Topical estrogens for the treatment of superficial dyspareunia related to genitourinary syndrome of menopause in women with a history of endometriosis: A clinical dilemma.

Estrogen withdrawal, which occurs with the cessation of ovulation, causes genitourinary syndrome of menopause in up to 50-85% of women. Symptoms may profoundly impact quality of life and sexual function, interfering with enjoyment of sex in up to three out of four individuals. Topical estrogens have been found to provide symptom relief with minimal systemic absorption and appear to be superior to systemic therapy as what regards genitourinary symptoms. However, conclusive data on their appropriateness in postmenopausal women with a history of endometriosis is not available and the hypothesis that exogenous estrogen stimulation may reactivate endometriotic foci or even promote their malignant transformation is still open. On the other hand, endometriosis affects around 10% of premenopausal women, many of which may be exposed to an acute hypoestrogenic depletion even before spontaneous menopause occurs. This considered, excluding on principle patients with a history of endometriosis from first-line treatment for vulvovaginal atrophy would mean excluding a considerable percentage of the population from adequate care. More robust evidence is urgently needed in these regards. Meanwhile, it would appear reasonable to tailor the prescription of topical hormones in these patients, taking into account the entity of symptoms and the impact such symptoms have on patients' quality of life, as well as the form of endometriosis and the possible risks hormonal may entail. Moreover, the application of estrogens on the vulva instead of the vagina could be efficacious, while outweighing the possible biological cost of hormonal treatment in women with a history of endometriosis.

Assessing the experience of dyspareunia in the endometriosis population: the Subjective Impact of Dyspareunia Inventory (SIDI).

STUDY QUESTION: Is the Subjective Impact of Dyspareunia Inventory (SIDI) a reliable tool to examine the experience of dyspareunia in the context of endometriosis? SUMMARY ANSWER: In this study, the SIDI showed good structural and psychometric properties, and thus can be used as a reliable questionnaire to assess the impact of endometriosis-related dyspareunia on multiple dimensions, such as sexuality and intimate relationships. WHAT IS KNOWN ALREADY: In the endometriosis population, dyspareunia has a tremendous negative impact on psychological health, overall sexual function and couple relationships. However, there is a paucity of tools that can be effectively used in either research or clinical practice to assess the subjective components of the dyspareunia experience, including coping strategies to deal with the pain. STUDY DESIGN, SIZE, DURATION: In this cross-sectional study, the validity of the SIDI was examined by considering the responses provided by 638 participants with endometriosis and dyspareunia, who participated in an online survey conducted between 8 November and 21 December 2021. Participants were recruited using snowball sampling that involved posting the invitation to participate in the study on the social media of a patient association. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women aged ≥18 with clinical or surgical diagnosis of endometriosis. The SIDI measures the subjective impact of dyspareunia and is composed of 16 items focused on the frequency of dyspareunia-related experiences in the last 6 months, rated on a 5-point Likert scale. Sexuality was assessed using the Female Sexual Function Index. Psychological health was measured using the Hospital Anxiety and Depression Scale and the Rosenberg Self-Esteem Scale. Sociodemographic and endometriosis-related information was collected using a researcher-made questionnaire. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Factor analysis revealed that the SIDI has a four-factor structure and allows for examining the impact of dyspareunia in terms of Sexual Concerns (Factor 1), Relationship Concerns (Factor 2), Partner Support (Factor 3) and Endurance of Pain (Factor 4). The SIDI showed good structural and psychometric properties (including internal consistency), was associated with sexual function and psychological health and was able to discriminate between participants with and without sexual dysfunction. LIMITATIONS, REASONS FOR CAUTION: Reasons for caution are related to the risk of self-selection bias depending on the study population and recruitment strategy. Moreover, all the information provided by the participants was self-reported, which may have affected the accuracy of the data collected, especially with regards to endometriosis-specific information. WIDER IMPLICATIONS OF THE FINDINGS: This study may provide a new brief tool that can be used by clinicians and researchers to assess the impact of dyspareunia from a multidimensional perspective and to consider subjective aspects that can be usefully integrated with information about pain severity, timing and localization. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this study. A.F. is the President of APE-Odv (Associazione Progetto Endometriosi-Organizzazione di volontariato (Endometriosis Project Association-Volunteer Organization)), the largest nonprofit endometriosis patient association in Italy. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Conservative treatment of Herlyn-Werner-Wunderlich syndrome: Analysis and long-term follow-up of 51 cases.

OBJECTIVE: The purpose of this study is to analyze the precise anatomical characteristics of a large group of patients with Herlyn-Werner-Wunderlich syndrome together with the long-term follow-up and the reproductive performance. STUDY DESIGN: Retrospective analysis of prospectively collected data. In two tertiary medical centers, from 2008 to 2021, 51 patients with HWWS underwent surgery via the same technique. Presenting symptoms, preoperative investigations, operative management, and long-term follow-up with obstetric outcome were assessed. RESULTS: The surgical procedure was successful in all cases with no major complications recorded. Postoperative course was uneventful. The median follow-up was 6,5 years, with a range from 6 months to 13 years. After surgery, among 14 patients who sought pregnancies, 12 (85,71%) were successful. Of these 11 patients had a total of 22 pregnancies, resulting in spontaneous miscarriage in 27% (6/22), premature birth (<37 weeks) in 36% (8/22) and full-term birth in 36% (8/22). Overall the pregnancies demonstrated had a good course. CONCLUSIONS: Early diagnosis is essential in establishing prompt and correct surgical treatment.

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.

Time to redefine endometriosis including its pro-fibrotic nature.

Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms. In rectovaginal nodules, the glandular epithelium is often not surrounded by stroma and frequently no epithelium can be identified in the wall of ovarian endometriomas. On the other hand, a smooth muscle component and fibrosis represent consistent features of all disease forms. Based on these observations, we believe that the definition of endometriosis should be reconsidered and reworded as 'A fibrotic condition in which endometrial stroma and epithelium can be identified'. The main reasons for this change are: (1) to foster the evaluation of fibrosis in studies on endometriosis pathogenesis using animal models; (2) to limit potential false negative diagnoses if pathologists stick stringently to the current definition of endometriosis requiring the demonstration of endometrial stromal and glands; (3) to consider fibrosis as a potential target for treatment in endometriosis. This opinion article is aimed at boosting the attention paid to a largely neglected aspect of the disease. We hope that targeting the fibrotic process might increase success in developing new therapeutic approaches.

Mental health in women with endometriosis: searching for predictors of psychological distress.

STUDY QUESTION: What factors affect the mental health of women with endometriosis? SUMMARY ANSWER: Not only pelvic pain, but also individual characteristics (i.e. self-esteem, body esteem and emotional self-efficacy), time from diagnosis and intimate relationship status influence the psychological health of endometriosis patients. WHAT IS KNOWN ALREADY: The negative impact of endometriosis on mental health has been widely demonstrated by the research literature, along with the fact that presence and severity of pelvic pain are associated with anxiety and depression. However, endometriosis is a complex multidimensional disease and factors other than pelvic pain, including individual differences, may contribute to explain the variability in women's mental health. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was conducted between 2015 and 2017 at an Italian academic department of obstetrics and gynaecology. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 210 consecutive endometriosis patients (age: 36.7 ± 7.0 years) were included. Demographic and endometriosis-related information was collected. Individual differences were assessed using validated measures evaluating self-esteem, body esteem and emotional self-efficacy. The Hospital Anxiety and Depression Scale (HADS) and the Ruminative Response Scale (RRS) were used to evaluate mental health. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the extant literature, we identified three categories of putative predictors (demographic variables, endometriosis-related factors and individual differences i.e. 'self'), whose psychological impact was examined using a hierarchical multiple regression approach. Being in a stable relationship (coded 1 ['yes'] or 0 ['no']) was associated with decreased rumination (RRS: ß = -0.187; P = 0.002). A shorter time from diagnosis was associated with greater anxiety (HADS-A: ß = -0.177; P = 0.015). Pelvic pain severity and 'self' were associated with all mental health variables (Ps < 0.01). Greater self-esteem, body esteem, and emotional self-efficacy were correlated with better psychological outcomes (Ps < 0.01). LIMITATIONS REASONS FOR CAUTION: Sexual functioning, pregnancy, infertility, cultural differences and gender beliefs have been found to be important in women with endometriosis. In our regression model, we did not test the psychological impact of these variables and this should be acknowledged as an important limitation. Moreover, the cross-sectional (rather than longitudinal) nature of this study does not allow a full examination of the temporal relationship between endometriosis and psychological outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Factors other than pelvic pain can significantly affect the mental health of women with endometriosis, and the role of individual differences requires further investigation. Targeted multidisciplinary interventions should include evaluation and enhancement of self-esteem and self-efficacy to improve women's psychological health. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Not applicable.

The distinguishing cellular and molecular features of the endometriotic ovarian cyst: from pathophysiology to the potential endometrioma-mediated damage to the ovary.

BACKGROUND: Clinical data suggest that the presence of an ovarian endometrioma may cause per se damage to the surrounding otherwise healthy ovarian tissue. However, the basic research has so far done a limited job in trying to understand the potential detrimental effect of an endometrioma presence in the context of the ovarian physiology. We have reviewed the literature with the aim of characterizing the pathophysiology of the endometrioma focusing mostly on factors and mechanisms potentially affecting the surrounding, otherwise normal, ovarian tissue. METHODS: Comprehensive searches of PUBMED were conducted to identify human studies published from 1991 to 2013 in the English language on the cellular and molecular characterization of the various endometrioma components. RESULTS: An endometrioma contains free iron, reactive oxygen species (ROS), proteolytic enzymes and inflammatory molecules in concentrations from tens to hundreds of times higher than those present in peripheral blood or in other types of benign cysts. The cyst fluid causes substantial changes in the endometriotic cells that it baths from gene expression modifications to genetic mutations The physical barrier between the cyst contents and the normal ovarian tissue is a thin wall composed of the ovarian cortex itself or fibroreactive tissue. ROS potentially permeating the surrounding tissues and proteolytic substances degrading the adjacent areas are likely to cause the substitution of normal ovarian cortical tissue with fibrous tissue in which the cortex-specific stroma is reduced. The fibrosis is associated with smooth muscle metaplasia and followed by follicular loss and intraovarian vascular injury. Follicular density in tissue surrounding the endometriotic cyst was consistently shown to be significantly lower than in healthy ovaries but this pathological change does not appear to be caused by the stretching of surrounding tissues owing to the presence of a cyst. CONCLUSIONS: There is sufficient molecular, histological and morphological evidence, in part deriving from knowledge of the pathophysiology, to support a deleterious effect of the endometrioma on the adjacent ovarian cortical tissue, independent of the mere mechanical stretching owing to its size.

Surgical versus low-dose progestin treatment for endometriosis-associated severe deep dyspareunia II: effect on sexual functioning, psychological status and health-related quality of life.

STUDY QUESTION: Does surgical and low-dose progestin treatment differentially affect endometriosis-associated severe deep dyspareunia in terms of sexual functioning, psychological status and health-related quality of life? SUMMARY ANSWER: Surgery and progestin treatment achieved essentially similar benefits at 12-month follow-up, but with different temporal trends. WHAT IS ALREADY KNOWN: Conservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results. STUDY DESIGN, SIZE, DURATION: Patient preference, parallel cohort study with 12-month follow-up. The effect of conservative surgery at laparoscopy versus 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 was compared. PARTICIPANTS/MATERIALS AND SETTING, METHODS: A total of 51 patients chose repeat surgery and 103 progestin treatment. Variations in sexual function, psychological well-being and quality of life were measured by means of the Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS) and the Endometriosis Health Profile-30 (EHP-30). MAIN RESULTS AND THE ROLE OF CHANCE: Four women in the surgery group and 21 women in the progestin group withdrew from the study for various reasons. Total FSFI scores, anxiety and depression scores and EHP-30 scores improved immediately after surgery, but worsened with time, whereas the effect during progestin use increased more gradually, but progressively, without overall significant between-group differences at 12-month follow-up. A tendency was observed towards a slightly better total FSFI score after surgery at the end of the study period. LIMITATIONS, REASONS FOR CAUTION: Treatments were not randomly allocated, 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. WIDER IMPLICATIONS OF THE FINDINGS: Both surgery and medical treatment with progestins are valuable options for improving the detrimental impact of endometriosis-associated dyspareunia on sexual functioning and quality of life. Women should be aware of the pros and cons of both options to decide which one best suits their needs. STUDY FUNDING/COMPETING INTEREST(S): 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.

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

STUDY QUESTION: 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? SUMMARY ANSWER: 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. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: 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. DESIGN: 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. PARTICIPANTS AND SETTING: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. GENERALIZABILITY TO OTHER POPULATIONS: Caucasian patients able to choose their treatment. STUDY FUNDING/COMPETING INTEREST(S): 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.

Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study.

We retrospectively assessed pregnancy outcome in 419 women who achieved a first spontaneous singleton pregnancy after surgery for endometriosis. A miscarriage was observed in 87 of 419 women (20.8%) and an ectopic pregnancy in eight (1.9%). Among the remaining 324 women, 14 (4.3%) experienced gestational hypertension/pre-eclampsia, 38 (11.7%) had a preterm delivery, five (1.5%) had placental abruption and 12 (3.7%) had placenta praevia. The incidence of placenta praevia was 7.6% in 150 women with rectovaginal lesions, 2.1% in 69 with ovarian endometriomas plus peritoneal implants, and 2.4% in 100 women with peritoneal implants only, whereas no case was observed in 100 women with ovarian endometriomas only.

Principles of phenomics in endometriosis.

BACKGROUND: Endometriosis has been associated with specific morphometric characteristics and pigmentary traits. The purpose of this study was to systematically review prior publications dealing with this aspect in order to revisit phenotypic information in the context of phenomics principles. METHODS: Comprehensive searches of Pubmed, Medline and Embase were conducted to identify studies, published from 1990 to 2011 in the English language literature, on the relationship between endometriosis and morphometric characteristics/pigmentary traits. RESULTS: We identified 11 studies on the association between endometriosis and body mass index (BMI) in the adult population and 5 studies on the same association during early life. While a modest inverse correlation was found between endometriosis and adult BMI, a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for confounding factors such as age, birthweight, age at menarche, parity and oral contraceptive use. Four papers have been published on the association between endometriosis and cutaneous naevi and five on the association between the disease and specific pigmentary traits. A skin phenotype characterized by the presence of naevi and freckles and by a high sensitivity to sun exposure is represented more frequently in women with endometriosis. CONCLUSIONS: Endometriosis appears to be associated with some phenotypic variations likely attributable to the strong effect of the environment on the expression and function of genes influencing the traits. Novel clues on endometriosis pathogenesis may derive from the analysis of the phenotypic traits associated with the disease.

Surgical measures for endometriosis-related infertility: a plea for research.

The precise relationship between endometriosis and infertility is debated. Surgery is considered to play a role within the framework of the therapeutic options to cure infertile women with the disease even though its effectiveness is generally modest. In fact, there is unquestionably the need to improve surgical techniques in this area. Specifically, two main aspects require optimization: 1) preventing the injury to the follicular reserve that follows surgical excision of ovarian endometriomas and 2) preventing post-surgical formation and re-formation of adhesions. The comparison between the excision/stripping and the vaporization/coagulation techniques represents the main point of debate on what is the best procedure to remove ovarian endometrioma. Randomized controlled trials showed that the excision technique is associated with a higher pregnancy rate and a lower rate of recurrence although it may determine severe injury to the ovarian reserve. Improvements to this latter aspect may be represented by a combined excisional-vaporization technique or by replacing diathermy coagulation with surgical ovarian suture. Barrier agents reduce but not eliminate the post-surgical adhesion formation in women with endometriosis. Encouraging evidence has been reported with Interceed, Oxiplex/AP gel and Adept solution. However, available studies are mainly based on II look laparoscopies performed few weeks after the intervention and data on fertility is lacking. Clinical trials including pregnancy rate as a specific outcome are warranted.

Individual patient data meta-analysis of randomized evidence to assess the effectiveness of laparoscopic uterosacral nerve ablation in chronic pelvic pain.

BACKGROUND: There have been conflicting results in randomized trials of the effects of laparoscopic uterosacral nerve ablation (LUNA) in chronic pelvic pain. Our objective was to perform a meta-analysis using individual patient data (IPD) to provide the most comprehensive and reliable assessment of the effectiveness of LUNA. METHODS: Electronic searches were conducted in the Medline, Embase, PsycInfo and Cochrane Library databases from database inception to August 2009. The reference lists of known relevant papers were searched for any further articles. Randomized trials comparing LUNA with no additional intervention were selected and authors contacted for IPD. Raw data were available from 862 women randomized into five trials. Pain scores were calibrated to a 10-point scale and were analysed using a multilevel model allowing for repeated measures. RESULTS: There was no significant difference between LUNA and No LUNA for the worst pain recorded over a 12 month time period (mean difference 0.25 points in favour of No LUNA on a 0-10 point scale, 95% confidence interval: -0.08 to 0.58; P = 0.1). CONCLUSIONS: LUNA does not result in improved chronic pelvic pain.

Gynecological endoscopy for symptomatic endometriosis.

The best available evidence on surgery for endometriosis-associated pain has been reviewed in order to define the benefit of various interventions in the most frequently encountered clinical conditions, and discuss the robustness of the reported data in light of the quality of the relevant study design. Methodological drawbacks limit the validity of observational, non-comparative studies on the effect of laparoscopy for stage I to IV disease. The results of three randomized, controlled trials, indicate that the absolute benefit increase of destruction of lesions compared with sham operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size decreased with time and the reoperation rate, based on long-term follow-up studies, was as high as 50%. In most case series on excisional surgery for rectovaginal endometriosis, substantial short-term pain relief was experienced by about 70-80% of the subjects who continued the study. However, at one-year follow-up approximately 50% of the women needed medical treatments. Major complications were observed in 3-10% of the patients. Medium-term recurrence of lesions was observed in about 20% of the cases, and around 25% of the women underwent repetitive surgery. Routine complementary performance of denervating procedures cannot be recommended based on the quality of the available information, as only a few symptomatic patients complain of exclusively midline, hypogastric pain. Pain recurrence and reoperation rates after conservative surgery for symptomatic endometriosis are high and probably underestimated. Clinicians and patients should be aware that the expected benefit is operator-dependent and, especially in complex conditions, acceptable results can be assured in referral centers.

'Blood On The Tracks' from corpora lutea to endometriomas.

OBJECTIVE: To detect a direct transition from a haemorrhagic corpus luteum to an endometriotic cyst by serial transvaginal ultrasonographic scans. DESIGN: Prospective observational study. SETTING: An academic tertiary care and referral centre for women with endometriosis. POPULATION: One hundred and nine women younger than 40 years, with regular menstrual cycles, undergoing first-line surgery for endometriomas, and not wanting postoperative oral contraception. METHODS: Three-monthly transvaginal ultrasonography during the luteal phase for 2 years after surgery. MAIN OUTCOME MEASURE: Sonographic identification of progression from a haemorrhagic corpus luteum to a recurrent endometriotic cyst. RESULTS: A haemorrhagic corpus luteum was identified in 13 women. Serial ultrasonographic scans demonstrated transition to an endometriotic cyst in 11 (85%) instances and resorption in two. A unilateral endometriotic cyst without previous detection of a cystic corpus luteum was observed in 14 women. CONCLUSIONS: Bleeding from a corpus luteum appears to be a critical event in the development of endometriomas.

The effect of surgery for symptomatic endometriosis: the other side of the story.

BACKGROUND: Surgery is often considered the best treatment option in women with symptomatic endometriosis. However, extent and duration of the therapeutic benefit are still poorly defined. METHODS: The best available evidence on surgery for endometriosis-associated pain has been reviewed to estimate the effect size of interventions in the most frequently encountered clinical conditions. RESULTS: Methodological drawbacks limit considerably the validity of observational, non-comparative studies on the effect of laparoscopy for stage I-IV disease. As indicated by the results of three RCTs, the absolute benefit increase of destruction of lesions compared with diagnostic only operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size tended to decrease with time and the re-operation rate, based on long-term follow-up studies, was as high as 50%. In most case series on excisional surgery for rectovaginal endometriosis, substantial short-term pain relief was experienced by approximately 70-80% of the subjects who continued the study. However, at 1 year follow-up, approximately 50% of the women needed analgesics or hormonal treatments. Major complications were observed in 3-10% of the patients. Medium-term recurrence of lesions was observed in approximately 20% of the cases, and around 25% of the women underwent repetitive surgery. CONCLUSIONS: Pain recurrence and re-operation rates after conservative surgery for symptomatic endometriosis are high and probably underestimated. Clinicians and patients should be aware that the expected benefit is operator-dependent.

Meta-analysis using individual patient data from randomised trials to assess the effectiveness of laparoscopic uterosacral nerve ablation in the treatment of chronic pelvic pain: a proposed protocol.

BACKGROUND: Currently, there are a number of clinical trials, but no international collaboration for collating research on effectiveness of laparoscopic uterosacral nerve ablation (LUNA) for alleviating chronic pelvic pain. OBJECTIVE: Meta-analysis was used by collecting individual patient data (IPD) from the existing trials, to provide a comprehensive assessment of the effectiveness of LUNA that will be generalisable in various clinical contexts. METHODS: IPD will be sought and collected from all relevant (both already finished and continuing) randomised trials identified through previous systematic reviews. After obtaining raw data and cleaning the database, analysis will be of all patients ever randomised based on the intention-to-treat principle using endpoints measured at 12 months following randomisation. PROPOSAL: We will update searches, contact all authors, obtain data in whatever form it can be provided, build a single database, produce results for individual studies, have them verified by original authors, explore of any heterogeneity and reasons behind it and finally pool all raw data in to a meta-analysis using appropriate statistical methods. The project will test the effectiveness of LUNA for women with chronic pelvic pain. It will also motivate collaborating primary investigators to undertake new primary studies to corroborate or improve upon the conclusions derived from the retrospective analysis.

Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favour of the menstrual reflux theory.

BACKGROUND: If the menstrual reflux or implantation theory of endometriosis is true, refluxed endometrial cells could reach the right hypochondrium transported by the clockwise peritoneal fluid current and would implant more easily on the right diaphragmatic leaf as they are stuck there by the falciform ligament. METHODS: To investigate if a lateral asymmetry exists in diaphragmatic endometriotic lesion distribution, all articles on diaphragmatic endometriosis identified by MEDLINE, EMBASE and PUBMED database searches were retrieved, and additional reports were collected by systematically reviewing all references. The number of women and the side of the lesion with respect to the falciform ligament of the liver were obtained from individual studies, and the combined frequency of right- and left-side diaphragmatic endometriosis was computed. In addition, seven personal cases were described. RESULTS: There were 16 reports including 47 subjects selected. Diaphragmatic endometriosis was on the right side in 31 (66%) patients, on the left in 3 (6%) and bilateral in 13 (27%). In the personal series, lesions were on the right side in five cases, on the left in one and bilateral in one. Considering only unilateral lesions, the observed proportion of right-sided endometriotic implants (36/40) was 90% (95% CI 76-97%; chi(2)(1) 32.6, P < 0.0001). CONCLUSIONS: The observed major asymmetry in diaphragmatic endometriotic lesion distribution in favour of the right leaf supports the menstrual reflux theory.