A comprehensive review of the new FIGO classification of ovulatory disorders.

BACKGROUND: The World Health Organization (WHO) system for the classification of disorders of ovulation was produced 50 years ago and, by international consensus, has been updated by the International Federation of Gynecology and Obstetrics (FIGO). OBJECTIVE AND RATIONALE: This review outlines in detail each component of the FIGO HyPO-P (hypothalamic, pituitary, ovarian, PCOS) classification with a concise description of each cause, and thereby provides a systematic method for diagnosis and management. SEARCH METHODS: We searched the published articles in the PubMed database in the English-language literature until October 2022, containing the keywords ovulatory disorders; ovulatory dysfunction; anovulation, and each subheading in the FIGO HyPO-P classification. We did not include abstracts or conference proceedings because the data are usually difficult to assess. OUTCOMES: We present the most comprehensive review of all disorders of ovulation, published systematically according to the logical FIGO classification. WIDER IMPLICATIONS: Improving the diagnosis of an individual's ovulatory dysfunction will significantly impact clinical practice by enabling healthcare practitioners to make a precise diagnosis and plan appropriate management.

Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR.

There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms.

Evolutionary algorithm-based classifier parameter tuning for automatic ovarian cancer tissue characterization and classification.

PURPOSE: Ovarian cancer is one of the most common gynecological cancers in women. It is difficult to accurately and objectively diagnose benign and malignant ovarian tumors using ultrasound and other tests. Hence, there is an imperative need to develop a computer-aided diagnostic (CAD) system for ovarian tumor classification in order to reduce patient anxiety and the cost of unnecessary biopsies. In this paper, we present an automatic CAD system for the detection of benign and malignant ovarian tumors using advanced image processing and data mining techniques. MATERIALS AND METHODS: In the proposed system, Hu's invariant moments, Gabor transform parameters and entropies are first extracted from the acquired ultrasound images. Significant features are then used to train a probabilistic neural network (PNN) classifier for classifying the images into benign and malignant categories. The model parameter (σ) for which the PNN classifier performs the best is identified using a genetic algorithm (GA). RESULTS: The proposed system was validated using 1300 benign images and 1300 malignant images, obtained from 10 patients with a benign disease and 10 with a malignant disease. We used 23 statistically significant (p < 0.0001) features. By evaluating the classifier using a ten-fold cross-validation technique, we were able to achieve an average classification accuracy of 99.8 %, sensitivity of 99.2 % and specificity of 99.6 % with a σ of 0.264. CONCLUSION: The proposed system is automated and hence is more objective, can be easily deployed in any computer, is fast and accurate and can act as an adjunct tool in helping physicians make a confident call about the nature of the ovarian tumor under evaluation.

Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification.

OBJECTIVE: The aim of the present study was to differentiate and specify the subtypes of adenomyosis. STUDY DESIGN: Surgically treated adenomyosis (n = 152) was subcategorized retrospectively into 4 subtypes on the basis of magnetic resonance imaging geography. Subtype I (n = 59) consisted of adenomyosis that occurs in the uterine inner layer without affecting the outer structures. Subtype II (n = 51) consisted of adenomyosis that occurs in the uterine outer layer without affecting the inner structures. Subtype III (n = 22) consisted of adenomyosis that occurs solitarily without relationship to structural components. Adenomyosis that did not satisfy these criteria composed subtype IV (n = 20). Stepwise logistic regression analysis was used for specification of the subtypes. RESULTS: Subtypes I-III were suggested as a product of direct endometrial invasion, endometriotic invasion from the outside, and de novo metaplasia, respectively. Subtype IV was a heterogeneous mixture of far advanced disease. CONCLUSION: Adenomyosis appears to consist of 3 distinct subtypes of different causes and an additional subtype of indeterminate cause.

Histologic classification of specimens from women affected by superficial endometriosis, deeply infiltrating endometriosis, and ovarian endometriomas.

In this retrospective observational study involving 176 patients and 271 biopsies, the histologic differentiation in superficial endometriosis, deeply infiltrating endometriosis, and ovarian endometriomas was evaluated according to a previously proposed classification system. Results showed a predominance of the undifferentiated glandular pattern (33.5%) and mixed glandular pattern (46.9%) in deeply infiltrating endometriosis lesions, whereas the well-differentiated glandular pattern (41.8%) was most frequently seen in superficial endometriosis lesions, and in ovarian endometriomas a predominance of both the undifferentiated (40.5%) and mixed patterns (37.8%) was observed.

Leptin concentrations in the peritoneal fluid of women with ovarian endometriosis are different according to the presence of a 'deep' or 'superficial' ovarian disease.

Some studies have suggested a possible role of leptin, an active cytokine produced by adipocytes, in the pathogenesis of pelvic endometriosis. The present study was designed to assess leptin levels in the peritoneal fluid (PF) of women with the 'deep' or 'superficial' types of ovarian endometriosis. Twenty-seven women with a single ovarian endometrioma having a mean diameter between 3 and 5 cm were included in the study. Patients were divided into two groups according to the type of ovarian endometriosis: Group A (n = 11) consisted of women with 'superficial' endometriomas located at the ovarian surface; Group B (n = 16) included patients with 'deep' intra-ovarian endometriomas. Women undergoing laparoscopy for unexplained infertility and not affected by pelvic and/or ovarian endometriosis were considered as controls (Group C, n = 10). Patients with an ovarian endometrioma had significantly increased PF leptin concentrations than endometriosis-free controls (Groups A and B vs. Group C, p < 0.01). Patients with 'superficial' endometriomas had significantly higher PF leptin levels compared with patients with 'deep' endometriomas (Group A vs. B, p < 0.01). This difference remained significant after correction for the BMI; moreover, a positive correlation between PF leptin and BMI was observed in Groups B and C, but not in women with 'superficial' endometrioma (Group A). Our observations suggest that: (a) leptin could play an active role in promoting the development of 'superficial' ovarian endometriomas and (b) 'superficial' and 'deep' ovarian endometriomas could have a different pathogenesis.

Ovarian carcinoma subtypes are different diseases: implications for biomarker studies.

BACKGROUND: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous) are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. METHODS AND FINDINGS: In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1) in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%-2.4%) but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1.2%-2.3%), but is a favourable prognostic marker within the high-grade serous subtype (RR 0.5, 95% CI 0.3%-0.8%). CONCLUSIONS: The association of biomarker expression with survival varies substantially between subtypes, and can easily be overlooked in whole cohort analyses. To avoid this effect, each subtype within a cohort should be analyzed discretely. Ovarian carcinoma subtypes are different diseases, and these differences should be reflected in clinical research study design and ultimately in the management of ovarian carcinoma.

[Ovarian epithelial dysplasia: myth or reality? Review]. / Dysplasie épithéliale ovarienne: mythe ou réalité? Revue de la littérature.

Ovarian epithelial dysplasia has been described in the ovarian surface epithelium by histologic, morphometric and nuclear profile studies. It could represent a potential precursor of ovarian malignancy in patients with genetic risk of ovarian cancer, although its natural history and progression to carcinoma are unpredictable. Diagnosis and identification of ovarian dysplasia would certainly be useful to understand the early steps of ovarian carcinogenesis. However, dysplasia in relation with ovulation induction seems to have a different pattern. We report dysplasia definitions and the current clinical management.

Ovulatory disorders and infertility.

Ovulatory disorders represent a major cause of infertility. The World Health Organization classification offers a useful frame for diagnosis and treatment. Polycystic ovary syndrome (PCOS) is the most common cause of oligoovulation and anovulation. Treatment of infertility associated with PCOS has changed in the last decade due to the introduction of new medications. Insulin-sensitizing drugs, such as metformin, became an integral part of treatment. Aromatase inhibitors will most probably replace clomiphene citrate in the future. Women who fail to ovulate or conceive after first-line treatment options are often referred for gonadotropin treatment. Laparoscopic ovarian drilling, which has been evaluated in well-designed trials, may be an alternative to gonadotropins. In vitro fertilization, which yields high pregnancy rates, is the final treatment option when all else fails. Hypogonadotropic anovulation is treated with exogenous gonadotropins, and little has changed in its management. Women with hypergonadotropic hypogonadism should be counseled for adoption or in vitro fertilization with donated oocytes as spontaneous and treatment-associated pregnancy rates are very low.

Deep endometriosis: definition, pathogenesis, and clinical management.

"Deep endometriosis" includes rectovaginal lesions as well as infiltrative forms that involve vital structures such as bowel, ureters, and bladder. The available evidence suggests the same pathogenesis for deep infiltrating vesical and rectovaginal endometriosis (i.e., intraperitoneal seeding of regurgitated endometrial cells, which collect and implant in the most dependent portions of the peritoneal cavity and the anterior and posterior cul-de-sac, and trigger an inflammatory process leading to adhesion of contiguous organs with creation of false peritoneal bottoms). According to anatomic, surgical, and pathologic findings, deep endometriotic lesions seem to originate intraperitoneally rather than extraperitoneally. Also the lateral asymmetry in the occurrence of ureteral endometriosis is compatible with the menstrual reflux theory and with the anatomic differences of the left and right hemipelvis. Peritoneal, ovarian, and deep endometriosis may be diverse manifestations of a disease with a single origin (i.e., regurgitated endometrium). Based on different pathogenetic hypotheses, several schemes have been proposed to classify deep endometriosis, but further data are needed to demonstrate their validity and reliability. Drugs induce temporary quiescence of active deep lesions and may be useful in selected circumstances. Progestins should be considered as first-line medical treatment for temporary pain relief. However, in most cases of severely infiltrating disease, surgery is the final solution. Great importance must be given to complete and balanced counseling, as awareness of the real possibilities of different treatments will enhance the patient's collaboration.

Classification of ovarian endometriotic cysts.

Current literature describes 3 different pathogenetic types of ovarian endometriotic cysts. Cortical invagination cysts arise when surface ovarian endometriotic deposits adhere to another structure (such as the broad ligament), blocking the egress of menstrual fluid produced by cycling endometriosis, which then collects and causes the ovarian cortex to invaginate. Surface inclusion cyst-related endometriotic cysts develop when endometriotic tissue colonizes preexisting inclusion cysts. Physiological cyst-related endometriotic cysts occur when endometriosis gains access to a follicle, such as at the time of ovulation. To determine whether routine histological examination is of use in the classification of endometriotic cysts, and if so, whether such classification is of clinical relevance, we reviewed the histology of endometriotic cysts of 29 women under 35 years of age. Young women were chosen so that ovarian cortex surrounding the endometriotic lining in invagination cysts could be identified by the finding of oocytes. Ten women (34%) had cortical invagination endometriotic cysts, but no inclusion or physiological cyst-related endometriomas were found. The remaining 19 women (66%) had unclassified endometriotic cysts, of which 14 (48% of total) had a fibrous wall between the endometriotic lining and medulla and 5 had extensive destruction of ovarian tissue. We concluded that cortical invagination cysts were the only common diagnosable sort of the 3 types currently being investigated and that unclassified cysts required further study to determine their pathogenesis. Our study highlights the need for a prospective study using standardized pathological and clinical methods.

In vitro fertilization in patients with ovarian endometriomas.

OBJECTIVE: The objective of the study was to establish whether operative treatment of recurrent ovarian endometriosis improves the prognosis of in vitro fertilization. METHODS AND MATERIAL: A retrospective analysis of one hundred endometriosis patients admitted to Tampere University Hospital for IVF treatment. Forty-five patients had an ovarian endometrioma during IVF treatment, 36 of the cases being recurrences after a previous operation. Fifty-five patients had ovarian endometriomas operated without recurrence. The patient groups with or without endometriosis did not differ in age, duration of infertility, sperm parameters, amount of gonadotropins required per oocyte and number of retrieved oocytes. RESULTS: The patients with ovarian endometriosis had more embryos (mean 3.9) than women without endometriomas (mean 2.8) (p<0.05) and the respective pregnancy rates per IVF cycle were 38% and 22%. Patients with endometriomas had a live birth rate of 27% compared with 20% in women with no endometriomas. CONCLUSIONS: The presence of a small endometrioma does not reduce the success of IVF treatment.

[Definition, description and classification of endometriosis]. / Définition, description et classification de l'endométriose.

The presence of ectopic endometrial tissue defines endometriosis. External endometriosis, the real one, can be observed everywhere in the woman body and in genitourinary tract in man. Macroscopic and histologic features depend on their duration, on their location and the period of the menstrual cycle. All the changes of eutopic endometrium can be exhibited by endometriotic foci: response to hormonal stimuli, decidualization, malignant transformation (neoplasm arising from endometriosis).... The revised American Fertility Society classification, most frequently used, establishes scores assigned to ovarian and peritoneal lesions. Adenomyosis or internal endometriosis involves the myometrium. This peculiar entity represents a diverticulosis of the endometrium into myometrium with smooth muscle hyperplasia.

Reproducibility of the revised American Fertility Society classification of endometriosis using laparoscopy or laparotomy.

OBJECTIVE: To assess the discrepancy between laparoscopic and laparotomic scoring methods using the revised American Fertility Society (AFS) classification of endometriosis. METHOD: In this prospective study, 84 patients with endometriosis were scored twice (laparoscopically and laparotomically) by the same subspecialty-certified reproductive endocrinologist. The magnitude of inter-method variability was reported quantitatively by the S.D. of the differences in scores between the pairs. The differences in the mean endometriosis scores between the two methods were assessed by the paired Student's t-test. P < 0.05 was considered as statistically significant. Discrepancy between the two methods in the staging of endometriosis patients was presented by kappa measure of agreement. RESULT: There was considerable variability in the scores between the two scoring methods by the same observer. Among individual components of the scoring system, the greatest variability occurred in the ovarian endometriosis and cul-de-sac obliteration subscores, with the least variability observed for peritoneum endometriosis. The inter-method variation in score was sufficient to alter the endometriosis staging in 34.5% of patients, including a difference of two stages in 3.6% of patients. The kappa coefficient was 0.49, indicating fair-to-good agreement between the two scoring methods. CONCLUSION: Inter-method variability between laparoscopic and laparotomic scoring methods was high for ovarian endometriosis subscore using the revised AFS classification of endometriosis. Agreement in endometriosis staging between the two methods was fair to good.

Guidelines to determine the route of oophorectomy with hysterectomy.

OBJECTIVES: Our purpose was to determine whether there is adequate visibility and access for transvaginal oophorectomy in most patients and the success rate of the transvaginal approach. The final goal was to establish objective guidelines for choosing the route of oophorectomy with hysterectomy. STUDY DESIGN: Patients underwent laparoscopy-assisted vaginal hysterectomy (n = 91) or vaginal hysterectomy (n = 875). Ovarian removal, either unilateral (n = 97) or bilateral (n = 187), was carried out for clinical or prophylactic reasons. The accessibility of the ovaries for transvaginal removal was assessed by stretching the infundibulopelvic ligament and grading the position of the ovaries from 0 (no descent) to III (descent past the hymenal ring with traction). RESULTS: In 158 patients transvaginal bilateral oophorectomy was performed without laparoscopic assistance. In another 29 patients bilateral transvaginal oophorectomy was performed with laparoscopy-assisted vaginal hysterectomy, and prophylactic bilateral oophorectomy by the transvaginal route was successful in all but 1 of 143 patients with ovaries of grade I or higher. In 20 patients laparoscopic lysis of adhesions was necessary to permit transvaginal oophorectomy. Ninety-seven patients underwent transvaginal unilateral oophorectomy, 74 with conventional vaginal hysterectomy and 23 with laparoscopy-assisted vaginal hysterectomy. Among the patients not having oophorectomy, all ovaries had sufficient mobility to have been removed transvaginally. CONCLUSION: Good surgical practice dictates that visibility and accessibility be the primary criteria for selecting the route of oophorectomy with hysterectomy. In most patients the ovaries are visible and accessible to transvaginal removal.

[Classification of US findings of ovarian masses in children].

The ultrasonographic findings of 25 lesions in 23 patients with surgically proven ovarian masses were reviewed. There were 10 cystic teratomas, two simple cysts, two follicular cysts, two mucinous cystadenomas, two NHL, one corpus luteum cyst, one hydrosalpinx, one serous cystadenoma, one yolk sac carcinoma, one dysgerminoma, one embryonal carcinoma, and one mixed form (yolk sac carcinoma, choriocarcinoma). All patients were less than 15 years old. We classified all cases into four patterns: cystic, cystic with mural nodule, mixed, and solid. Eight lesions of the cystic pattern included two simple cysts, two follicular, cysts and one corpus luteum cyst. The other lesions were benign, too. Nine lesions with the cystic with mural nodule pattern consisted of eight cystic teratomas and one mucinous cystadenoma. All lesions were benign. The mixed pattern was seen in four lesions, half of which were malignant, i. e., one embryonal carcinoma and one yolk sac carcinoma. Four lesions with the solid pattern were all malignant masses: one dysgerminoma, two NHL and one mixed form. In this classification, the cystic and cystic with mural nodule patterns are benign, while mixed and solid patterns are highly suggestive of malignancy.