Lower Urinary Tract Symptoms in Greek Women After Menopause: The LADY Study.

INTRODUCTION AND HYPOTHESIS: The genitourinary syndrome of menopause (GSM), apart from symptoms related to vulvovaginal atrophy (VVA), also consists of lower urinary tract symptoms (LUTS). Based on the common embryological origin of the genital and lower urinary system, the presence of estrogen receptors, and the high prevalence of VVA and LUTS in the menopausal population, the two conditions can coexist. This study is aimed at investigating the prevalence and risk factors of LUTS in a sample of Greek peri- and postmenopausal women. METHODS: Four hundred and fifty (450) women, aged 40-70 years, attending three outpatient gynecology clinics for routine examination, completed a structured interview and responded to a validated questionnaire (International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms, ICIQ-FLUTS). RESULTS: Urinary urgency or frequency affected 51.6% and dysuria 43.6% of the participants. Mild urgency or frequency was described by 25.6%, moderate by 14.4%, and severe by 11.6% of the women. Mild dysuria was reported by 26.26%, moderate by 5.8%, and severe by 11.6%. Age, weight, BMI, and number of pregnancies and abortions correlated with a higher ICIQ-FLUTS score. Women with moderate/severe symptoms of VVA, such as irritation, a burning sensation, and pruritus of the vulva or vagina, had a higher ICIQ-FLUTS score than women without such symptoms (beta coefficient 2.42, CI 1.204, 3.635, p < 0.001). CONCLUSIONS: Lower urinary tract symptoms are very common among peri- and postmenopausal women and are linked to symptoms of VVA. Our data support the need for prompt evaluation of women transitioning to menopause, as these symptoms compromise the quality of life.

Treating Pain and Fat Necrosis after Breast Cancer Surgery with Fat Grafting: Is one Session Enough?

BACKGROUND: Chronic pain after breast cancer surgery is affecting up to 60% of patients, causing significant morbidity to patients. Lately, fat grafting has been applied as a therapy for chronic neuropathic pain. METHODS: We report a series of eighteen patients, who were treated for pain after breast cancer surgery. Twelve patients had a breast conserving therapy, two a mastectomy and four an autologous flap-based reconstruction. While most presented with neuropathic pain, six patients had fat necrosis in their history. Most patients presented with severe pain (77%) and were treated with fat grafting sessions, performed by water-assisted liposuction. RESULTS: All patients responded to the interventions; the median number of fat grafting sessions was 2, the median duration of the interventions was 4 months, and the median follow-up period was 56.5 months. The median pain prior to the fat grafting procedure had an intensity of 8 (range 7-9) numeric rating scale points; after the first intervention, this was reduced to 4 (range 2.3-5.8); and after the second intervention, it was down to 2 (range 0.8-3.3). Patients with pain intensities of 4-5 had a good chance of achieving analgesia after one session. CONCLUSIONS: Fat grafting could be a new treatment modality for symptomatic fat necrosis: complete or partial suction of the necrosis and/or fat grafting around the necrosis to reduce inflammation and pain. Fat grafting proved a valuable tool, reducing pain or even achieving analgesia after breast cancer surgery presenting with a highly favorable risk-benefit ratio. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Assisted reproduction technology outcomes in women with infertility and preexisting diabetes mellitus: a systematic review.

OBJECTIVE: To assess maternal and neonatal outcomes in women with or without preexisting diabetes mellitus (DM) undergoing assisted reproduction technology (ART) treatment. METHODS: Prospective or retrospective controlled trials reporting on women with or without preexisting DM undergoing ART treatment were considered eligible. Twelve electronic databases were systematically searched up to December 2020. The risk of bias was assessed by the Cochrane Risk OF Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Each primary outcome was extracted and pooled as maternal- or neonatal-related. RESULTS: Two studies were included in the systematic review, reporting on both maternal- and neonatal-related parameters after ART treatment. Due to the limited data, no meta-analysis was conducted. Preterm birth, placenta previa, and excessive bleeding during pregnancy were observed more often in pregnancies complicated by preexisting DM conceived by ART compared with pregnancies without DM. There was no difference in the risk for placental abruption between the groups. Regarding the neonatal outcomes, large-for-gestational-age (LGA) embryos and neonatal intensive care unit (NICU) admission were more commonly reported for women with preexisting DM. In one study, preexisting DM was marginally associated with infant mortality. CONCLUSIONS: Despite the scarce data, preexisting DM in pregnancies conceived by ART is associated with increased risk for maternal and neonatal complications. TRIAL REGISTRATION: Registered in PROSPERO (registration number: 143187).

Are neonatal outcomes of triplet pregnancies different from those of singletons according to gestational age?

OBJECTIVES: Multiple pregnancies sustain the high pace of extreme prematurity. Little evidence is available about triplet gestation given the evolution in their management during the last decades. The aim of the study was to compare the neonatal outcomes of triplets with those of matched singletons in a cohort study. METHODS: An observational retrospective cohort study of triplets and matched singletons born between 2004 and 2017 matched by gestational age was conducted. Additionally, the investigation performed in regard to data from the overall Greek population of interest. The primary outcome was mortality or severe neonatal morbidity based on pregnancy type. RESULTS: A total of 237 triplets of 24-36 weeks' gestation and 482 matched singletons were included. No differences in the primary outcome between triplets and singletons were found. Rates of severe neonatal morbidities did not differ significantly between triplets and singletons. A threshold of 1000 gr for birthweight and 28 weeks' gestation for gestational age determined survival on triplets [OR: 0.08 (95% CI: 0.02-0.40, p=0.0020) and OR: 0.13 (95% CI: 0.03-0.57, p=0.0020) for gestational age and birthweight respectively]. In Greece stillbirths in triplets was 8 times higher than that of singletons (OR: 8.5, 95% CI: 6.9-10.5). From 3,375 triplets, 94 were stillborn, whereas in singletons, 4,659 out of 1,388,273. In our center 5 times more triplets than the expected average in Greece were delivered with no significant difference in stillbirths' rates. CONCLUSIONS: No significant differences were identified in mortality or major neonatal morbidities between triplets and matched singletons highlighting the significance of prematurity and birthweight for these outcomes.

Decline in anti-Müllerian hormone concentrations following radioactive iodine treatment in women with differentiated thyroid cancer: A systematic review and meta-analysis.

AIM: Radioactive iodine (RAI) is frequently used as adjuvant therapy in patients with differentiated thyroid cancer (DTC). However, its effect on ovarian reserve has not been fully elucidated, with studies yielding inconsistent results. The aim of this study was to systematically review and meta-analyze the best available evidence regarding the effect of RAI on ovarian reserve in premenopausal women with DTC. METHODS: A comprehensive literature search was conducted in PubMed, Cochrane and Scopus, through to December 6th, 2020. Data were expressed as weighted mean difference (WMD) with a 95% confidence interval (CI). The I2 index was used to assess heterogeneity. RESULTS: Four prospective studies were included in the qualitative and quantitative analysis. Anti-Müllerian hormone (AMH) concentrations decreased at three (WMD -1.66 ng/ml, 95% CI -2.42 to -0.91, p<0.0001; I2 0%), six (WMD -1.58, 95% CI -2.63 to -0.52, p=0.003; I2 54.7%) and 12 months (WMD -1.62 ng/ml, 95% CI -2.02 to -1.22, p<0.0001; I2 15.5%) following a single RAI dose compared with baseline (three studies; n=104). With respect to follicle-stimulating hormone (FSH) concentrations, no difference was observed at six (WMD +3.29 IU/l, 95% CI -1.12 to 7.70, p=0.14; I2 96.8%) and 12 months (WMD +0.13 IU/l, 95% CI -1.06 to 1.32, p=0.83; I2 55.2%) post-RAI compared with baseline (two studies; n=83). No data were available for antral follicle count. CONCLUSIONS: AMH concentrations are decreased at three months and remain low at 6 and 12 months following RAI treatment in women with DTC. No difference in FSH concentrations post-RAI is observed.

Treating Anisomastia and Tuberous Breast with Fat Grafting: Technique and Evaluation of Outcomes Using BREAST-Q Surveys.

BACKGROUND: In the surgical correction of tuberous breast deformity, implants and regional flaps play a prominent role. Lately, fat grafting has been used as an alternative, but there is evidence that patient satisfaction is higher after correction with implants compared with lipofilling. METHODS: We report a tuberous breasts correction series of ten cases, enrolled between 2015 and 2018. Percutaneous fasciotomies and fat grafting were performed by the Body-Jet technique. Analysis of outcomes was undertaken with BREAST-Q surveys. RESULTS: The breast satisfaction scores increased from 0 to 75 (p < 0.01), the psychological well-being scores from 20 to 70 (p < 0.01) and the sexual well-being scores from 18.5 to 58 (p = 0.02), while the physical well-being scores remained stable (from 68 to 63, p = 0.2). The median outcome satisfaction score was 86. CONCLUSION: Scores of patient-reported outcomes after lipofilling can reach and even exceed those of patients corrected with implants, at the cost of more interventions. Fat grafting is beginning to establish itself as a true alternative in the treatment of tuberous breast deformity in patients with the appropriate fat deposits. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Fat Grafting and Auto-Augmentation Mastopexy After Breast Implant Removal: Technique and Evaluation of Outcomes Using BREAST-Q.

BACKGROUND: Auto-augmentation mastopexy after implant removal has been described as a possible alternative for women who do not opt for implant replacement and decline major reconstructive surgery. OBJECTIVES: This study aimed to evaluate patient satisfaction after auto-augmentation mastopexy relative to the final breast volume and to assess the role of fat grafting on patients' satisfaction and quality of life according to the BREAST-Q questionnaire. METHODS: Forty-seven breasts from 28 patients who underwent implant removal and auto-augmentation mastopexy were reviewed; 9 patients (group 1) were primarily treated with several fat grafting sessions with subsequent auto-augmentation, 5 (group 2) were treated primarily with auto-augmentation, but subsequently expressed a wish for breast augmentation by lipofilling, and 14 patients (group 3, control) had only auto-augmentation. RESULTS: Group 1 patients maintained their breast volume, and showed significant improvements in breast satisfaction, psychosocial well-being, and contentment with breast surgery outcomes (P = 0.01, ˂0.01, and ˂0.01, respectively). However, the physical well-being of this group, as well as response to final cup size or interaction parameters, did not improve (P = 0.06). In group 2, all except 1 patient had breast volume reduction to A cup, as was the case with one-third of the patients in control group 3 (group 3A, n = 5) who scored lower, and thus were less satisfied with the breast auto-augmentation than group 3B, who achieved final bigger cup sizes (P ˂ 0.01). CONCLUSIONS: Auto-augmentation mastopexy resulted in substantial improvements in the parameters measured by BREAST-Q. Thus, combined auto-augmentation mastopexy and lipofilling provided a better alternative treatment after breast implant removal.

Breast cancer in women younger than 35 years old.

PURPOSE: Women ≤ 35 years old with breast cancer constitute a special group. Considering the impact of the disease and its prognosis, these patients face some specific problems that are not present in older women. What are the prognostic features of the survival rate in very young women with breast cancer? METHODS: Retrospective analysis of very young women with breast cancer from the Surgical-Oncologic Breast Cancer Department at "Theagenio" Anticancer Hospital, 2003-2016. Patient and tumor characteristics, treatment options and follow-up information were collected. Univariate-multivariate analyses were conducted and survival rates were calculated. RESULTS: The median age was 34 years old. 53 patients (41%) had T1, 36 (28%) had T2, 7 (5.4%) had T3 and 33 (25.6%) had T4 stage tumors. Most women, 114 (88.4%), had ductal carcinoma in their histology. Furthermore, positive axillary lymph nodes were present in 62 women (48%). In the immunochemistry report, 91 patients (70.5%) were hormone receptor positive, HER2 was overexpressed in 32 patients (24.8%) and 27 patients presented with triple-negative subtype. Out of 65 patients tested for Ki-67, 51 (78.5%), had a high expression (cut-off value of 20%). After adjusting for all possible factors, the risk of recurrence and death was six times higher in the positive lymph node group, (p < 0.001). The median disease-free and overall survival was 133 and > 173 months, respectively. CONCLUSION: Breast cancer in very young women appears with large size and high-grade tumors, high incidence of infiltrated axillary lymph nodes, high Ki-67 expression and intrinsic subtypes with poor prognosis. As a result, these women need to be treated by a multidisciplinary team.

Association between body mass index and oocyte maturation in patients triggered with GnRH agonist who are at high risk for severe ovarian hyperstimulation syndrome: an observational cohort study.

RESEARCH QUESTION: Is body-mass index (BMI) associated with oocyte maturation in women at high risk for developing severe ovarian hyperstimulation syndrome (OHSS) who are triggered with gonadotrophin releasing hormone (GnRH) agonist? DESIGN: Prospective observational cohort study. A total of 113 patients at high risk for severe OHSS (presence of at least 19 follicles ≥11 mm) pre-treated with gonadotrophin releasing hormone (GnRH) antagonists and recombinant FSH were administered 0.2 mg triptorelin to trigger final oocyte maturation. Patients were classified in two groups depending on their BMI: ΒΜΙ less than 25 kg/m2 (n = 72) and ΒΜΙ 25 kg/m2 or over (n = 41). Baseline, ovarian stimulation and embryological characteristics, as well as luteal-phase hormone profiles, were compared in patients classified into the two BMI groups. The main outcome measure was the number of mature oocytes. RESULTS: A significantly higher number of mature (metaphase II) oocytes (19 [18-21] versus 16 [13-20], P = 0.029) was present in women with BMI less than 25 kg/m2 compared with those with BMI 25 kg/m2 or greater. The number of retrieved oocytes, the number of fertilized oocytes, oocyte retrieval, maturation and fertilization rates were similar in the two groups. A significantly higher dose of recombinant FSH was required for patients with BMI 25 kg/m2 or greater compared with patients with BMI less than 25 kg/m2 (1875 [1650-2150] IU versus 1650 [1600-1750] IU, P = 0.003) and the two groups displayed different luteal phase hormonal profiles. CONCLUSIONS: Among women at high risk for developing severe OHSS who are triggered with a standard dose (0.2 mg) of the GnRH agonist triptorelin, women with BMI 25 kg/m2 or greater had significantly fewer mature oocytes, required a higher total dose of recombinant FSH compared with women with BMI less than 25 kg/m2.

Protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) in endometriosis and normal endometrium.

Given the involvement of different extracellular matrix (ECM) metalloproteinases (MMPs) in endometriosis, the protein expression pattern of tissue inhibitor of metalloproteinase-3 (TIMP3) was analyzed in this study in endometriosis and normal endometrium. Tissue samples were collected prospectively from 64 premenopausal patients undergoing operative laparoscopy. Protein expression of TIMP3 was analyzed immunohistochemically in endometriotic lesions (n = 30) and normal eutopic endometrium from patients with (n = 35) and without (n = 29) endometriosis. Comparison between the three different groups of tissue samples showed that TIMP3 was differentially expressed between the three groups (p = .04). Pair-wise comparisons showed that TIMP3 expression was lower in endometriotic lesions as compared with normal eutopic endometrium from controls (p = .006); the same non-significant trend was found, in the comparison between endometriosis lesions and matched eutopic endometrium. There were no differences in TIMP3 expression in the normal eutopic endometrium between patients with and without endometriosis. In conclusion, TIMP3 seems to be involved in the pathogenesis, pathophysiology, and maintenance of endometriosis and it might be useful as a diagnostic and prognostic marker of endometriosis. Future studies should further investigate this issue, as well as the interplay between TIMPs and different extracellular MMPs in endometriosis.

Egg freezing and late motherhood.

Egg freezing was initially used as an intervention for iatrogenic ovarian insufficiency. Nowadays, it is not considered an experimental procedure, and it is increasingly popular among healthy women who wish to maintain their reproductive potential (fertility preservation). This review summarises the evidence on egg freezing technology, reproductive outcomes and long-term effects, as well as its psychological and socioeconomic implications. Egg freezing technology is advancing, with vitrification being the current method of choice, due to its effectiveness. The reproductive outcomes following egg freezing appear to be promising, though the strong negative association with maternal age has to be taken into consideration. Unfortunately, data on long-term outcomes are missing, raising safety issues. Egg freezing has several socioeconomic implications involving health risks, as well as financial and psychological factors.

Thyroid function and autoimmunity during ovarian stimulation for intracytoplasmic sperm injection.

The aim of the present study was to assess changes in thyroid function and thyroid autoimmunity (TAI) throughout ovarian stimulation (OS) for intracytoplasmic sperm injection (ICSI) and the association of these changes with ICSI outcome. A flexible gonadotrophin-releasing hormone (GnRH) antagonist protocol was used in 42 women and their thyroid function and TAI were assessed at baseline and five times during OS (Days 3 and 5 of the menstrual cycle, the day of hCG administration, the day of ovum pick-up and the day of the pregnancy test). The primary outcome measure was the change in thyroid function throughout OS. No overall change was recorded in thyrotropin-stimulating hormone (TSH) concentrations throughout OS (P=0.066). In women who became pregnant (n=8), an increase in TSH concentrations was noted on the day of the pregnancy test compared with Day 3 of the menstrual cycle (3.410±1.200 vs 2.014±0.950µIU mL-1, respectively; P=0.001; mean ± s.d.). TAI was present in 11 of 42 women. Biochemical pregnancy was negatively correlated with changes in TSH (r=-0.7, P=0.004). No such association was noted regarding the live birth rate. The present study provides evidence that TSH concentrations could increase during OS, especially in women who become pregnant.

Immunohistochemical expression pattern of metastasis suppressors KAI1 and KISS1 in endometriosis and normal endometrium.

OBJECTIVE: To analyze the expression pattern of metastasis suppressors KAI1 and KISS1 in the endometrium of patients with and without endometriosis. STUDY DESIGN: In this pilot study, tissue samples were prospectively collected from 38 patients with endometriosis and 29 without endometriosis, undergoing operative laparoscopy in the proliferative phase of the menstrual cycle; diagnosis or absence of endometriosis was confirmed histologically. Protein expression of KAI1 and KISS1 were analyzed immunohistochemically in endometriotic lesions and the eutopic endometrium of patients with endometriosis and without endometriosis. RESULTS: KAI1 expression was significantly decreased in the glandular eutopic endometrium of endometriosis patients as compared with that of patients without endometriosis (p=0.008). On the other hand, in endometriosis patients, KAI1 expression was significantly increased in the ectopic as compared with the eutopic endometrial stroma (p=0.021). There were no other significant differences in KAI1 expression between different groups. KISS1 expression in the ectopic glandular endometrium was significantly increased as compared with the eutopic glandular endometrium from patients with (p=0.004) and without endometriosis (p=0.008). There was no significant difference in KISS1 protein expression in the stromal endometrium between the three groups. CONCLUSIONS: KAI1 and KISS1 are implicated in the pathogenesis and maintenance of endometriosis. Future studies should investigate whether KAI1 and KISS1 could be used as markers for early and minimally invasive detection of endometriosis based on their differential protein expression pattern in the eutopic endometrium of patients with and without endometriosis.

Endometriosis and ovarian cancer risk: a systematic review of epidemiological studies.

BACKGROUND: A possible etiological association between endometriosis and ovarian cancer has been repeatedly reported in the literature. OBJECTIVE: Our aim was to evaluate published epidemiological data on this issue. REVIEW METHODS: We conducted an extensive search of the literature in MEDLINE, of articles ever published until February 2014, using the key-words "endometriosis" and "ovarian" and one of the following terms in the title: "cancer" or "malignancy" or "malignant" or "tumor" or "neoplasia" or "neoplasm" or "transformation." Retrieved papers were checked for further relevant publications. RESULTS: Overall, our search yielded 1 prospective cohort study, 10 retrospective cohort, and 5 case-control studies. A meta-analysis of these studies was not considered to be appropriate, due to differences in data reporting, study design, and adjustment for confounding factors. LIMITATIONS: The main limitation of studies found, with one exception, was the lack of operative confirmation of endometriosis. CONCLUSION: An association of endometriosis with clear-cell and endometrioid ovarian cancer was a consistent finding in most studies. On the other hand, existing epidemiological evidence linking endometriosis with ovarian cancer is insufficient to change current clinical practice. Prospective cohort studies, with prior laparoscopic confirmation, localization, and staging of endometriosis are needed, in order to further clarify this issue.

Prediction of maternal and neonatal adverse outcomes in pregnant women treated for hypothyroidism.

OBJECTIVE: To examine whether the concentrations of maternal serum TSH and free thyroxine (fT4) through pregnancy, the presence of thyroid autoimmunity (TAI) or the dose of levo-thyroxine (LT4) replacement can predict the occurrence of maternal or fetal/neonatal complications in pregnant women treated for maternal hypothyroidism. DESIGN: The study included 92 women with singleton pregnancies and primary hypothyroidism on LT4 replacement. Maternal serum TSH, fT4, thyroid auto-antibodies and doses of LT4 were monitored throughout pregnancy. All maternal and fetal/neonatal complications were recorded. RESULTS: The overall prevalence of maternal and neonatal complications was 24.1%. Neither maternal TSH/fT4 concentrations, presence of TAI nor dose of LT4 could predict the occurrence of complications. Pre-pregnancy body mass index (BMI) was higher in women who developed maternal complications [odds ratio (OR) 1.3, 95% confidence interval (CI) 1.1-1.5, p=0.007) and gestational week at delivery was lower in pregnancies complicated by neonatal (OR 0.5, 95% CI 0.3-0.8, p=0.001) or any type of complications (OR 0.6, 95% CI 0.4-0.9, p=0.008). CONCLUSIONS: The occurrence of maternal or fetal/neonatal complications in pregnant women treated for hypothyroidism cannot be predicted by maternal TSH/fT4 through pregnancy, presence of TAI or dose of LT4 replacement.

Serum inhibin-B and follicle stimulating hormone as predictors of the presence of sperm in testicular fine needle aspirate in men with azoospermia.

OBJECTIVE: Inhibin-B (Inh-B) is produced by Sertoli cells and controls Follicle Stimulating Hormone (FSH) secretion through a negative feedback mechanism. The primary aim of this study was to compare Iotanh-B with FSH as predictors of the recovery of sperm in testicular fine needle aspirate in men with azoospermia. DESIGN: In 51 men with azoospermia basal values of Luteinizing Hormone (LH), FSH, prolactin and testosterone as well as Inh-B values before and 24 h and 48 h after the administration of 300 IU recombinant human FSH were determined. Testicular Fine Needle Aspiration (FNA) was also carried out. Thirty-one young healthy men were also enrolled in the study as controls. RESULTS: There was significant difference between men with azoospermia and controls with regard to the basal Inh-B levels [median (interquartile range) 37.2 (36) vs. 103.0 (90) pg/mL, respectively, p=0.003] but not to the stimulated Inh-B levels [40.5 (41) vs. 73.0 (44) pg/mL, p=0.113 at 24 h and 34.3 (34) vs. 82.0 (50) pg/mL, p=0.098 at 48 h)]. The Area Under Curve in Receiver Operating Characteristic curves were similar for Inh-B and FSH (0.610 vs. 0.716, respectively, p=0.151) as far as prediction of sperm retrieval is concerned. CONCLUSIONS: Basal serum Inh-B values are significantly lower in men with azoospermia compared to controls. However, Inh-B is not superior to FSH in predicting the presence of sperm in testicular fine needle aspirate.

Genome-wide microarray gene expression, array-CGH analysis, and telomerase activity in advanced ovarian endometriosis: a high degree of differentiation rather than malignant potential.

The aim of the present study was to investigate whether endometriosis and cancer share common molecular characteristics. Tissue samples were collected prospectively during diagnostic laparoscopy of patients with primary infertility. Using high-density oligonucleotide microarrays, (Affymetrix Gene Chip HG-U133 Set) the genome-wide gene expression profile of advanced ovarian endometriosis was analyzed compared with matched normal endometrium. Expression of TERT, the gene encoding the telomerase reverse transcriptase subunit, and telomerase activity were analyzed in eutopic and ectopic endometrium. Genome-wide, high-resolution array-CGH was used to screen for genomic aberrations in endometriosis. Expression microarray data were validated quantitatively with RT-PCR. The genes RARRES1 and RARRES2 (retinoic acid receptor responder 1 and 2) were found to be up-regulated in endometriosis, suggesting a high degree of differentiation. Consistently, down-regulated genes included those involved in the cell cycle, cell metabolism and homeostasis. Expression of TERT and telomerase activity were present in eutopic but absent in ectopic endometrium. Array-CGH revealed a normal genomic pattern without gross amplifications and deletions. In conclusion, these data suggest that advanced ovarian endometriosis represents a highly differentiated tissue with minimal or no malignant potential.