Immunoreactivity of Kisspeptin and Kisspeptin Receptor in Eutopic and Ectopic Endometrial Tissue of Women With and Without Endometriosis.

Endometriosis is characterized by the presence of ectopic endometrial tissues. Mechanisms of tissue dissemination in endometriosis may be similar to those involved in tumor metastasis. We hypothesize that dysregulation of kisspeptin (KISS1), a metastasis suppressor in endometrial carcinoma, may contribute to the pathogenesis of endometriosis. In this study, we characterized the immunoreactivity of kisspeptin and its receptor, KISS1R, in eutopic and ectopic endometrial tissue of women with and without endometriosis, in proliferative and secretory menstrual cycle phases. Immunohistochemistry was performed using KISS1 and KISS1R antibodies on samples from women with (n = 35) and without (n = 14) endometriosis. Samples from women with endometriosis included eutopic endometrium (n = 20) samples, superficial endometriotic implants (SUP, n = 10) deep infiltrating endometriotic implants (DIE, n = 15), and ovarian endometriomas (OMA, n = 15). Immunoreactivity was quantified using histoscores. KISS1 and KISS1R immunoreactivity was significantly lower in eutopic endometrial stroma of women with versus without endometriosis, regardless of the menstrual cycle phase (P = 0.001 and P = 0.015 respectively). In endometriotic implants, KISS1 levels were significantly lower in both glandular and stromal components of DIE (P < 0.01) and OMA (P < 0.01) compared to SUP. KISS1R immunoreactivity was lower in the glandular component of OMA (P = 0.035) compared to SUP. KISS1 and KISS1R levels are lower in eutopic endometrial stroma from women with versus without endometriosis, consistent with a role for decreased KISS1 expression in the pathogenesis of endometriosis. As deeply invasive lesions showed lower KISS1 levels than superficial lesions, downregulation of KISS1 levels may contribute to implant invasiveness.

Correlates of vaginal laxity symptoms in women attending a urogynecology clinic in Saudi Arabia.

OBJECTIVE: To evaluate the prevalence of vaginal laxity (VL) and its correlates in a cohort of women attending a urogynecology clinic in a tertiary referral center in Saudi Arabia. METHODS: In this retrospective study, demographic information, clinical characteristics, and POP-Q system measurements for women attending the King Fahad Medical City Urogynecology Clinic (January 2013 to April 2015) were analyzed. Women with and without VL were compared across these variables. RESULTS: Out of 376 women attending the clinic for various reasons, 135 (35.9%) reported VL. VL was more common in younger women (P<0.001). Parity, menopausal status, and diabetes were not associated with this symptom. A history of cesarean delivery was protective (aOR 0.39; 95% CI, 0.17-0.90). A bulge symptom and "vaginal wind" were predictors (aOR 3.25; 95% CI, 1.46-7.23 and aOR 15.48; 95% CI, 6.93-34.56, respectively). There was no correlation between VL and POP-Q measurements. VL was not associated with the presence of clinically significant prolapse (stage 2-4), compared with nonsignificant prolapse (stage 0-1) (P=0.869, P=0.152, and P=0.783 for anterior, posterior, and central vaginal compartment, respectively). CONCLUSIONS: In this cohort, VL was common, more prevalent in younger women, and had poorly defined clinical correlates.

Live Birth Rate after Surgical and Expectant Management of Endometriomas after In Vitro Fertilization: A Systematic Review, Meta-Analysis, and Critical Appraisal of Current Guidelines and Previous Meta-Analyses.

Controversy exists regarding surgical management of endometriomas in infertile women before in vitro fertilization (IVF) because growing evidence indicates that surgery may impair the ovarian response. The objective of the present systematic review and meta-analysis was to compare surgical and expectant management of endometriomas regarding IVF outcomes. Prospective and retrospective controlled studies were found via the Cochrane Library, Embase, and MEDLINE databases. Thirteen studies (1 randomized controlled trial and 12 observational studies, N = 2878) were pooled, and similar live birth rates were observed in the surgically and expectantly managed groups (odds ratio = 0.83; 95% confidence interval [CI], 0.56-1.22; p = .98). The clinical pregnancy rates (odds ratio = 0.83; 95% CI, 0.66-1.05; p = .86), the number of mature oocytes retrieved, and the miscarriage rates were not statistically different between study groups. However, the total number of oocytes retrieved was lower in the surgery group (mean difference = -1.51; 95% CI, -2.60 to -0.43; p = .02). Findings suggest that surgical management of endometriomas before IVF therapy yields similar live birth rates as expectant management. However, future properly designed randomized controlled trials are warranted.

Nerve Growth Factor Is Associated With Sexual Pain in Women With Endometriosis.

Endometriosis is present in 1 in 10 reproductive-age women, and half experience deep dyspareunia (pelvic pain with sexual intercourse). Our objective was to investigate nerve growth factor (NGF) and its receptors (TrkA/p75NTR) in endometriosis-associated deep dyspareunia. A total of 32 women with endometriosis in the posterior pelvic compartment (cul-de-sac/uterosacrals) were included, either with (n = 17) or without (n = 15) deep dyspareunia symptoms confirmed by endovaginal ultrasound-assisted palpation on examination. Expression of NGF, TrkA, and p75NTR in the surgically excised cul-de-sac/uterosacral endometriosis was examined by immunohistochemistry and Histoscore blinded to pain phenotypes. Additionally, endometriotic stromal cells (ESCs; n = 3) from ectopic endometriosis lesions were cultured and incubated with/without NGF and/or Trk inhibitor K252a, followed by expression analysis of prostaglandin-endoperoxide synthase 2 (PTGS-2)/cyclooxygenase 2 (COX-2; reverse transcription quantitative real-time polymerase chain reaction and Western blot) and prostaglandin E2 (PGE2) secretion (enzyme-linked immunosorbent assay). We found that the immunointensity of NGF and TrkA, but not p75NTR, was significantly elevated in endometriotic stroma and epithelium from women with deep dyspareunia compared to women without deep dyspareunia. Nerve growth factor immunoreactivity in the stroma was also significantly associated with deep dyspareunia intensity and local nerve bundle density. In cultured ESCs, NGF significantly increased PTGS-2/COX-2 mRNA and protein levels as well as PGE2 secretion, and these effects could be abolished by pretreatment of Trk inhibitor K252a. In conclusion, elevated NGF levels were associated with deep dyspareunia in women with cul-de-sac/uterosacral endometriosis. This association may be mediated by increased nerve bundle density and by COX-2/PGE2 stimulation via Trk receptor. Nerve growth factor signaling may play an important role in endometriosis-associated sexual pain.

HOXB4 Immunoreactivity in Endometrial Tissues From Women With or Without Endometriosis.

Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC). HOXB4 localization and immunoreactivity was assessed using immunohistochemistry and histoscore analysis. Data were analyzed with and without stratification by menstrual cycle phase. HOXB4 protein was present in the nuclei of endometrial glandular epithelial cells but not in stromal cells. HOXB4 immunoreactivity was reduced in DIE samples compared to all other groups. A smaller reduction in HOXB4 immunoreactivity was observed in SE samples compared to EC samples. HOXB4 immunoreactivity was significantly greater in proliferative compared to secretory phase samples in the EC group but not in EE, Eoma, or DIE groups. Among only proliferative phase samples, HOXB4 immunoreactivity was reduced in EE, Eoma, and DIE groups compared to EC. Based on these data, we suggest that an impaired capacity of eutopic and ectopic endometrial tissue to upregulate levels of HOXB4 during the proliferative phase may play a role in the pathogenesis of endometriosis and that further downregulation of HOXB4 may enhance ectopic implant invasiveness.