Umberto Leone Roberti Maggiore

A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes

BACKGROUND Traditionally, pregnancy was considered to have a positive effect on endometriosis and its painful symptoms due not only to blockage of ovulation preventing bleeding of endometriotic tissue but also to different metabolic, hormonal, immune and angiogenesis changes related to pregnancy. However, a growing literature is emerging on the role of endometriosis in affecting the development of pregnancy and its outcomes and also on the impact of pregnancy on endometriosis. The present article aims to underline the difficulty in diagnosing endometriotic lesions during pregnancy and discuss the options for the treatment of decidualized endometriosis in relation to imaging and symptomatology; to describe all the possible acute complications of pregnancy caused by pre-existing endometriosis and evaluate potential treatments of these complications; to assess whether endometriosis affects pregnancy outcome and hypothesize mechanisms to explain the underlying relationships. METHODS This systematic review is based on material searched and obtained via Pubmed and Medline between January 1950 and March 2015. Peer-reviewed, English-language journal articles examining the impact of endometriosis on pregnancy and vice versa were included in this article. RESULTS Changes of the endometriotic lesions may occur during pregnancy caused by the modifications of the hormonal milieu, posing a clinical dilemma due to their atypical appearance. The management of these events is actually challenging as only few cases have been described and the review of available literature evidenced a lack of formal estimates of their incidence. Acute complications of endometriosis during pregnancy, such as spontaneous hemoperitoneum, bowel and ovarian complications, represent rare but life-threatening conditions that require, in most of the cases, surgical operations to be managed. Due to the unpredictability of these complications, no specific recommendation for additional interventions to the routinely monitoring of pregnancy of women with known history of endometriosis is advisable. Even if the results of the published studies are controversial, some evidence is suggestive of an association of endometriosis with spontaneous miscarriage, preterm birth and small for gestational age babies. A correlation of endometriosis with placenta previa (odds ratio from 1.67 to 15.1 according to various studies) has been demonstrated, possibly linked to the abnormal frequency and amplitude of uterine contractions observed in women affected. Finally, there is no evidence that prophylactic surgery would prevent the negative impact of endometriosis itself on pregnancy outcome. CONCLUSIONS Complications of endometriosis during pregnancy are rare and there is no evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore, pregnant women with endometriosis can be reassured on the course of their pregnancies although the physicians should be aware of the potential increased risk of placenta previa. Current evidence does not support any modification of conventional monitoring of pregnancy in patients with endometriosis.

Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: An ex vivo study

ObjectiveMicroablative fractional CO2 laser has been proven to determine tissue remodeling with neoformation of collagen and elastic fibers on atrophic skin. The aim of our study is to evaluate the effects of microablative fractional CO2 laser on postmenopausal women with vulvovaginal atrophy using an ex vivo model. MethodsThis is a prospective ex vivo cohort trial. Consecutive postmenopausal women with vulvovaginal atrophy managed with pelvic organ prolapse surgical operation were enrolled. After fascial plication, the redundant vaginal edge on one side was treated with CO2 laser (SmartXide2; DEKA Laser, Florence, Italy). Five different CO2 laser setup protocols were tested. The contralateral part of the vaginal wall was always used as control. Excessive vagina was trimmed and sent for histological evaluation to compare treated and nontreated tissues. Microscopic and ultrastructural aspects of the collagenic and elastic components of the matrix were studied, and a specific image analysis with computerized morphometry was performed. We also considered the fine cytological aspects of connective tissue proper cells, particularly fibroblasts. ResultsDuring the study period, five women were enrolled, and 10 vaginal specimens were finally retrieved. Four different settings of CO2 laser were compared. Protocols were tested twice each to confirm histological findings. Treatment protocols were compared according to histological findings, particularly in maximal depth and connective changes achieved. All procedures were uneventful for participants. ConclusionsThis study shows that microablative fractional CO2 laser can produce a remodeling of vaginal connective tissue without causing damage to surrounding tissue.

Hemostasis by bipolar coagulation versus suture after surgical stripping of bilateral ovarian endometriomas: a randomized controlled trial.

STUDY OBJECTIVE To estimate whether the suture of the ovary is superior to bipolar coagulation in preserving ovarian reserve in infertile women undergoing laparoscopic stripping of bilateral endometriomas. DESIGN Randomized controlled trial (Canadian Task Force classification I). SETTING University teaching hospital. PATIENTS 100 patients with bilateral endometriomas. INTERVENTIONS Patients underwent stripping of bilateral endometriomas and were randomized to undergo hemostasis by use of either laparoscopic suturing (LS group) or bipolar coagulation (BC group). Changes in ovarian reserve were investigated by measuring the levels of anti-Mullerian hormone (AMH) and basal follicle-stimulating hormone (FSH) before surgery and at 3, 6 and 12 months from surgery. MEASUREMENTS AND MAIN RESULTS At 3-month, 6-month, and 12-month follow-up, in both study groups, postsurgical AMH levels were significantly lower and basal FSH levels were significantly higher than before surgery. There was no significant difference in the mean percentage decrease of AMH levels in the BC group and LS group at 3-, 6-, and 12-month follow-up. The mean percentage increase in basal FSH was higher in the BC group than in the LS group at both 3-month (p = .023) and 6-month follow-up (p = .029), but not at 12-month follow-up. Pregnancy rate, time to conception, and rate of endometrioma recurrence was similar in the 2 study groups. CONCLUSION Laparoscopic stripping of ovarian endometriotic cyst significantly decreases serum AMH levels and increases basal FSH levels independent from the method used to obtain hemostasis on the ovarian tissue.

Treatment of pain associated with deep endometriosis: alternatives and evidence.

Pain is the most evident clinical manifestation of deep infiltrating endometriosis (DIE). Several hormonal and immunologic mechanisms are markedly altered in DIE compared with superficial peritoneal and ovarian endometriosis, and may explain its most aggressive behavior and the presence of severe pain symptoms. Hormonal therapies, such as combined hormonal contraceptives and progestogens, should be regarded as first-line treatment, as they are efficacious, safe, and well tolerated. Gonadotropin-releasing hormone agonists may be used in patients with symptoms persisting after the administration of first-line therapies. Scanty literature is available for danazol treatment in patients with DIE and, however, it has become less popular due to the high rates of androgenic adverse events (AEs). The partial relief of pain that often is achieved with available therapies and its recurrence after the suspension of the treatment have brought to the development of new therapies (such as aromatase inhibitors, oral GnRH antagonists) that are currently under investigation. Surgical excision of DIE should be considered in patients with pain symptoms persisting after first-line hormonal therapies. The benefits of surgery in terms of pain improvement should be always balanced with the risk of intraoperative complications and for this reason surgical cases should be referred to tertiary centers for the treatment of DIE. A multidisciplinary approach is mandatory in patients with DIE involving the bowel and/or the urinary tract.

Desogestrel‐only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open‐label comparative study

To compare the efficacy of two hormonal therapies in treating symptoms caused by bowel endometriosis.

Aromatase and endometriosis: estrogens play a role

Endometriosis is an estrogen‐dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus. Epidemiological and clinical studies show that estrogen is essential for the growth of endometriosis. There are several molecular links between estrogen production and inflammation in endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2, resulting in production of estrogen that induces prostaglandin E2 expression within endometriotic lesions. Furthermore, estrogen promotes the secretion of several inflammatory cytokines and growth factors, which contribute to the progression of endometriosis and stimulate estrogen production. On the basis of the local estrogen biosynthesis in endometriotic implants, nonsteroidal aromatase inhibitors have been successfully used to treat pain symptoms caused by endometriosis. These agents do not cause the disappearance of endometriosis; they cannot be considered routine treatment and should only be administered in adequately controlled clinical studies.

Norethisterone acetate versus norethisterone acetate combined with letrozole for the treatment of ovarian endometriotic cysts: a patient preference study

OBJECTIVE To compare the efficacy of norethisterone acetate (NETA; group N) or letrozole combined with NETA (group L) in treating endometriotic ovarian cysts. STUDY DESIGN This patient-preference study included 20 patients in group N and 20 patients in group L. The primary aim of the study was to compare the volume of the endometriomas during and after treatment. The secondary outcome was the evaluation of the changes in pain symptoms during and after treatment. RESULTS After six months of treatment, the volume of the endometriomas significantly decreased compared with baseline in both study groups; it was smaller in group L than in group N (p=0.026). The rate of satisfied patients at six months of treatment was similar between the study groups (p=0.451). No significant difference was reported between the two study groups in the amelioration of pain symptoms and in the incidence of adverse events. CONCLUSIONS Letrozole combined with NETA is more efficacious than NETA alone in reducing the volume of endometriotic cysts but in none of the 40 patients included in the study did the endometriomas disappear. The efficacy of aromatase inhibitors, however, should be balanced with the need to administer long-term treatment.

Bladder Endometriosis: A Systematic Review of Pathogenesis, Diagnosis, Treatment, Impact on Fertility, and Risk of Malignant Transformation

CONTEXT The bladder is the most common site affected in urinary tract endometriosis. There is controversy regarding the pathogenesis, clinical management (diagnosis and treatment), impact on fertility, and risk of malignant transformation of bladder endometriosis (BE). OBJECTIVE To systematically evaluate evidence regarding the pathogenesis, diagnosis, medical and surgical treatment, impact on female fertility, and risk of malignant transformation of BE. EVIDENCE ACQUISITION A systematic review of PubMed/Medline from inception until October 2016 was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered in the PROSPERO registry (www.crd.york.ac.uk/prospero; CRD42016039281). Eighty-seven articles were selected for inclusion in this analysis. EVIDENCE SYNTHESIS BE is defined as the presence of endometrial glands and stroma in the detrusor muscle. Ultrasonography is the first-line technique for assessment of BE owing to its accuracy, safety, and cost. Clinical management can be conservative, using hormonal therapies, or surgical. When conservative treatment is preferred, estrogen-progestogen combinations and progestogens should be chosen because of their favorable profile that allows long-term therapy. Surgery should guarantee complete removal of the bladder nodule to minimize recurrence, so transurethral surgery alone should be avoided in favor of segmental bladder resection. There is not a strong rationale for hypothesizing a detrimental impact of BE per se on fertility. Furthermore, current evidence does not support the removal of bladder endometriotic lesions because of the potential risk of malignant transformation since this phenomenon is exceedingly rare. CONCLUSIONS BE is a challenging condition, and the common coexistence of other types of endometriosis means that clinical management of BE should involve collaboration between gynecologists and urologists. PATIENT SUMMARY In this article we review available knowledge on bladder endometriosis. The review provides a useful tool to guide physicians in the management of this complex condition.

Dienogest in the treatment of endometriosis

Introduction: Dienogest (DNG) is an oral progestin, derivative of 19-nortestosterone, that has recently been introduced for the treatment of endometriosis. Areas covered: This review examines the clinical efficacy, safety and tolerability of DNG in the treatment of endometriosis. The material included in the current manuscript was searched and obtained via Medline, Pubmed and EMBASE, from inception until February 2014. The term ‘dienogest’ was associated with the following search terms: ‘endometriosis’, ‘pharmacokinetics’, ‘safety’ and ‘efficacy’. Expert opinion: Several trials demonstrated the clinical efficacy, safety and tolerability of DNG. However the use of DNG is associated with some limitations. So far, no study investigated the potential of contraceptive effect of this treatment and therefore, it should be recommended with other methods of contraception (e.g., barrier methods). A further limitation of the use of DNG as daily therapy in the long term is that the cost of the therapy is higher than other progestins available on the market and combined oral contraceptives. Therefore, future studies should be designed to compare the efficacy and safety of DNG with other progestins.

Pharmacokinetics and toxicity of antimuscarinic drugs for overactive bladder treatment in females.

Introduction: Antimuscarinics (AMs) are the mainstay of pharmacological treatment of overactive bladder (OAB), a symptom complex defined by the presence of urinary urgency, usually associated with frequency and nocturia, with or without urgency urinary incontinence. The AMs used to treat OAB differ in their pharmacological profiles, which may affect their potential for causing adverse effects (AEs). Areas covered: The present article aims to review the literature about pharmacokinetics (PK) of the different AMs used in the treatment of OAB. Furthermore, the AEs related to the use of these drugs and their incidence are presented. This systematic review is based on material searched and obtained via Medline, Pubmed and EMBASE up to March 2012 using the search terms “adverse events, pharmacokinetics, tolerability” in combination with “darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium.” Expert opinion: Antimuscarinics are the first-line pharmacological treatment for OAB. Despite the development of new molecules that improve their efficacy/safety profile, there are some drugs that are pharmacokinetically more appropriate to be prescribed in specific populations such as patients with neurological disease or the elderly. Moreover, research should be encouraged in evaluating antimuscarinics in conjunction with other drugs such as estrogens or beta-agonists. The identification of prognostic criteria for pharmacological therapy would be helpful.