Applicability and Suitability of the Embryological-Clinical Classification of Female Genital Malformations: A Systematic Review.

Complex urogenital malformations are clinically highly relevant; thus, they must be appropriately diagnosed and classified before initiating treatment. Background/Objectives: This study aimed to evaluate the applicability and suitability of the embryological-clinical classification of female genital malformations. Methods: A systematic review of cases of genital malformations reported in the literature from 2000 to 2020 was conducted. Case reports and series with the following combinations: "female genital tract" AND (malformation OR anomaly OR müllerian anomaly OR uterine anomaly OR cervical anomaly OR vaginal anomaly OR cloacal anomaly OR urogenital sinus); and "female genital tract" AND (renal agenesis OR ectopic ureter) were searched. A total of 3124 articles were identified, of which 824 cases of genital malformation were extracted. The characteristics of each malformation were included in a database for further analyses. Results: Using the embryological-clinical classification, 89.9% of the published cases and 86.5% of the 52 cases defined as unclassifiable by their authors have been classified in this review. In 73 cases (72.2%), the classification of the malformation using the AFS system was incomplete because although the type of uterine anomaly of the AFS classification matched that of the embryological-clinical classification, characteristics of the urinary system or the vagina were overlooked when using the AFS system. Following a dispersion matrix, we have been able to show that the embryological-clinical classification system is able to classify and subclassify the genitourinary malformations more accurately. Conclusions: The applicability of the embryological-clinical classification has been confirmed after classifying most of the cases of genital malformation previously published. This system also provides a more complete and accurate classification than other classifying systems exclusively based on Müllerian duct development or uterovaginal parameters, demonstrating its suitability.

Anastrozole and levonorgrestrel-releasing intrauterine device in the treatment of endometriosis: a randomized clinical trial.

BACKGROUND: To study the effectiveness of an aromatase inhibitor (Anastrozole) associated with levonorgestrel-releasing intrauterine device (LNG-IUD, Mirena®) in the treatment of endometriosis. METHODS: Prospective, randomized clinical trial. SETTING: University Hospital (single center). Elegibility criteria: Endometriomas > 3 × 4 cm, CA-125 > 35 U/mL and endometriosis symptoms. PATIENTS: Thirty-one women randomized to anastrozole + Mirena® + Conservative Surgery(CS) (n = 8), anastrozole + Mirena® + transvaginal ultrasound-guided puncture-aspiration (TUGPA) (n = 7), Mirena® + CS (n = 9), or Mirena® + TUGPA (n = 7). INTERVENTIONS: Anastrozole 1 mg/day and/or only Mirena® for 6 months; CS (ovarian and fertility-sparing) or TUGPA of endometriomas one month after starting medical treatment. MAIN OUTCOME MEASURES: Visual analogic scale for symptoms, CA-125 levels, ultrasound findings of endometriomas and recurrences. RESULTS: A significant improvement in symptoms during the treatment (difference of 43%, 95% CI 29.9-56.2) occurred, which was maintained at 1 and 2 years. It was more significant in patients including anastrozole in their treatment (51%, 95% CI 33.3-68.7). For CA-125, the most significant decrease was observed in patients not taking anastrozole (73.8%, 95% CI 64.2-83.4 vs. 53.8%, 95% CI 25.7-81.6 under Mirena® + anastrozole). After CS for endometriosis, a reduction of ultrasound findings of endometriomas and long-term recurrence occurred, with or without anastrozole. At 4.2 ± 1.7 years (95% CI 3.57-4.85), 88% of the patients who underwent CS were asymptomatic, without medication or reoperation, compared to only 21% if TUGPA was performed, with or without anastrozole (p = 0.019). CONCLUSIONS: Dosing anastrozole for 6 months, starting one month before CS of endometriosis, reduces significantly the painful symptoms and delays recurrence, but has no other significant advantages over the single insertion of LNG-IUD (Mirena®) during the same time. Anastrozole and/or only Mirena® associated with TUGPA are not effective. TRIAL REGISTRATION: Eudra CT System of the European Medicines Agency (London, 29-Sept-2008) Nº EudraCT: 2008-005744-17 (07/11/2008). Date of enrolment of first patient: 15/01/2009.

Long-term outcomes of transvaginal ultrasound-guided aspiration versus traditional conservative surgery as treatment for endometriomas: A retrospective study of cohorts.

AIM: To evaluate if the long-term results (on fertility, need of hysterectomy and persistence of endometriosis) after a minimally invasive intervention (transvaginal ultrasound-guided puncture-aspiration [TUGPA]) for endometriomas are significantly different from performing the traditional conservative surgery (CS) by laparoscopy or laparotomy. METHODS: We performed a retrospective study of cohorts on patients undergoing surgery for ovarian endometriomas between January 1998 and April 2015. Cohort 1 consisted of 75 women whose first intervention for endometriomas had been TUGPA. For the cohort 2, we selected a randomized paired case in which the first operation for endometriomas had been CS by laparoscopic or laparotomy (another set of 75 patients). RESULTS: There were significantly more recurrences and the time to recurrence and repetition of operations were also significantly shorter in patients with TUGPA. However, there were no significant differences in overall pregnancy/delivery outcomes, in hysterectomy performances, or in endometriosis persistence at the last follow-up visit. There were no significant differences related to the symptoms or to analytical presurgical values but the application of multivariate analysis with binary logistic regression to each dependent variable adjusted for age, symptoms, and presurgical analyses showed a significant risk of recurrence and reoperation of TUGPA versus CS. CONCLUSIONS: Those patients with endometriomas who underwent TUGPA (with or without associated medications) had a significant increase in recurrence and the need for reoperation. However, in the long-term there were no significant differences in the results of pregnancy/childbirth, need for hysterectomy, or in the clinical or doubtful persistence of endometriosis.

Classical McIndoe Technique Versus the McIndoe Technique with a Neovaginal PACIENA Prosthesis® and No Skin Graft.

An observational, retrospective study was completed to compare the results of the PACIENA clinical trial (using the modified McIndoe technique) with a historical control group of nine patients who were operated on at San Juan University Hospital (1992-2015) using the classic technique. The PACIENA clinical trial included seven patients with vaginal agenesis who were operated on at two reference sites (May 2017-May 2018) using a neovaginal polylactic acid (PLA) prosthesis (PACIENA® prosthesis) and avoiding the use of a skin graft. The results illustrate a reduction in the length of surgery, 86.43 ± 4.75 min in the group with no skin graft compared to 155.56 ± 28.44 in the control group (p < 0.05); and reduction in the length of hospitalization time. Differences were also registered in the length of the neovagina, the average being 8.93 ± 1.42 cm for cases and 6.56 ± 1.13 cm for controls, with no differences in neovaginal epithelialization times or in the satisfaction of sexual relations occurring between groups. The modification of the classical McIndoe technique using the neovaginal PACIENA® prosthesis appears to be successful, obtaining good clinical results with shorter surgery and hospitalization times.

Disorders of Sex Development: Classification, Review, and Impact on Fertility.

In this review, the elements included in both sex determination and sex differentiation are briefly analyzed, exposing the pathophysiological and clinical classification of disorders or anomalies of sex development. Anomalies in sex determination without sex ambiguity include gonadal dysgenesis, polysomies, male XX, and Klinefelter syndrome (dysgenesis and polysomies with a female phenotype; and sex reversal and Klinefelter with a male phenotype). Other infertility situations could also be included here as minor degrees of dysgenesis. Anomalies in sex determination with sex ambiguity should (usually) include testicular dysgenesis and ovotesticular disorders. Among the anomalies in sex differentiation, we include: (1) males with androgen deficiency (MAD) that correspond to those individuals whose karyotype and gonads are male (XY and testes), but the phenotype can be female due to different hormonal abnormalities. (2) females with androgen excess (FAE); these patients have ovaries and a 46,XX karyotype, but present varying degrees of external genital virilization as a result of an enzyme abnormality that affects adrenal steroid biosynthesis and leads to congenital adrenal hyperplasia; less frequently, this can be caused by iatrogenia or tumors. (3) Kallman syndrome. All of these anomalies are reviewed and analyzed herein, as well as related fertility problems.

Clinical pilot study to evaluate the neovaginal PACIENA prosthesis® for vaginoplasty without skin grafts in women with vaginal agenesis.

BACKGROUND: To evaluate the feasibility and clinical outcomes of vaginoplasties using a neovaginal polylactic acid prosthesis made with 3-dimensional (3D) printing technology as an intraneovaginal mould. METHODS: This was an interventionist, prospective, and multicentre clinical pilot investigation of a sanitary product (PACIENA prosthesis®) aiming to recruit and operate on 8 patients over 6 months with a follow-up period of 6 months. Only six patients with Rokitansky syndrome and one patient with Morris syndrome (7 patients in total) were operated on in two university hospitals: "La Fe", Valencia (H1) and "Arrixaca", Murcia (H2). INTERVENTIONS: Extensive surgical dissection of a defined space between the urethra and bladder in the front and of the rectum in the back as well as insertion of the PACIENA prosthesis® covered with Interceed® were performed. After 12 days, the prosthesis was changed to the silicone-covered version for daily application. RESULTS: In the 6 patients with Rokitansky syndrome (86%), the primary endpoint (satisfactory vaginal outcome in terms of appearance, function, and sensation without relevant additional morbidity) was achieved, although only 2 patients (28%) were sexually active at the end of 6 months of follow-up. The patient with Morris syndrome withdrew from the study after 1 month. Patients without bacterial colonization showed positive Schiller tests at 1 month, and subsequent biopsies showed adequate keratinization and epidermization. Epithelization and iodopositivity were delayed in the patients who developed inflammatory granulomas. CONCLUSIONS: Good anatomical and functional results can be achieved with the PACIENA prosthesis® for vaginoplasties without skin grafts. However, adequate patient selection and education, good surgical techniques and haemostasis, postoperative support, and prevention of bacterial colonization are important. TRIAL REGISTRATION: This clinical study was approved by the Ethical Clinical Investigation Committee of San Juan University Hospital on September 27, 2016, to be conducted in the participating centres; it was authorized by the Spanish Agency of Medicines and Health Products (AEMPS) on April 24, 2017 (exp. no. 585/16/EC), to be carried out in that hospitals.

Endometriosis and ovarian cancer: Their association and relationship.

OBJECTIVES: To study endometriosis-associated borderline or malignant ovarian epithelial tumors by analyzing their differential clinical features, as well as the histological pattern, survival and immunohistochemical data compared with those without associated endometriosis. STUDY DESIGN: Setting: Hospital Marina Baixa and San Juan University Hospital, Alicante, Spain. This retrospective study included clinical and pathological data from 36 operated cases with endometriosis-associated ovarian epithelial tumors and 305 cases of ovarian epithelial tumors without endometriosis, including borderline and invasive tumors. We also studied hormonal receptors and p53 protein expression in 13 cases with endometriosis-associated endometrioid and clear cell tumors, and report two cases with histologically-confirmed previous endometriosis. RESULTS: Associated endometriosis was observed in 10.5% of patients with borderline or invasive ovarian epithelial tumor, 53% of those with endometrioid, and 22% with clear cell tumors. Patients with endometriosis-associated ovarian epithelial tumors were younger, had lower parity, were more frequently premenopausal, had a lower tumor stage or were borderline, and in general had better prognosis and longer survival, although they also more frequently had an associated endometrial carcinoma. Associated endometriosis and endometrioid tumors were generally estrogen-receptor positive, whereas they were negative in the clear cell tumor component. p53 protein positivity was generally observed in clear cell tumors and in associated endometriosis. Two reported cases with previous, known endometriosis were followed in their evolution to borderline endometrioid carcinoma and clear cell carcinoma, respectively. CONCLUSIONS: Our results and review of the literature suggest that the association of ovarian epithelial tumors and endometriosis is a factor for good prognosis for ovarian cancer and that this association might correspond in many cases to an intermediate stage in the development of endometriosis to endometrioid, clear cell, or other invasive carcinomas.

Diagnostic imaging and cataloguing of female genital malformations.

UNLABELLED: To help physicians and radiologists in the diagnosis of female genito-urinary malformations, especially of complex cases, the embryology of the female genital tract, the basis for Müllerian development anomalies, the current classifications for such anomalies and the comparison for inclusion and cataloguing of female genital malformations are briefly reviewed. The use of the embryological system to catalogue female genito-urinary malformations may ultimately be more useful in correlations with clinical presentations and in helping with the appropriate diagnosis and treatment. Diagnostic imaging of the different genito-urinary anomalies are exposed, placing particular emphasis on the anomalies within group II of the embryological and clinical classification (distal mesonephric anomalies), all of them associated with unilateral renal agenesis or dysplasia. Similarly, emphasis is placed on cases of cervico-vaginal agenesis, cavitated noncommunicated uterine horns, and cloacal and urogenital sinus anomalies and malformative combinations, all of them complex malformations. Diagnostic imaging for all these anomalies is essential. The best imaging tools and when to evaluate for other anomalies are also analysed in this review. TEACHING POINTS: • The appropriate cataloguing of female genital malformations is controversial. • An embryological classification system suggests the best diagnosis and appropriate management. • The anomalies most frequently diagnosed incorrectly are the distal mesonephric anomalies (DMAs). • DMAs are associated with unilateral renal agenesis or renal dysplasia with ectopic ureter. • We analyse other complex malformations. Diagnostic imaging for these anomalies is essential.

The presentation and management of complex female genital malformations.

BACKGROUND: Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. METHODS: A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. RESULTS: From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. CONCLUSIONS: Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations.

Epithelial ovarian cancers and endometriosis.

AIMS: To determine the prevalence of endometriosis in epithelial ovarian cancers (EOC) and the association among their histological subtypes and with endometrial carcinoma. METHODS: An observational cohort study performed in 192 patients operated on for EOC, 30 women with atypical endometriosis and 17 with p53 positive endometriosis. Data on associated endometriosis and endometrial carcinomas, histological subtypes, tumor stage, clinical and pathological characteristics and survival were analyzed. RESULTS: Twenty cases of EOC (10.4%) had also endometriosis (12.7 in borderline and 9.3% in invasive cases), being a synchronous finding in most cases. Endometriosis associated with serous or mucinous EOC was observed in 2.2 and 2.7% of cases, respectively. However, this association was observed in 50 of endometrioid and 23% of clear cell EOC. Age, parity and tumor stage were lower in endometriosis-associated EOC patients; and all associated cases were type I (Kurman and Shih's classification) and showed better results in survival rate. Endometrial carcinoma was more frequently associated with endometrioid EOC (25%). CONCLUSIONS: There is a significant association between endometriosis, including atypical forms, and endometrioid and clear cell carcinomas, but not with other EOC histotypes. The presence of endometriosis in EOC suggests a better prognosis and an intermediate stage within the progression endometriosis-carcinoma.

Ovarian teratoma-associated anti-NMDAR encephalitis: a systematic review of reported cases.

The association of ovarian teratoma and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a serious and potentially fatal pathology that occurs in young women and that is under-recognized. Our objectives were to analyze prevalence and outcome of this association, and increase awareness over this pathology. MEDLINE and SCOPUS for all studies published prior to November 30, 2013 including the search terms: "encephalitis" and "teratoma" were considered. All articles (119) reporting one or more cases of anti-NMDAR encephalitis and confirmed ovarian teratoma (174 cases) were included. No language restrictions were applied. Suspicious cases with no evidence of ovarian teratoma (n = 40) and another type of encephalitis also associated to ovarian teratoma (n = 20) were also considered for comparison and discussion. Data of publication and case report, surgery and outcome were collected. The distribution of published cases is heterogeneous among different countries and continents, probably in relation with level of development and health care. The mean patient age is 24 years and in the majority of cases (74%), a mature teratoma was identified, sometimes microscopically following ovarian removal or at autopsy. The clinical presentation featured psychiatric symptoms and behavioural changes, with a median delay for surgery of 28 days. Twelve women died (7%), most frequently from encephalitis-related complications. In conclusion, the association ovarian teratoma and anti-NMDAR encephalitis is relatively unknown or not reported in many countries and among gynecologists. Heightened recognition of behavioral changes, diagnosis through transvaginal ultrasound and subsequent tumor removal in addition to diagnostic confirmation through the presence of anti-NMDAR antibodies must be emphasized.

Large bilateral tubercular pyosalpinx in a young woman with genitourinary malformation: a case report.

INTRODUCTION: Tuberculosis is a chronic infectious disease, and the morbidity associated with it has major health implications. When tuberculosis affects the genital organs of young females, it has the devastating effect of causing irreversible damage to their fallopian tubes, resulting in a possible tubercular pyosalpinx and infertility. However, the disease often remains silent or presents with very few specific symptoms. In adolescents and young women, tuberculosis can also present with hypogastric recurrent symptoms and affectation of the general state, but because in our country genital tuberculosis is uncommon, its diagnosis is unlikely. CASE PRESENTATION: We describe the case of an 18-year-old Spanish woman who had been sexually active for 1 year, nulliparous, who presented with hypogastric discomfort and repeated urinary symptoms complicated with pelvic inflammatory disease after a hysterosalpingography. Genital tuberculosis was not suspected. The echographical findings and tumor markers mimicked those of ovarian tumors, and she was also a carrier of a genitourinary malformation (pelvic kidney and septate uterus). A laparotomy was performed and revealed large pelvic abscesses. On her right adnexum, the large pyosalpinx was free (floating pyosalpinx). Drainage, adhesiolysis and bilateral salpingectomy were performed, and cultures were taken. Histopathological study showed bilateral granulomatous abscessificated salpingitis with suspicion of genital tuberculosis, and cultures were positive for Mycobacterium tuberculosis. She followed a tuberculostatic treatment for 6 months. Eight years later, she presents with normal menstruations and is waiting for an in vitro fertilization cycle. CONCLUSIONS: No other reported case showing similar association of genital tuberculosis and genitourinary malformation was found. The associated genitourinary malformation in this case probably has no relation but it could contribute to diagnosis delay and/or to reactivate the pathology. The hysterosalpingographical findings and the observation of a floating pyosalpinx must alert the clinician to genital tuberculosis, but the diagnosis is suggested by the histopathological studies and confirmed by cultures. In this case study, the necessity of considering the risk of pelvic inflammatory disease reactivation after hysterosalpingography, of suspecting the diagnosis of genital tuberculosis and of establishing the differential diagnosis with ovarian tumors in the presence of large pyosalpinges is highlighted.

Reproductive outcome in uterine malformations with or without an associated unilateral renal agenesis.

OBJECTIVE: To analyze reproductive performance in women with genital malformations and to determine whether pregnancy outcomes are influenced by the asrenal agenesis (URA). STUDY DESIGN: This was a retrospective study of 174 patients with genitourinary malformations, with available images for reevaluation and classification and a history ofpregnancies. The main outcome measure was the reproductive performance depending on the type of uterine malformation and urinary tract anomalies. RESULTS: The lowest percentage of women who had only live births occurred in women with bicornuate unicollis uterus (28%). Considering only uterine anomalies that might be associated with URA, those cases had significantly better perinatal outcomes (72% had only living children) than those with no renal agenesis (40%). Of the total number of pregnancies (n=355), patients with URA were associated with term deliveries and living children, whereas women with uterine malformation without URA were more associated with abortions, premature births, and breech presentation. CONCLUSION: Uterine malformations are associated with a high rate of abortions, preterm births, breech presentation, and reproductive losses, but reproductive performance is significantly better for a given type of uterine malformation if it is associated with URA; that is, if the Müllerian anomaly is the consequence of mesonephric or Wolffian anomaly. Different embryological origin for the uterine malformations (mesonephric versus isolated Müllerian anomalies), the absence of 1 renal artery, and previous extrauterine surgery could be related.

Is a bowel resection necessary for deep endometriosis with rectovaginal or colorectal involvement?

BACKGROUND: The purpose of this paper is to report the long-term results of surgery without bowel resection in patients suffering from deep infiltrating endometriosis with rectovaginal or colorectal involvement. METHODS: This retrospective observational study identified 42 patients suffering with deep infiltrating endometriosis who underwent surgery. Conservative surgery was performed in 23 women (only one of them with bowel resection), and 19 women underwent a hysterectomy and bilateral salpingo-oophorectomy (HBSO). In the conservative surgery group, a later HBSO was performed in eight patients as a second operation. Pregnancies, recurrences, reoperations, use of hormone replacement therapy, and outcomes during long-term follow-up were analyzed. RESULTS: The average follow-up duration was 7 ± 5.7 years in conservative surgery cases. Only one patient was treated with sigmoid bowel resection in 1997 and had complications. In this conservative surgery group, 13 patients (56%) received medical treatment after surgery, 10 patients wanted to get pregnant (of whom seven [70%] were successful), and eight patients underwent a subsequent HBSO because of recurrent symptoms and/or endometrioma. Therefore, HBSO was performed in 27 patients, of whom 14 (51.8%) used hormone replacement therapy for 5.6 ± 3.6 years. No recurrences or complications were observed in patients after HBSO with or without hormone replacement therapy. CONCLUSION: Good clinical results can be obtained by performing only conservative surgery and/or HBSO without bowel resection, an alternative that could reduce the number of colorectal resections that are performed very frequently nowadays. After HBSO, patients may use hormone replacement therapy for several years with total satisfaction and well-being.

Endometriosis: a disease that remains enigmatic.

Endometriosis, a gynecologic pathology, is defined by the presence of a tissue similar to uterine endometrium, which is located in places other than physiologically appropriate. These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous, endogenous, or local hormonal stimuli. Endometriosis affects 8%-10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. In several instances, endometriosis persists as a minimal or mild disease, or it can resolve on its own. Other cases of endometriosis show severe symptomatology that ends when menopause occurs. Endometriosis can, however, reactivate in several postmenopausal women when iatrogenic or endogenous hormones are present. Endometriosis is occasionally accompanied by malignant ovarian tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is widely debated, and its variable morphology appears to represent a continuum of individual presentations and progressions. Endometriosis has no pathognomonic signs or symptoms; it is therefore difficult to diagnose. Because of its enigmatic etiopathogenesis, there is currently no satisfactory therapy for all patients with endometriosis. Treatments include medications, surgery, or combined therapies; currently, the only procedures that seem to cure endometriosis are hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the most controversial and enigmatic aspects of this disease.

Effect of human interferon-alpha-2b on experimental endometriosis in rats: comparison between short and long series of treatment.

OBJECTIVE: A randomised and controlled experimental study was carried out to determine the effect of short and long series of treatment with recombinant human interferon-alpha-2b on surgically induced endometriosis in rats. STUDY DESIGN: Ninety-six Wistar adult female rats, which had undergone an autotransplant into the peritoneal cavity of four endometrial fragments measuring 4.5mm at the side, were randomly divided into three groups. One third of the animals were manipulated like the treated animals but were not given treatment and served as control (group C). Another third (group S) were treated with three doses (one every 48 h, 100,000 U per dose) of recombinant human interferon-alpha-2b (subcutaneous route), and the last third (group L) were treated with fifteen doses of interferon (100,000 U every 48 h). RESULTS: Before interferon was administered, there were no differences between groups in the average growth of experimental endometriosis per animal (17.3±6.7, 18.1±9.2, 16.4±5.6mm in groups C, S and L respectively). After the treatment, experimental endometriosis per animal was significantly smaller in the groups treated with interferon than in the control non-treated group (p<0.001), and in the group treated with 15 doses versus the group treated with 3 doses (p<0.05), (17.6±7.5, 14.0±9.5, 9.4±6.0mm in groups C, S, and L respectively). While the implants of the animals in the control group showed no change in size throughout the study (120 days) (+1.96% of variation), the mean size of the implants in the treated rats decreased, (22.7% with the short and 42.8% with the long series of treatment with interferon). Only one implant in group C (0.8%) disappeared, while this occurred in 27 cases (22.5%) in group S (p<0.001) and in 45 (37.5%) in group L (p<0.001 versus group C and p<0.05 versus group S). CONCLUSION: The long series of treatment with human interferon-alpha-2b was more effective than the short one in reducing the size of surgically induced endometriosis in the peritoneal cavity of the rat.