Annalisa Abbiati

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.

Surgery for endometriosis-associated infertility: a pragmatic approach

Laparoscopic treatment for endometriosis-associated infertility is gaining widespread popularity supported mostly by uncontrolled studies, but the purported benefit of surgery may be overvalued. We have therefore analysed the best available evidence with the aim of defining an approximate estimate of the effect size of conservative surgery for infertile women with endometriosis in various clinical conditions. The overall increase in post-operative likelihood of conception over background pregnancy rate may be estimated to be between 10 and 25%. The effect of surgery for peritoneal lesions is limited, and an estimate of benefit should be decreased by the fact that preoperative identification of the subjects actually with the condition is unfeasible. The benefit of excision of ovarian endometriomas is difficult to define due to multiple confounding factors and methodological drawbacks in the considered studies. Excision of rectovaginal endometriosis is of doubtful value and associated with worrying morbidity. The role of surgery before, after or as an alternative to IVF needs clarification. In conclusion, the absolute benefit increase of surgery for endometriosis-associated infertility appears smaller than previously believed. Complete and detailed information on risks and benefits of treatment alternatives must be offered to infertile patients to allow unbiased choices between possible options.

Endometriosis: Current Therapies and New Pharmacological Developments

Endometriosis is a chronic inflammatory condition that is responsive to management with steroids. The establishment of a steady hormonal environment and inhibition of ovulation can temporarily suppress ectopic implants and reduce inflammation as well as associated pain symptoms. In terms of pharmacological management, the currently available agents are not curative, and treatment often needs to be continued for years or until pregnancy is desired. Similar efficacy has been observed from the various therapies that have been investigated for endometriosis. Accordingly, combined oral contraceptives and progestins, based on their favourable safety profile, tolerability and cost, should be considered as first-line options, as an alternative to surgery and for post-operative adjuvant use. In situations where progestins and oral contraceptives prove ineffective, are poorly tolerated or are contraindicated, gonadotrophin-releasing hormone analogues, danazol or gestrinone may be used. Future therapeutic options for managing endometriosis must compare favourably against existing agents before they can be considered for inclusion into current practice. Finally, as reproductive prognosis is not ameliorated by medical treatment, it is not indicated for women seeking conception.

Endometriotic ovarian cysts do not negatively affect the rate of spontaneous ovulation

STUDY QUESTION Do endometriotic ovarian cysts influence the rate of spontaneous ovulation? SUMMARY ANSWER Endometriotic cysts, no matter what their volume, do not influence the rate of spontaneous ovulation in the affected ovary. WHAT IS KNOWN ALREADY Endometriotic ovarian cysts may negatively affect spontaneous ovulation in the affected ovary. STUDY DESIGN, SIZE, DURATION This was a prospective observational study performed between September 2009 and June 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS This study included women of reproductive age with regular menstrual cycles and unilateral ovarian endometriomas (diameter ≥20 mm) desiring to conceive. Exclusion criteria were: hormonal therapies in the 3 months prior to study entry and previous adnexal surgery. Patients underwent serial transvaginal ultrasound to assess the side of ovulation (for up to six cycles). MAIN RESULTS AND THE ROLE OF CHANCE Ovulation was monitored in 1199 cycles in 244 women (age, mean ± SD, 34.3 ± 4.9 years). 55.3% of the patients had left endometriomas and 44.7% had right endometriomas (P = 0.024). The mean (±SD) diameter of the endometriomas was 5.3 cm (±1.7 cm). Ultrasonographically documented ovulation occurred in 596 cycles in the healthy ovary (49.7%; 95% CI, 46.8-52.6%) and in 603 cycles in the affected ovary (50.3%; 95% CI, 47.1-53.2%; P = 0.919). This observation was confirmed in patients with diameter of the cyst ≥4 cm (n = 166) and in those with diameter of the cyst ≥6 cm (n = 45). One hundred and five patients spontaneously conceived (43.0%; 95% CI, 36.7-49.5%). LIMITATIONS, REASON FOR CAUTION The high pregnancy rate reported in this study was observed in a selected population of women with endometriomas and cannot be extrapolated to all patients with endometriosis. WIDER IMPLICATIONS OF THE FINDINGS Since ovarian endometriomas do not impair spontaneous ovulation, the impact on fertility of surgical excision of ovarian endometriomas should be further investigated.

Chronic pelvic pain in women: etiology, pathogenesis and diagnostic approach

Chronic pelvic pain (CPP), defined as non-cyclic pain of 6 or more months, is a frequent disorder that may negatively affect health-related quality of life. In women several causes are recognised, although in a not negligible proportion of patients a definite diagnosis cannot be made. Different neurophysiological mechanisms are involved in the pathophysiology of CPP. Pain may be classified as nociceptive or non-nociceptive. In the first case the symptom originates from stimulation of a pain-sensitive structure, whereas in the second pain is considered neuropatic or psychogenic. Patients history is crucial and is generally of utmost importance for a correct diagnosis, being sometimes more indicative than several diagnostic investigations. The main contributing factors in women with CPP can still be identified by history and physical examination in most cases. Many disorders of the reproductive tract, urological organs, gastrointestinal, musculoskeletal and psycho-neurological systems may be associated with CPP. Excluding endometriosis, the most frequent causes of CPP are: post-operative adhesions, pelvic varices, interstitial cystitis and irritable bowel syndrome. CPP is a symptom, not a disease, and rarely reflects a single pathologic process. Gaining womens trust and developing a strong patient-physician relationship is of utmost importance for the long-term outcome of care.

‘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.

Comparison of contraceptive ring and patch for the treatment of symptomatic endometriosis

OBJECTIVE To evaluate the efficacy and tolerability of a contraceptive vaginal ring and transdermal patch in the treatment of endometriosis-associated pain. DESIGN Patient preference cohort study. SETTING Academic center. PATIENT(S) Two-hundred and seven women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis. INTERVENTION(S) Continuous, 12-month treatment with a vaginal ring supplying 15 mcg of ethinyl E and 120 mcg of etonogestrel per day or a transdermal system delivering 20 mcg of ethinyl E and 150 mcg norelgestromin per day. MAIN OUTCOME MEASURE(S) Satisfaction with treatment. RESULT(S) One-hundred and twenty-three women preferred the ring, and 84 preferred the patch. Forty-four ring users (36%) and 51 patch users (61%) withdrew. Thirty-six of 79 subjects (46%) in the ring group and 14 of 33 (42%) in the patch group shifted from continuous to cyclic use because of irregular bleeding. Pain symptoms were reduced by both treatments, with the ring being more effective than the patch in patients with rectovaginal lesions. According to an intention-to-treat analysis, 88 of 123 ring users (72%) and 40 of 84 patch users (48%) were satisfied with the treatment received. CONCLUSION(S) Patients who preferred the ring were significantly more likely to be satisfied and to comply with treatment than those who chose the patch. Both systems were associated with poor bleeding control when used continuously.

Repetitive surgery for recurrent symptomatic endometriosis: What to do?

In spite of the increasing number of operative laparoscopies performed for endometriosis associated pelvic pain, postoperative symptomatic recurrences are very common. Reoperation is often considered the best treatment option, but the extent and duration of the effect of second-line surgery is still unclear. The best available evidence has been reviewed in order to define the results of repetitive conservative surgery, the effects of pelvic denervating procedures and postoperative medical treatments, as well as the long-term outcome of definitive surgery. Because of the paucity of published data, estimating the real risk of symptomatic recurrence and need for reoperation after repetitive conservative surgery for endometriosis is very difficult. Based on the limited information available, the long-term outcome appears suboptimal, with a cumulative probability of pain recurrence between 20% and 40%, and of a further surgical procedure between 15% and 20%. These figures are probably an underestimate related to drawbacks in study design, exclusions of dropouts, and publication bias and should be considered with caution. Systematic complementary performance of denervating procedures in addition to reoperation cannot be recommended, as only a few symptomatic patients complain of predominantly midline, hypo-gastric pain. The outcome of hysterectomy for endometriosis-associated pain at medium-term follow-up seems quite satisfactory. Nevertheless, about 15% of patients had persistent symptoms, and 3-5% experienced worsening of pain. Concomitant bilateral oophorectomy reduced the risk of reoperation due to recurrent pelvic pain by six times. However, at least one gonad should be preserved in young women, especially in those with objections to the use of oestrogen-progestogens. Medical treatment appears to have limited and inconsistent effects when used for only a few months after conservative procedures. Data on the benefit of prolonged drug regimens with oral contraceptives or progestogen are lacking. The risk of recurrence of endometriosis during hormone replacement therapy seems marginal if combined preparations or tibolone are used and oestrogen-only treatments are avoided. The opportune surgical solution in women with recurrent symptoms after previous conservative procedures for endometriosis should be based on the desire for conception as well as on psychological characteristics. Studies on surgical management of recurrent rectovaginal endometriosis are warranted, due to the peculiar technical difficulties as well as the high risk of complications associated with this challenging disease form.

Surgery for Deep Endometriosis: A Pathogenesis-Oriented Approach

Background: Deep endometriosis is usually associated with severe symptoms and constitutes a complex treatment challenge. Methods: The available evidence has been revisited with the aim of defining an effective diagnostic workup and a safe surgical strategy based on pathogenetic findings. Results: Vaginal, rectal, and bladder detrusor endometriosis appear to be caused by intraperitoneal seeding of regurgitated endometrial cells which implant in the posterior and anterior cul-de-sac and trigger an inflammatory process leading to adhesion of contiguous organs. Excision of posterior deep lesions implies removal of a fibrotic cast of the Douglas’s pouch which may involve the posterior vaginal fornix and the rectal muscular layer, with a not negligible risk of major complications. Removal of full-thickness bladder detrusor endometriosis entails excision of the bladder dome or posterior wall, generally well above the trigone. Transurethral resection is contraindicated. A radical approach to obstructive uropathy is suggested, with resection of the stenotic ureteral tract and reimplantation with antireflux vesicoureteral plasty. Conclusion: Infiltrating endometriotic lesions appear to originate intraperitoneally sharing common pathogenetic mechanisms. Involvement of the intestinal and urologic apparatuses should be identified before surgery, in order to schedule intraoperative consultation and to inform the woman about the type of intervention required and its potential sequelae.

‘Here comes the sun’: pigmentary traits and sun habits in women with endometriosis

BACKGROUND There is limited but interesting evidence suggesting that endometriosis may be associated with specific pigmentary traits and sun habits. In this case-control study, we aimed to further clarify this point. MATERIALS AND METHODS Consecutive patients with a first laparoscopic diagnosis of endometriosis according to Holt and Weiss criteria were selected as cases. Controls were women who underwent laparoscopy during the same study period, but who were found to be free of the disease. Selected women were interviewed and examined by two trained physicians. An unconditional logistic regression model that included age and baseline variables significantly differing between the two groups was used to estimate the adjusted odds ratios (OR). RESULTS There were 98 women with endometriosis and 94 controls selected. Overall, women with the disease had a more photo-sensitive phenotype and were exposed less to sun or ultraviolet radiation. A statistically significant difference was documented for eye color, skin reaction to first sun exposure, freckles score and the use of tanning creams. The adjusted OR (95% CI) for the disease was 1.95 (1.02-3.72) for women with green/blue eyes, 2.19 (1.12-4.28) for those who frequently/always had skin burn reaction to first sun exposure, 5.67 (1.98-16.24) for those with a higher number of freckles and 0.35 (0.15-0.85) for the use of tanning creams. CONCLUSIONS Women with endometriosis have a specific photo-sensitive phenotype and protect themselves more from the sun. This latter habit may be consequent to the former. We speculate that there is a shared genetic background between pigmentation and endometriosis.