Different Forms Of Endometriosis Research Articles

Deep endometriosis – impact on infertility, endometriosis fertility index, and reproductive prognosis (comparative study)

Introduction Deep infiltrating endometriosis (DIE) is the most severe form of endometriosis, contributes to pelvic pain syndrome, extragenital symptoms, fertility problems, and diminished reproductive prognosis for affected individuals. It is recommended to use the Endometriosis Fertility Index (EFI) to assess reproductive prognosis and conduct clinical research to compare reproductive prognosis in different forms of endometriosis. Objective Comparison of the impact of the DIE and others forms of endometriosis on EFI, patients' fertility and on reproductive prognosis to understand the management approach. Materials and methods A cohort study included 190 reproductive-age women, divided according to the #Enzian classification: the main group - 85 patients with DIE, the control group - 105 women with other forms of endometriosis. The EFI was utilized for reproductive prognosis. Pain was evaluated with Visual Analog Scale (VAS). Statistical analyses were performed using SPSS, with calculation of the Mann-Whitney U and Pearson's chi-square test (χ²). Results In main group, the frequency of infertility was 83.5% compared to the control group's 71.4% (p > 0.05). The EFI in main group was 7.18±0.25 points vs the control group's 7.13±0.28 points (p = 0.852). Patients in the main group suffered from intense pelvic pain (>7 points by the VAS, p < 0.01), including severe dyspareunia (7.85±0.33 points vs 2.18±0.46 points in control group, p < 0.01). Conclusions Our results suggest that infertility in women with DIE may be more often associated with sexual abstinence due to significant dyspareunia rather than organic impairments. Thus, EFI in patients with DIE does not reflect all aspects of infertility and has reservations, and consideration of both physical symptoms and sexual health is crucial in managing DIE to optimize fertility outcomes. These findings open the way to the feasibility of surgical treatment of DIE to improve sexual quality of life, which will reduce the need for IVF and increase the chances of spontaneous pregnancy in patients, but this conclusion requires further investigation in randomized clinical trials.

Сравнение профиля сывороточных аутоантител у женщин при разных формах эндометриоза

Сравнение профиля сывороточных аутоантител у женщин при разных формах эндометриоза

Magnetic resonance imaging for non-invasive diagnosis of various forms of endometriosis in women with infertility

BACKGROUND: Endometriosis is one of the most common causes of infertility, affecting approximately 6%10% of women of reproductive age. For many decades, laparoscopic surgery has been considered the gold standard for diagnosing various forms of endometriosis. However, diagnostic laparoscopy, despite its widespread use, is an invasive and expensive procedure with certain risks. Current scientific literature increasingly shows that the methods of radiological diagnosis (ultrasound and magnetic resonance imaging [MRI]) are the main and most promising for verification of endometriosis. The advantages of MRI over ultrasound are multiplanar images, high tissue contrast, and smaller size of detectable heterotopias.
 AIM: To assessing the sensitivity and specificity of MRI for diagnosing different forms of endometriosis.
 METHODS: A retrospective analysis of the medical histories and instrumental studies of 129 women of reproductive age (mean age of the participants was 30.54.6 years) with a clinical diagnosis of infertility and suspected genital endometriosis was conducted. At the first stage of the study, the patients underwent a comprehensive MRI with one-stage magnetic resonance hysterosalpingography to assess the pelvis and tubal patency. Further, laparoscopic surgery (LS) was performed to confirm/refute the diagnosis of genital endometriosis, provide surgical treatment, or further search for possible causes of infertility. The results obtained with MRI and LS were compared, and the sensitivity and specificity of MRI for diagnosing external and internal genital endometriosis were assessed.
 RESULTS: According to the data obtained, the specificity of MRI for diagnosing peritoneal endometriosis was 74% (95% confidence interval [CI], 57%85%), and the sensitivity was 94% (95% CI, 87%99%). Diagnostic accuracy of the technique was 86% (95% CI, 79%91%). The most frequent localization of endometrioid heterotopias was retrocervical (41%). The specificity of this technique for diagnosing endometrioid ovarian cysts was 92% (95% CI, 82%97%), and the sensitivity amounted for 98% (95% CI, 90%100%). Diagnostic accuracy of the technique was 94% (95% CI, 88%96%). The specificity and sensitivity of MRI for the diagnosis of adenomyosis were 96% (95% CI, 92%99%) and 99% (95% CI, 87%100%), respectively. Diagnostic accuracy of the technique was 97% (95% CI, 93%99%). Our results were consistent with the literature data on the accuracy of MRI for diagnosing endometriosis.
 CONCLUSIONS: Based on the results, MRI is a promising non-invasive method for diagnosing various forms of endometriosis. The performance of a comprehensive MRI allows obtaining sufficiently accurate information about the condition of the pelvic organs, detecting the manifestations of genital endometriosis, and reducing the time for examining women with infertility.

Expression of ZEB1 in different forms of endometriosis: A pilot study

ObjectivesEpithelial-Mesenchymal Transition (EMT), a cellular process in which epithelial cells lose epithelial characteristics while acquire mesenchymal features, is believed to contribute to migration and invasion abilities of the endometriotic cells. Studies on gene expression of the transcription factor ZEB1, a crucial transcription factor of EMT, show that there is probably a modified expression in the endometriotic lesions.The aim of the study was to compare the expression levels of ZEB1 in types of endometriotic lesions with different biological behavior such as endometriomas and deep infiltrating endometriotic nodules. Study DesignWe have studied 19 patients with endometriosis and 8 patients with benign gynecological lesions without endometriosis.The endometriosis patient group included 9 women with only endometriotic cysts without deep infiltrating endometriotic lesion (DIE) and 10 women with DIE who had developed concurrent endometriotic cysts.The technique applied to investigate ZEB1 expression levels is Real-Time PCR. The results of the reaction were normalized by simultaneously investigating the expression of the house-keeping gene G6PD. ResultsAnalysis of the samples showed underexpression of ZEB1 in the eutopic endometrium of women with only endometriotic cysts when compared to normal endometrium. A tendency of higher ZEB1 expression, without reaching significant difference, was found between the endometriotic cysts and their paired eutopic endometrium.In women with DIE, no significant difference was found between their eutopic and normal endometrium. No significant difference was found between the endometriomas and DIE lesions.ZEB1 shows different expression profile in the endometriotic cysts of women with and without DIE when the cyst is compared to their paired eutopic endometrium. ConclusionsIt therefore appears that ZEB1 expression differs between different types of endometriosis. The expression levels of ZEB1 in the eutopic endometrium could affect the development of infiltrating lesions or not. However, the most important observation is the different ZEB1 expression profile of endometriomas between women with and without DIE. Although, they both share the same histologic characteristics, they show different ZEB1 expression indicating different pathogenetic mechanisms of endometriomas in cases with and without DIE. Therefore, future research on endometriosis should consider DIE and ovarian endometriosis as different diseases.

MiR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis.

Micro-RNAs expression can vary between different forms of endometriosis, but data on miRNA expression in cesarean scar endometriosis is lacking. The present study is comprised of 30 patients with endometriosis in the cesarean scar (scar endometriosis, SE), 14 patients with deep infiltrating endometriosis (DIE), 47 patients with endometrioma (ovarian endometrial cyst, OE), and 33 patients with healthy ovarian tissue as the control group (CG). In the initial experiment to identify possible dysregulated miRNAs, the levels of 754 miRNAs in formalin-fixed paraffin-embedded tissue (FFPE) samples from OE, high-grade ovarian cancer, endometrioid ovarian cancer, and CG were measured. We identified seven potentially dysregulated miRNAs: miR-1-3p, miR-31-3p, miR-125b-1-3p, miR-200b-3p, miR-548d, miR-502, and miR-503. We then examined the expression profiles of each of these miRNAs individually in the SE, DIE, OE, and CG FFPE samples using RT-qPCR. miR-31-3p had significantly higher levels of expression and miR-125b-1-3p had significantly lower levels of expression in SE compared to the controls. Overall, the higher expression levels of miR-31-3p and the lower expression levels of miR-125b-1-3p are consistent with the benign nature of SE. Importantly, the results of the present study demonstrate the possibility of using miRNA to monitor the risk of malignant transformation of endometriosis tissue.

Insights from genomic studies on the role of sex steroids in the aetiology of endometriosis.

Endometriosis is a chronic neuro-inflammatory disorder the defining feature of which is the growth of tissue (lesions) that resembles the endometrium outside the uterus. Estimates of prevalence quote rates of ~10% of women of reproductive age, equating to at least 190 million women world-wide. Genetic, hormonal and immunological factors have all been proposed as contributing to risk factors associated with the development of lesions. Twin studies report the heritable component of endometriosis as ~50%. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that appear over-represented in patients with endometriosis, particularly those with more extensive disease (stage III/IV). In different sample populations, there has been replication of SNPs near genes involved in oestrogen and other steroid regulated pathways including ESR1 (oestrogen receptor alpha), GREB1, HOXA10, WNT4 and MAPK kinase signalling. Comparisons with GWAS conducted on other patient cohorts have found links with reproductive traits (age at menarche) and disorders (fibroids, endometrial and ovarian cancer) and common co-morbidities (migraine, depression, asthma). In summary, genetic analyses have provided new insights into the hormone-regulated pathways that may contribute to increased risk of developing endometriosis some of which may act in early life. New studies are needed to clarify the relationship between the many SNPs identified, the genes that they regulate and their contribution(s) to development of different forms of endometriosis. We hope that more advanced methods allowing integration between GWAS, epigenetic and tissue expression data will improve risk analysis and reduce diagnositic delay.Lay summaryEndometriosis is a debilitating reproductive disorder affecting ~10% of reproductive-age women, and those assigned female at birth, which causes a range of symptoms including chronic pain and infertility. The reason why some, but not all these individuals, develop the lesions that characterise the disease are poorly understood, but recently attention has focused on genetic risk factors to explain why the incidence is higher in some families. Studies on large cohorts of patients with comparison of their DNA to women without endometriosis or with other disorders have documented changes in genes associated with steroid hormone production or action. The results provide further evidence that endometriosis shares genetic risk factors with other disorders of the reproductive system and a platform for new ideas related to risk, biomarkers and therapies.

Features of pain syndrome in genital endometriosis and migraine

Migraine is often concurrent with endometriosis; however, the mechanisms of comorbidity of these conditions are inadequately studied. Pain is considered as the most significant clinical symptom and maladaptive manifestation of both migraine and endometriosis. Studying the relationship between the clinical manifestations of pain syndrome in patients with endometriosis and migraine is important, since it will contribute to the understanding of the mechanisms of comorbidity of these diseases.Objective: to analyze the features of pain syndrome in patients with migraine and genital endometriosis to clarify the neurogenic mechanisms of their comorbid relationship.Patients and methods. A total of 125 patients who had gone to a gynecologist for endometriosis were examined for the presence of migraine. In accordance with the inclusion criteria, 79 patients (mean age, 34.68±7.11 years) with genital endometriosis confirmed by diagnostic laparoscopy participated in the further study. Two age-matched groups were formed: a study group consisted of 38 patients with endometriosis and concomitant migraine; a comparison group included 41 patients with endometriosis without migraine. All the patients underwent clinical neurological examination, questionnaire survey, pelvic ultrasound, assessment of the severity of pelvic pain according to the pelvic pain index, and determination of the level of central sensitization (CS) using the CS Inventory.Results and discussion. 42% out of the 125 patients who had visited their gynecologist for endometriosis suffered from concomitant migraine, which confirms the comorbidity of these diseases. Chronic pelvic pain (CPP), dysmenorrhea, dyspareunia, and dyschesia were more common in patients with endometriosis and migraine; there were more patients with asymptomatic endometriosis in the comparison group. The patients of the two groups did not differ in the presentation of different forms of endometriosis, which favors the leading role of central mechanisms in the pathogenesis of pain syndrome in comorbidity of these diseases.In addition, there was a statistically significant increase in the presentation of CPP and dysmenorrhea in patients with chronic migraine compared to those with episodic migraine and to those without migraine. Significantly higher levels of CS according to CSI and pelvic pain index were found in patients with chronic migraine and endometriosis, which suggests that CS plays a key role in the comorbidity of these diseases.Conclusion. The phenomenon of CS is one of the mechanisms of comorbidity of migraine and endometriosis, contributes to both the worsening of various painful manifestations of endometriosis and the increase in migraine attacks, thereby causing obvious maladaptation in patients. The role of CS in the comorbidity of migraine and endometriosis opens up possibilities for the elaboration of a comprehensive interdisciplinary approach to treating these diseases.

Adolescence and endometriosis: symptoms, ultrasound signs and early diagnosis

To evaluate the ultrasonographic presence of different forms of endometriosis and the associated clinical symptoms in adolescent women. Retrospective observational study. University hospital. Two hundred and seventy women aged 12-20 years referred to the gynecologic ultrasound unit from January 2014 to June2019. Two-dimensional, three-dimensional, and power Doppler ultrasound (US) pelvic examination (transvaginal or transrectal in pre-sexually active adolescents) were performed in all included adolescents. Medical history was collected for each patient before the scan. All possible locations of endometriosis evaluated and recorded using a dedicated ultrasound mapping sheet and severity of painful symptoms evaluated through a visual analogue scale (VAS). Dysmenorrhea was detected in 147 (54.4%) of 270 patients and heavy menstrual bleeding in 76 (28.1%) of 270. At least one ultrasound feature of endometriosis was identified in 36 (13.3%) of 270 cases. Ovarian endometriomas were found in 22 (11%) patients, adenomyosis in 16 (5.2%), and deep infiltrating endometriosis (DIE) in 10 (3.7%). Ultrasound signs of endometriosis were found in 21% of adolescents who reported dysmenorrhea and 33% with dyspareunia. The presence of DIE at ultrasound was associated with bowel symptoms in 33% of patients and associated with dyspareunia in 25% of patients. The detection rate of pelvic endometriotic lesions at ultrasound was 13%. The rates of dysmenorrhea, dyspareunia and heavy menstrual bleeding in adolescents with endometriosis ultrasound signs were statistically significantly higher compared with those without. In patients with dysmenorrhea, the detection rate of pelvic endometriosis at ultrasound increased to 20%. Professionals involved with teens should be aware of the clinical presentation of endometriosis to reduce the delay between the onset of symptoms and the diagnosis, referring these young women to dedicated centers.

Role of magnetic resonance tomography in diagnosis of genital endometriosis among women of reproductive age

Aim. To estimate the informativity of the technique of magnetic resonance tomography (MRT) of pelvic organs in diagnosis of genital endometriosis in women of reproductive age.
 Materials and methods. The results of pelvic organs MRT from 415 women aged 1845 years were analyzed. The examination was implemented using the apparatus Philips Intera 1.5 Tl. The method of copying the results of MR-investigations was used to receive the data on localization, degree of dissemination of endometriosis foci and concomitant diseases of female reproductive system, which were later compared with the results of the existing echographic studies of pelvic organs.
 Results. The study demonstrated higher informativity of magnetic resonance tomography in diagnosis of different forms of endometriosis and gynecological pathology associated with it, unlike echography. Out of 415 women, who underwent magnetic resonance tomography of pelvic organs, endometriosis was diagnosed in 20 % of the examined women, while echographic study only in 4 %. When implementing ultrasound, the signs of malignant neoplasms of the uterine neck and ovaries were not detected in a part of patients, whereas revealed with MRT of pelvic organs and further confirmed by the results of histological studies.
 Conclusions. Application of magnetic resonance tomography permits to improve significantly diagnosis of endometriosis that is important for determination of adequate tactics of treatment, taking into account the existing concomitant gynecological pathology.

Serum concentrations of CCL20/MIP-3alpha in women with endometriosis.

IntroductionEndometriosis is a chronic disease defined by the presence of uterine mucosa outside the uterine cavity. Abnormal levels of cytokines, growth factors, adhesion molecules and metalloproteinases have been found in patients with endometriosis. A review of the literature revealed no papers on CCL20 serum levels in women with endometriosis.Material and methodsThe study included 32 women who underwent laparoscopy in the Polish Mother’s Memorial Hospital-Research Institute, Lodz, Poland. Patients were divided into 2 groups: the study and control group. The study group was divided into three subgroups according to endometriosis form. Twenty patients were included in the study group and 12 patients acted as controls. CCL20 concentrations value were determined using a quantitative sandwich ELISA kit (R&D Systems). Results were statistically analyzed by SPSS STATISTICS 24.0.0 software. A significance level of 0.05 was used.ResultsThe mean serum level of CCL20 in the study group was 7.4 pg/ml. In controls the mean value was 10.95 pg/ml. The concentration of CCL20 was statistically significantly lower in the study group than in controls (p = 0.004). Within the study group the highest values were reported in patients with endometrial ovarian cysts (8.55 pg/ml), intermediate in the DIE subgroup (8.24 pg/ml) and the lowest in patients with peritoneal endometriosis (6.74 pg/ml). Differences between subgroups were not statistically significant (p = 0.385).ConclusionsOur study revealed statistically significantly decreased CCL20 serum levels in women with endometriosis. No significant differences of CCL20 serum levels between patients with different forms of endometriosis were observed.

Features of pain syndrome in women with different forms of endometriosis

The objective: to assess the type and intensity of pain in women with different endometriosis forms. Materials and methods. The research included 65 women with diagnosis of external genital endometriosis who formed I group. 38 patients with internal genital endometriosis consisted II group. Control group involved 30 persons of reproductive age without diagnosis of genital endometriosis. Visual Analogue Scale (VAS) was used to determine intensity of pain. Results. Chronic pelvic pain was more typical for patients in II group than in I (χ2=12.11; p<0.001). Also 69.23% women in I group and 86.84% in II suffered from dysmenorrhea, 43.08% and 42.11% respectively – from dyspaurenia, 10.77% and 15.79% – from dyschezia. 57.89% women in II group complained of pain which was not connected with menstrual cycle that was more often, than in I group (χ2=4.73; p=0.03). 10.77% patients with external genital endometriosis had no complaints against none women with internal endometriosis. According to VAS results mild (43.08%) and moderate (46.15%) pain was more often by external endometriosis. Only 10.77% of persons in I group indicated on severe pain. While, by internal endometriosis quantity of women with mild and moderate pain was less than by external one (28.95% and 36.84% respectively) and one third of individuals in this groups suffered from severe pain (34.21%; χ2=6.98; p=0.008). Conclusion. Pain syndrome is the typical clinical manifestation in women with endometriosis. Type of pain, its intensity is more severe by internal genital endometriosis than by external one. Key words: endometrios, pain, assessment.

Ovarian endometriosis and fertility preservation: a challenge in 2018.

Endometriosis is a benign, estrogen-dependent gynecological disorder. It is now well established that three different forms of endometriosis can occur in the pelvic cavity, namely peritoneal endometriosis, ovarian endometriosis and deep endometriotic nodules of the rectovaginal septum. Treatment of endometriosis-associated infertility has been investigated using both medical and surgical modalities. Surgery for ovarian endometriosis can lead to premature ovarian insufficiency (POI) and further infertility, so one of the most important goals of therapy should be preserving fertility. Procedures combining stripping and ablation should be considered the first-line approach for ovarian endometrioma-related infertility, in order to protect the ovarian reserve, which may already be depleted even before surgery. Autotransplantation of ovarian tissue should be considered in case of mandatory radical treatment (oophorectomy), or if conservative treatment poses a risk. For patients at risk of POI, particularly those undergoing gonadotoxic treatment, two main fertility preservation options exist: oocyte vitrification or reimplantation of fresh or frozen ovarian tissue. Both have advantages and disadvantages.

The clinical manifestations and anamnestic risk factors of different forms of endometriosis in Russian women: subgroup analyses in the framework of the international study FEELING

The clinical manifestations and anamnestic risk factors of different forms of endometriosis in Russian women: subgroup analyses in the framework of the international study FEELING

The clinical manifestations and anamnestic risk factors of different forms of endometriosis in Russian women: subgroup analyses in the framework of the international study FEELING

The clinical manifestations and anamnestic risk factors of different forms of endometriosis in Russian women: subgroup analyses in the framework of the international study FEELING

Classifications of endometriosis

In the article a review of the main classifications of endometriosis is presented. Main drawbacks of existing classifications have been revealed. A need for a new classification of the disease, which has to be empirical, evidence-based, containing terms that have unambiguous definitions, applicable for various clinical situations, taking into account new clinical forms and able to predict a course of the disease (including the development of pain syndrome and infertility), it’s outcomes and a risk of recurrence is stressed. The new classification of endometriosis has to be based on resolutions of a consensuses and applicable for new guidelines for diagnosis and treatment. For the new classification it is essential to be approachable and easy-to-use in routine clinical practice. It has to allow a physician to determine a stage the disease promptly and meaningfully. A new Protocol taking into account a combination of different forms of endometriosis (superficial, deep infiltrative, adenomyosis, endometriomas, extragenital), color of endometriotic lesions, special aspects of clinical course, results of hormonal examination, reproductive plans and prior hormonal therapy is proposed.

From Endometriosis to Pregnancy: Which is the “Road-Map”?

In the last decade, pregnancy was considered as a therapeutic period for patients affected by endometriosis and painful symptoms. However, several studies have taken into consideration how endometriosis affects pregnancy achievement and pregnancy development, including obstetric complications. The adverse effects of endometriosis on the development of pregnancy include miscarriage, hypertensive disorders and pre-eclampsia, placenta previa, obstetric hemorrhages, preterm birth, small for gestational age, and adverse neonatal outcomes. The aim of this review is to analyze the current literature regarding the relationship between different forms of endometriosis (endometrioma, peritoneal endometriosis, deep endometriosis) and infertility, and the impact of endometriosis on pregnancy outcomes.

The combination of endoscopic techniques in the diagnosis and treatment of various forms of infertility in women

To improve the methods of simultaneous laparoscopy and hysteroscopy for the diagnosis and treatment of various forms of secondary infertility. 420 women with various forms of infertility were examined and treated at the Caspian Hospital (Institute of Obstetrics and Gynecology). Patients were divided into three groups: tubal-peritoneal infertility - 212 women, different forms of endometriosis - 113 patients, polycystic ovarian disease - 95 women. We proposed safer method of laparoscopic surgery. There were no injuries of internal organs and bleeding from the puncture site if Veress needle and the first 'blind' trocar were deployed according to proposed method. We consider that choice of operative hysteroscopy technique should be differentiated in case of benign gynecological diseases. Anesthesia-free operative hysteroscopy by S. Bettocchi may be performed if diagnostic hysteroscopy is tolerable. Simultaneous laparoscopy and hysteroscopy are safe for patients.

Different Expression of Hypoxic and Angiogenic Factors in Human Endometriotic Lesions.

Endometriosis is associated with local angiogenic and hypoxic mechanisms. Indeed, peritoneal fluid of women with endometriosis generates a specific microenvironment to support the growth and development of ectopic endometrial tissues. The association between proangiogenic markers and hypoxic processes in different endometriosis phenotypes was investigated in the present study, analyzing the expression of several genes, related to hypoxic signaling pathway and involved in angiogenic processes, in nonpregnant women with different forms of endometriosis. Samples of ovarian endometrioma (OMA; n = 16) or deep infiltrating endometriosis (DIE; n = 11) were collected, and in addition, control endometrium was collected from healthy women by hysteroscopy. The gene expression of the hypoxia-inducible factors (HIF) 1/2α, protease-activated receptors (PARs) ¼, and vascular endothelial growth factor (VEGF) A was evaluated by quantitative reverse-transcription polymerase chain reaction. Ovarian endometrioma expresses high levels of HIF-1/2α, PAR-1/4, and VEGF-A, while DIE did not show significantly different gene expression compared to endometrium from unaffected women. A positive correlation between the expression of HIF-1/2α and VEGF-A mRNA was observed in OMA. The overall data point out that the heterogeneity of the disease reflects differences in expression levels of genes associated with hypoxia and angiogenesis, suggesting that such conditions may have an active role in the development of the disease.

The management of patients with combination of different forms of endometriosis (a case report)

The management of patients with combination of different forms of endometriosis (a case report)

Detection of proliferative potential in ectopic endometrium in women with different forms of endometriosis

To investigate the proliferative potential in ectopic endometrium was determined by immunohistochemistry the expression of proliferating cell nuclear antigen (PCNA), which is considered a factor in the growth of tumors. In ectopic endometrium also determined the expression of carcino-embryonic antigen (CEA), which is considered a predictor of malignancy of tumors.Histological examination of extirpation uterus was conducted in 35 women of first groups with internal endometriosis, the second group consisted of 52 patients with external endometriosis and the third group consisted of 19 patients with extragenital endometriosis, which was performed resection of endometriosis lesions.The study revealed that the majority of endometrial ectopia was CEA-negative, on the basis of which we can speak of a low propensity to malignancy potential of all forms of endometriosis.Lack of expression of CEA in all patients with extragenital endometriosis may indicate the lowest probability of malignant transformation of endometrioid heterotopias is in their extragenital localization