Rectovaginal Endometriotic Lesions Research Articles

P-304 Sexual function in women with endometriosis: an online survey

Abstract Study question What factors are associated with sexual function in women with endometriosis? Summary answer In this study, the most important variables associated with sexual function were dyspareunia (especially deep and introital dyspareunia combined), infertility, fatigue, and psychological comorbidities. What is known already Endometriosis is a chronic gynaecologic disease that affects women of reproductive age, with negative consequences on multiple life domains, including sexuality. Although it has been demonstrated that endometriosis-related sexual issues may negatively affect women’s intimate relationships, their subjective experience remains overlooked, either in research or clinical practice. In this regard, the impact of dyspareunia (especially deep dyspareunia) has been highlighted in several studies, but the role of symptoms other than pain, such as fatigue, infertility, and psychological comorbidities, has not been yet clarified. Moreover, little is known about how women deal with dyspareunia and the quality of doctor-patient communication. Study design, size, duration This observational study was conducted between 8 November and 21 December 2021 in collaboration with the largest Italian patient association, Associazione Progetto Endometriosi (APE [Endometriosis Project Association]). Data were collected through a self-administered online survey hosted on Qualtrics (Qualtrics Ltd.). Women were invited to participate in the study via APE’s Facebook page and newsletters. The online survey was anonymous, and women were allowed to complete it only after providing their electronic consent. Participants/materials, setting, methods Participants were 612 women (age: 36.41 ± 6.72 years) with a surgical or clinical diagnosis of endometriosis and a sexual partner. They completed the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS), and the Rosenberg Self-Esteem Scale (RSES). Demographic and gynaecologic data – including endometriosis stage, type of lesions, symptoms (e.g., pelvic pain, fatigue, infertility), treatment –, and information regarding women’s subjective experience of dyspareunia were collected using a researcher-made questionnaire. Main results and the role of chance Dyspareunia was experienced by 524 (86%) women. Sexual dysfunction (FSFI total score < 26.55) was reported by 479 (78%) participants. Multiple regression analyses revealed that sexual function (FSFI total score) was associated with dyspareunia (β = −.108, P = .008), infertility (β = −.082, P = .040), fatigue (β = −.108, P = .021), and symptoms of anxiety and depression (HADS total score; β = −.127, P = .021). Women with sexual dysfunction were more likely to report rectovaginal endometriotic lesions (59% vs. 47%, P = .016) and stage 4 endometriosis (43% vs. 32%, P = .002), to experience deep and introital dyspareunia combined (50% vs. 21%, P < .001), with greater symptoms of anxiety and depression (F [2,595] = 21.812, P < .001, Wilk’s Λ = .932, η2p = .068) and lower self-esteem (t [589] = 5.111, P < .001). Women with dyspareunia and sexual dysfunction reported greater fear of pain and consequent inability to relax during intercourse, avoidance of sex, worries about their sexual life, sexual dissatisfaction, and feelings of guilt towards the partner (Ps < .001), along with poorer support and understanding from doctors (P = .006) than women with dyspareunia who did not report sexual dysfunction. Limitations, reasons for caution This is one of the largest studies on sexual function in women with endometriosis. However, there are reasons for caution when interpreting our results due to the self-reported nature of all the data (including medical information) and the risk of selection bias due to our recruitment strategy. Wider implications of the findings Our results clearly indicate that the majority of women with endometriosis experience sexual problems that are mostly (but not solely) due to dyspareunia. The assessment of sexual function should be included in routine clinical practice with these patients, also considering its association with psychological symptoms and self-esteem. Trial registration number Not applicable

Reprint of: Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities

OBJECTIVE: To review the histogenesis of peritoneal, ovarian, and rectovaginal endometriotic lesions. DESIGN: The comparison of morphologic, morphometric, and histochemical data observed in each type of lesion. SETTING: A university hospital department of gynecology. PATIENT(S): Patients complaining of infertility or pelvic pain with laparoscopically proved endometriosis. INTERVENTION(S): Laparoscopy was performed, and biopsy specimens from the endometriotic lesions were histologically studied. RESULT(S): Three types of endometriotic lesions must be considered: peritoneal, ovarian, and rectovaginal. Morphologic and morphometric data show similarities between eutopic endometrium and red peritoneal lesions, suggesting that these lesions are the first stage of early implantation of endometrial glands and stroma. After partial shedding, the red lesions regrow constantly. The shedding induces an inflammatory reaction, provoking scarification, and the lesions become black. The subsequent fibrosis leads to areas of white opacification that are inactive. The pathogenesis of ovarian endometriomas is a source of controversy. Although there seems to be a consensus concerning the invagination theory, there is still a contradiction between the implantation theory and the metaplasia theory. We recently showed that the mesothelium covering the ovary can invaginate into the ovarian cortex, pushing back the primordial follicles. The presence of mesothelial invagination in continuum with endometriotic tissue suggests that metaplastic histogenesis of ovarian endometriotic lesions occurs. Rectovaginal endometriotic nodules must be considered adenomyomas, consisting of smooth muscle with active glandular epithelium and scanty stroma. Immunocytochemical results show poor differentiation and hormonal independence of these lesions and indicate a close relation with their mesodermal mullerian origin. CONCLUSION(S): Peritoneal, ovarian and rectovaginal endometriotic lesions must be considered as three separate entities with different pathogeneses.

Ileocecal endometriosis: clinical and pathogenetic implications of an underdiagnosed condition

To review our experience with surgical treatment of ileocecal endometriosis. Observational study. Tertiary university hospital in Italy. Eight consecutive patients with infiltrating ileocecal endometriosis operated on between 2003 and 2005. All of the women underwent laparotomic ileocecal or cecal resection and had radical treatment of rectovaginal endometriosis as well. Long-term relief of pelvic pain, constipation, and dyschezia. There were no postoperative intestinal complications. At a mean ± SD follow-up of 106 ± 10 months, all of the patients reported significant improvement of pelvic pain and bowel symptoms. Infiltrating ileocecal endometriosis requiring bowel resection was associated in all cases with infiltrating rectovaginal endometriosis, possibly reflecting a common pathogenesis. A thorough clinical evaluation of women with rectovaginal endometriosis might allow an improvement in the difficult preoperative diagnosis of ileocecal endometriosis. Our data support the long-term efficacy of the radical surgical resection of associated ileocecal and rectovaginal endometriotic lesions in reducing pelvic pain, constipation, and dyschezia.

Epithelial to mesenchymal transition (EMT) seems to be regulated differently in endometriosis and the endometrium

Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties, a prerequisite for the establishment of endometriotic lesions. However, the role EMT might play in the pathophysiology of endometriosis is still unknown. Therefore, we examined five recognized markers for EMT in endometrium and endometriosis: E-cadherin, N-cadherin, Twist, Snail and Slug. Immunohistochemistry was used for peritoneal, ovarian and rectovaginal endometriotic lesions (n=27) and endometrium (n=13). Reverse transcription polymerase chain reaction was applied to tissue samples and primary cell cultures of endometriotic lesions (n=9) and endometrium (n=8). In endometriosis and endometrium E-cadherin, N-cadherin, Twist, Snail and Slug were expressed on protein and mRNA level. E-cadherin expression was strong in epithelial cells, but single E-cadherin-negative cells were frequently present in endometriosis. In endometriosis N-cadherin, Twist and Snail expression were upregulated in comparison with endometrium. The expression of E- and N-cadherin was inversely correlated, while that of N-cadherin and Twist was positively correlated. This study strongly suggests that EMT may be regulated differently in endometriosis and the endometrium. Future research should further elucidate the regulation of EMT in the endometrium and endometriosis.

Differential expression of steroidogenic enzymes according to endometriosis type

To evaluate, in peritoneal, ovarian, and rectovaginal endometriotic lesions, expression of steroidogenic enzymes involved in the activation and inactivation of estrogens: 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1) and 2 (HSD17B2), estrone sulfotransferase (EST), and steroid sulfatase (STS). Academic gynecology research unit. Retrospective study. Disease-free (n = 41) patients and patients with endometriosis (n = 79) were included for quantitative polymerase chain reaction (q-PCR) (15 disease-free, 33 endometriosis) and immunohistochemistry (26 disease-free, 46 endometriosis) studies. Q-PCR and immunohistochemistry. Evaluation of mRNA and protein expression. Glandular HSD17B1, HSD17B2, and STS protein expression were demonstrated. HSD17B2 mRNA values were higher in the secretory phase of the menstrual cycle in the endometrium of disease-free women, but not in the eutopic endometrium of patients with endometriosis. HSD17B1 mRNA was equally expressed in the various tissues investigated, and EST mRNA was expressed at low levels in the different lesion types. HSD17B2 mRNA expression was decreased in ovarian and rectovaginal endometriosis compared with eutopic endometrium, while STS mRNA was increased in rectovaginal lesions compared with ovarian lesions. Ratios between pro- and antiestrogenic enzymes (STS/EST and HSD17B1/HSD17B2) were more in favor of estrogens in ovarian and rectovaginal endometriosis. In endometriosis development, local activation of estrogens appears to be important. STS and HSD17B1 inhibitors may therefore prove useful to treat the disease.

Role of Surgery in Endometriosis-Associated Subfertility

Analysis of published series reveals that no more than a fourth of subfertile patients undergoing surgery for peritoneal endometriotic implants, rectovaginal endometriotic lesions, or recurrent endometriomas achieved conception spontaneously. First-line surgery for ovarian endometriotic cysts appears associated with a better reproductive performance, that is, a mean postoperative pregnancy rate of ∼50%. At the same time, excision of endometriomas paradoxically seems to induce gonadal damage. With the exception of peritoneal disease, no randomized trials are available to assess the effect of surgery in subfertile women with endometriosis. Therefore, it is not possible to define the absolute benefit increase of the treatment of ovarian and rectovaginal lesions. The decision to undergo surgery for endometriosis-associated subfertility must be shared with the woman after detailed information and taking into account several additional conditions, such as presence of pain, large or complex adnexal masses, bowel or ureteral stenosis, and coexisting infertility factors. When considering surgery, a therapeutic equipoise should be reached that includes demonstrated benefits, potential morbidity, and costs of treatment alternatives. Particularly in case of recurrent endometriosis, in vitro fertilization should generally be preferred to surgery. The role of surgery in endometriosis-associated subfertility includes temporary pain relief in symptomatic women desiring a spontaneous conception.

Surgical versus medical treatment for endometriosis-associated severe deep dyspareunia: I. Effect on pain during intercourse and patient satisfaction

Does surgical or medical treatment for endometriosis-associated severe deep dyspareunia achieve better results in terms of patients' satisfaction (main study outcome), variation of coital pain and frequency of intercourse? Surgery and progestin therapy were equally effective in the treatment of deep dyspareunia in women with rectovaginal endometriosis, whereas medical therapy performed significantly better than excisional treatment in those without deeply infiltrating lesions. Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. This study reports a direct comparison between the two treatment options in women with severe pain during intercourse. Patient preference, parallel cohort study with a 12-month follow-up. The effect of conservative surgery at laparoscopy was compared with treatment with a low-dose of norethisterone acetate per os (2.5 mg/day) in women with persistent/recurrent severe deep dyspareunia after first-line surgery. A total of 51 patients chose repeat surgery and 103 progestin treatment. Patient satisfaction was graded according to a five-category scale. Variations in pain during intercourse were measured by means of a 100-mm visual analogue scale. In the surgery group, a marked and rapid short-term dyspareunia score reduction was observed, followed by partial recurrence of pain. The pain relief effect of the progestin was more gradual, but progressive throughout the study period. At a 12-month follow-up, the frequency of intercourse per month (mean ± SD) was 4.6 ± 1.8 in the surgery group and 5.3 ± 1.5 in the norethisterone acetate group (P = 0.02). A total of 22/51 (43%) women were satisfied in the surgery group compared with 61/103 (59%) in the progestin group [adjusted odds ratios (OR), 0.36; 95% confidence interval (CI), 0.16-0.82; P = 0.015]. Corresponding figures in women with and without rectovaginal endometriotic lesions were, respectively, 13/24 (54%) versus 18/35 (51%; adjusted OR, 0.77; 95% CI, 0.22-2.67; P = 0.68), and 9/27 (33%) versus 43/68 (63%; adjusted OR, 0.23; 95% CI, 0.07-0.76, P = 0.02). BIAS, CONFOUNDING, AND OTHER REASONS FOR CAUTION: Treatments were not randomly assigned, and distribution of participants as well as of dropouts between study arms was unbalanced. However, the possibility of choosing the treatment allowed assessment of the maximum potential effect size of the interventions. Caucasian patients able to choose their treatment. This study was supported by a research grant from the University of Milan School of Medicine (PUR number 2009-ATE-0570). None of the authors have a conflict of interest.

Absence of aromatase protein and mRNA expression in endometriosis

Aromatase has been reported to be involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of endometriosis patients. The objective of the present study was to investigate its expression and localization in three distinct types of endometriosis. Human peritoneal, ovarian and rectovaginal endometriotic lesions and matched eutopic endometrium were collected from patients during laparoscopy. Aromatase protein localization (immunohistochemistry, n = 63) and mRNA expression [quantitative polymerase chain reaction (Q-PCR), n = 64] were assessed. No aromatase protein was detected by immunohistochemistry in either the glandular or stromal compartment of endometriotic lesions or eutopic endometrium, while it was strong in placental syncytiotrophoblasts, granulosa and internal theca cells from pre-ovulatory follicles, and luteal cells from corpus luteum. By Q-PCR, low but discernible levels of aromatase expression were found in endometriomas, probably due to follicular expression. Transcripts for aromatase were barely detectable in only a few peritoneal and rectovaginal endometriotic lesions, and a few eutopic endometrium samples, probably due to contaminating surrounding tissues (adipose tissue, intact peritoneum). Unlike previous studies, we observed no aromatase protein in any of the endometriosis types, and barely detectable aromatase mRNA expression, suggesting that locally produced aromatase (within endometriotic lesions) may be less implicated in endometriosis development than previously postulated. Potential factors responsible for these discrepancies are discussed.

OC24: The role of magnetic resonance imaging and transvaginal ultrasonography in patients with an adnexal mass and chronic pelvic pain or infertility

Objectives: Previously we showed that sonovaginography is an accurate ultrasonographic tool in the assessment of rectovaginal endometriosis. The aim of this study was to compare the diagnostic accuracy of sonovaginography and NMR in the diagnosis of rectovaginal endometriosis. Methods: This was a longitudinal prospective study in which 28 women with rectovaginal endometriosis suspected from the medical history and/or pelvic examination were enrolled. The study group underwent transvaginal ultrasonography and sonovaginography was performed in the same session as follows: an assistant inserted a Foley catheter into the vagina and an ultrasound probe covered with a specific balloon to swell the vagina. The balloon was filled with water (mean 40 mL) and soon after 60–180 mL saline solution was inserted through the Foley catheter to fill the vagina in order to create an acoustic window through the vagina to detect rectovaginal lesions. Within a mean of 30 days after the examination patients were scheduled for pelvic NMR. Once all the diagnostic tests had been performed, patients underwent laparoscopic surgery to enucleate the endometriotic lesion, which was sent for pathological examination. Results: Twenty-three (82.1%) patients had rectovaginal endometriotic lesions. The sensitivity of sonovaginography was 91.7%, specificity 75%, PPV 95.6% and NPV 60%; the area under the receiver-operating characteristic (ROC) curve was 0.87. In comparison, NMR had a sensitivity of 73.9%, specificity 60%, PPV 89.5% and NPV 33.3%, with an area under the ROC curve of 0.67. The procedure was well tolerated with a median visual analogue scale score of 2 (range, 0–8). Conclusions: Sonovaginography is a well tolerated procedure, with higher accuracy than NMR in the detection of rectovaginal endometriosis.

Treatment of symptomatic rectovaginal endometriosis with an estrogen–progestogen combination versus low-dose norethindrone acetate

To evaluate the efficacy, safety, and tolerability of an estrogen-progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis. Randomized controlled trial. Academic center. Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis. Twelve-month, continuous treatment with oral ethinyl E2, 0.01 mg, plus cyproterone acetate, 3 mg/day, or norethindrone acetate, 2.5 mg/day. Degree of satisfaction with therapy. Seven women in the ethinyl E2 plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects (n=5), treatment inefficacy (n=6), or loss to follow-up (n=1). At 12 months, dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain, and dyschezia scores were substantially reduced without major between-group differences. Both regimens induced minor unfavorable variations in the serum lipid profile. According to an intention-to-treat analysis, 28 (62%) out of 45 patients in the ethinyl E2 plus cyproterone acetate group and 33 (73%) out of 45 in the norethindrone acetate group were satisfied with the treatment received. Low-dose norethindrone acetate could be considered an effective, tolerable, and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception.

Sonovaginography is a new technique for assessing rectovaginal endometriosis

Objective To evaluate the efficacy of a new technique, the sonovaginography, for the assessment of rectovaginal endometriosis. Design Prospective study. Setting University hospital. Patient(s) Forty-six women were scheduled for laparotomic or laparoscopic surgery because of rectovaginal endometriosis suspected on the basis of patient history and/or clinical examination. Intervention(s) Before surgery, all the women underwent transvaginal ultrasonography and then sonovaginography. The latter is based on transvaginal ultrasonography combined with the introduction of saline solution to the vagina that creates an acoustic window between the transvaginal probe and the surrounding structures of the vagina. Ultrasound findings were compared with the results of surgical exploration and histological examination. Main outcome measure(s) We assessed the accuracy of transvaginal ultrasonography and of sonovaginography for the detection and the location and extension assessment of rectovaginal endometriotic lesions, as well as compared patient compliance between the procedures. Result(s) Sonovaginography diagnosed rectovaginal endometriosis more accurately than did transvaginal ultrasonography, with a sensitivity and specificity of 90.6% and 85.7%, respectively, whereas the transvaginal ultrasonography has shown a sensitivity and specificity of 43.7% and 50%, respectively. Patient discomfort did not differ significantly between the procedures. Conclusion(s) Sonovaginography is a reliable and simple method for the assessment of rectovaginal endometriosis and provides information on location, extension, and infiltration of the lesions, which are important factors in selecting the kind of surgery.

Vascularization of peritoneal, ovarian and rectovaginal endometriotic lesions

Objective: Efforts to elucidate mechanisms responsible for the development of endometriosis are still ongoing. We have demonstrated that endometrial tissue is angiogenic throughout the menstrual cycle, using the chorio allantoic membrane model (Maas et al., 2000). This may allow survival and growth at ectopic locations. Evidence supporting this assumption has been provided by Charnock-Jones et al. (2000), who interfered in the angiogenic process by capturing vascular endothelial growth factor with its soluble receptor. This resulted in the regression of induced endometriotic lesions in immunodeficient mice. In tumor biology, targeting of vasculature is being used to induce tumor ischaemia and infarction. This approach may be applicable to treat endometriosis as well. The vascularization of peritoneal lesions has been described in detail. However, little is known about the vascularization of ovarian endometriotic cysts and deep invasive rectovaginal septum endometriosis. Therefore, we studied the vasculature and tissues surrounding the lesions in peritoneal, ovarian and rectovaginal endometriosis.

Use of a levonorgestrel-releasing intrauterine device in the treatment of rectovaginal endometriosis

Objective: To evaluate the effectiveness of a levonorgestrel-releasing IUD as therapy for endometriosis of the rectovaginal septum. Design: Prospective therapeutic non-randomized, self-controlled clinical trial analyzing changes in pain symptoms and size of lesions induced by the levonorgestrel-releasing IUD over 12 months. Setting: Tertiary referral center for treatment of deep endometriosis. Patient(s): Eleven symptomatic patients with rectovaginal endometriosis. Intervention(s): A levonorgestrel-releasing IUD was inserted and maintained for 12 months. Main Outcome Measure(s): Severity of dysmenorrhea, pelvic pain, and deep dyspareunia were assessed before insertion of the IUD and throughout treatment. The size of rectovaginal endometriotic lesions were evaluated by using transrectal and transvaginal ultrasonography. Result(s): Dysmenorrhea, pelvic pain, and deep dyspareunia greatly improved and the size of the endometriotic lesions was significantly reduced by treatment. Conclusion(s): Insertion of a levonorgestrel-releasing IUD alleviates pain and reduces the size of lesions in patients with endometriosis of the rectovaginal septum.

Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities

Objective: To review the histogenesis of peritoneal, ovarian, and rectovaginal endometriotic lesions. Design: The comparison of morphologic, morphometric, and histochemical data observed in each type of lesion. Setting: A university hospital department of gynecology. Patient(s): Patients complaining of infertility or pelvic pain with laparoscopically proved endometriosis. Intervention(s): Laparoscopy was performed, and biopsy specimens from the endometriotic lesions were histologically studied. Result(s): Three types of endometriotic lesions must be considered: peritoneal, ovarian, and rectovaginal. Morphologic and morphometric data show similarities between eutopic endometrium and red peritoneal lesions, suggesting that these lesions are the first stage of early implantation of endometrial glands and stroma. After partial shedding, the red lesions regrow constantly. The shedding induces an inflammatory reaction, provoking scarification, and the lesions become black. The subsequent fibrosis leads to areas of white opacification that are inactive. The pathogenesis of ovarian endometriomas is a source of controversy. Although there seems to be a consensus concerning the invagination theory, there is still a contradiction between the implantation theory and the metaplasia theory. We recently showed that the mesothelium covering the ovary can invaginate into the ovarian cortex, pushing back the primordial follicles. The presence of mesothelial invagination in continuum with endometriotic tissue suggests that metaplastic histogenesis of ovarian endometriotic lesions occurs. Rectovaginal endometriotic nodules must be considered adenomyomas, consisting of smooth muscle with active glandular epithelium and scanty stroma. Immunocytochemical results show poor differentiation and hormonal independence of these lesions and indicate a close relation with their mesodermal müllerian origin. Conclusion(s): Peritoneal, ovarian and rectovaginal endometriotic lesions must be considered as three separate entities with different pathogeneses.