureterorenal units (71%), there was complete resolution of hydroureteronephrosis. CONCLUSIONS: On the basis of previous studies demonstrating the value of endoureterotomy with stenting for the treatment of benign ureteral strictures in adults, we developed a modified endoscopic approach for the treatment of POMU and applied this technique in meticulously selected cases. Our results showed that this approach is a valid option for the treatment of children with POMU.