Carbon dioxide (CO2) laser ablation of symptomatic vaginal endometriosis: a pilot study.

Deep dyspareunia affects almost half of the women with endometriosis and is associated with vaginal endometriotic lesions. Our pilot study's objective is to assess the feasibility and effectiveness of CO2-laser ablation under colposcopic guidance for the treatment of symptomatic vaginal endometriosis. A non-comparative pilot study has been performed. Only women with histologically proven vaginal endometriosis, who declared the presence of moderate or severe deep dyspareunia, resistant to at least 6 months of conventional hormonal treatment, were deemed eligible for the study. All treatments were performed in an outpatient setting with a colposcopic-guided, hand-directed CO2-laser. Variation in pain symptoms was measured with a 0- to 10-point numerical rating scale (NRS), in sexual functioning with the Female Sexual Function Index (FSFI), in psychological status with the Hospital Anxiety and Depression Scale (HADS), and in quality of life with the Short Form-12 questionnaire (SF-12). Satisfaction with treatment was evaluated according to a five-category scale (very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, very dissatisfied). Nineteen women were enrolled. No complications occurred. At 12-month follow-up, significant improvements were observed in deep dyspareunia and dyschezia scores, in FSFI, HADS, and in the physical component summary scores of SF-12, whereas the mental component score of SF-12 did not vary substantially. Most women (84%) were satisfied with the treatment received. CO2-laser ablation for vaginal endometriosis could represent a valuable alternative option for women with symptomatic lesions, both in terms of amelioration of pain symptoms and improvement in quality of life and sexual function.

Bowel surgery as a fertility-enhancing procedure in patients with colorectal endometriosis: methodological, pathogenic and ethical issues.

Bowel surgery for colorectal endometriosis is being promoted to infertile women without severe sub-occlusive symptoms, with the objective of improving the likelihood of conception. Contrary to rectal shaving, bowel surgery involving full-thickness disk excision and segmental resection entails opening of the intestinal lumen thus increasing the risk of postoperative infectious complications. About 1 in 10 patients undergoing colorectal resection for intestinal endometriosis will experience severe sequelae, including anastomotic dehiscence, rectovaginal fistula formation, and bladder and bowel denervation. Similar to other surgical procedures aiming at enhancing fertility in women with endometriosis, bowel surgery has been introduced into clinical practice without adequate evaluation through randomized controlled trials. According to systematic literature reviews based mainly on case series, the incremental gain of adding bowel procedures to standard surgery appears uncertain in terms of pregnancy rate after both natural attempts and IVF. Considering the methodological drawbacks and the high risk of bias in the available observational studies, it is not possible to exclude the suggestion that the benefit of colorectal surgery has been overestimated. Given the risk of harms to women's health and the important ethical implications, less emphasis should be put on strict statistical significance and more emphasis should be placed on the magnitude of the effect size. In this regard, the published data may not be generalizable, as the surgeons publishing their results may not be representative of all surgeons. Until the results of adequately designed and conducted RCTs are available, colorectal surgery with the sole intent of improving the reproductive performance of infertile patients with intestinal endometriosis should be performed exclusively within research settings and by highly experienced surgeons. Women should be informed about the uncertainties regarding the harms and benefits of bowel surgery in different clinical conditions, and preoperative counselling must be conducted impartially with the objective of achieving a truly shared medical decision.

Medical treatment or surgery for colorectal endometriosis? Results of a shared decision-making approach.

STUDY QUESTION: What is the degree of patient satisfaction in women with symptomatic colorectal endometriosis who choose medical or surgical treatment after a shared decision-making (SDM) process? SUMMARY ANSWER: The degree of satisfaction with treatment was high both in women who chose medical treatment with a low-dose oral contraceptive (OCP) or a progestin, and in those who chose to undergo surgical resection of bowel endometriosis. WHAT IS KNOWN ALREADY: Hormonal therapies and surgery for colorectal endometriosis have been investigated in non-comparative studies with inconsistent results. STUDY DESIGN, SIZE, DURATION: Parallel cohort study conducted on 87 women referring to our centre with an indication to surgery for colorectal endometriosis. A standardised SDM process was adopted, allowing women to choose their preferred treatment. Median follow-up was 40 [18-60] months in the medical therapy group and 45 [30-67] in the surgery group. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients with endometriosis infiltrating the proximal rectum, the rectosigmoid junction, and the sigmoid, not causing severe sub-occlusive symptoms were enroled. A total of 50 patients chose treatment with an OCP (n = 12) or a progestin (n = 38), whereas 37 women confirmed their previous indication to surgery. Patient satisfaction was graded according to a 5-category scale. Variations in bowel and pain symptoms were measured by means of a 0-10 numeric rating scale. Constipation was assessed with the Knowles-Eccersley-Scott Symptom Questionnaire (KESS), health-related quality of life with the Short Form-12 questionnaire (SF-12), psychological status with the Hospital Anxiety and Depression scale (HADS) and sexual functioning with the Female Sexual Function Index (FSFI). MAIN RESULTS AND THE ROLE OF CHANCE: Six women in the medical therapy group requested surgery because of drug inefficacy (n = 3) or intolerance (n = 3). Seven major complications were observed in the surgery group (19%). At 12-month follow-up, 39 (78%) women in the medical therapy group were satisfied with their treatment, compared with 28 (76%) in the surgery group (adjusted odds ratio (OR), 1.37; 95% confidence interval (CI), 0.45-4.15; intention-to-treat analysis). Corresponding figures at final follow-up assessment were 72% in the former group and 65% in the latter one (adjusted OR, 1.74; 95% CI, 0.62-4.85). The 60-month cumulative proportion of dissatisfaction-free participants was 71% in the medical therapy group compared with 61% in the surgery group (P = 0.61); the Hazard incidence rate ratio was 1.21 (95% CI, 0.57-2.62). Intestinal complaints were ameliorated by both treatments. Significant between-group differences in favour of medical treatment were observed at 12-month follow-up in diarrhoea, dysmenorrhoea, non-menstrual pelvic pain and SF-12 physical component scores. The total HADS score improved significantly in both groups, whereas the total FSFI score improved only in women who chose medical therapy. LIMITATIONS REASONS FOR CAUTION: As treatments were not randomly assigned, selection bias and confounding are likely. The small sample size exposes to the risk of type II errors. WIDER IMPLICATIONS OF THE FINDINGS: When adequately informed and empowered through a SDM process, most patients with non-occlusive colorectal endometriosis who had already received a surgical indication, preferred medical therapy. The possibility of choosing the preferred treatment may allow maximisation of the potential effect of the interventions. STUDY FUNDING/COMPETING INTEREST(S): This study was financed by Italian fiscal contribution '5 × 1000'-Ministero dell'Istruzione, dell'Università e della Ricerca-devolved to Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. P.V., M.P.F., R.R., D.D., A.R., P.M., O.D.G. and M.C. declare that they have no conflicts of interest. E.S. received grants from Ferring and Serono.

Management of Endometriosis: Toward Value-Based, Cost-Effective, Affordable Care.

Endometriosis management seems to be influenced by outcome-independent biomedical, pharmacological, and technological developments. The propensity towards doing more affects several aspects of care, sometimes translating into proposals that are not based on sound epidemiological principles and robust evidence. Different stakeholders share the interest for doing more testing and using novel and costly drugs or devices in patients with endometriosis. Although some women may benefit from such an approach, the majority do not, and some may be harmed. Moreover, an uncontrolled increase in expenditures for endometriosis management without demonstrated and proportional health benefits would waste the finite resources of national health care services and would risk cost-related non-adherence. Cost-effectiveness analyses should be systematically pre-planned in future trials on endometriosis, and the concept of "value" of medical interventions should guide investigators and health care policymakers. Reducing low-value care, financial toxicity, and the burden of treatment is respectful not only of endometriosis patients, but also of the entire society. Whenever possible, long-term therapeutic strategies should be tailored to each woman's needs, and high-value tests and treatments should be chosen based on her priorities and preferences. Moreover, listening to patients, understanding their concerns, avoiding disease labelling, explaining plainly what is known and what is unknown, and giving constant reassurance and encouragement may be exceedingly important for the successful management of endometriosis and may change the patient's perception of her clinical condition. Physician empathy has no untoward effects, does not cause harms, and may determine whether a woman successfully copes or desperately struggles with her disease during reproductive life.

Shifting from Oral Contraceptives to Norethisterone Acetate, or Vice Versa, because of Drug Intolerance: Does the Change Benefit Women with Endometriosis?

BACKGROUND/AIMS: Oral contraceptives (OC) and norethisterone acetate (NETA) are among first-line medical therapies for symptomatic endometriosis, but their use is sometimes associated with intolerable side effects. We investigated whether shifting from low-dose OC to NETA (2.5 mg/day), or vice versa, improved tolerability. METHODS: Sixty-seven women willing to discontinue their treatment because of intolerable side effects despite good pain relief, were enrolled in a self-controlled study, and shifted from OC to NETA (n = 35) or from NETA to OC (n = 32). The main study outcome was satisfaction with treatment 12 months after the change. Tolerability, pain symptoms, health-related quality of life, psychological status, and sexual functioning were also evaluated. RESULTS: After treatment change, good tolerability was reported by 37% of participants who shifted to NETA, and by 52% of those who shifted to OC. At 12-month assessment, 51% of women intolerant to OC were satisfied with NETA, and 65% of those intolerant to NETA were satisfied with OC (intention-to-treat analysis). Other study variables did not vary substantially. CONCLUSIONS: In selected endometriosis patients, shifting from OC to NETA, or vice versa, because of side effects, improved tolerability. Better results were observed when substituting NETA with OC rather than the other way round.

'Money for nothing'. The role of robotic-assisted laparoscopy for the treatment of endometriosis.

Despite higher costs for robotic-assisted laparoscopy (RAL) than standard laparoscopy (SL), RAL treatment of endometriosis is performed without established indications. PubMed/MEDLINE was searched for 'robotic surgery' and 'endometriosis' or 'gynaecological benign disease' from January 2000 to December 2016. Full-length studies in English reporting original data were considered. Among 178 articles retrieved, 17 were eligible: 11 non-comparative (RAL only) and six comparative (RAL versus SL). Non-comparative studies included 445 patients. Mean operating time, blood loss and hospital stay were 226 min, 168 ml and 4 days. Major complications and laparotomy conversions were 3.1% and 1.3%. Eight studies reported pain improvement at 15-month follow-up. Comparative studies were all retrospective; 749 women underwent RAL and 705 SL. Operating time was longer for RAL in five studies. Major complications and laparotomy conversions for RAL and SL were 1.5% versus 0.3% and 0.3% versus 0.5%. One study reported pain reduction for RAL at 6-month follow-up. RAL treatment of endometriosis did not provide benefits over SL, overall and among subgroups of women with severe endometriosis, peritoneal endometriosis and obesity. Available evidence is low-quality, and data regarding long-term pain relief and pregnancy rates are lacking. RAL treatment of endometriosis should be performed only within controlled studies.

Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis.

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, METHODS: Of 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 I(2) 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 (I(2) = 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) (I(2) = 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 CAUTION: Qualitative and quantitative heterogeneity among studies was high. At sensitivity analysis, I(2) 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. STUDY FUNDING/COMPETING INTEREST: None.

Adenomyosis and reproductive performance after surgery for rectovaginal and colorectal endometriosis: a systematic review and meta-analysis.

The relationship between rectovaginal-bowel endometriosis and fertility is unclear. Nevertheless, extirpative surgery, including colorectal resection, is being fostered as a fertility-enhancing procedure. Adenomyosis and deep endometriosis often coexist. As the uterine condition may further impact on reproductive outcome, this work performed a systematic literature review with the objective of identifying all English-language reports on surgical treatment for rectovaginal and colorectal endometriosis, including bowel resection, in which participants were screened preoperatively for uterine adenomyosis. Risk ratios (RR) were then combined in a meta-analysis. In the five selected observational studies, in women seeking pregnancy, 7/59 (11.9%) with concomitant adenomyosis conceived, compared with 74/172 (43.0%) in those without adenomyosis. Adenomyosis was never excised. One in 10 women experienced a major surgical complication. The RR of clinical pregnancy ranged from 0.23 to 0.46, with absence of heterogeneity among studies (I(2)=0.0%). Pooling of the results yielded a common RR of 0.32 (95% confidence interval 0.16 to 0.66). No small-study effect was detected (Egger's test). Screening for adenomyosis before suggesting difficult and risky procedures may allow identification of a subgroup of patients at particularly worse prognosis for which surgery would have a marginal effect on the likelihood of conception. Deep endometriosis may infiltrate the rectum, vagina and sigmoid colon. These severe forms are usually associated with pain, but their relationship with fertility is unclear. Despite lack of convincing evidence, extirpative surgery, including colorectal resection, is being fostered as a fertility-enhancing procedure, although these procedures may cause major complications. Adenomyosis (i.e. the infiltration of the uterine wall by endometrial glands) often coexists with deep endometriosis, and several investigators believe that the former condition may have a detrimental effect on fertility more than the latter. If this is true, screening for adenomyosis may allow preoperative identification of a subgroup of patients at particularly worse prognosis for whom difficult and risky surgery would have a marginal or no effect on the likelihood of conception. To disentangle this issue, we performed a systematic literature review with the objective of identifying all English-language reports on surgical treatment for rectovaginal and colorectal endometriosis, including bowel resection, in which participants were also investigated preoperatively for uterine adenomyosis. Risk ratios (RR) were then combined in a meta-analysis. In the five selected observational studies, in women seeking pregnancy, 7/59 (11.9%) women with concomitant adenomyosis conceived, compared with 74/172 (43.0%) in those without adenomyosis. One in 10 women experienced a major surgical complication. The RR of clinical pregnancy consistently ranged from 0.23 to 0.46. Pooling of the results yielded a common RR of 0.32 (95% CI 0.16-0.66). Adenomyosis was associated with a 68% reduction in the likelihood of pregnancy in women seeking conception after surgery for rectovaginal and colorectal endometriosis.

Long-term adjuvant therapy for the prevention of postoperative endometrioma recurrence: a systematic review and meta-analysis.

Ovulation seems crucial in the pathogenesis of ovarian endometriomas. Therefore, suppression of ovulation should be protective against cyst relapse after excision. The objective of this systematic review was to assess the effect of long-term postoperative medical treatment on the risk of endometrioma recurrence. A MEDLINE search was conducted to identify all the comparative studies published in the last 12 years in the English language literature on the relation between long-term postoperative adjuvant therapy and risk of endometrioma recurrence. Of the 12 articles assessed in detail, four were finally selected based on surgery for endometriotic cysts, postoperative medical treatment use for ≥ 12 months vs. expectant management, and ultrasonographic and/or histological diagnosis of endometrioma recurrence. A total of 965 women were enrolled, 726 of whom were in three cohort studies and 239 in one randomized controlled trial. Oral contraceptives (OCs) were always used as postoperative adjuvant treatment. The absolute effect of postoperative OC use was assessed by comparing "always" and "never" users. A recurrent endometrioma was identified in 33 of 423 (8%) "always" OC users and in 117 of 341 (34%) women who underwent expectant management (pooled odds ratio 0.12; 95% confidence interval 0.05-0.29). To define the effect of duration of use, "always" users were compared with "ever" users, and "ever" with "never" users, with a pooled odds ratio of, respectively, 0.21 (95% confidence interval 0.11-0.40) and 0.39 (95% confidence interval 0.23-0.66). Postoperative OC use dramatically decreased the risk of ovarian endometrioma recurrence, especially in women who used OCs regularly and for prolonged periods.

Mitigating the economic burden of GnRH agonist therapy for progestogen-resistant endometriosis: why not?

STUDY QUESTION: Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens? SUMMARY ANSWER: An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief. WHAT IS KNOWN ALREADY: Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted. STUDY DESIGN SIZE DURATION: A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected. PARTICIPANTS/MATERIALS SETTING METHODS: Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or 'draw-back' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or 'draw-back' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%). LIMITATIONS REASONS FOR CAUTION: The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed. WIDER IMPLICATIONS OF THE FINDINGS: Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: N/A.

Effect of patient selection on estimate of reproductive success after surgery for rectovaginal endometriosis: literature review.

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.

"You are so beautiful"*: behind women's attractiveness towards the biology of reproduction: a narrative review.

Female beauty has always attracted human beings. In particular, beauty has been interpreted in terms of reproductive potential and advantage in selection of mates. We have reviewed the recent literature on female facial and physical beauty with the objective of defining which parameters could influence female attractiveness. Symmetry, averageness, and sexual dimorphism with regards to facial beauty, as well as waist-to-hip ratio (WHR), breast size, and body mass index (BMI) for physical beauty, have been assessed. In current societies, it appears that facial attractiveness results from a mixture of symmetry and averageness of traits, high forehead and cheekbones, small nose and chin, full lips, thin eyebrows, and thick hair. A low WHR reliably characterized physical attractiveness, whereas inconsistencies have been observed in the evaluation of breast size and BMI. The importance of breast size appears to vary with time and sex of evaluators, whereas the impact of BMI is related to socio-economic conditions. The various hypotheses behind beauty and the role of attractiveness in mate choice and sexual selection are here described in terms of continuation of human species. Intriguing associations are emerging between features of attractiveness and some reproductive disorders, as both are substantially influenced by sex steroid hormones.

'Waiting for Godot': a commonsense approach to the medical treatment of endometriosis.

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.

Advances in the medical management of bowel endometriosis.

Endometriosis infiltrating the bowel can be treated medically in accurately selected women not seeking conception and without overt obstructive symptomatology. When the rectosigmoid junction is involved, the probabilities of intestinal symptoms relief, undergoing surgery after treatment failure, and developing bowel obstruction during hormonal treatment are around 70%, 10%, and 1-2%, respectively. When the lesion infiltrates exclusively the mid-rectum, thus in cases of true rectovaginal endometriosis, the probabilities of intestinal symptoms relief and undergoing surgery are about 80% and 3%, respectively. Endometriotic obstructions of the rectal ampulla have not been reported. A rectosigmoidoscopy or colonoscopy should be performed systematically before starting medical therapies, also to rule out malignant tumours arising from the intestinal mucosa. Progestogens are safe, generally effective, well-tolerated, inexpensive, and should be considered as first-line medications for bowel endometriosis. Independently of symptom relief, intestinal lesions should be checked periodically to exclude nodule progression during hormonal treatment.

Industry funding of patient and health consumer organisations: systematic review with meta-analysis.

OBJECTIVE: To investigate pharmaceutical or medical device industry funding of patient groups. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Ovid Medline, Embase, Web of Science, Scopus, and Google Scholar from inception to January 2018; reference lists of eligible studies and experts in the field. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies including cross sectional, cohort, case-control, interrupted time series, and before-after studies of patient groups reporting at least one of the following outcomes: prevalence of industry funding; proportion of industry funded patient groups that disclosed information about this funding; and association between industry funding and organisational positions on health and policy issues. Studies were included irrespective of language or publication type. REVIEW METHODS: Reviewers carried out duplicate independent data extraction and assessment of study quality. An amended version of the checklist for prevalence studies developed by the Joanna Briggs Institute was used to assess study quality. A DerSimonian-Laird estimate of single proportions with Freeman-Tukey arcsine transformation was used for meta-analyses of prevalence. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality of the evidence for each outcome. RESULTS: 26 cross sectional studies met the inclusion criteria. Of these, 15 studies estimated the prevalence of industry funding, which ranged from 20% (12/61) to 83% (86/104). Among patient organisations that received industry funding, 27% (175/642; 95% confidence interval 24% to 31%) disclosed this information on their websites. In submissions to consultations, two studies showed very different disclosure rates (0% and 91%), which appeared to reflect differences in the relevant government agency's disclosure requirements. Prevalence estimates of organisational policies that govern corporate sponsorship ranged from 2% (2/125) to 64% (175/274). Four studies analysed the relationship between industry funding and organisational positions on a range of highly controversial issues. Industry funded groups generally supported sponsors' interests. CONCLUSION: In general, industry funding of patient groups seems to be common, with prevalence estimates ranging from 20% to 83%. Few patient groups have policies that govern corporate sponsorship. Transparency about corporate funding is also inadequate. Among the few studies that examined associations between industry funding and organisational positions, industry funded groups tended to have positions favourable to the sponsor. Patient groups have an important role in advocacy, education, and research, therefore strategies are needed to prevent biases that could favour the interests of sponsors above those of the public. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017079265.

Is Shifting to a Progestin Worthwhile When Estrogen-Progestins Are Inefficacious for Endometriosis-Associated Pain?

The purpose of this study was to assess the proportion of patients satisfied with their treatment after a change from a low-dose oral contraceptive (OC) to norethisterone acetate (NETA) because of inefficacy of OC on pain symptoms. To this end, prospective, self-controlled study was conducted on 153 women using OC as a treatment for endometriosis and with persistence of one or more moderate or severe pain symptoms. At baseline and during 12 months after a shift from OC to oral NETA, 2.5 mg/d, pelvic pain was measured by means of a 0- to 10-point numerical rating scale and a multidimensional categorical rating scale. Variations in health-related quality of life, psychological status, and sexual function were also evaluated with validated scales. At the end of the study period, participants indicated the degree of satisfaction with their treatment according to a 5-degree scale from very satisfied to very dissatisfied. A total of 28 women dropped out of the study, the main reason was intolerable side effects (n = 15). At 12-month assessment, 70% of participants were very satisfied or satisfied with NETA treatment (intention-to-treat analysis). Statistically significant improvements were observed in health-related quality of life, psychological status, and sexual function. At per-protocol analysis, almost half of the patients (58/125) reported suboptimal drug tolerability. However, complaints were not severe enough to cause dissatisfaction, drug discontinuation, or request for surgery. These encouraging results could be used to counsel women with symptomatic endometriosis not responding to OC and to inform their decisions on modifications of disease management.

Medical treatment of endometriosis-related pain.

Available medical treatments for symptomatic endometriosis act by inhibiting ovulation, reducing serum oestradiol levels, and suppressing uterine blood flows. For this, several drugs can be used with a similar magnitude of effect, in terms of pain relief, independently of the mechanism of action. Conversely, safety, tolerability, and cost differ. Medications for endometriosis can be categorized into low-cost drugs including oral contraceptives (OCs) and most progestogens, and high-cost drugs including dienogest and GnRH agonists. As the individual response to different drugs is variable, a stepwise approach is suggested, starting with OCs or low-cost progestogens, and stepping up to high-cost drugs only in case of inefficacy or intolerance. OCs may be used in women with dysmenorrhea as their main complaint, and when only superficial peritoneal implants or ovarian endometriomas <5 cm are present, while progestogens should be preferred in women with severe deep dyspareunia and when infiltrating lesions are identified.

The limited oncogenic potential of unilocular adnexal cysts: A systematic review and meta-analysis.

The reported frequency of malignant diseases in unilocular cysts varies in different studies, giving conflicting results. To quantify the risk of malignancies among echoic and anechoic unilocular adnexal cysts, in premenopausal and postmenopausal women, we performed a PubMed/MEDLINE search of papers published in English evaluating the histopathological diagnoses of removed ovarian cysts diagnosed as simple unilocular cysts at pre-operative ultrasound examination. From 34 selected publications, we extracted data on ovarian malignancy in the total series, and separately for premenopausal and postmenopausal women, and women with cysts < 5 cm and ≥5 cm in diameter. Of the 2177 surgically removed lesions classified as unilocular cysts on pre-operative ultrasound, 24 (1.1%; 95% CI: 0.74-1.66) were malignant (among these 12 had borderline malignancy: 0.6%). The rates were lower for premenopausal women (6/987, 0.6%) than postmenopausal ones (12/372, 3.2%). Of the 2290 surgically removed lesions classified as anechoic unilocular cysts on ultrasound, 20 (0.9%; 95% CI: 0.57-1.35) were malignant (among these 8 had borderline malignancy: 0.3%). The rates were lower for premenopausal women (3/907, 0.3%) than postmenopausal ones (13/681, 1.9%) (Pearson chi-square P = 0.002). When we performed meta-analysis selecting studies including only anechoic unilocular cysts published after 2000 and with 100 or more patients, the estimate was 0.5 (95% CI 0.1-1.2) with no heterogeneity (heterogeneity chi-square P = 0.175). The oncogenic risk of unilocular adnexal cysts is low, suggesting that the final choice about surgical treatment of these cysts should be based on the combination of each patient's overall risk profile as well as personal priorities.

A stepped-care approach to symptomatic endometriosis management: a participatory research initiative.

OBJECTIVE: To assess the proportion of patients with symptomatic endometriosis satisfied with their medical treatment 12 months after enrollment in a stepped-care management protocol. DESIGN: Prospective, single-arm, self-controlled study. SETTING: Academic department. PATIENT(S): A cohort of 157 consecutive patients referred or self-referred to our center for symptomatic endometriosis. INTERVENTIONS(S): Systematic detailed information process on medical and surgical treatment followed by a shared decision to start a stepped-care protocol including three subsequent medical therapy steps (oral contraception [OC]; 2.5 mg/d norethindrone acetate [NETA]; 2 mg/d dienogest [DNG]) and a fourth surgical step. Stepping up was triggered by drug inefficacy/intolerance. MAIN OUTCOME MEASURE(S): Satisfaction with treatment was assessed according to a five-category scale (very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, very dissatisfied). Variations were measured in pain symptoms with the use of a 0-10-point numeric rating scale (NRS), in quality of life with the use of the Short Form 12 questionnaire (SF-12), and in sexual functioning with the use of the Female Sexual Function Index (FSFI). RESULT(S): At the end of the 12-month study period, 106 women were still using OC, 23 were using NETA, three were using DNG, and four had undergone surgery. Twenty-one participants (13%) dropped out from the study. In intention-to-treat analysis, excluding five drop-outs for pregnancy desire, the overall satisfaction rate with the stepped-care protocol was 62% (95/152; 95% CI 55%-70%). By 12-month follow-up, significant improvements were observed in all pain symptom scores and in SF-12 physical and mental component summary scores, whereas FSFI scores did not vary substantially. CONCLUSION(S): Most women with endometriosis-associated pelvic pain who chose a stepped-care approach were satisfied with OC and a low-cost progestin for the treatment of their symptoms. The need to step up to an expensive progestin or surgery was marginal.

Oral and depot progestin therapy for endometriosis: towards a personalized medicine.

INTRODUCTION: Endometriosis is an estrogen-dependent chronic inflammatory disorder that requires a life-long management plan. Long-term adherence to treatment is pivotal to ensure an effective clinical management. In this optic, one of the cornerstone of endometriosis medical treatment is represented by progestins. Areas covered: This narrative review examines the clinical efficacy, safety and tolerability of oral and depot progestins used in the treatment of endometriosis. The material included in the current manuscript was obtained with a MEDLINE search through PubMed from inception until February 2017. Expert opinion: Progestins are effective in controlling pain symptoms in the majority of women with endometriosis, and their effect seems not inferior to that achieved with other compounds used to treat the disease, such as gonadotropin-releasing hormone agonist. Available progestins include a broad range of both oral and depot compounds, and represent, in most cases, an inexpensive treatment option. In addition, progestins do not increase significantly thrombotic risk and could be adopted in those women with metabolic or cardiovascular contraindication to estrogen-progestins. The choice between the different available compounds should be tailored for every woman with preference to the most cost-effective treatment, depending on the most complained symptom and disease location.