Hysteroscopic Evaluation of Endometrial Changes in Breast Cancer Women with or without Hormone Therapies: Results from a Large Multicenter Cohort Study.

STUDY OBJECTIVE: The primary aim of our study was to investigate the incidence of endometrial pathologies, especially endometrial cancer, in women with breast cancer treated with tamoxifen (TAM), aromatase inhibitors (AIs), or receiving no treatment (NT). The secondary aim was to identify, in this cohort, ultrasonographic findings that represent robust indications for hysteroscopy and endometrial biopsy, to avoid unnecessary second-level diagnostic procedures. DESIGN: Multicenter retrospective cohort study (Clinical Trial ID: NCT03898947). SETTING: Data were collected from different Italian centers: Regina Elena National Cancer Institute of Rome, Arbor Vitae Centre of Rome, Gaetano Martino University Hospital of Messina, and Villa Sofia-Cervello Hospital of Palermo. PATIENTS: We selected and consecutively included patients with a history of breast cancer who had undergone hysteroscopy for ultrasonographic or clinical indications between January 2007 and December 2016. INTERVENTIONS: Diagnostic hysteroscopy with endometrial biopsy or operative hysteroscopy, when clinically indicated. MEASUREMENTS AND MAIN RESULTS: A higher percentage of patients in the TAM and AI groups had a normal endometrium compared with those in the NT group, whereas the incidence of endometrial polyps was higher in the NT group than in the others; no significant differences were observed among the 3 groups for other benign conditions or for premalignant and malignant uterine diseases, such as endometrial atypical hyperplasia and adenocarcinoma. CONCLUSION: TAM treatment does not seem to be associated with a higher rate of endometrial cancer in women with breast cancer compared with women treated with AIs or NT.

Fertility Sparing Strategies in Patients Affected by Placental Site Trophoblastic Tumor.

OPINION STATEMENT: Placental site trophoblastic tumor (PSTT) is the least common and the most ambiguous gestational trophoblastic tumor. Presentation of PSTT may occur in the course of gestation or from 1 week to 14 years after a normal or an abnormal pregnancy (mole, ectopic pregnancy, abortion). The indicators of aggressive behavior for this tumor are not well established. Due to the rarity of this disease that usually affects women of childbearing potential, we aimed to review the current literature, to identify risk factors and the best conservative therapeutic choices among the cases described. We performed a systematic literature search of articles in English language, published from 1996 to 2017 and indexed in PubMed and Scopus. Based on selective inclusion/exclusion criteria, we considered eight papers eligible for the review. Five were case reports and three were retrospective studies. We extracted and organized data into three different categories depending on the main treatment used. A total of 12 cases were treated with laparotomy; in 5 cases, the treatment was not curative. Therefore, a total abdominal hysterectomy was needed. Five cases were treated successfully with a minimally invasive approach, 2 with uterine evacuation, 2 with hysteroscopic resection, and 1 with a combined hysteroscopic/laparoscopic resection. Only 1 case treated with exclusive chemotherapy proved curative for the patient. Preservation of fertility in PSTT patients of childbearing age should be considered and as showed by the abovementioned studies, is a possible and safe therapeutic choice. Laparotomy for local uterine resection with the modified Strassman approach could be offered in patients at clinical stage 1 that are very motivated to retain fertility, extensively informing the patient of the risks and benefits related to this choice.

Epigenetic and genetic landscape of uterine leiomyomas: a current view over a common gynecological disease.

PURPOSE: Despite the numerous studies on the factors involved in the genesis and growth of uterine leiomyomas, the pathogenesis of these tumors remains unknown. Intrinsic abnormalities of the myometrium, abnormal myometrial receptors for estrogen, and hormonal changes or altered responses to ischemic damage during the menstrual period may be responsible for the initiation of (epi)genetic changes found in these tumors. Considering these elements, we aimed to offer an overview about epigenetic and genetic landscape of uterine leiomyomas. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Several studies showed that leiomyomas have a monoclonal origin. Accumulating evidence converges on the risk factors and mechanisms of tumorigenesis: the translocation t (12;14) and deletion of 7q were found in the highest percentages of recurrence; dysregulation of the HMGA2 gene has been mapped within the critical 12q14-q15 locus. Estrogen and progesterone are recognized as promoters of tumor growth, and the potential role of environmental estrogens has been poorly explored. The growth factors with mitogenic activity, such as transforming growth factor-ß3, fibroblast growth factor, epidermal growth factor, and insulin-like growth factor-I are elevated in fibroids and may have a role as effectors of the tumor promotion. CONCLUSION: The new clues on genetics and epigenetics, as well as about the growth factors that control normal and pathological myometrial cellular biology may be of great help for the development of new effective and less invasive therapeutic strategies in the near future.

Endometrial preparation with Dienogest before hysteroscopic surgery: a systematic review.

PURPOSE: Hysteroscopic surgery is considered the gold standard for the minimal invasive treatment of many endouterine diseases such as endometrial polyps or submucous myomas. Recently, many studies have evaluated the effect of preoperative administration of a number of drugs to reduce endometrial thickness and achieve important intraoperative advantages. The purpose of this systematic review is to summarize the available evidence about the use of Dienogest, an orally administrable progestin, for endometrial preparation before hysteroscopic surgery. METHODS: All studies published on this topic and indexed on PubMed/MEDLINE, Embase or Google scholar databases were retrieved and analysed. RESULTS: We retrieved five studies about this topic. Considered together, the published data analyses allow us to conclude that Dienogest is effective in reducing the thickness of the endometrium, the severity of bleeding and also of operative time, with a lower number of side effects compared with other pharmacological preparations or no treatment. CONCLUSION: Administration of Dienogest may be an effective and safe treatment for endometrial thinning before operative hysteroscopy. However, this conclusion is based on few reports and further studies to prove or disprove it are warranted.

Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome.

PURPOSE: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferer's quality of life. The aim of this review is to highlight the newest diagnostic strategies and potential therapeutic techniques. METHODS: A comprehensive literature review was performed on MEDLINE, PubMed, and Cochrane databases gathering all literature about "Interstitial cystitis" and "Painful Bladder Syndrome". Visual analogue scales, epidemiological strategies, pain questionnaires and similar techniques were not included in this literature survey. RESULTS: The etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. To date, its prevalence is estimated to be in the range of 45 per 100,000 women and 8 per 100,000 men, whereas joint prevalence in both sexes is 10.6 cases per 100,000. There are no "gold standards" in the diagnosis or detection of IC/PBS, therefore, several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers. CONCLUSION: Due to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

Work load and management in the delivery room: changing the direction of healthcare policy.

Nurse staffing, increased workload and unstable nursing unit environments are linked to negative patient outcomes including falls and medication errors on medical/surgical units. Considering this evidence, the aim of our study was to overview midwives' workload and work setting. We created a questionnaire and performed an online survey. We obtained information about the type and level of hospital, workload, the use of standardised procedures, reporting of sentinel and 'near-miss' events. We reported a severe understaffing in midwives' work settings and important underuse of standard protocols according to the international guidelines, especially in the South of Italy. Based on our results, we strongly suggest a change of direction of healthcare policy, oriented to increase the number of employed midwives, in order to let them fulfil their duties according to the international guidelines (especially one-to-one care). On the other hand, we encourage the adoption of standardised protocols in each work setting.

Inositol's and other nutraceuticals' synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives.

The incidence of metabolic syndrome (MetS), type II diabetes (T2D) and polycystic ovarian syndrome (PCOS) has been progressively increasing. Insulin resistance (InsR) seems to play a key role in a majority of phenotypes of these conditions, altering metabolic homeostasis, within muscle, liver, adipose and other tissues. Hyperinsulinemia is often associated with InsR and causes hormonal imbalances especially within ovaries and adrenals. Inositol is a polyalcohol, naturally occurring as nine stereoisomers, including D-chiro-inositol (DCI) and myo-inositol (MI), which have prominent roles in the metabolism of glucose and free fatty acids. MI and DCI have been classified as insulin-sensitizers and seem to adequately counteract several InsR-related metabolic alterations with a safe nutraceutical profile. Based on our analysis of selected studies that investigated MI and/or DCI, we conclude that supplementation with MI and/or DCI complement each other in their metabolic actions and act in synergy with other insulin sensitizing drugs and/or nutraceuticals. Nevertheless, considering the possible severe bias due to different methodologies across published studies, we conclude that there is a need for further studies on larger cohorts and with greater statistical power. These should further clarify outcomes and suitable therapeutic dosages of MI and DCI, possibly based on each patient's clinical status.

Dienogest as preoperative treatment of submucous myomas for hysteroscopic surgery: a prospective, randomized study.

The aim of this single-center, prospective, randomized, parallel-group study was to compare Dienogest and Danazol as endometrial preparation in patients who have to undergo hysteroscopic surgery for submucous myomas. We enrolled 80 consecutive eligible patients, in reproductive age, affected by submucous myomas. Pre- and posttreatment characterization of endometrium was performed by hysteroscopic visual observation and histologic confirmation. The enrolled patients were randomly assigned to two groups: 40 were treated with 2 mg of Dienogest/die, 40 with 100 mg of Danazol/die, both orally for 5 weeks, starting on day 1 of menstruation. Posttreatment comparison of endometrial patterns showed a significant more marked effect of Dienogest, respect to Danazol, in atrophying endometrium ("normotrophic non-responders" versus "hypotrophic"-"atrophic", p = 0.028). Intraoperative data showed no significant difference between the two groups for cervical dilatation time (p = 0.326), while in the Dienogest group, we found a significant reduction of operative time (p = 0.001), infusion volume (p = 0.001), and severity of bleeding (p = 0.042). Moreover, Dienogest caused less side effects (p = 0.008). According to our data analysis, Dienogest, respect to Danazol, is more effective for the preparation of the endometrium in patients who have to undergo hysteroscopic surgery for submucous myomas, and causes less side effects.

Natural Killer T cell subsets in eutopic and ectopic endometrium: a fresh look to a busy corner.

PURPOSE: Invariant Natural Killer T cells (iNKT) are a specialized subset of T cells that use their T cell receptor to recognize self and foreign lipids presented by CD1d as cognate antigens. iNKT have been shown to have either protective or harmful roles in many pathological states, including microbial infection, autoimmune disease, allergic disease and cancer. Accumulating evidence seems to suggest that this unique T cell subset combines both classically innate and adaptive immunologic characteristic. Considering these recent data, the aim of work was to review the current knowledge about iNKT in eutopic and ectopic endometrium. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: Currently, the immune paradigm of reproduction is gradually changing shape: recent data confirmed that cytokine milieu influences the development and plasticity of different subtype of mononuclear cells, and in turn it can be influenced by the cytokine production of the latter. Among the different NKT cell populations, the recently characterized iNKT seems to share actions typical both of innate and adaptive immunity, being capable of secreting Th1 as well as Th2 cytokine pattern. Moreover, several subtypes of iNKT were identified, who partially express the same master transcription factors of the corresponding T cells counterpart. CONCLUSIONS: Although the data about iNKT's actions in eutopic and ectopic endometrium are still scarce, it is possible to hypothesize that future investigation can shed light on this point, thus allowing a better knowledge about the regulation of these two microenvironments.

Regulation of apoptotic pathways during endometriosis: from the molecular basis to the future perspectives.

PURPOSE: Endometriosis is defined as the presence of endometrial-like endometrial cells, glands and stroma outside the uterus, causing a strong inflammatory-like microenvironment in the affected tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration, documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease. Considering the pivotal role of interaction between immune and endometriotic cells, in this paper, we aim to shed light about the role of apoptosis pathways in modulating the fine-regulated peritoneal microenvironment during endometriosis. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: In normal conditions, endometriotic cells, refluxed through the fallopian tubes into the peritoneal cavity, should be attacked and removed by phagocytes and NK cells. During endometriosis, the breakdown of peritoneal homeostasis causes the failure of scavenging mechanisms, allowing the survival of endometriotic cells. The consequent so-called "immunoescaping" of endometriotic cells could be due, at least in part, to the reduction of apoptotic-mediated pathways previously described. CONCLUSION: Considering the large amount of evidence retrieved from in vitro as well as in vivo models, the reduced apoptosis of endometriotic cells together with the increased apoptosis of peritoneal fluid mononuclear cells may address the peritoneal homeostasis to a permissive environment for the progression of the disease.

Management of women with epilepsy: from preconception to post-partum.

PURPOSE: The physiological changes during pregnancy can significantly alter antiepileptic drug (AED)'s absorption, distribution, metabolism and elimination, thus influencing their plasma concentration. Considering that the risks of using old and new AEDs during pregnancy are still debated, our aim is to review the available evidence on this topic. METHODS: Narrative overview, synthesizing the findings of literature retrieved from searches of computerized databases. RESULTS: The old AEDs generation (benzodiazepines, phenytoin, carbamazepine, phenobarbital and valproic acid) is teratogenic: minor congenital malformations, such as facial dysmorphism and other anomalies, occur in 6-20% of infants exposed to AEDs in utero; this value is two times greater than the value reported in the general population. Major congenital malformations (MCM) such as cleft lip and cleft palate, heart defects (atrial septal defect, Fallot's tetralogy, ventricular septal defect, aortic coarctation, patent ductus arteriosus, and pulmonary stenosis) and urogenital anomalies were estimated to be 4-6% of infants born from mothers treated with AEDs, compared to 2-3% of the general population. CONCLUSION: It is essential to inform women treated with AED that planning pregnancy is necessary, when possible. The problems related to antiepileptic therapy and the possibilities of prenatal diagnosis should be accurately discussed with the patient, when possible before pregnancy: individual circumstances, desire to have children, severity of epilepsy, risks of seizures, family history of congenital malformations and all other potential risk factors must be considered, involving the patient in shared clinical decision-making.

Data comparison between pharmacological induction of labour and spontaneous delivery. A single centre experience.

OBJECTIVES: To assess the differences in the maternal and fetal outcomes between pharmacological induced and sponta-neous labour in nulliparous women. MATERIAL AND METHODS: Observational cohort study carried out over a period of 2 years. INCLUSION CRITERIA: nulliparous sin-gleton pregnancies, with cephalic fetal presentation, elective labour induction with intra-vaginal prostaglandin E2 (PGE2) gel (Prepidil® 2 mg) at a gestational age of 41 weeks. CONTROL GROUP: patients who entered labour spontaneously at a gestational age of ≥ 40 weeks. The main demographic maternal characteristics and intra- and postpartum data were extracted from computer records and obstetrics diaries and were used for the analysis. RESULTS: One hundred and three patients with induction of labour and 97 with spontaneous labour were enrolled. Cesarean delivery was performed in 18 cases (17.5%), all in the induction group. There were no differences in newborn weights between the 2 groups while both the 1-minute and 5-minute Apgar scores were significantly higher in the spontaneous group (p = 0.014 and p = 0.0003, respectively). Women in the induction group had a significantly longer duration of I stage labour in comparison with spontaneous group (p < 0.0001). CONCLUSIONS: Primiparous women whose labour was induced spent a longer time in labour than women who presented in spontaneous labour. Clinicians should keep in mind that a slow rate of dilation in a woman being induced may be normal. For this reason, an arrest diagnosis needs to be carefully considered.

Gonadotrophin-releasing hormone analogue or dienogest plus estradiol valerate to prevent pain recurrence after laparoscopic surgery for endometriosis: a multi-center randomized trial.

OBJECTIVES: To evaluate the efficacy of dienogest + estradiol valerate (E2V) and gonadotrophin-releasing hormone analogue (GnRH-a) in reducing recurrence of pain in patients with chronic pelvic pain due to laparoscopically diagnosed and treated endometriosis. DESIGN: Multi-center, prospective, randomized study. SETTING: Three university departments of obstetrics and gynecology in Italy. POPULATION: Seventy-eight women who underwent laparoscopic surgery for endometriosis combined with chronic pelvic pain. METHODS: Post-operative administration of dienogest + E2V for 9 months (group 1) or GnRH-a monthly for 6 months (group 2). MAIN OUTCOME MEASURES: A visual analogue scale was used to test intensity of pain before laparoscopic surgery at 3, 6 and 9 months of follow up. A questionnaire to investigate quality of life was administered before surgery and at 9 months of follow up. RESULTS: The visual analogue scale score did not show any significant differences between the two groups (p = 0.417). The questionnaire showed an increase of scores for all women compared with pre-surgery values, demonstrating a marked improvement in quality of life and health-related satisfaction with both treatments. No significant differences were found between the groups. The rate of apparent endometriosis recurrence was 10.8% in group 1 and 13.7% in group 2 (p = 0.962). CONCLUSION: Both therapies seemed equally efficacious in preventing endometriosis-related chronic pelvic pain recurrence in the first 9 months of follow-up.

Thyroid diseases in pregnancy: a current and controversial topic on diagnosis and treatment over the past 20 years.

BACKGROUND: Management of thyroid diseases during pregnancy requires special considerations because maternal thyroid diseases can have adverse effects on both pregnancy and fetus. Universal screening for thyroid diseases in pregnant women is not currently supported by studies with high evidence whereas guidelines have been released for individuals at high risk, although controversies are still in debate. Iodine prophylaxis should be performed systematically to women during pregnancy. MATERIALS AND METHODS: An electronic search of PubMed/Medline and EMBASE concerning thyroid diseases and pregnancy have been conducted over the past 20 years and summarized. RESULTS: Data regarding prevention and treatment of thyroid diseases during pregnancy are reported from analysis of the literature. CONCLUSIONS: As thyroid dysfunction may cause profound impact on mother's and fetus's health, implementation by strict application of clinico-diagnostic flowchart and recommendations is of paramount importance when dealing with thyroid diseases during pregnant state.

Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease.

INTRODUCTION: Environmental toxicants can act as endocrine disrupters on the female reproductive system. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is resistant to degradation and due to its lipophilic nature, accumulates in the fat tissue and in the food chain. Human and animal exposure to TCDD affects levels of the steroid receptors and steroid-responsive gene expression and has an impact on metabolism and serum transport of steroids. Gene expression is commonly altered in endometriosis and in the eutopic endometrium of women with the disease. Aberrantly expressed genes include those associated with the regulation of transcription, proliferation, sex steroid metabolism, apoptosis, cell cycle, the immune response and cell adhesion. METHODS: In this paper, we review the evidence about TCDD's effect on eutopic and ectopic endometrium, in order to unravel the machinery behind the dysregulation of immune and hormonal homeostasis caused by this environmental toxicant. CONCLUSION: The evidence collected in this review suggests that TCDD could modulate transcription at multiple levels, including the epigenetic level, and via microRNAs, thus disturbing the physiologic processes mediated through the aryl hydrocarbon receptor pathways. Exposure to TCDD also modulates the immune response by influencing the production and action of endometrial cytokines and chemokines, destroying mucosal immunity of the reproductive tract and re-directing the tissue distribution and behavior of leukocytes. Despite this large body of evidence, current human-based epidemiological studies on the association between TCDD and endometriosis remain controversial.

Desogestrel versus danazol as preoperative treatment for hysteroscopic surgery: a prospective, randomized evaluation.

The aim of this single-center, prospective, randomized, parallel-group study was to compare desogestrel and danazol as preoperative endometrial preparation for hysteroscopic surgery. We enrolled 200 consecutive eligible patients, in reproductive age, with endouterine diseases. Pre- and post-treatment characterization of endometrium was performed by hysteroscopic visual observation and histologic confirmation. The enrolled patients were randomly assigned to two groups: 100 were treated with 75 µg of desogestrel/die, 100 with 100 mg of danazol/die, both orally for 5 weeks, starting on Day 1 of menstruation. We recorded intraoperative data (cervical dilatation time, operative time, infusion volume and severity of bleeding) and drugs' side effects. Post-treatment comparison of endometrial patterns showed a significant more marked effect of desogestrel, respect to danazol, in atrophying endometrium ("normotrophic non-responders" versus "hypotrophic"-"atrophic", p = 0.031). Intraoperative data showed no significant differences between the two groups for cervical dilatation time (p = 0.160), while in the desogestrel group we found a significant reduction of operative time (p = 0.020), infusion volume (p = 0.012), and severity of bleeding (p = 0.004). Moreover, desogestrel caused less side effects (p = 0.031). According to our data analysis, desogestrel showed most marked effect in inducing endometrial atrophy, allowed a better intraoperative management and caused less side effects during treatment.

Would it be too late? A retrospective case-control analysis to evaluate maternal-fetal outcomes in advanced maternal age.

PURPOSE: To evaluate maternal-fetal outcomes in women of advanced maternal age (AMA; >35 years old) and women of physiological maternal age as controls (C; <35 years old). METHODS: Single-center, retrospective case-control analysis, from January 1 to December 31, 2013. For each group, we evaluated obstetric history, number of twin pregnancies, delivery mode, incidence of obstetric diseases and neonatal outcomes (5-min Apgar score, neonatal weight, meconium stained fluid rate, admission to the neonatal intensive care unit rate, and incidence of congenital malformations). Data are presented as n (%) and analyzed with χ (2) test and Fisher exact test (when required). A p value < 0.05 was considered statistically significant. Moreover, we calculated the odds ratio (OR), with confidence interval (CI) at 95 %. RESULTS: We enrolled 1,347 pregnant women, 210 (15.6 %) in AMA and 1,137 (84.4 %) C. AMA patients showed a higher rate of previous (anamnestic) spontaneous abortion (SA; p = 0.001; OR = 2.10) and previous (anamnestic) voluntary pregnancy termination (p = 0.022; OR = 1.59), iterative cesarean section (p = 0.026; OR = 2.33), SA (p = 0.001; OR = 12.82), preterm delivery (p = 0.001; OR = 69.84), congenital malformations (p = 0.036; OR = 3.94). In C there was a greater number of nulliparous (p = 0.009; OR = 0.52) and vaginal deliveries (p = 0.025; OR = 0.41). There were not any statistically significant differences between the two groups for twin pregnancies (p = 0.862; OR = 0.97), first cesarean section (p = 0.145; OR = 0.95), other obstetric diseases and neonatal outcomes. CONCLUSION: AMA could be considered an important risk factor only for SA and PTD and does not influence neonatal outcomes except for congenital malformations.

3D sonohysterography vs hysteroscopy: a cross-sectional study for the evaluation of endouterine diseases.

PURPOSE: To assess the concordance between the presumed diagnosis obtained with the 3D sonohysterography (SHG) and with the diagnostic hysteroscopy (HYS); to determine whether the 3D SHG has the accuracy needed to be considered as a diagnostic screening standard in cases of suspected endouterine pathology. METHODS: We selected 224 patients who voluntarily decided to undergo 3D SHG from a population with suspected presence of endouterine disease at TVS. The patients underwent first 3D SHG and then diagnostic HYS. We recorded each patient's discomfort/pain during the two techniques. We used the "Bayes Theorem" to calculate the sensitivity and specificity of the 3D SHG as compared to HYS. RESULTS: Overall the 3D SHG diagnosis was confirmed in 156/224 cases (69.64 %). Concordance for endometrial thickening was 0 %; for Asherman's syndrome was 50.00 %; for polyp was 77.78 %; and for myoma, mucus accumulation and Müllerian anomalies (arcuate uterus, septate and subseptate uterus) was 100.00 %. Furthermore, 3D SHG was better tolerated than HYS. CONCLUSION: Despite the diagnostic accuracy and mini-invasiveness of 3D SHG, we suggest that it cannot be a substitute of HYS in endouterine disease diagnosis, but it could be considered as a good method of screening to address patients to hysteroscopic confirmation.

Morphologic patterns of human endometrial epithelium in women with uterine myomata treated with leuprorelin acetate.

AIM: We studied morphologic modifications of the endometrium induced by leuprorelin acetate, a gonadotropin-releasing hormone agonist, in women with uterine myomata. METHODS: Transmission and scanning electron microscopy observations were performed after 2 or 6 cycles of therapy (every 28 days). RESULTS: A near-normal endometrium was observed after 2 months of therapy, while treatment with 6 cycles of leuprorelin acetate induced a uniform morphologic regression of the uterine mucosa. CONCLUSIONS: The study demonstrates that leuprorelin acetate induces a unique and time-dependent regression of the endometrial mucous membrane.