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Vercellini P.,University of Milan | Crosignani P.,University of Milan | Somigliana E.,Infertility Unit | Vigan P.,Center For Research In Obstetrics And Gynaecology Crog | And 2 more authors.
Human Reproduction | Year: 2011

Conservative surgical treatment for symptomatic endometriosis is frequently associated with only partial relief of pelvic pain or its recurrence. Therefore, medical therapy constitutes an important alternative or complement to surgery. However, no available compound is cytoreductive, and suppression instead of elimination of implants is the only realistic objective of pharmacological intervention. Because this implies prolonged periods of treatments, only medications with a favourable safety/tolerability/efficacy/cost profile should be chosen. In the past few years, innumerable new drugs for endometriosis, which would interfere with several hypothesized pathogenic mechanisms, have been studied and their use foreseen. However, robust evidence of in vivo safety and efficacy is lacking and, at the moment, the principal modality to interfere with endometriosis metabolism is still hormonal manipulation. Regrettably, in spite of consistent demonstration of a major effect on pain even in patients with deeply infiltrating lesions, progestins are underestimated and dismissed in favour of more scientifically fashionable and up-to-the-minute alternatives. Moreover, oral contraceptives (OCs) dramatically reduce the rate of post-operative endometrioma recurrence and should now be considered an essential part of long-term therapeutic strategies in order to limit further damage to future fertility. Finally, women who have used OC for prolonged periods will be protected from an increased risk of endometriosis-associated ovarian cancer. To avoid the several subtle modalities for distorting facts and orientating opinions in favour of specific compounds, progestins and monophasic OC used continuously are here proposed as the reference comparator in all future randomized controlled trials on medical treatment for endometriosis. © 2010 The Author. Source


Vercellini P.,University of Milan | Buggio L.,University of Milan | Somigliana E.,Infertility Unit | Dridi D.,University of Milan | And 2 more authors.
Human reproduction (Oxford, England) | Year: 2014

STUDY QUESTION: Is the prevalence of blue eye colour higher in women with deep endometriosis?SUMMARY ANSWER: Blue eye colour is more common in women with deep endometriosis when compared with both women with ovarian endometriomas and women without a history of endometriosis.WHAT IS KNOWN ALREADY: Recent and intriguing evidence suggests that women with deep endometriosis may have particular phenotypic characteristics including a higher prevalence of a light-colour iris. Available epidemiological evidence is however weak.STUDY DESIGN, SIZE, DURATION: Case-control study performed in a large academic department specializing in the study and treatment of endometriosis. Individual iris colour was evaluated in daylight and categorized in three grades, namely blue-grey (blue), hazel-green (green) and brown. One observer assessed iris colour. In addition, the women themselves were invited to indicate the colour of their eyes according to the same classification system. Cases with discordant eye colour determinations between the observer and the woman were excluded from the final analysis.PARTICIPANTS MATERIALS, SETTINGS, METHODS: Two hundred and twenty-three women with deep endometriosis (cases), 247 with ovarian endometriomas and 301 without a history of endometriosis were enrolled.MAIN RESULTS AND THE ROLE OF CHANCE: After exclusion of 52 discordant cases, the proportions of brown, blue and green eye colours were, respectively, 61, 30 and 9% in the deep endometriosis group, 74, 16 and 10% in the endometrioma group and 75, 15 and 10% in the non-endometriosis group. Women in the deep endometriosis group had a statistically significant excess of blue eyes and a reduced proportion of brown eyes compared with the two control groups (P = 0.002 and P < 0.001, respectively). The proportion of blue eyes was almost identical in the ovarian endometrioma group and the non-endometriosis group, and that of green eyes was substantially similar in all study groups. The OR (95% CI) of having blue eyes in women with deep endometriosis compared with women with ovarian endometriosis and with those without endometriosis was, respectively, 2.2 (1.4-3.6) and 2.5 (1.6-3.9).LIMITATIONS, REASON FOR CAUTION: We cannot exclude that some women without a previous diagnosis of endometriosis indeed had the disease. However, this would have led to a reduction of the observed difference in proportion of blue eyes, thus to a potential underestimation of the real strength of the association. Moreover, under-ascertainment is possible with regard to peritoneal disease, but unlikely with deep endometriotic lesions and ovarian endometriomas.WIDER IMPLICATIONS OF THE FINDINGS: There are two possible explanations for our findings. Both may have intriguing implications for future research on endometriosis. Firstly, genes involved in the control of iris colour transmission may lie in a region with a strong pattern of linkage disequilibrium with genes involved in the invasiveness of endometriosis. Alternatively, blue eye colour could be considered an indicator of a photo-sensitive phenotype resulting in limited exposure to sunlight and UVB radiation. Limited sunlight exposure is associated with reduced circulating 25-hydroxyvitamin D3, an element that has recently been linked to endometriosis development. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com. Source


Vercellini P.,University of Milan | Vercellini P.,Center For Research In Obstetrics And Gynecology Crog | Barbara G.,University of Milan | Buggio L.,University of Milan | And 3 more authors.
Reproductive BioMedicine Online | Year: 2012

The effect of rectovaginal endometriosis on fertility is unclear. Several authors foster radical surgery, including colorectal resection, as a fertility-enhancing procedure. However, interpretation of data is difficult, as the baseline fertility status is often undefined and it is not always possible to discriminate between spontaneous conceptions and those resulting from IVF. A systematic literature review was performed with the aim of defining the pregnancy rate specifically in patients who were infertile before surgery and who sought spontaneous pregnancy. A PubMed search was conducted to identify English language studies published between 2005 and 2011 evaluating reproductive performance after surgery for rectovaginal and rectosigmoid endometriosis. According to the results of the 11 selected studies, the mean post-operative conception rate in all women seeking pregnancy independently of preoperative fertility status and IVF performance was 39% (95% CI 35-43%; 223/571), but dropped to 24% (95% CI 20-28%; 123/510) in infertile patients who sought spontaneous conception (odds ratio 0.50, 95% CI 0.38-0.65%). Patients' selection significantly influences the estimate of the effect of rectovaginal endometriosis excision on infertility. This should be carefully taken into consideration at preoperative counselling. Rectovaginal endometriosis usually is associated with pain symptoms, but the effect of this disease form on fertility is uncertain, as burial of foci beneath rectouterine adhesions with exclusion of the deepest part of the pelvis may limit interference with fertilization processes. Several authors foster radical surgery, including colorectal resection, as a fertility-enhancing procedure. However, interpretation of data is difficult, as the baseline fertility status is often undefined and it is not always possible to discriminate between spontaneous conceptions and those resulting from IVF. A systematic literature review was performed with the aim of defining the pregnancy rate specifically in patients who were infertile before surgery and who sought pregnancy spontaneously. A PubMed search was conducted to identify English language studies published between 2005 and 2011 evaluating reproductive performance after surgery for rectovaginal and rectosigmoid endometriosis. According to the results of the 11 selected studies, the mean post-operative conception rate in all women seeking pregnancy independently of preoperative fertility status and IVF performance was 39% (223/571), but dropped to 24% (123/510) in infertile patients who sought conception spontaneously. The 15% difference is statistically significant. Infertile patients with rectovaginal endometriosis considering surgery, should be carefully informed of the real probability of post-operative conception avoiding generic overestimations. © 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. Source


Vercellini P.,University of Milan | Vercellini P.,Center For Research In Obstetrics And Gynaecology Crog | Consonni D.,Epidemiology Unit | Dridi D.,University of Milan | And 5 more authors.
Human Reproduction | Year: 2014

STUDY QUESTION: Is adenomyosis associated with IVF/ICSI outcome in terms of clinical pregnancy rate? SUMMARY ANSWER: In a meta-analysis of published data, women with adenomyosis had a 28% reduction in the likelihood of clinical pregnancy at IVF/ICSI compared with women without adenomyosis. WHAT IS KNOWN ALREADY: Estimates of the effect of adenomyosis on IVF/ICSI outcome are inconsistent. STUDY DESIGN, SIZE, DURATION: A systematic literature review and meta-analysis were conducted. A Medline search was performed to identify all the comparative studies published from January 1998 to June 2013 in the English language literature on IVF/ICSI outcome in women with and without adenomyosis. Two authors independently performed the literature screening, scrutinized articles of potential interest, selected relevant studies and extracted data. Studies were categorized based on research design.PARTICIPANTS, SETTING, METHODSOf the 17 articles assessed in detail, 9 were finally selected based on diagnosis of adenomyosis at magnetic resonance imaging or transvaginal ultrasonography. The quality of studies was evaluated by means of the Newcastle-Ottawa scale. A total of 1865 women were enrolled in the 9 selected studies, 665 of whom in 4 prospective observational studies, and 1200 in 5 retrospective studies. The dichotomous data for clinical pregnancy and secondary outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CIs) and were combined in a meta-analysis using the random-effects model. The heterogeneity Cochrane's Q and the I2 statistics were calculated. Egger's approach to testing the significance of funnel plot asymmetry was also used. MAIN RESULTS AND THE ROLE OF CHANCE: The clinical pregnancy rate achieved after IVF/ICSI was 123/304 (40.5%) women with adenomyosis versus 628/1262 (49.8%) in those without adenomyosis. The RR of clinical pregnancy ranged from 0.37 (95% CI, 0.15-0.92) to 1.20 (95% CI, 0.58-2.45), with a significant heterogeneity among studies (I2 = 56.8%, P = 0.023). Pooling of the results yielded a common RR of 0.72 (95% CI, 0.55-0.95). A funnel plot showed no indication of asymmetry among studies (Egger's test, P = 0.696). In a meta-regression model, no association was observed between prevalence of endometriosis and the likelihood of clinical pregnancy. Three studies reported the pregnancy rate per cycle. The common RR was 0.71 (95% CI, 0.51-0.98; I 2 = 78.1%, P = 0.010). The RR observed in a study with donated oocytes was 0.90 (95% CI, 0.75-1.08). The number of miscarriages per clinical pregnancy was reported in seven studies. A miscarriage was observed in 77/241 women with adenomyosis (31.9%) and in 97/687 in those without adenomyosis (14.1%). The RR of miscarriage ranged from 0.57 (95% CI, 0.15-2.17) to 18.00 (95% CI, 4.08-79.47) (I2 = 67.7%, P = 0.005). Pooling of the results yielded a common RR of 2.12 (95% CI, 1.20-3.75).LIMITATIONS, REASONS FOR CAUTIONQualitative and quantitative heterogeneity among studies was high. At sensitivity analysis, I2 statistic regarding the main outcome was reduced under the 50% threshold removing one trial, but the resulting confidence interval crossed unity. Also the confidence interval of the common RR of the four studies reporting only one IVF/ICSI cycle included unity. Only part of the studies could be included in the assessment of secondary outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Adenomyosis appears to impact negatively on IVF/ICSI outcome owing to reduced likelihood of clinical pregnancy and implantation, and increased risk of early pregnancy loss. Screening for adenomyosis before embarking on medically assisted reproductive procedures should be encouraged. The potentially protective role of long down-regulation protocols needs further evaluation. In future studies on the association between adenomyosis and IVF/ICSI outcome, a matched case-control design should be adopted, live birth should be the default primary outcome and only the results regarding the first cycle should be considered. © 2014 The Author. Source


Vercellini P.,University of Milan | Frattaruolo M.P.,University of Milan | Somigliana E.,Infertility Unit | Jones G.L.,University of Sheffield | And 3 more authors.
Human Reproduction | Year: 2013

Study Questio: NDoes 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 KNOWNConservative surgery and hormonal therapies have been used independently for endometriosis-associated deep dyspareunia with inconsistent results.STUDY Design: , SIZE, DURATIONPatient 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, METHODSA 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 CAUTIONTreatments 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. © 2013 The Author. Source

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