Giussy Barbara

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.

Medical treatment for rectovaginal endometriosis: what is the evidence?

BACKGROUND Rectovaginal endometriosis usually causes distressing pain. Surgical treatment may be effective but is associated with a high risk of morbidity and major complications. Information on the effect of medical alternatives for pain relief in this condition is scarce. METHODS A comprehensive literature search was conducted to identify all the English language published observational and randomized studies evaluating the efficacy of medical treatments on pain associated with rectovaginal endometriosis. A combination of keywords was used to identify relevant citations in PubMed, MEDLINE and EMBASE. RESULTS A total of 217 cases of medically treated rectovaginal endometriosis were found; 68 in five observational, non-comparative studies, 59 in one patient preference cohort study, and 90 in a randomized controlled trial. An aromatase inhibitor was used in two of the non-comparative studies, vaginal danazol in one, a GnRH agonist in one, and an intrauterine progestin in one. Two estrogen-progestin combinations used transvaginally or transdermally were evaluated in the patient preference study, whereas an oral progestin and an estrogen-progestin combination were compared in the randomized controlled trial. With the exception of an aromatase inhibitor used alone, the antalgic effect of the considered medical therapies was high for the entire treatment period (from 6 to 12 months), with 60-90% of patients reporting considerable reduction or complete relief from pain symptoms. CONCLUSIONS Despite problems in interpretation of data, the effect of medical treatment in terms of pain relief in women with rectovaginal endometriosis appear substantial.

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.

Post-operative endometriosis recurrence: a plea for prevention based on pathogenetic, epidemiological and clinical evidence

Prevention of the recurrence of post-operative endometriosis is crucial for future fertility. The incidence of disease relapse can be influenced by major demographic changes and by the use of long-term adjuvant medical treatment. Decrease in age at menarche, number of pregnancies and duration of breastfeeding and increase in age at first birth all lead to an increase in the overall number of ovulations and menstruations a woman has within a reproductive lifespan. These changes impact during the decade at highest risk for endometriosis, i.e. between 25 and 35 years of age, and may substantially expand the hiatus between first-line surgical treatment and conception attempt. Several lines of evidence suggest that ovulation inhibition reduces the risk of endometriosis recurrence. After pooling the results of a cohort and a randomized controlled trial on long-term post-operative oral contraceptive use, a recurrent endometrioma developed in 26/250 regular users (10%; 95% CI 7-15%) compared with 46/115 never users (40%; 95% CI 31-50%), with a common OR of 0.16 (95% CI 0.04-0.65). After first-line surgery for endometriosis, women should be invited to seek conception as soon as possible. Alternatively, oral contraceptive use until pregnancy is desired should be considered.

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.

The effect of second-line surgery on reproductive performance of women with recurrent endometriosis: A systematic review

Estimates of endometriosis recurrence after primary surgery are around 10% per annum during the first postoperative quinquennium. The aim of this study was to define the effect of reoperation in women seeking conception. A MEDLINE and PubMed search was conducted to identify English language studies published in the last 30 years evaluating reproductive performance after second‐line surgery. Repeat surgery for recurrent endometriosis and identification of women seeking pregnancy were selected. Two authors abstracted data on standardized forms. The initial literature screening yielded 41 citations, but 19 were excluded because no data on reoperation were described, seven as no original figures were included, three because analyses were performed on the same cohort, and one because extremely skewed data were reported. A total of 313 patients who sought pregnancy after repetitive surgery for recurrent endometriosis were found, 139 in six non‐comparative studies, and 174 in five retrospective comparative studies. Overall, pregnancy was achieved in 81 women (26%; 95% confidence interval (CI), 21–31%), without significant difference between the laparotomy (27%) and laparoscopy (25%) approach. Three studies compared pregnancy rate after second‐line (28/124; 23%) and primary surgery (236/577; 41%; common odds ratio (OR), 0.44; 95% CI, 0.28–0.68%), and two compared the probability of conception after in‐vitro fertilization (IVF) (14/27; 30%) and repetitive surgery (10/50; 20%; common OR, 1.51; 95% CI, 0.58–3.91%). Conclusions. The probability of conception after repeat surgery for recurrent endometriosis appeared limited and reduced compared with that after primary surgery. The results of IVF were not inferior to those of reoperation.

Impact of endometriosis on quality of life and mental health: pelvic pain makes the difference

Abstract Introduction: No prior study of endometriosis has investigated the psychological impact of having asymptomatic endometriosis versus endometriosis with pelvic pain in a systematic way. This study aimed at examining the impact of endometriosis on quality of life, anxiety and depression by comparing asymptomatic endometriosis, endometriosis with pelvic pain, and healthy, pain-free controls. The psychological impact of different types of endometriosis pain was also tested. Methods: One hundred and ten patients with surgically diagnosed endometriosis (78 with pelvic pain and 32 without pain symptoms) and 61 healthy controls completed two psychometric tests assessing quality of life, anxiety and depression. Endometriosis participants indicated on a numerical rating scale the intensity of four types of pain (dysmenorrhea, dyspareunia, non-menstrual pelvic pain and dyschezia). Results: Endometriosis patients with pelvic pain had poorer quality of life and mental health as compared with those with asymptomatic endometriosis and the healthy controls. No significant differences were found between asymptomatic endometriosis and the control group. Dysmenorrhea had significant effects only on physical quality of life; non-menstrual pelvic pain affected all the variables; no significant effects were found for dyspareunia and dyschezia. Conclusions: Pain significantly affects women’s experience of endometriosis. The medical treatment of endometriosis with pain may not be sufficient and psychological intervention is recommended.