The Role of Hysteroscopy in the Assessment of Fallopian Tubal Patency: A Comprehensive Review and Meta-analysis.

Hysteroscopy has been recognized as a reliable method for the evaluation of female infertility for several years. The outpatient setting is particularly convenient, as patients do not require general anesthesia and do not have to stay overnight. In recent years, more and more articles have dealt with the role of diagnostic hysteroscopy in tubal evaluation. Twenty-four articles were included in this comprehensive review and 14 of them were also included in a meta-analysis. This review provides an overview of the different techniques of hysteroscopic tubal evaluation, with a focus on perioperative changes in cul-de-sac volume, the air bubble technique ("Parryscope" technique), the Flow technique and selective hysteroscopic pertubation with methylene blue dye (SHPMBD). In pooled analyses, SHPMBD achieved the highest sensitivity for tubal patency (91.7%, 95% confidence interval, CI: 88.8-94.0), whereas the air bubble technique revealed the highest specificity of all methods (98.4, 95% CI: 95.3-99.6). Furthermore, in a meta-analysis of all methods on the assessment of single tubes, an overall sensitivity of 87.1% and an overall specificity of 79.8% (95% CI: 76.4-82.9) could be shown. In conclusion, the techniques of hysteroscopic tubal evaluation are well-tolerated, clinically relevant, and reliable.

Incidence and Causes of Tubal Occlusion in Infertility: A Retrospective Cohort Study.

Background and Objectives: Fallopian tubal pathology is a primary risk factor for female infertility, with simple proximal disease and proximal disease extending more distally being more common than pure distal occlusion. Proximal tubal occlusion is often attributed to ascending events, such as pelvic inflammatory disease. Conversely, while distal occlusion can also be attributable to ascending pelvic inflammatory disease, it can also have a pelvic origin, such as through endometriosis and ruptured appendicitis. The aim of this study was to identify certain causes of infertility and their association with tubal occlusion. The focus was on the location of tubal occlusion, uni- versus bilateral occlusion, and other causes of infertility, including male factors. Methods: In a retrospective study cohort study, 373 women aged between 18 and 40 years, treated from 1 January 2017 to 31 December 2022, were included. Fallopian tube patency was tested using either hysterosalpingography, hysterosalpingo-contrast sonography, or laparoscopic chromopertubation. Results: In total, 95 of 373 women (25.5%) revealed at least one occluded tube, with unilateral occlusion being more common than bilateral occlusion (60/95, 63.2% vs. 35/95, 36.8%). The majority of tubal occlusions occurred proximally (86.2%). According to the adjusted multivariate regression models, the presence of hydrosalpinx (odds ratio, OR, 13.323, 95% confidence interval, CI: 2.679-66.253, p = 0.002), myomas (OR 2.108, 95%CI: 1.008-4.409; p = 0.048), and an abnormal sperm test result of the male partner (OR 2.105, 95%CI: 1.156-3.833; p = 0.015) were statistically significant associated factors for tubal occlusion. Conclusions: Fallopian tube patency testing is still of major relevance in fertility evaluation. The presence of uterine myomas, hydrosalpinges, and a male factor significantly increase the risk.

Elinzanetant, a new combined neurokinin-1/-3 receptor antagonist for the treatment of postmenopausal vasomotor symptoms.

INTRODUCTION: In many postmenopausal women, quality of life is decreased due to vasomotor symptoms. Efficient and well-tolerated non-hormonal treatment options are needed. AREAS COVERED: The present review summarizes what is known about the etiology of postmenopausal vasomotor symptoms as a rationale for the mechanism of action of Elinzanetant, a new neurokinin (NK)-1/-3 receptor antagonist, as well as its efficacy and side effect profile. EXPERT OPINION: Elinzanetant likely exerts an antagonistic effect on the NK-3 receptor in the preoptic thermoregulatory zone, but also an additional antagonistic effect on the NK-1 receptor possibly leading to a reduction in vasodilatation and heat-sensing neuro-activity. Elinzanetant's reported peak drug concentrations are reached within one hour and the terminal elimination half-life is approximately 15 hours. Two phase IIb clinical trials evaluated the safety profile and efficacy of several doses. There were no serious adverse events, which also included a lack of evidence of drug-related hepatotoxicity. Overall, Elinzanetant seems to be well-tolerated. In the SWITCH-1 study, the 120 mg/day and 160 mg/day regimen showed good efficacy for the treatment of vasomotor symptoms and led to significant improvements in quality of life. Thus, 120 mg oral Elinzanetant/day was used in phase III trials, whose results have not yet been published.

Prevalence of functional hypothalamic amenorrhea in a cohort of women referred because of polycystic ovary syndrome.

In this unselected population of women referred to a center specialized in gynecologic endocrinology for suspicion of PCOS, a minimum rate of misdiagnosed FHA patients of about 2% was found. It is necessary to evaluate reliable markers for the differential diagnosis between PCOS and FHA to avoid incorrect treatment, which might lead to negative long-term effects in women with undiagnosed FHA.

Treatment trajectories of gender incongruent Austrian youth seeking gender-affirming hormone therapy.

Objective: The aim of this study was to describe the treatment trajectories of Austrian children and adolescents with gender incongruence seeking gender-affirming medical care. Methods: Patients who presented with gender incongruence at the pediatric outpatient clinic for differences in sex development at a large university hospital in Austria from January 2008 to December 2022 were included in a retrospective chart review, and analyzed regarding referral numbers, patient characteristics, treatment trajectories, fertility preservation, and legal gender marker changes. Results: Of 310 eligible patients, 230 (74.2%) were assigned female at birth (AFAB), and 80 (25.8%) were assigned male at birth (AMAB). The number of referrals increased steeply from 2008 to 2018, whereafter it stabilized at around 50 per year. At the time of initial presentation, the median age of patients was 15.6 years (IQR 14.3-16.8). AMAB individuals tended to be younger (median 14.9 years, IQR 13.9-16.8) than AFAB individuals (median 15.8 years, IQR 14.4-16.8; p= 0.012). 207 (66,8%) completed the assessment process and were eligible for gender affirming medical treatment (GAMT). Of those, 89% (186/207) commenced gender affirming hormone therapy in the pediatric outpatient clinic (79/186 received GnRHa monotherapy, 91/186 GnRHa and sex steroids, and 16/186 sex steroid monotherapy). Of the 54 AMAB individuals receiving GAMT, 6 (11.1%) completed fertility preservation prior to therapy initiation. Only 1/132 AFAB adolescents receiving GAMT completed fertility preservation. Chest masculinization surgery was performed in 22 cases (16.7%), and breast augmentation in two cases (3.7%) between the ages of 16 and 18. Changes in legal gender marker were common, with 205 individuals (66.1%) having changed their legal gender marker. Conclusion: This is the first time that treatment trajectories, fertility preservation rates, and changes of legal gender marker have been described in Austrian adolescents with gender incongruence seeking GAMT. The majority received GAMT and changed their legal gender marker, while gender affirming surgery rates were low, and utilization of fertility preservation treatment options was rare.

Periconceptional Counselling in Women with Autoimmune Inflammatory Rheumatic Diseases.

Systemic autoimmune rheumatic diseases (SARDs) in pregnancy represent a complex challenge for both patients and healthcare providers. Timely preparation for pregnancy enables adequate disease control, thereby reducing the risk of disease flare and pregnancy complications. Interdisciplinary care starting from the pre-pregnancy period throughout pregnancy and during breastfeeding ensures better fetal and maternal outcomes. This review provides a comprehensive guide to pre-pregnancy counselling in SARDs, an overview of medication management strategies tailored to pregnancy, disease activity and pregnancy monitoring in patients, and the promotion of shared decision making between healthcare providers and patients. Guidelines from international organizations were selected to provide a basis for this review and guidance through the quintessential discussion points of care.

The LH:FSH Ratio in Functional Hypothalamic Amenorrhea: An Observational Study.

BACKGROUND: In functional hypothalamic amenorrhea (FHA), luteinizing hormone and follicle-stimulating hormone levels show high interindividual variability, which significantly limits their diagnostic value in differentiating FHA from polycystic ovary syndrome (PCOS). Our aim was to profile the LH:FSH ratio in a large sample of patients with well-defined FHA. METHODS: This observational study included all consecutive patients with FHA presenting to the Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, between January 2017 and August 2023. The main parameters of interest were the LH level, the FSH level, and the LH:FSH ratio. In a subgroup analysis, we compared the LH:FSH ratio of patients with PCO morphology (PCOM) on ultrasound with that of patients without PCOM. RESULTS: A total of 135 patients were included. Only a minority of patients revealed FSH and LH levels ≤ 2.0 mIU/mL (13% and 39%, respectively). Most patients (81.5%) had an LH:FSH ratio ≤ 1.0, while a minority (2.2%) had a ratio ≥ 2.1. The LH:FSH ratio was similar in patients with and without PCOM. CONCLUSION: In a well-defined FHA sample, the LH:FSH ratio was ≤ 1 in most patients. The LH:FSH ratio may prove useful in distinguishing FHA from PCOS but needs further investigation.

Prolactin levels in functional hypothalamic amenorrhea: a retrospective case-control study.

PURPOSE: Functional hypothalamic amenorrhea (FHA) is due to hypothalamic dysregulation. Literature lacks data about prolactin in FHA women, although both prolactin levels and FHA are associated with stress. Moreover, polycystic ovarian morphology is common in FHA and there is an association between FHA and polycystic ovary syndrome. Thus, the aim of this study was to assess prolactin levels in FHA patients and controls with a special focus on factors influencing prolactin levels, that could be considered as "sensors" of the hypothalamic-pituitary dysregulation. METHODS: In a retrospective cohort study, 140 women with clearly defined FHA were compared to 70 healthy, normally ovulating women matched for age. The main outcome parameter was prolactin. Factors associated with prolactin levels > 12 µg/L were tested using a multivariable binary logistic regression model. RESULTS: The median prolactin level was 11.5 µg/L (interquartile range, IQR 7.5-14.4), which was similar to the control group (median 10.7, IQR 8.3-14.5; p = 0.065). Only two women had hyperprolactinemia (prolactin > 25 µg/L; 1.4%). In a multivariable binary logistic regression model eating disorder (odds ratio, OR 0.206; p = 0.040), excessive exercise (OR 0.280; p = 0.031) and TSH (OR 1.923; p = 0.020) were significantly associated with prolactin levels > 12 µg/L. CONCLUSION: Women with FHA have similar prolactin levels to healthy age-matched individuals. Eating disorders and excessive exercise where associated with prolactin levels < 12 µg/L, in contrast to TSH.

Different Impacts of Cryopreservation in Endothelial and Epithelial Ovarian Cells.

The aim of our laboratory-based study was to investigate the extent of delayed-onset cell death after cryopreservation in endothelial and epithelial cell lines of ovarian origin. We found differences in percentages of vital cells directly after warming and after cultivation for 48 to 72 h. A granulosa cell line of endothelial origin (KGN) and an epithelial cell line (OvCar-3) were used. In both DMSO-containing and DMSO-free protocols, significant differences in vitality rates between the different cell lines when using open and closed vitrification could be shown (DMSO-containing: KGN open vs. OvCar open, p = 0.001; KGN closed vs. OvCar closed, p = 0.001; DMSO-free: KGN open vs. OvCar open, p = 0.001; KGN closed vs. OvCar closed, p = 0.031). Furthermore, there was a marked difference in the percentage of vital cells immediately after warming and after cultivation for 48 to 72 h; whereas the KGN cell line showed a loss of cell viability of 41% using a DMSO-containing protocol, the OvCar-3 cell loss was only 11% after cultivation. Using a DMSO-free protocol, the percentages of late-onset cell death were 77% and 48% for KGN and OvCar-3 cells, respectively. Our data support the hypothesis that cryopreservation-induced damage is cell type and cryoprotective agent dependent.

A case-control study about markers of stress in normal-/overweight women with polycystic ovary syndrome and in controls.

Background: Polycystic ovary syndrome (PCOS) is linked to an elevated risk of psychological disorders, decreased quality of life and emotional distress. Serum cortisol as a potential stress marker has been found to be increased in women with PCOS. The aim of this study was to evaluate both saliva stress markers and subjective psychological distress in women with PCOS. Methods: In a prospective case-control study, 31 PCOS women and 31 healthy controls were included. Salivary cortisol, and metanephrines were collected in the morning and in the evening. Emotional distress and quality of life were assessed by means of the Perceived Stress Scale (PSS-10) and the Short Form-36 (SF-36). Multivariable generalized linear models were applied to test the influence of various parameters on numerical outcome parameters. Results: After correction for age and body mass index (BMI), there were no statistically significant differences of salivary biomarkers between PCOS women and healthy controls (p>0.05). PCOS patients revealed significantly higher increased PSS total scores and lower quality of life in all SF-36 modules apart from pain (p< 0.05). The PSS total score was positively correlated to prolactin in PCOS women (r= 0.450; p= 0.011). In overweight/obese PCOS patients, a higher BMI, a higher Ferriman Gallwey score and higher age significantly predicted the PSS total score (p< 0.05). Conclusion: Stress measured by salivary biomarkers did not differ between PCOS women and healthy controls, whereas stress scores evaluated by questionnaires were significantly greater in women with PCOS. A higher BMI, hirsutism and a higher age seem to be the main modulators of subjective stress in PCOS. Prolactin might serve as a biomarker for chronic stress in PCOS women.

Outcome of Gastric Bypass Surgery on Patients with Polycystic Ovary Syndrome: A Review.

Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is associated with obesity. The most effective method to achieve and maintain long-term weight loss is by the Roux-en-Y gastric bypass (RYGB). In this review, an overview about metabolic and PCOS-specific outcomes after RYGB in obese PCOS women is provided. The RYGB leads to an adequate excess weight loss and reduction in BMI in this patient population. Testosterone levels decline significantly at 6- and 12-months follow-up, as does the incidence of hirsutism and cycle irregularities. Data about fertility are scarce in this patient population. In conclusion, RYGB surgery seems to be an efficient treatment option for obese PCOS patients and leads to weight loss and improvements in metabolic parameters as well as in an improvement of PCOS-specific characteristics. However, larger prospective studies are warranted, which include all PCOS-specific outcome data in one patient population at the same time.

Iron status in women with infertility and controls: a case-control study.

Background: Iron deficiency is a common problem in subfertile women. The influence of iron status on unexplained infertility is unknown. Methods: In a case-control study, 36 women with unexplained infertility and 36 healthy non-infertile controls were included. Parameters of iron status including serum ferritin and a serum ferritin <30 µg/dL served as main outcome parameters. Results: Women with unexplained infertility demonstrated a lower transferrin saturation (median 17.3%, IQR 12.7-25.2 versus 23.9%, IQR 15.4-31.6; p= 0.034) and a lower mean corpuscular hemoglobin concentration (median 33.6 g/dL, IQR 33.0-34.1 versus 34.1 g/dL, IQR 33.2-34.7; p= 0.012). Despite the fact that there was no statistically significant difference in median ferritin levels (p= 0.570), women with unexplained infertility had ferritin levels <30µg/L more often (33.3%) than controls (11.1%; p= 0.023). In a multivariate model, unexplained infertility and abnormal thyroid antibodies were associated with ferritin <30µg/L (OR 4.906, 95%CI: 1.181-20.388; p= 0.029 and OR 13.099; 2.382-72.044; p= 0.029, respectively). Conclusion: Ferritin levels <30µg/L were associated with unexplained infertility and might be screened in the future. Further studies with a focus on iron deficiency and iron treatment on women with unexplained infertility are warranted.

Stress and polycystic ovarian morphology in functional hypothalamic amenorrhea: a retrospective cohort study.

BACKGROUND: Women with functional hypothalamic amenorrhea (FHA) reveal polycystic ovarian morphology (PCOM) in up to 50%. If stress sensitivity in women with polycystic ovary syndrome (PCOS) is the reason why PCOS women are prone to develop FHA, patients with FHA caused by stress should reveal PCOM more often. METHODS: In a retrospective cohort study, 38 stress-associated and 38 excessive exercise-induced FHA women were included. The main outcome parameter was PCOM. In addition, the focus was on general patient characteristics as well as on prolactin, dehydroepiandrosterone-sulphate (DHEAS), and anti-Mullerian hormone (AMH). RESULTS: PCOM was found in 34/76 patients (44.7%). The stress group showed a higher prevalence of PCOM than the excessive exercise group (57.9% versus 31.6%, p = 0.019) as well as higher prolactin levels (median 13.2ng/mL versus 11.7ng/mL, p = 0.008) and a trend towards higher DHEAS levels (p = 0.058). CONCLUSIONS: In FHA women, the PCOM prevalence was significantly higher in the stress-group than in the excessive exercise-group. The well-known stress sensitivity in women with PCOS might explain why PCOS women are prone to develop FHA as well as the high PCOM prevalence in FHA women.

An Overview of Postoperative Intraabdominal Adhesions and Their Role on Female Infertility: A Narrative Review.

Postoperative intraabdominal adhesions can occur after more than 90% of gynecologic surgeries. They not only cause chronic pelvic pain and small bowel obstruction, but are also one of the main reasons for infertility. Adhesions are not only a burden for the affected patients, but are also a burden for the healthcare system, since the treatment of adhesion-associated complications costs a considerable amount of money. The gold standard for the diagnosis of adhesions is by laparoscopy, although other methods, such as transvaginal hydro-laparoscopy, are being discussed as better alternatives. Ideally, adhesions are avoided inherently, by operating carefully and by using microsurgical principles. If this is not possible, gel barriers have been shown to be successful in reducing postoperative adhesions.

The Prevalence of Fallopian Tube Occlusion in Women with Polycystic Ovary Syndrome Seems Similar to Non-Subfertile Women: A Retrospective Cohort Study.

There are limited data on how non-infectious risk factors influence tubal patency in women with subfertility. With hormonal shifts influencing tubal secretions, it has been argued that subfertile women with polycystic ovary syndrome (PCOS) have lower tubal patency. In a retrospective study, 216 women, who underwent diagnostic evaluation for PCOS and infertility, were included. Fallopian tube patency was tested using HSG, HyCoSy, and laparoscopic chromopertubation in 171 (79.2%), 28 (13.0%), and 17 (7.9%), respectively. Bilateral patency was found in 193 women (89.4%), unilateral patency in 13 (6.0%) and bilateral occlusion in 10 (4.6%) patients. Women with PCOS phenotypes C (odds ratio, OR 0.179, 95% CI: 0.039-0.828) and D (OR 0.256, 95% CI: 0.069-0.947) demonstrated lower risks for Fallopian tube occlusion. In conclusion, our data suggest that about 5% of infertile women with PCOS also have bilateral tubal occlusion, which seems similar to the rate in non-subfertile women. With 11% of participants having unilateral or bilateral tubal occlusion, this should reassure women with PCOS that their hormonal challenges do not seem to increase their risk for tubal factor subfertility.

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.

Basal and dynamic relationships between serum anti-Müllerian hormone and gonadotropins in patients with functional hypothalamic amenorrhea, with or without polycystic ovarian morphology.

BACKGROUND: To evaluate in women with functional hypothalamic amenorrhea (FHA), whether there is a difference between patients with and without polycystic ovarian morphology (PCOM) concerning the response to a gonadotropin releasing hormone (GnRH) stimulation test and to pulsatile GnRH treatment. METHODS: In a retrospective observational study, 64 women with FHA who underwent a GnRH stimulation test and 32 age-matched controls without PCOM were included. Pulsatile GnRH treatment was provided to 31 FHA patients and three-month follow-up data were available for 19 of these. RESULTS: Serum levels of gonadotropins and estradiol were lower in FHA women than in controls (p < 0.05). FHA patients revealed PCOM in 27/64 cases (42.2%). FHA patients without PCOM revealed lower anti-Müllerian hormone (AMH) levels than controls (median 2.03 ng/mL, IQR 1.40-2.50, versus 3.08 ng/mL, IQR 2.24-4.10, respectively, p < 0.001). Comparing FHA patients with and without PCOM, the latter revealed lower AMH levels, a lower median LH increase after the GnRH stimulation test (240.0%, IQR 186.4-370.0, versus 604.9%, IQR 360.0-1122.0; p < 0.001) as well as, contrary to patients with PCOM, a significant increase in AMH after three months of successful pulsatile GnRH treatment (median 1.69 ng/mL at baseline versus 2.02 ng/mL after three months of treatment; p = 0.002). CONCLUSIONS: In women with FHA without PCOM, the phenomenon of low AMH levels seems to be based on relative gonadotropin deficiency rather than diminished ovarian reserve. AMH tended to rise after three months of pulsatile GnRH treatment. The differences found between patients with and without PCOM suggest the former the existence of some PCOS-specific systemic and/or intra-ovarian abnormalities.

Polycystic Ovary Syndrome Phenotype D Versus Functional Hypothalamic Amenorrhea With Polycystic Ovarian Morphology: A Retrospective Study About a Frequent Differential Diagnosis.

The two most frequent causes of secondary amenorrhea are polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhea (FHA). Despite several studies showing differences in hormonal profile between these groups, the differential diagnosis remains challenging, in particular between FHA women with polycystic ovarian morphology (FHA-PCOM) and PCOS patients without hyperandrogenism (phenotype D, PCOS-D). In a retrospective case-control study, 58 clearly defined patients with FHA-PCOM were compared to 58 PCOS-D patients, matched 1:1 for age and BMI. Significantly higher levels of LH, estradiol, testosterone, and a higher luteinizing hormone (LH): follicle stimulating hormone (FSH) ratio as well as lower sexual hormone binding globulin (SHBG) levels were found in PCOS-D patients (p< 0.05). Optimized cut-off values for the prediction of FHA-PCOM were calculated by the Youden index. The highest sensitivity was found for an estradiol serum level <37.5 pg/mL (84.5%, 95% confidence interval, CI: 72.6-92.6), whereas a LH : FSH ratio <0.96 had the highest specificity (94.8, 95% CI: 85.6-98.9). A linear discriminant analysis including testosterone, SHBG and LH was able to correctly classify 87.9% of FHA-PCOM patients (bootstrap 95% CI: 80.2 - 94.0%). In conclusion, this model including serological parameters could be an easy and reliable tool to distinguish between FHA-PCOM and PCOS-D patients, especially in situations where the clinical profile is not obvious.