Is Chronic Endometritis Associated with Tubal Infertility? A Prospective Cohort Study.

STUDY OBJECTIVE: Chronic endometritis (CE), which often presents asymptomatically, is associated with recurrent pregnancy loss, recurrent implantation failure after in vitro fertilization, and endometriosis. Data connecting CE with fallopian tubal occlusion are limited. The aim was to assess a potential association of CE, defined by the presence of syndecan-1 (CD138)-positive plasma cells in endometrial tissue samples, with fallopian tube patency and other factors for infertility, including endometriosis, adenomyosis, and hydrosalpinges. DESIGN: Prospective, monocentral pilot study. SETTING: Tertiary care center. PATIENTS: A cohort of 100 women who were infertile was enrolled from July 2019 to December 2020. INTERVENTIONS: Hysteroscopy with endometrial biopsy and laparoscopy with chromopertubation. MEASUREMENTS AND MAIN RESULTS: CE was found in 13 women (13.0%) and was associated with endometriosis (p = .034) and unilateral/bilateral fallopian tube blockage (p = .013). In women with endometriosis, the mean number of CD138-positive cells was positively correlated with the revised American Society for Reproductive Medicine score (r = .302, p = .028). In a binary regression model, the presence of a hydrosalpinx on one or both sides (odds ratio 15.308; 95% confidence interval, 1.637-143.189; p = .017) and the finding of CE in the endometrial tissue sample (odds ratio 5.273; 95% confidence interval, 1.257-22.116; p = .023) were significantly associated with fallopian tubal occlusion. CONCLUSION: CE was significantly associated with blockage of the fallopian tubes and endometriosis. Endometriosis stage was associated with the number of CD138-positive cells in endometrial biopsies.

Detection of hysteroscopic fluid in the pouch of Douglas: a prospective cohort study about the predictability of bilateral tubal occlusion.

PURPOSE: To determine whether an increase in cul de sac (CDS) fluid after hysteroscopy is predictive of tubal patency. METHODS: In a prospective clinical cohort study, 115 subfertile women undergoing laparoscopic and hysteroscopic surgery at the Medical University of Vienna were invited to participate. The primary outcome was determining whether an increase in fluid in the pouch of Douglas was reflective of unilateral or bilateral tubal patency. Vaginal sonography before and after hysteroscopy was performed to detect fluid in the pouch of Douglas, directly followed by laparoscopy with chromopertubation. RESULTS: Laparoscopic chromopertubation revealed bilateral Fallopian tube occlusion in 28 women (24.3%). Twenty-seven/40 patients (67.5%) with no fluid shift had bilateral occlusion during the consecutive laparoscopy (p < 0.001). One/75 patients (1.3%) showing a fluid shift had bilateral occlusion (sensitivity of a present fluid shift for uni- or bilateral patency 85.1%, 95% CI: 81.7-99.9, specificity: 96.4%, 95% CI: 75.8-91.8). Intracavitary abnormalities (odds ratio, OR, 0.038; p = 0.030) and adhesions covering one or both tubes (OR 0.076; p = 0.041) increased the risk for a false abnormal result, i.e., uni- or bilateral tubal patency despite the lack of a fluid shift. CONCLUSION: When CDS fluid does not change after hysteroscopy, this is a sensitive test for tubal occlusion and further testing may be warranted. However, if there is an increase in CDS fluid after hysteroscopy, particularly for a patient without fluid present prior, this is both sensitive and specific for unilateral or bilateral tubal patency.

Assessment of Tubal Patency: A Prospective Comparison of Diagnostic Hysteroscopy and Laparoscopic Chromopertubation.

STUDY OBJECTIVE: To evaluate whether the presence of a visualizable "flow" effect in the fallopian tube ostia in hysteroscopy was predictive of tubal patency. DESIGN: A prospective cohort study. SETTING: In a prospective study, infertile women who underwent surgery because of infertility between March and November 2018 were included. The main outcome parameter was fallopian tube patency assessed by laparoscopic chromopertubation. The predictive parameter tested was the presence of hysteroscopic tube flow. PATIENTS: Seventy-two infertile women. INTERVENTIONS: Combined hysteroscopy and laparoscopy with chromopertubation. RESULTS: One-hundred forty-four fallopian tubes were evaluated, with 88 (61.1%) patent tubes at laparoscopic chromopertubation. A positive hysteroscopic flow effect was recorded for 94 (65.3%) ostia and was accurate in predicting patency (p < .001), with a sensitivity of 85.3% (95% confidence interval [CI], 76.1-91.9) and a specificity of 66.1% (95% CI, 52.2-78.2). A multivariate binary regression model revealed that the presence of a hydrosalpinx (odds ratio = 8.216; 95% CI, 1.062-63.574; p = .044) and peritubal adhesions (odds ratio = 3.439; 95% CI, 1.142-10.353; p = .028) were associated with a false-normal flow result. A hazy hysteroscopic picture was found in 15 of 21 (71.4%) and 5 of 51 (9.8%) cases with and without bilateral tubal occlusion, respectively (p < .001, sensitivity = 71.4% [95% CI, 47.8-88.7], specificity = 90.2% [95% CI, 78.6-96.7]). CONCLUSIONS: The presence of hysteroscopic tubal flow was a reliable indicator of tubal patency. A hydrosalpinx or peritubal adhesions increase the risk for a false-normal result. A hazy hysteroscopic picture suggests bilateral tubal occlusion. Using the hysteroscopic flow effect, one can provide additional information for the patient.

Hysteroscopic Assessment of Tubal Patency: A Randomized Comparison between the Flow and Parryscope Techniques.

STUDY OBJECTIVE: To evaluate the accuracy of the "Parryscope" and "flow" techniques for hysteroscopic assessment of tubal patency. DESIGN: Prospective randomized clinical trial. SETTING: From May to October 2019, women with subfertility undergoing laparoscopic and hysteroscopic surgery at the Medical University of Vienna were invited to participate in the study. The primary outcome was accuracy of Fallopian tube patency relative to the gold standard of laparoscopic chromopertubation. PATIENTS: Sixty women with subfertility. INTERVENTIONS: Hysteroscopy with either the "Parryscope" or the "flow" techniques for tubal assessment, directly followed by laparoscopy with chromopertubation. MEASUREMENTS AND MAIN RESULTS: Hysteroscopic prediction of fallopian tube patency was possible in a statistically significant manner in both study groups (p <0.05). The Parryscope technique achieved higher sensitivity (90.6%, 95% CI: 61.7-98.4) and specificity (100%, 95% CI: 90.0-100.0) than the flow technique (sensitivity: 73.7%, 95% CI: 48.8-90.9 and specificity: 70.7%, 95% CI: 54.5-83.9). CONCLUSION: Using the Parryscope technique to determine if air bubbles traverse the ostia can provide valuable additional information during hysteroscopy and is more accurate in predicting fallopian tubal occlusion than the flow method.

Does anti-Mullerian hormone predict the outcome of further pregnancies in idiopathic recurrent miscarriage? A retrospective cohort study.

PURPOSE: To evaluate whether anti-Mullerian hormone, basal follicle-stimulating hormone, luteinizing hormone, estradiol, and female age would predict future outcomes in women with idiopathic recurrent miscarriage. METHODS: One hundred and sixteen women with idiopathic recurrent miscarriage were retrospectively included. Luteal support with or without a combined treatment regimen for idiopathic recurrent miscarriage was applied in a tertiary-care center in Vienna. Occurrence and outcome of further pregnancies were analyzed. RESULTS: Within a median follow-up duration of 42.3 months, 94 women (81.0%) achieved one or more pregnancies. Further miscarriages occurred in 47 patients in whom only a higher number of previous miscarriages was predictive (OR 3.568, 95% CI 1.457-8.738; p = 0.005). Fifty-seven women had a live birth > 23 + 0 gestational weeks. In a multivariate analysis, age (OR 0.920, 95% CI 0.859-0.986; p = 0.019) and the number of previous miscarriages (OR 0.403, 95% CI 0.193-0.841; p = 0.016), but not AMH (OR 1.191, 95% CI 0.972-1.461; p = 0.091) were significantly predictive. CONCLUSION: AMH seems of either no or only minor relevance for the prediction of further miscarriages and live birth in women with idiopathic recurrent miscarriage.

Accuracy of Tubal Patency Assessment in Diagnostic Hysteroscopy Compared with Laparoscopy in Infertile Women: A Retrospective Cohort Study.

STUDY OBJECTIVE: To evaluate whether the presence of a visualizable "flow" effect in the fallopian tube ostia in hysteroscopic routine evaluation is predictive of tube patency. DESIGN: A retrospective cohort study (Canadian Task Force Classification II-2). SETTING: Data from all patients who underwent surgery because of infertility at the study center between 2008 and 2016 were analyzed retrospectively. The main outcome parameter was fallopian tube patency as assessed by laparoscopic chromopertubation. The predictive parameters tested were the presence of hysteroscopic tube "flow," general patient characteristics, and intraoperative findings. PATIENTS: Five hundred eleven infertile women who underwent combined hysteroscopy and laparoscopy were included. INTERVENTIONS: All women underwent combined hysteroscopy and laparoscopy. Some had other interventions when necessary, but no additional interventions were taken because of this study. RESULTS: In an analysis of 998 fallopian tubes, the hysteroscopic assessment of fallopian tube "flow" was highly accurate in predicting fallopian tube patency (p < .001), with a sensitivity of 86.4% (95% confidence interval [CI], 83.7-88.8) and a specificity of 77.6% (95% CI, 72.1-82.5). Risk factors for a false-negative hysteroscopy result were the presence of uterine myomas (odds ratio [OR] = 2.11; 95% CI, 1.10-4.05; p = .025), the presence of a hydrosalpinx on the analyzed side (OR = 2.50, 95% CI, 1.17-5.34; p = .019), and the presence of peritubal adhesions surrounding the analyzed tube (OR = 2.87; 95% CI, 1.21-6.76; p = .016). CONCLUSION: A visualizable tube "flow" in hysteroscopy was accurate in the prediction of tubal patency, with a positive predictive value of about 91%. Knowledge about hysteroscopic fallopian tube "flow" can help to plan the future approach in an individual patient.

Anti-Mullerian hormone is linked to the type of early pregnancy loss in idiopathic recurrent miscarriage: a retrospective cohort study.

We correlated Anti-Mullerian hormone (AMH) levels and other parameters for ovarian reserve to the gestational age at the time of pregnancy loss in women with idiopathic recurrent miscarriage. In a retrospective study, 79 patients had suffered a total of 266 miscarriages. When comparing women with an "unembryonic" to those with an "embryonic" most recent miscarriage, there was no difference in median age (36.3 years, IQR 31.6-40.1 versus 34.2 years, IQR 29.9-38.0; p = 0.303) but in median AMH levels (0.7, IQR 0.2-18, versus median 1.8, IQR 1.3-3.3, respectively, p = 0.044) and in the rate of patients with an AMH ≤ 1 ng/mL (23/37, 62.2%, versus 8/42, 19%; p < 0.001). Thus, AMH might add to the diagnostic process in recurrent miscarriage in the future.

Severe haematoperitoneum caused by ovarian bleeding after transvaginal oocyte retrieval: a retrospective analysis and systematic literature review.

A case series of haematoperitoneum caused by ovarian bleeding after transvaginal oocyte retrieval (TVOR) is presented and all published cases summarized. In a retrospective case series, four patients with ovarian bleeding after TVOR were included. In addition, a pooled analysis of all published cases (n = 32) who underwent surgical intervention for severe haematoperitoneum caused by ovarian bleeding after TVOR was carried out. Main outcome measures were incidence, risk factors, course and intraoperative findings. In the pooled analysis, the incidence was 0.08%. The first sign of haematoperitoneum was evident in 33.3% within the first postoperative hour, and, cumulatively, in 93.3% within 24 h. The median time between TVOR and surgical intervention was 10 h. In four patients, the ovary could not be preserved, which was associated with a longer time interval between TVOR and the onset of symptoms (median 18 h versus 2.5 h; P = 0.004) as well as between TVOR and surgical intervention (median 21.5 h versus 8.5 h; 0.004). In conclusion, severe haematoperitoneum occurs in 0.08% after TVOR. Late-onset bleeding is common. A longer time interval between TVOR and surgical intervention might put a patient at risk of ovariectomy.

Raf-1 levels determine the migration rate of primary endometrial stromal cells of patients with endometriosis.

Endometriosis is a disease characterized by the localization of endometrial tissue outside the uterine cavity. The differences observed in migration of human endometrial stromal cells (hESC) obtained from patients with endometriosis versus healthy controls were proposed to correlate with the abnormal activation of Raf-1/ROCKII signalling pathway. To evaluate the mechanism by which Raf-1 regulates cytoskeleton reorganization and motility, we used primary eutopic (Eu-, n = 16) and ectopic (Ec-, n = 8; isolated from ovarian cysts) hESC of patients with endometriosis and endometriosis-free controls (Co-hESC, n = 14). Raf-1 siRNA knockdown in Co- and Eu-hESC resulted in contraction and decreased migration versus siRNA controls. This phenotype was reversed following the re-expression of Raf-1 in these cells. Lowest Raf-1 levels in Ec-hESC were associated with hyperactivated ROCKII and ezrin/radixin/moesin (E/R/M), impaired migration and a contracted phenotype similar to Raf-1 knockdown in Co- and Eu-hESC. We further show that the mechanism by which Raf-1 mediates migration in hESC includes direct myosin light chain phosphatase (MYPT1) phosphorylation and regulation of the levels of E/R/M, paxillin, MYPT1 and myosin light chain (MLC) phosphorylation indirectly via the hyperactivation of ROCKII kinase. Furthermore, we suggest that in contrast to Co-and Eu-hESC, where the cellular Raf-1 levels regulate the rate of migration, the low cellular Raf-1 content in Ec-hESC, might ensure their restricted migration by preserving the contracted cellular phenotype. In conclusion, our findings suggest that cellular levels of Raf-1 adjust the threshold of hESC migration in endometriosis.

Pilot study on sex hormone levels and fertility in women with malignant gliomas.

The standard treatment of patients with high-grade gliomas based on conformal radiation therapy (RT) with or without chemotherapy (CT) may induce endocrine deficiencies of pituitary and subsequently also of peripheral hormones. In 24 premenopausal women with high-grade gliomas treated with RT and CT, hormonal changes and their impact on quality of life were investigated. Serum concentrations of gonadal, pituitary and of thyroid hormones were measured at various time points after initial anti-neoplastic therapy. Additionally, endovaginal ultrasound was performed and patients' quality of life (QLQ) and female role functioning were assessed. Of 24 patients, 23 (96%) reported a change in their menstrual pattern. Twenty-one patients reported at least transient amenorrhoea with a mean duration of 26.1 months (3-96 months). Increased prolactin serum levels were found in 10 women, 8 of them with amenorrhoea. Thirteen women showed menopausal or perimenopausal hormone pattern, 3 a pattern compatible with hypogonadism. Changes in thyroid hormone levels were seen in 8 patients. Furthermore, patients complained about fatigue and menopausal symptoms, like flushes, weakness and gain of weight. They felt a decrease of libido combined with the loss of attractiveness as a female, and an increased need for tender care and security. The hormonal deficiencies in female patients with malignant gliomas require thorough evaluation and individualized diagnosis and sometimes intervention.

The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women.

OBJECTIVE: To evaluate the effect of red clover isoflavone supplementation over vasomotor and overall menopausal symptoms in postmenopausal women. METHODS: One hundred and nine postmenopausal women aged 40 or more were assigned to randomly receive either two daily capsules of the active compound (80 mg red clover isoflavones, Group A) or placebo of equal appearance (Group B) for a 90-day period. After a washout period of 7 days, medication was crossed over and taken for 90 days more. Daily hot flush and night sweat frequency and overall menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97 and 187 days. RESULTS: Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline. All indices significantly decreased after red clover phase in Group A, corresponding, respectively to a 73.5%, 72.2% and 75.4% average decrement. These decrements were significantly higher than those observed for Group B after placebo phase (8.2%, 0.9% and 6.7% respectively). In Group A, after washout and placebo phases all values significantly increased. In Group B, all indices remained similar after placebo and washout phases, however significantly dropping after red clover treatment. These values were also significantly lower than those observed in Group A after placebo phase. No side effects were encountered after treatment with the active compound or placebo. CONCLUSION: Red clover isoflavone supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women.

Are the Stage and the Incidental Finding of Endometriosis Associated with Fallopian Tube Occlusion? A Retrospective Cohort Study on Laparoscopic Chromopertubation in Infertile Women.

Endometriosis seems to have a strong negative effect on female fertility. The aim of this study was to assess the rate of tubal occlusion diagnosed via laparoscopic chromopertubation in infertile women with endometriosis and compare the results to infertile women without endometriosis. In this retrospective cohort study, 275 infertile women with endometriosis and 49 infertile women without endometriosis undergoing diagnostic laparoscopy for primary or secondary infertility with chromopertubation at the Medical University of Vienna between January 2012 and December 2020 have been investigated. During the laparoscopic assessment of tubal patency, significantly more fallopian tubes were occluded in the endometriosis group compared to the control group (25.8 versus 15.3%; p = 0.029). Unilateral and bilateral occlusion was found significantly more often in patients with endometriosis (p = 0.021). In the multivariate analysis, only the rASRM stage (the revised classification of endometriosis by the American Society for Reproductive Medicine) showed a significant association with bilateral occlusion (OR 1.400, 95%CI: 1.018-1.926; p = 0.038). Both a higher rASRM stage (OR 2.181, 95%CI: 1.191-3.995; p = 0.012) and secondary infertility (OR 1.514, 95%CI: 1.156-1.983; p = 0.003) were associated with an increased risk for any kind of fallopian tube occlusion. Endometriosis seems to be associated with an increased risk for fallopian tube occlusion. The rate of tubal occlusion increased significantly with the rASRM stage.

A modified technique of laparoscopic ovarian drilling for polycystic ovary syndrome using the monopolar hook electrode.

The aim of our study was to review our experience with a modified technique of laparoscopic ovarian drilling (LOD) using a monopolar hook electrode. We retrospectively included 38 clomiphene-resistant women with polycystic ovary syndrome undergoing LOD. A laparoscopic monopolar hook electrode was used to make three to six incisions in the ovarian capsule. It resulted in a rate of spontaneous ovulation of 75.8%, an overall one-year pregnancy rate of 80.6% and a subsequent live birth rate of 67.7%. We consider our LOD technique using the monopolar hook electrode practicable. Whether it leads to a more extensive destruction of the ovarian capsule and thereby of the ovarian reserve remains open.

Pregnancy outcome in women with polycystic ovary syndrome comparing the effects of laparoscopic ovarian drilling and clomiphene citrate stimulation in women pre-treated with metformin: a retrospective study.

BACKGROUND: Ovarian stimulation in women with polycystic ovary syndrome (PCOS) increases the risk for perinatal complications. Ovulation induction by laparoscopic ovarian drilling (LOD) might improve the overall pregnancy outcomes. The aim of our study was to assess the adverse events or effects on pregnancy of LOD and clomiphene citrate (CC) stimulation in patients who received metformin. SETTING: Academic research institution. We retrospectively analyzed the courses of 40 spontaneous pregnancies after LOD for CC-resistance, 40 pregnancies after CC stimulation, and 40 pregnancies after metformin treatment alone. Patients in the LOD and the CC groups had been pre-treated with Metformin. Primary outcome parameters were: the rate of multiple pregnancies; the rate of early pregnancy losses/miscarriages; the development of gestational diabetes, pregnancy-induced hypertension, and preeclampsia/HELLP-syndrome; premature delivery; and birth weight. RESULTS: The rate of twin pregnancies did not differ between the CC group (12.5%), the LOD group (7.5%), and the metformin only group (2.5%, p=0.239). Seventeen women suffered an early miscarriage. There were no differences with regard to the rates of gestational diabetes, pregnancy-induced hypertension, preeclampsia, and preterm delivery. By analyzing all pregnancy complications together, the overall pregnancy complication rate was highest in the CC group (70.0%, 28/40), followed by the LOD group (45.0%, 18/40), and the metformin only group (47.5%, 19/40; p=0.047). CONCLUSIONS: CC, but not LOD, increases the complication rate in pregnant patients who received metformin.

Luteinizing hormone and androstendione are independent predictors of ovulation after laparoscopic ovarian drilling: a retrospective cohort study.

BACKGROUND: Our objective was to investigate luteinizing hormone, follicle-stimulating hormone, testosterone, and androstenedione as predicitve markers for ovulation after laparoscopic ovarian drilling. METHODS: We retrospectively analyzed 100 clompihen-resistant patients with the polycystic ovary syndrome who underwent laparoscopic ovarian drilling at our department. The main outcome measure was spontaneous postoperative ovulation within three months after laparoscopic ovarian drilling. In order to predict spontaneous ovulation, we tested the following parameters by use of a univariate followed by a multivariate regression model: Preoperative serum levels of LH, FSH, testosterone, and androstenedione as well as patients' age and body mass index. In addition, we focused on pregnancy and life birth rates. RESULTS: Spontaneous ovulation was documented in 71/100 patients (71.0%). In a univariate and multivariate analysis, luteinizing hormone (OR 1.58, 95%CI: 1.30-1.92) and androstenedione (OR 3.03, 95%CI: 1.20-7.67), but not follicle-stimulating hormone and testosterone were independent predictors of ovulation. Using a cut-off for luteinizing hormone and androstenedione of 12.1 IU/l and 3.26 ng/ml, respectively, spontaneous ovulation was observed in 63/70 (90.0%) and 36/42 patients (85.7%) with elevated and in 8/30 (26.7%) and 35/58 (60.3%) patients with low luteinizing hormone and androstenedione levels, respectively. The sensitivity, specificity, positive and negative predictive values for luteinizing hormone and androstendione as predictors of spontaneous ovulation after ovarian drilling were 88.7% (95%CI: 79.0-95.0%), 75.9% (95%CI: 56.5-89.7%), 90.0% (95%CI: 80.5-95.8%), and 73.3% (95%CI: 54.1-87.7%) for luteinizing hormone, and 50.7% (95%CI: 38.6-62.8%), 79.3% (95%CI: 60.3-92.0%), 85.7% (95%CI: 71.5-94.6%), and 39.7% (95%CI: 27.0-53.4%) for androstenedione, respectively. Complete one-year follow-up was available for 74/100 patients (74%). We observed a one-year pregnancy rate and a resulting life-birth rate of 61% and 51%, respectively. CONCLUSIONS: Luteinizing hormone and androstenedione prior to laparoscopic ovarian drilling are independent predictors of spontaneous ovulation within three months of surgery. We suggest to preferentially performing laparoscopic ovarian drilling in patients with high luteinizing hormone and androstenedione levels.

The Prevalence of Incidental Endometriosis in Women Undergoing Laparoscopic Ovarian Drilling for Clomiphene-Resistant Polycystic Ovary Syndrome: A Retrospective Cohort Study and Meta-Analysis.

To evaluate the incidence of endometriosis in polycystic ovary syndrome (PCOS) patients who did not present with any endometriosis symptoms and underwent laparoscopic ovarian drilling (LOD) for clomiphene citrate (CC) resistance, 225 and 630 women with CC-resistant PCOS without classic endometriosis symptoms were included in a retrospective study and a meta-analysis, respectively. All women underwent LOD. The main outcome parameter was the prevalence of incidental endometriosis. Laparoscopy revealed endometriosis in 38/225 (16.9%) women (revised American Fertility Society (rAFS) stage I: 33/38, 86.8%; rAFS stage II: 5/38, 13.2%). When women with CC-resistant PCOS without endometriosis were compared, lower body mass index (BMI) and lower 25-hydroxy-vitamin D levels were associated with the presence of endometriosis at laparoscopy (odds ratios (OR): 0.872, 95% confidence intervals (95%CI): 0.792-0.960; p = 0.005 and OR: 0.980, 95%CI: 0.962-0.999; p = 0.036; respectively). The inclusion criteria for the meta-analysis were fulfilled by 4/230 reports about LOD. After correction for study heterogeneity, the pooled prevalence of incidental endometriosis was 7.7% in women with CC-resistant PCOS. In conclusion, the rate of incidental endometriosis in women with CC-resistant PCOS might reflect the prevalence of asymptomatic endometriosis. All cases were affected by minimal or mild disease. Since the literature lacks reports on associated clinical outcomes, the relevance of this entity in such patients should be the subject of further studies.

Are hypothyroidism and hypogonadism clinically relevant in patients with malignant gliomas? A longitudinal trial in patients with glioma.

BACKGROUND: So far, the development and course of therapy-induced deficiencies in hypothalamic-pituitary hormones in adult patients with malignant gliomas has not received much attention. However, such deficiencies may impact patient's quality of life substantially. METHODS: In this monocentric longitudinal trial, we examined hormonal levels of TSH, T3, T4, fT3, fT4, FSH, LH, testosterone, estradiol and prolactin in patients with malignant high grade gliomas before the start of radiochemotherapy (RCT), at the end of RCT and then every three months for newly diagnosed patients and every six months in patients diagnosed more than two years before study inclusion. Growth hormone was not measured in this trial. RESULTS: 436 patients (198 female, 238 male) with high-grade gliomas, aged 19-83 years (median 50 years), were included in this study. Low levels of thyroid hormones were observed in around 10% of patients within the first six months of follow up and increasingly after 36 months. Half of premenopausal women at study entry developed premature menopause, 35% showed hyperprolactinemia. Low testosterone levels were measured in 37% of men aged less than 50 years and in 35/63 (55%) of men aged 50 years or older. DISCUSSION: The results of this study show that a significant percentage of patients with malignant gliomas develop hormonal deficiencies mandating regular clinical follow up, state of the art counseling and if clinically necessary substitution therapy.

TNFalpha -308 C-->t and -863 C-->a polymorphisms and spermiogram characteristics.

BACKGROUND: Genetic factors may play a role in male infertility. METHODS: In a prospective case-control study, we assessed the allele and genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms, detected by PCR of sperm DNA, of 577 Caucasian men recruited in an infertility clinic. Semen sampling was performed and spermiogram results were correlated to genetic data. RESULTS: The allele frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were not significantly different between non-normozoospermic (n = 447) and normozoospermic (n = 130) men [758/894 (85%) and 134/894 (15%) vs. 213/269 (82%) and 43/260 (18%), p = 0.5, odds ratio (OR) 1.1, 95% confidence interval (CI) 0.74-1.76, and 749/894 (84%) and 145/894 (16%) vs. 212/260 (82%) and 48/260 (18%), p = 0.4, OR 1.2, 95% CI 0.78-1.76, respectively]. The genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were also not significantly different between non-normozoospermic and normozoospermic men. In addition, mutant alleles were not overrepresented in subgroups of men with the oligoasthenoteratozoospermia syndrome and asthenozoospermia. CONCLUSION: The TNFalpha -308 C-->T and -863 C-->A polymorphisms are not associated with spermiogram characteristics and do not represent molecular markers for genetic susceptibility to male infertility.