Nicola Berlanda

Surgical excision of endometriomas and ovarian reserve: a systematic review on serum antimüllerian hormone level modifications

OBJECTIVE To evaluate serum antimüllerian hormone (AMH) level modification after surgical excision of ovarian endometriomas. DESIGN Systematic review. MEDLINE search from January 1990 to April 2012 using the combination of medical terms endometriosis, endometrioma, endometriotic cyst, and AMH or antimüllerian hormone, MIF or müllerian inhibiting factor. Reference lists of selected studies were checked for additional potential contributions. SETTING Not applicable. PATIENT(S) Women with ovarian endometriomas requiring surgery. INTERVENTION(S) Serum AMH level assessment. MAIN OUTCOME MEASURE(S) Serum AMH level modifications. RESULT(S) Eleven articles satisfied our selection criteria. Data pooling were deemed inopportune owing to the heterogeneity of the study designs and of the reported parameters. Nine of 11 studies documented a statistically significant reduction of serum AMH level after surgery. The two studies failing to document this decrease were published by the same study group and partly overlapped. The magnitude of the decline was more evident in women operated on for bilateral endometriomas. CONCLUSION(S) Evidence deriving from the evaluation of serum AMH level modifications after surgical excision of endometriomas supports a surgery-related damage to ovarian reserve.

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.

Identifying the indications for laparoscopically assisted vaginal hysterectomy: a prospective, randomised comparison with abdominal hysterectomy in patients with symptomatic uterine fibroids.

Objective To compare laparoscopically assisted vaginal hysterectomy (LAVH) and total abdominal hysterectomy (TAH) in patients with uterine fibroids.

Emerging drugs for endometriosis.

Medical treatment of endometriosis relies on drugs that suppress ovarian steroids and induce an hypoestrogenic state that causes atrophy of ectopic endometrium. Gonadotrophin-releasing hormone (GnRH) analogues, danazol, progestogens and oestrogen-progestin combinations have all proven effective in relieving pain and reducing the extent of endometriotic implants. However, symptoms often recur after discontinuation of therapy and hypoestrogenism-related side effects limit the long-term use of most medications. Furthermore, these therapies are of limited value in patients with a desire to become pregnant because they inhibit ovulation. An important target for current research is to identify effective therapies that can be safely administered in the long term. GnRH analogues with add-back therapy, progestogens and continuous oral contraceptive are options available for a medium or long-term systemic treatment. Mifepristone, an antiprogestogen, may constitute an alternative if encouraging preliminary data on its effectiveness and tolerability are confirmed. A very appealing area of interest is the possibility of treating endometriosis without suppressing ovarian function. Aromatase inhibitors might have such characteristics as they have been shown to inhibit oestrogen production selectively in endometriotic lesions, without affecting ovarian function; the clinical role of these drugs in the treatment of endometriosis is under evaluation. Levonorgestrel medicated intrauterine device has proven effective in relieving dysmenorrhoea associated with endometriosis, as well as pain associated with rectovaginal endometriosis. Although a systemic absorption is present determining side effects, this approach is promising in the long-term management of this condition. A fundamental objective of research in endometriosis treatment is to develop new therapeutic approaches based on the findings from experimental studies on the aetiopathogenesis of the disease; current research is focusing on anti-inflammatory drugs and modulators of the immune system. TNF-binding protein-1 and IL-12 have proved effective in reducing endometriotic lesions in animal models, while pentoxifylline and INF-α2b have shown encouraging results in clinical studies. This area may be of paramount importance in the near future in order to develop a therapy that could prevent or eradicate endometriosis rather than merely relieving the symptoms.

Bipolar Electrocoagulation versus Suture of Solitary Ovary after Laparoscopic Excision of Ovarian Endometriomas

STUDY OBJECTIVE To compare the functional ovarian damage associated with the use of bipolar coagulation versus ovarian suture after laparoscopic excision of ovarian endometriomas in patients with a solitary ovary. DESIGN Retrospective study (Canadian Task Force classification II-3). SETTING Tertiary care center. PATIENTS Forty-seven consecutive women with a single ovary and regular menses who underwent laparoscopic stripping of one or more ovarian endometriomas between June 1996 and June 2001. Intervention. Twenty-one patients had bipolar electrocoagulation (group A), while 26 had suturing of the ovary (group B). Plasma follicle-stimulating hormone (FSH) and estradiol levels were determined before surgery and re-evaluated at 3-, 6-, and 12-month follow-up. MEASUREMENTS AND MAIN RESULTS At 12-month follow-up, six patients (29%) in group A had oligo-amenorrhea versus three patients (12%) in group B (p = .14). Follicle-stimulating hormone levels between 10 and 20 mlU/mL were found in five patients (24%) in group A and in three patients (12%) in group B, whereas FSH levels above 20 mlU/mL were found in three patients (14%) in group A and in no patient in group B. Eight patients (38%) in group A had FSH levels greater than 10 mlU/mL versus three patients (12%) in group B (p = .042). Overall, repeated analysis of variance showed a marginally significant difference (p = .06) in FSH values between the two groups. CONCLUSION Our results suggest that bipolar electrocoagulation of the ovarian parenchyma after laparoscopic stripping of an endometriotic ovarian cyst adversely affects ovarian function.

Ureteral and vesical endometriosis. Two different clinical entities sharing the same pathogenesis.

Ureteral or vesical endometriotic lesions affect about 1% of women with endometriosis. The diagnosis may be difficult when specific symptoms are lacking. A delay in diagnosis can lead to significant morbidity. An adequate comprehension of the circumstances in which ureteral and vesical endometriosis present or should be suspected, aided by advances in imaging techniques and laparoscopic surgery, may allow a significant progress in the treatment of these conditions. The pathogenesis, diagnosis, and treatment of ureteral and vesical endometriosis are reviewed, with the aim of increasing the degree of awareness of the clinicians and helping in devising an adequate clinical management plan for the lesser understood aspects of the disease. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the participant should be better able to explain the most likely pathogenesis of ureteral and vesical endometriosis, recall the clinical presentation and risk factors for endometriosis of the bladder and ureter, and summarize treatment strategies for endometriosis of the bladder and ureter.

Estrogen-progestins and progestins for the management of endometriosis

Endometriosis is characterized by frequent recurrences of symptoms and lesions even after extirpative surgery. Because medical therapies control but do not cure the disease, long periods of pharmacologic management may be needed until pregnancy desire or, sometimes, physiologic menopause. Hormonal drugs suppress ovulation and menstruation and have similar beneficial effects against pain. However, only estrogen-progestins and progestins have safety/tolerability/cost profiles that allow long-term use. These compounds induce atrophy of eutopic and ectopic endometrium, have antiinflammatory and proapoptotic properties, and can be delivered via different modalities, including oral, transdermal, subcutaneous, intramuscular, vaginal, and intrauterine routes. At least two-thirds of symptomatic women are relieved from pain and achieve appreciable improvements in health-related quality of life. Progesterone resistance may cause nonresponse in the remaining one-third. When using estrogen-progestins continuously, individualized, tailored cycling should be explained to improve compliance. All combinations demonstrated a similar effect on dysmenorrhea, independently from progestin type. Estrogen-progestins with the lowest possible estrogen dose should be chosen to combine optimal lesion suppression and thrombotic risk limitation. Progestins should be suggested in women who do not respond or manifest intolerance to estrogen-progestins and in those with dyspareunia and/or deep lesions. Progestins do not increase significantly the thrombotic risk and generally may be used when estrogens are contraindicated. Estrogen-progestins and progestins reduce the incidence of postoperative endometrioma recurrence and show a protective effect against endometriosis-associated epithelial ovarian cancer risk.

The outcomes of repeat surgery for recurrent symptomatic endometriosis

Purpose of review To evaluate the efficacy of second-line surgery in the management of recurrent endometriosis. Recent findings Long-term probability of pain recurrence after repeat conservative surgery for recurrent endometriosis varies between 20 and 40%. The association of presacral neurectomy to the treatment of endometriosis might be effective in reducing midline pain; however, no studies have evaluated this procedure among patients with recurrent disease. The medium-term outcome of hysterectomy for endometriosis-associated pain is quite satisfactory; nevertheless, probability of pain persistence after hysterectomy is 15% and risk of pain worsening 3–5%, with a six times higher risk of further surgery in patients with ovarian preservation as compared to ovarian removal. The conception rate among women undergoing repetitive surgery for recurrent endometriosis associated with infertility is 26%, whereas the overall crude pregnancy rate after a primary procedure is 41%. Summary Repeat conservative surgery for pelvic pain associated with recurrent endometriosis has the same efficacy and limitations as primary surgery. Conversely, after repeat conservative surgery for infertility, the pregnancy rate is almost half the rate obtained after primary surgery. More data are needed to define the best therapeutic option in women with recurrent endometriosis, in terms of pain relief, pregnancy rate and patient compliance.

Role of surgery in endometriosis-associated subfertility.

Analysis of published series reveals that no more than a fourth of subfertile patients undergoing surgery for peritoneal endometriotic implants, rectovaginal endometriotic lesions, or recurrent endometriomas achieved conception spontaneously. First-line surgery for ovarian endometriotic cysts appears associated with a better reproductive performance, that is, a mean postoperative pregnancy rate of ∼50%. At the same time, excision of endometriomas paradoxically seems to induce gonadal damage. With the exception of peritoneal disease, no randomized trials are available to assess the effect of surgery in subfertile women with endometriosis. Therefore, it is not possible to define the absolute benefit increase of the treatment of ovarian and rectovaginal lesions. The decision to undergo surgery for endometriosis-associated subfertility must be shared with the woman after detailed information and taking into account several additional conditions, such as presence of pain, large or complex adnexal masses, bowel or ureteral stenosis, and coexisting infertility factors. When considering surgery, a therapeutic equipoise should be reached that includes demonstrated benefits, potential morbidity, and costs of treatment alternatives. Particularly in case of recurrent endometriosis, in vitro fertilization should generally be preferred to surgery. The role of surgery in endometriosis-associated subfertility includes temporary pain relief in symptomatic women desiring a spontaneous conception.

Beyond infertility: obstetrical and postpartum complications associated with endometriosis and adenomyosis.

The risk of pregnancy and neonatal complications in women with endometriosis and adenomyosis is debatable. A literature review looking at rates, presentation, and management of spontaneous hemoperitoneum, enlargement, abscess, and rupture of an endometrioma, uterine rupture, and bowel perforation in pregnant women with endometriosis was conducted. Moreover, studies addressing differences in early pregnancy (miscarriage), late pregnancy (gestational diabetes mellitus, preeclampsia, prematurity, placenta previa, placental abruption, cesarean section, hemorrhages) and neonatal outcomes (weight at birth) between endometriosis and adenomyosis patients versus control subjects were reviewed. The overall prevalence of endometriosis-related spontaneous hemoperitoneum in pregnancy is estimated to be ∼0.4%. Only four cases of endometrioma rupture in pregnancy have been reported. Although during pregnancy there is no way to anticipate the onset of complications from preexisting endometriosis, it is important, when a specific abdominal pain occurs, to suspect rare but potentially life-threating events. Population-based studies suggest a possible association of endometriosis with preterm birth and placenta previa. Limits of the published studies are noted and discussed.