MRI classification of uterosacral ligament involvement in endometriosis: the Hôtel-Dieu classification.

OBJECTIVE: This study aimed to establish the first-ever MRI classification of uterosacral ligament (USL) involvement in deep infiltrating endometriosis (DIE), based on reliable preoperative MRI features correlated with positive predictive values (PPVs) determined through histopathological analysis. METHODS: Twenty-two women underwent surgery with histopathology due to symptoms highly suggestive of endometriosis. The 22 preoperative MRIs were analysed retrospectively, blinded to histopathology, and a classification of the preoperative aspect of USLs linked to PPVs was designed. RESULTS: According to their aspects, 6 radiological types of USL were identified. The "L-category" corresponded to linear types with regular or irregular margins, including types 1, 2, 3A, and 3B. The "N-category" corresponded to haemorrhagic or nodular types, including types 4, 5A, 5B, and 6. For the L-category, PPVs ranged from 75% to 88%, depending on the USL radiological type. For the N-category, PPVs were 100% for each type. In women with endometriosis symptoms, MRI underestimated USL involvement, especially for type 1. Among the 6 uteri with lateral deviation, only one false-positive result concerning the stretched USL was induced. CONCLUSIONS: In women with endometriosis symptoms, our MRI classification identified 2 USL categories, corresponding to 2 kinds of PPV; in these symptomatic patients, a normal MRI does not rule out a DIE diagnosis. ADVANCES IN KNOWLEDGE: Our MRI classification of USL involvement in endometriosis may be used as a non-invasive staging of the disease, making it much clearer for clinicians and patients. Hence, we are able to propose a suitable diagnostic and therapeutic procedure for each radiological type.

The "freeze-all" strategy seems to improve the chances of birth in adenomyosis-affected women.

OBJECTIVE: To compare assisted reproductive technologies (ARTs) outcomes between fresh vs. freeze-all strategies in infertile women affected by adenomyosis. DESIGN: A single-center observational study. SETTINGS: University hospital-based research center. PATIENTS: Adenomyosis-affected women undergoing blastocyst embryo transfer after in vitro fertilization and intracytoplasmic sperm injection between January 1, 2018, and November 31, 2021. The diagnosis of adenomyosis was based on imaging criteria (i.e., transvaginal ultrasound and/or magnetic resonance imaging). INTERVENTION(S): Women who underwent a freeze-all strategy were compared with those who underwent a fresh embryo transfer (ET) strategy. MAIN OUTCOME MEASURE(S): Cumulative live birth rate (LBR). RESULTS: A total of 306 women were included in the analysis: 111 in the fresh ET group and 195 in the freeze-all group. The adenomyosis phenotype (internal diffuse adenomyosis, external focal adenomyosis, and adenomyoma) was not significantly different between the two groups. The cumulative LBR (86 [44.1%] vs. 34 [30.6%], respectively), and the cumulative ongoing pregnancy rate (88 [45.1%] vs. 36 [32.4%], respectively) were significantly higher in the freeze-all group compared with the fresh ET group. After multivariate logistic regression analysis, the freeze-all strategy in women with adenomyosis was associated with significantly higher odds of live birth compared with fresh ET (odds ratio = 1.80; 95% confidence interval = 1.02-3.16). CONCLUSION: The freeze-all strategy in women afflicted with adenomyosis undergoing ART was associated with significantly higher cumulative LBRs. Our preliminary results suggest that the freeze-all strategy is an attractive option that increases ART success rates. Additional studies, with a randomized design, should be conducted to further test whether the freeze-all strategy enhances the pregnancy rate in adenomyosis-affected women.

Magnetic resonance imaging presentation of diffuse and focal adenomyosis before and after pregnancy.

RESEARCH QUESTION: Is there a change in magnetic resonance imaging (MRI) criteria of diffuse and focal phenotypes of adenomyosis before and after pregnancy? DESIGN: A retrospective, monocentric, observational study in a single academic tertiary referral centre for endometriosis diagnosis and management. Women were followed for symptomatic adenomyosis, and without a prior history of surgery who give birth after 24+0 weeks. For each patient, pelvic MRI pre- and post-pregnancy was performed by two experienced radiologists with the same image acquisition protocol. Diffuse and focal adenomyosis MRI presentation were analysed before and after pregnancy. RESULTS: Between January 2010 and September 2020, of the 139 patients analysed, 96 (69.1%) had adenomyosis at MRI distributed as follow: 22 (15.8%) presented diffuse adenomyosis, 55 (39.6%) focal adenomyosis and 19 (13.7%) both phenotypes. The frequency of isolated diffuse adenomyosis on MRI was significantly lower before versus after pregnancy (n = 22 [15.8%] versus n = 41 [29.5%], P = 0.01). The frequency of isolated focal adenomyosis was significantly higher before pregnancy than after pregnancy (n = 55 [39.6%] versus n = 34 [24.5%], P = 0.01). The mean volume of all focal adenomyosis lesions on MRI decreased significantly after pregnancy, from 6.7 ± 2.5 mm3 to 6.4 ± 2.3 mm3, P = 0.01. CONCLUSION: The current data indicate that, based on MRI, there is an increase in diffuse adenomyosis and a decrease in focal adenomyosis after pregnancy.

Adolescent endometriosis: prevalence increases with age on magnetic resonance imaging scan.

OBJECTIVE: To evaluate the prevalence on magnetic resonance imaging (MRI) of ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) in adolescents presenting with severe dysmenorrhea. DESIGN: Prospective study. SETTING: Clinic. PATIENT(S): A total of 345 adolescents aged 12-20 years referred to the radiologic MRI department unit between September 2019 and June 2020. INTERVENTION(S): Multiplanar pelvic MRI with cine MRI was performed. Data on the medical history with systematic questioning were collected for each patient before the scan. MAIN OUTCOME MEASURE(S): Data on the endometriosis phenotypes (OMA and/or DIE), distribution of anatomical lesions, and adenomyosis were evaluated and recorded using a dedicated MRI spreadsheet. Myometrial contractions were systematically reported for each case. The data were correlated with the characteristics of the patients and severity of painful symptoms evaluated using a visual analog scale. RESULT(S): The prevalence rates of endometriosis and adenomyosis were 39.3% (121 patients) and 11.4% (35 patients), respectively. Among the adolescents with endometriosis, 25 (20.7%) presented with OMA, and 107 (88.4%) presented with DIE. The odds ratios (confidence intervals) for each pairwise comparison between the age distributions were 2.3 (1.4-3.8) for 15-18 vs. <15 years of age and 3.3 (1.2-8.5) for 18-20 vs. <15 years of age, highlighting a predominance of cases after 18 years of age. Uterine contractions were visualized in 34.4% of cases, with no particular association with endometriosis. No clinical risk factor was identified as being particularly associated with endometriosis. Notably, the visual analog scale score was the same for cases with and without endometriosis. CONCLUSION(S): Severe endometriosis phenotypes (OMA and/or DIE) can be observed in adolescents with intense dysmenorrhea, with a linear increase in prevalence over time resulting in a clear predominance after 18 years of age. Endometriosis in adolescents is a challenging clinical problem with a long delay in diagnosis. Imaging can help reduce this delay in young patients with suggestive symptoms. CLINICAL TRIAL REGISTRATION NUMBER: NCT05153512.

Influence of endometrioma size on ART outcomes.

RESEARCH QUESTION: Does endometrioma size affect the number of oocytes retrieved after ovarian stimulation in women with endometriosis-related infertility undergoing IVF/intracytoplasmic sperm injection (ICSI)? DESIGN: Cohort study of infertile women with unilateral or bilateral endometrioma(s) associated with deep infiltrating endometriosis, undergoing their first IVF/ICSI cycle between January 2014 and November 2021. A total of 326 women with an adequate imaging work-up with transvaginal ultrasound and/or magnetic resonance imaging performed by senior radiologists before the start of ovarian stimulation was included. Prognostic factors associated with the number of oocytes retrieved were analysed. IVF/ICSI outcomes were compared between five groups defined according to the largest endometrioma diameter (<2, 2 to <4, 4 to <6, 6 to <8 and ≥8 cm). RESULTS: Factors that significantly reduced the number of oocytes retrieved after adjustment by multiple linear regression were women's age (regression coefficient -0.18; 95% confidence interval [95% CI] -0.31 to-0.06; P = 0.005), smoking habit (-2.02; 95% CI -3.42 to -0.62; P = 0.005), day 3 FSH concentration (-0.20; 95% CI -0.39 to -0.02; P = 0.031) and a previous history of surgery for ovarian endometriosis (-1.32; 95% CI -2.63 to -0.02; P = 0.047). Antral follicle count and oestradiol concentration on the trigger day were positively correlated with the number of oocytes retrieved (0.14; 95% CI 0.08 to 0.19; P < 0.001 and 0.003; 95% CI 0.002 to 0.004; P < 0.001, respectively). The mean number of oocytes retrieved was not significantly different between the five groups (P = 0.413), nor were the cumulative live birth rate, the number of cancelled cycles and perinatal outcomes. CONCLUSIONS: No significant difference in the number of oocytes retrieved was observed according to endometrioma size. This study suggests that ovarian stimulation can be of benefit to women irrespective of the endometrioma size.

Endometriosis increases the rate of spontaneous early miscarriage in women who have adenomyosis lesions.

RESEARCH QUESTION: In women with radiologically diagnosed adenomyosis, is the presence of endometriosis associated with a higher rate of miscarriage? DESIGN: An observational cohort study of women who received medical care for benign gynaecological conditions between May 2005 and May 2018. Women who had adenomyosis lesions visualized by uterine magnetic resonance imaging (MRI) were included. Women who had never been pregnant were excluded. Women with adenomyosis identified by MRI but who did not have endometriosis lesions (control group) were compared with women with adenomyosis and endometriosis lesions (study group). Primary outcome was rate of a previous history of early miscarriage. RESULTS: A total of 214 pregnancies in the study group and 53 pregnancies in the control group were analysed. The rate of a previous miscarriage was significantly higher among women with adenomyosis and endometriosis lesions compared with women in the control group (61/214 [28.5%] versus 6/53 [11.3%], respectively, P = 0.009). A multivariable generalized estimating equation logistic regression model, adjusted for adenomyosis and endometriosis phenotypes, found that the association between endometriosis and adenomyosis significantly increased the risk of miscarriage (OR 3.2, 95% CI 1.1 to 9.65). The risk was significantly higher with deep infiltrating endometriosis (OR 4.37, 95% CI 1.32 to 14.53). CONCLUSIONS: Women affected by endometriosis had a significantly higher rate of previous spontaneous miscarriage than women without endometriosis with adenomyosis lesions identified by MRI. Mechanistic studies are needed to establish the complex link between the presence of endometriosis and adenomyosis and the rate of spontaneous miscarriage.

Adenomyosis: An update regarding its diagnosis and clinical features.

Adenomyosis is a common gynecologic disease characterized by invasion of endometrial glands and stroma within the myometrium. Clinically, it can result in abnormal uterine bleeding, pelvic pain, and infertility. Adenomyosis has historically been diagnosed by histology of hysterectomy specimens. As a result of the development of imaging techniques, the diagnosis is nowadays possible by means of transvaginal pelvic ultrasound or pelvic magnetic resonance imaging. The use of pelvic imaging has demonstrated the existence of different forms of adenomyosis, notably allowing distinction between lesions of the external myometrium and those of the internal myometrium. The epidemiological and clinical characteristics may depend on the anatomical location of the adenomyosis lesions. In order to provide the best management for women with adenomyosis, the objective of this review is to provide an update regarding the diagnosis of adenomyosis and its clinical features according to the different adenomyosis phenotypes.

Uterine Sarcomas: Are There MRI Signs Predictive of Histopathological Diagnosis? A 50-Patient Case Series with Pathological Correlation.

PURPOSE: To make clear distinction between two radiological types of uterine sarcomas. METHODS: 50 preoperative MRI were analyzed retrospectively, blinded to histopathology: 11 endometrial stromal sarcomas (ESS), 19 leiomyosarcomas (LMS), 18 carcinosarcomas/malignant mixed Mullerian tumors (MMMT), and 2 smooth muscle tumors of uncertain malignant potential (STUMP). RESULTS: According to their locations, two radiological types of sarcomas were identified: type 1: intracavitary (ESS, MMMT) and type 2: intramyometrial (LMS, STUMP). In both types, all tumors displayed intermediate T2-weighted signal (p < 0.001) and high diffusion-weighted imaging (DWI) b1000 signal (p < 0.001). Dynamic contrast-enhanced (DCE) MRI showed intratumoral pathologic vessels (98%) and heterogeneity at venous phase (p < 0.001). In the type 1 subgroup, all tumors displayed local spread: invasion of junctional zone on T2-weighted imaging (T2WI), irregular margins on DWI, and disruption of arcuate arteries subendometrial ring on DCE-MRI. In the type 2 subgroup, all tumors displayed irregular margins on T2WI, DWI, and DCE-MRI. Tumor heterogeneity was due to necrosis (p < 0.001). Most commonly the tumor was single (61%). In both types, apparent diffusion coefficient (ADC) lesser than or equal to 0.86 × 10-3 mm2/s (sensitivity = 73%, specificity = 92%) was suggestive of malignancy. CONCLUSION: It may be feasible to get close to histological type of a uterine sarcoma based on our topographic classification into two radiological subgroups, corresponding to two kinds of diagnostic difficulties. Advances in knowledge. MRI signs suggestive of histopathological malignancy are identifiable, considering the triad T2WI/DWI/DCE-MRI, easily for type 1 but less easily for type 2; the threshold value for ADC is 0.86 × 10-3 mm2/s.

Imaging for evaluation of endometriosis and adenomyosis.

Endometriosis and adenomyosis are two frequent diseases that impair women's quality of life by causing pain and infertility. Both endometriosis and adenomyosis are heterogeneous diseases that manifest as different forms. Adenomyosis may be described as diffuse adenomyosis, focal adenomyosis especially of the outer myometrium and cystic adenomyoma. Endometriosis has three phenotypes: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). These two diseases are closely linked, and it is now clear that adenomyosis can either arise on its own or coexist with endometriosis. There is a strong clinical relationship between endometriosis and adenomyosis according to their respective phenotypes. Various classifications are available to describe both diseases. Transvaginal ultrasonography (TVUS) and/or pelvic magnetic resonance imaging (MRI) are the first examination performed when endometriosis or adenomyosis are suspected. These two imaging techniques, used in a combination manner, allow accurate description of both endometriosis and adenomyosis, to assess the diagnosis and to improve clinical and surgical care. In this review, we described the different imaging aspects of endometriosis and adenomyosis to help the less experienced radiologist or gynecologist in the diagnosis and evaluation of those diseases.

Adenomyosis is associated with specific proton nuclear magnetic resonance (1H-NMR) serum metabolic profiles.

OBJECTIVE: To determine whether the adenomyosis phenotype affects the proton nuclear magnetic resonance (1H-NMR)-based serum metabolic profile of patients. DESIGN: Cohort study. SETTING: University hospital-based research center. PATIENTS: Seventy-seven patients who underwent laparoscopy for a benign gynecologic condition. INTERVENTIONS: Pelvic magnetic resonance imaging and collection of a venous peripheral blood sample were performed during the preoperative workup. The women were allocated to the adenomyosis group (n = 32), or the control group (n = 45). The adenomyosis group was further subdivided into two groups: diffuse adenomyosis of the inner myometrium (n = 14) and focal adenomyosis of the outer myometrium (n = 18). Other adenomyosis phenotypes were excluded. MAIN OUTCOME MEASURES: Metabolomic profiling based on 1H-NMR spectroscopy in combination with statistical approaches. RESULTS: The serum metabolic profiles of the patients with adenomyosis indicated lower concentrations of 3-hydroxybutyrate, glutamate, and serine compared with controls. Conversely, the concentrations of proline, choline, citrate, 2-hydroxybutyrate, and creatinine were higher in the adenomyosis group. The focal adenomyosis of the outer myometrium and the diffuse adenomyosis phenotypes also each exhibited a specific metabolic profile. CONCLUSION: Serum metabolic changes were detected in women with features of adenomyosis compared with their disease-free counterparts, and a number of specific metabolic pathways appear to be engaged according to the adenomyosis phenotype. The metabolites with altered levels are particularly involved in immune activation as well as cell proliferation and cell migration. Nevertheless, this study did find evidence of a correlation between metabolite levels and symptoms thought to be related to adenomyosis. Further studies are required to determine the clinical significance of these differences in metabolic profiles.

Infertility in women with bowel endometriosis: first-line assisted reproductive technology results in satisfactory cumulative live-birth rates.

OBJECTIVE: To evaluate the assisted reproductive technology (ART) cumulative live-birth rate (LBR) in a cohort of bowel endometriosis patients with no prior history of surgery for endometriosis. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENT(S): One hundred and one consecutive infertile bowel-endometriosis patients with no prior history of surgery for endometriosis in whom the diagnosis of endometriosis was based on published imaging criteria using transvaginal sonography and magnetic resonance imaging. INTERVENTION(S): First-line ART. MAIN OUTCOME MEASURE(S): Cumulative LBR, with statistical analysis via Kaplan Meier method with a "conservative" method, whereby it was assumed that no live births took place for patients who did not return. RESULT(S): Between January 2016 and December 2018, 101 bowel endometriosis patients underwent 176 ART cycles. The mean number of deep-infiltrating endometriosis lesions per patient was 3 ± 0.9, with a mean number of bowel lesions of 1.3 ± 0.6. Seventy-three percent of the patients had associated endometriomas, and 88.1% had associated adenomyosis. Overall, the cumulative LBR after four ART cycles was 64.4%, using the conservative Kaplan-Meier method. CONCLUSION(S): The ART cumulative LBR was very satisfactory (64.4%) in bowel endometriosis patients with no prior history of surgery for endometriosis. In light of these data, clinicians should carefully weigh the pros and cons before systematically referring infertile bowel endometriosis patients to fertility-preserving surgery because as first-line ART appears to offer satisfactory results.

Focal adenomyosis is associated with primary infertility.

OBJECTIVE: To study the association between adenomyosis and infertility, according to the adenomyosis phenotype as diagnosed by magnetic resonance imaging (MRI). DESIGN: A single-center, cross-sectional study. SETTING: University hospital-based research center. PATIENT(S): Patients between 18 and 42 years of age who were surgically explored for benign gynecological conditions at our institution between May 2005 and May 2018. Only women with uterine MRIs performed by a senior radiologist were retained for this study. INTERVENTION(S): Primary and secondary infertile women were compared with women without infertility. In addition, the women were diagnosed according to the MRI findings as having adenomyosis (focal adenomyosis of the outer myometrium [FAOM] and/or diffuse adenomyosis phenotypes) or no adenomyosis. MAIN OUTCOME MEASURE(S): Primary and secondary infertility-associated factors. RESULT(S): A total of 496 women were included in the study population. Three groups were compared: a no infertility group (n = 361), a primary infertility group (n = 84), and a secondary infertility group (n = 51). Among them, 248 women did not present adenomyosis lesions and 248 women had a radiological diagnosis of adenomyosis. The presence of FAOM was significantly associated with primary infertility. Diffuse adenomyosis was not found to be associated with infertility. The distribution of endometriosis or leiomyomas was not significantly different between the groups. After a multinomial regression model including the women's age and associated endometriosis or leiomyoma, the presence of FAOM was identified as an independent associated factor of primary infertility (adjusted odds ratio 1.9; 95% confidence interval 1.1-3.3). CONCLUSION(S): The presence of FAOM was associated with primary infertility. This study opens the door to future clinical and basic studies aimed at better characterization of FAOM and its infertility-related physiopathology.

Focal adenomyosis of the outer myometrium and deep infiltrating endometriosis severity.

OBJECTIVE: To determine whether the presence of focal adenomyosis of the outer myometrium (FAOM) at preoperative magnetic resonance imaging is associated with the severity of deep infiltrating endometriosis. DESIGN: Observational cross-sectional study involving 255 symptomatic deep infiltrating endometriosis patients. Comparisons were performed according to the presence of FAOM. SETTING: University hospital. PATIENT(S): Women with a preoperative magnetic resonance imaging and complete surgical exeresis of endometriotic lesions with histologically documented deep infiltrating endometriosis. INTERVENTION(S): Surgical management for deep infiltrating endometriosis. MAIN OUTCOME MEASURE(S): The presence of multiple deep infiltrating endometriosis lesions, the mean number and location of deep infiltrating endometriosis lesions, and the mean total revised American Society for Reproductive Medicine scores. RESULT(S): The prevalence of FAOM at preoperative magnetic resonance imaging in the 255 patients with deep infiltrating endometriosis was 56.5%. The mean number of deep infiltrating endometriosis lesions was significantly higher in the FAOM(+) group than in the FAOM(-) group: 3.5 ± 2.1 vs. 2.2 ± 1.5. The mean total revised American Society for Reproductive Medicine score was higher in case of FOAM coexisting with deep infiltrating endometriosis. After adjusting for confounding factors, the presence of FAOM was significantly associated with multiple deep lesions. CONCLUSION(S): FAOM was significantly associated with greater deep infiltrating endometriosis severity. This needs to be integrated into the management strategy. Furthermore, a pathogenic link between deep infiltrating endometriosis and FAOM cannot be excluded.

Complex Stenoses and CT Features of the Nasolacrimal Canal in Congenital Nasolacrimal Duct Obstruction.

PURPOSE: To study the CT appearance of the nasolacrimal canal (NLC) in cases of congenital nasolacrimal duct obstruction (CNLDO) where there is a tactile sensation of a hard contact (HC) stop in the duct preventing stent intubation. METHODS: The authors retrospectively reviewed all consecutive cases of chronic CNLDO observed between 2003 and 2018 in which an apparent HC obstruction prevented nasolacrimal intubation. CT scans were reviewed to determine the cause of probing failure: distal stenosis, loss of parallelism of the NLC walls, abnormal angulations or an adjacent obstacle blocking tear outflow. RESULTS: Nine patients (12 sides) met the following criteria: CNLDO + HC + probing failure. The mean age at the time of the first HC was 3.9 years (range: 0.8-8.1 years) and at the time of a second confirmation of HC with subsequent dacryocystorhinostomy was 7.8 years (range: 4.1-9.2 years). Nasolacrimal duct opacification was noted in 33% of cases (4/12). Abnormalities of the NLC occurred in 8 of the 12 cases of CNLDO (8/12 = 66.6%) and on the asymptomatic side in 1 case (1/6 = 16.6%). A canine tooth bud situated in the same plane as the NLC was observed in 9 cases of CNLDO (9/12 = 75%) and on the asymptomatic side in 2 cases (2/6 = 33.3%). CONCLUSIONS: HC noted during probing is a sensitive but relatively nonspecific sign which, nevertheless, does indicate either a complex obstruction or at least potential intubation difficulties. As confirmed by CT imaging, a significant anatomical variant is not necessarily predictive of epiphora, but nevertheless may complicate the intubation procedure.The authors describe hard contact palpation during probing for CLNDO and its relationship to anatomic location and etiologies of obstruction in the nasolacrimal canal by CT imaging.

Complex Bony Congenital Nasolacrimal Duct Obstruction Caused by an Adjacent Canine Tooth Bud.

The authors report the case of a 7-year old child with failed probing with stent intubation, who was found to have an unusual curvature of the nasolacrimal duct on the symptomatic side. CT imaging revealed a permanent maxillary canine tooth adjacent to the duct. It appeared that the relationship of the tooth bud to the curved nasolacrimal duct was most likely responsible for the symptoms of epiphora on this anomalous side.

Inhibin A and inhibin B producing ovarian fibrothecoma revealed by suppression of follicle stimulating hormone (FSH) in a post-menopausal woman: report of the first case.

In this report, we describe the first case ever reported in the literature, of an inhibin-A (INHA) and inhibin-B (INHB) producing fibrothecoma. A post-menopausal woman was referred to our unit because of follicle stimulating hormone (FSH) level below the reference interval for postmenopausal women. By contrast luteinizing hormone, hCG, and estradiol levels were within normal range. This discrepancy suggested the secretion of FSH inhibitory factors. INHB and INHA levels were markedly elevated for age, 475 pg/mL and 100 pg/mL, respectively. Ultrasonography and MRI showed a pelvic mass of indeterminate nature. Abnormal inhibin secretion is generally observed in granulosa cell tumors. In this case this etiology was unlikely because of low estradiol and AMH levels. Surgical exploration revealed a 10 cm mass of the left ovary proven histologically to be an ovarian fibrothecoma (OFT). After tumor removal, INHB and INHA levels decreased rapidly. Only three cases of OFT with an important secretion of INHB have been reported to date. INHA secretion has never been associated with OFT. There is a need to develop coupled hormone and imaging strategies to diagnose the source of INH secretion in case of FSH/LH discrepancy.