CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study.

BACKGROUND AND OBJECTIVE: Endometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients. MATERIALS AND METHODS: The Visual Analog Scale (VAS) assessed pain in diagnosed EM. INDIVIDUALS: Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels. RESULTS: In the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05). CONCLUSION: DNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways.

NLRP3 concentration, oxidants, and antioxidants in plasma of endometriosis patients undergoing treatment with dienogest.

OBJECTIVE: NOD-like receptor pyrin domain-containing 3 (NLRP3) is a cytosolic multi-protein complex that induces inflammation and is negatively regulated by progesterone. Previous researches have reported abnormal induction of reactive oxygen species (ROS) and progesterone resistance in endometriosis (EM). Since progesterone regulates ROS level and, consequently, inflammation, our objective is to investigate whether dienogest (DNG) regulates NLRP3 and whether the regulation of NLRP3 inflammasome by DNG in the blood plasma of patients with EM can affect oxidant and antioxidant markers. METHODS: Plasma samples were obtained from control and EM patients experiencing pain symptoms to measure the level of NLRP3, oxidants, and antioxidants. Subsequently, these patients were given oral DNG 2 mg/day for six months for drug treatment. After six months, plasma samples were collected from the patients for re-examination. RESULTS: The findings indicate that DNG reduced NLRP3 concentration and oxidant production while increasing antioxidant production in blood plasma. By reducing NLRP3, DNG was able to alleviate inflammation and pain caused by inflammation in EM patients. CONCLUSION: In conclusion, the use of DNG in EM patients resulted in a decrease in NLRP3 concentration in the patient's plasma. Furthermore, this effect was enhanced by balancing oxidant/antioxidant levels, which may contribute to reducing inflammation associated with EM.

Does transcutaneous electrical nerve stimulation reduce the laparoscopic related shoulder pain?

OBJECTIVE: Although laparoscopic surgery is a good substitute for laparotomy in reducing postsurgical pain, many patients complain of shoulder pain after laparoscopic surgery and require pain-relief. Post-operative pain management leads to increased patient satisfaction. Transcutaneous Electrical Nerve Stimulation (TENS) is a non-pharmacological, noninvasive modality that reduces pain by activating the descending inhibitory systems in the central nervous system. Given the importance of decreasing shoulder pain after gynecological laparoscopy, the current study aimed to investigate the management of shoulder pain in these patients using TENS. METHODS: This was a retrospective case-control study. A total of 112 women aged 18-45 years who experienced shoulder pain due to gynecologic laparoscopic surgery were included in the study. Patients were divided into TENS and control groups. In the TENS group, TENS was used twice for 20 minutes each, but in the control group, the patients received regular treatment. Patients were evaluated at intervals of 2, 4, 8, 24, 48, and 72 hours after laparoscopy for shoulder pain score. RESULTS: The results showed a significant decrease in visual analog scale scores at 2, 4, and 8-hour in the TENS group compared with the control group. At 24 hours evaluation, although the pain was reduced, the difference was not significant. At 48- and 72-hour assessment, all patients in each group reported zero score for severity of pain. CONCLUSION: The findings suggest that TENS significantly reduces postoperative shoulder pain.

Evaluation of expression of biomarkers of PLAGL1 (ZAC1), microRNA, and their non-coding RNAs in patients with endometriosis.

Since the PLAGL1 (ZAC1) gene is expressed in the human endometrium. It may be involved in the etiology of endometrial disorders by its abnormal regulation and expression. This study aimed to investigate the Zac1 gene and related microRNA and LncRNA and its alterations in patients with endometriosis. Blood plasma, ectopic (EC) and eutopic (EU) endometrial samples were gathered from 30 patients with endometriosis and 30 healthy fertile women, and the Q-PCR technique was used to determine the expression level of Zac1 mRNA and microRNAs (miR-1271-5p, hsa-miR-490-3pin) and LncRNAs (TONSL-AS1 TONSL, KCNQ1OT1 KCNQ1). According to the results, the Zac1 gene and KCNQ1OT1 KCNQ1, TONSL-AS1 TONSL LncRNA expression were significantly decreased in the endometriosis group versus the control group (P < 0.05). MiR-1271-5p and hsa-miR-490-3pin microRNA expression were significantly raised in the endometriosis group as opposed to the control group (P < 0.05). In summary, this research for the first time revealed that identifying Zac1 expression provides us with new indicators for evaluating endometriosis.

The effect of diluted ropivacaine in distending fluid on cramping pain after hysteroscopic surgeries: a randomized clinical trial study.

OBJECTIVE: The effect of ropivacaine on postoperative hysteroscopy has not yet been evaluated; this study investigated the effect of diluted ropivacaine in distending media during hysteroscopy on postoperative cramping pain. METHODS: This double-blind randomized clinical trial was conducted on 60 women who underwent hysteroscopy at a tertiary hospital. Normal saline was used as the distending fluid in both groups. The intervention group received 10 mL of 2% ropivacaine in only one bottle of 1,000 mL normal saline as a distending fluid, while the control group received 10 mL of normal saline in 1,000 mL normal saline during hysteroscopy. Patients' pain scores were evaluated before hysteroscopy and at 2, 6, 12, 24, and 48 hours after hysteroscopy. RESULTS: Based on the results, the pain measured by visual analog scale (VAS) score was significant at 6 and 12 hours after the intervention was significantly lower than that in the ropivacaine group (3.03±1.57 vs. 4±1.49, P=0.02 at 6 hours and 1.28±1.36 vs. 2.4±1.43, P=0.003 at 12 hours). There were no significant differences in the VAS scores at 2, 24, and 48 hours after the intervention between the two groups. CONCLUSION: Ropivacaine in the distending fluid during hysteroscopy is associated with a significant reduction in pain within a few hours after hysteroscopy with no remarkable adverse effects.

A targeted educational programme improves fundamental knowledge of menstrual pain and endometriosis in young women: The Endometriosis Awareness Promotion Project.

RESEARCH QUESTION: Would a properly designed educational programme offered to young women improve their awareness and fundamental knowledge of menstrual pain and endometriosis? DESIGN: A multinational cross-sectional study using a pen-and-paper questionnaire among women aged 19-24 years was conducted between 2017 and 2019 to assess fundamental knowledge of menstrual pain and endometriosis. Improvement in knowledge was also analysed using a separate questionnaire completed before, and 1-3 months after, a group discussion, lecture on menstrual pain and endometriosis, or both. RESULTS: Among three groups of students (college [n = 271], medical [n = 877] and nursing [n = 763]), knowledge of menstrual pain and endometriosis was lowest among college students, modest among nursing students and fair among medical students (P < 0.001 for each). The experience of cyclical pain, even when painkillers were taken, was reported by 15.5%, 4.6% and 3.8% of students, respectively. Most students managed their cyclical pain by enduring it or by taking over-the-counter medication. An informative education programme with group discussions, lectures, or both, was successful in improving knowledge and consequences of menstrual pain and endometriosis. Proper education and dissemination of knowledge to college students failed to motivate them to visit gynaecologists; however, medical and nursing students became highly interested in visiting gynaecologists. CONCLUSIONS: An educational programme can improve awareness and knowledge of endometriosis and dysmenorrhoea among young women. The programme motivated nursing and medical students, but not college students, to seek medical attention for early detection and management of endometriosis.

Treatment of Ovarian Hyperstimulation Syndrome in a Mouse Model by Cannabidiol, an Angiogenesis Pathway Inhibitor.

Studies suggest that ovarian hyperstimulation syndrome (OHSS) can be treated by reducing the level of vascular endothelial growth factor (VEGF). However, due to the side effects of commercially available VEGF-reducing drugs, they can be ruled out as a suitable treatment for OHSS; therefore, researchers are looking for new medications to treat OHSS. This study is aimed at investigating the effects of cannabidiol (CBD) in an OHSS model and to evaluate its efficacy in modulating the angiogenesis pathway and VEGF gene expression. For this purpose, 32 female mice were randomly divided into four groups (eight mice per group): control group, group 2 with OHSS induction, group 3 receiving 32 nmol of dimethyl sulfoxide after OHSS induction, and group 4 receiving 30 mg/kg of CBD after OHSS induction. The animals' body weight, ovarian weight, vascular permeability (VP), and ovarian follicle count were measured, and the levels of VEGF gene and protein expression in the peritoneal fluid were assessed. Based on the results, CBD decreased the body and ovarian weights, VP, and corpus luteum number compared to the OHSS group (p < 0.05). The peritoneal VEGF gene and protein expression levels reduced in the CBD group compared to the OHSS group (p < 0.05). Also, CBD caused OHSS alleviation by suppressing VEGF expression and VP. Overall, CBD downregulated VEGF gene expression and improved VP in OHSS.

Post-thawing and culture comparison of three routine slow freezing methods for human ovarian tissue cryopreservation: Histological, molecular, and hormonal aspects.

To find the gold standard out of three pre-established routine slow freezing (SF) methods, ovarian cortex tissues of nine transsexual individuals were cryopreserved and compared to each other, as well as the control (fresh) samples. Histological, genomic, and endocrinological effects of the SFs were assessed post-thawing and after a seven-day culture period. SF1 included 10% dimethyl-sulfoxide (Me2SO) in the base medium (BM), SF2 had 1.5 M/L ethylene-glycol (EG) and 0.1 M/L sucrose in the BM, and SF3 consisted of 6% Me2SO, 6% EG and 0.15 M/L sucrose in the BM. The cortical tissue strips went under a programmed cooling process and were stored in liquid nitrogen. Histological criteria (tissue damage and follicular quality), as well as gene expression levels, were assessed in the thawed and control tissues. Half of the thawed and control tissues were cultured for seven days and their histology, genetic profile, and hormonal status were examined as the reflection of the avascular tension effect. Post-thawing tissue damage was similar between all groups but significantly increased post-culture (P < 0.05). The percentages of high-quality follicles diminished in all SFs after thawing and culture (P < 0.05) except for the similarity of post-thawing SF3, compared to control. The genetic profile of the tissue after thawing and culture suggested quiescence/activation balance in SF1 and 2 and significant down-regulation in SF3, compared to the control specimens (P < 0.05). Post-thawing BAX:BCL2 was higher than control in SF1 and SF3 (P < 0.05), while this ratio in SF2 was similar to the control. However, after culture this ratio was similar to that of control in SF3 and diminished in SF1 and 2 (P < 0.05). The expression levels of gap-junction genes showed dramatic pre- and post-thawing fluctuations in all groups. After culture, estradiol in SF3 was significantly higher than SF1 and 2 (P < 0.05). In addition, progesterone in SF3 was similar to control but significantly lower in SF1 and 2 (P < 0.05). In conclusion, all SFs showed advantages and disadvantages, and the follicular quality and its function depend on the type of cryoprotectant and the speed of thawing. The effects of freezing/thawing continue to appear during the seven days of culture. According to the results of this study, SF3 seems to be more promising in keeping the follicles functional and safe from cell damage during culture.

Hemoperitoneum due to bleeding from a vein overlying a subserous uterine myoma: a case report.

BACKGROUND: Fibroids are the most common pelvic tumors in women; serious complications are rare but can be life-threatening. CASE PRESENTATION: We present a case report of a 38-year-old Persian woman with acute abdominal pain and a history of uterine fibroids. The patient refused to undergo a laparoscopic myomectomy. Her ultrasound examination revealed free fluid in the abdominal cavity, and her vital signs were indicative of vasogenic shock. A diagnostic laparoscopy was performed to identify and control the source of bleeding: 400 ml of blood and blood clots were removed. Active bleeding was seen from a vein overlying a subserosal myoma. A laparotomic myomectomy was performed, and the patient was discharged 3 days after surgery with no complications. CONCLUSION: Surgeons should consider the possibility of this complication in women with acute abdominal pain and a history of uterine leiomyoma.

Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial.

BACKGROUND: Human papillomavirus (HPV) is one of the most significant risk factors for cervical cancer. The HPV vaccine has a very significant impact on the incidence of cervical cancer. The present study aimed to investigate the impact of prophylactic quadrivalent HPV vaccine in the treatment of women with cervical intraepithelial neoplasia (CIN 1-3). METHODS: This randomized controlled trial was conducted in the Shahid Sadoughi University of Medical Sciences (SSUMS), Yazd, Iran, from October 2011 to November 2015 in women with histologically confirmed residual/recurrent CIN 1 or high-grade CIN (CIN 2-3). Eligible women were assigned randomly to an intervention and a control group. Women in the intervention group were given HPV vaccinations while those in the control group were not. Participants were followed up for 24 months. Primary and secondary outcomes, and adverse effects of the treatment in the two groups were compared using Student's t test, the chi-square test, or Fisher's exact test. P values < 0.05 or less were considered statistically significant. RESULTS: Three-hundred and twelve women were randomized to the two groups; the data of 138 in the intervention group and 104 in the control group were analyzed. The mean age of the women was 32.59 ± 4.85 years. Differences in age, marital status, and grades of CIN weren't significant between the two groups. At the end of the two-year follow-up period, the number of women with CIN 2-3 in the intervention and control groups was reduced by 75% (from 93 to 23) versus 40% (from 69 to 41). The efficacy of the HPV vaccine in women with CIN 1-3 was 58.7% (p = 0.018). No serious adverse effects related to the vaccines were reported. CONCLUSIONS: The prophylactic quadrivalent HPV vaccine after treatment may have a therapeutic effect in women with residual/recurrent CIN 1 or high-grade CIN (CIN 2-3). TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20190603043801N1. Registered 24 July 2019 - Retrospectively registered, http://www.irct.ir/user/trial/40017/view.