Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.

Functional characteristics of a broad spectrum of TBX6 variants in Mayer-Rokitansky-Küster-Hauser syndrome.

PURPOSE: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene deletion and loss-of-function variants in TBX6 have been identified in association with MRKHS. We aimed to expand the spectrum of TBX6 variants in MRKHS and explore the biological effect of the variant alleles. METHODS: Rare variants in TBX6 were called from a combined multiethnic cohort of 622 probands with MRKHS who underwent exome sequencing or genome sequencing. Multiple in vitro functional experiments were performed, including messenger RNA analysis, western blotting, transcriptional activity assay, and immunofluorescence staining. RESULTS: We identified 16 rare variants in TBX6 from the combined cohort, including 1 protein-truncating variant reported in our previous study and 15 variants with unknown effects. By comparing the prevalence of TBX6 variants in the Chinese MRKHS cohort vs 1038 female controls, we observed a significant mutational burden of TBX6 in affected individuals (P = .0004, odds ratio = 5.25), suggesting a causal role of TBX6 variants in MRKHS. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms. The c.423G>A (p.Leu141=) and c.839+5G>A variants impaired the normal splicing of TBX6 messenger RNA, c.422T>C (p.Leu141Pro) and c.745G>A (p.Val249Met) led to decreased protein expression, c.10C>T (p.Pro4Ser) and c.400G>A (p.Glu134Lys) resulted in perturbed transcriptional activity, and c.356G>A (p.Arg119His) caused protein mislocalization. We observed incomplete penetrance and variable expressivity in families carrying deleterious variants, which indicates a more complex genetic mechanism than classical Mendelian inheritance. CONCLUSION: Our study expands the mutational spectrum of TBX6 in MRKHS and delineates the molecular pathogenesis of TBX6 variants, supporting the association between deleterious variants in TBX6 and MRKHS.

Mode of birth in monochorionic versus dichorionic twin pregnancies: a retrospective study from a large tertiary centre in Germany.

BACKGROUND: Optimal mode of birth for twins, in particular monochorionic twins, has been the subject of much debate. This retrospective study compared maternal and newborn outcomes after vaginal birth in monochorionic and dichorionic twins, utilizing a large institutional database. METHODS: Retrospective analysis focusing on 98 monochorionic-diamniotic (MC-DA) and 540 dichorionic-diamniotic (DC-DA) twin births extracted from the perinatal database of a large German hospital. Pregnancies ≥36 weeks of gestation with two viable foetuses born between 2004 and 2014 divided into planned vaginal and planned caesarean delivery were included. Descriptive analysis was performed for maternal characteristics. Odds ratios (OR) with 95% confidences intervals (CI) tested the predictive effect of vaginal birth on neonatal and maternal outcomes. RESULTS: 51.0% MC-DA and 46.7% DC-DA twin pregnancies were planned vaginal births and 44.0% MC-DA mothers and 43.7% DC-DA mothers actually gave birth vaginally. The overall rate of caesarean section (CS) during the years under observation was 79.6% for MC-DA and 77.0% for DC-DA pregnancies. There were no significant differences in neonatal outcome between the subsamples, although acidosis was observed more often in the second DC-DA twin and Apgar scores < 7 were observed more often in MC-DA twins. CONCLUSION: Vaginal birth may be recommended as an option to women with monochorionic twins as no significant differences in outcomes were found between MC-DA and DC-DA twins. However, over half of planned vaginal twin births resulted in CS.

[Burden of Affected Persons with MRKH Syndrome: Effect of an Intervention to Support Surgical Neovaginal Placement]. / Belastung von Betroffenen mit MRKH-Syndrom: Effekt einer Intervention zur Unterstützung bei Neovagina-Anlage.

The diagnosis of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), a rare variant of female sexual development, is usually made during puberty. The uncertainty in self-image and the impos-sibility of becoming pregnant often lead to considerable stress. Although psychosomatic support is consistently recommended in the literature, there have been only a few studies on the psychological aspects of MRKHS. The aim of the present study is to investigate the quality of life or distress of women with MRKHS undergoing neovaginal surgery and, on the other hand, to evaluate effects of the intervention for support during treatment. Methods In an explorative quasi-experimental pre-post study at a national centre for neovaginal surgery, all patients were offered a psychosomatic intervention (intervention group IG, n=23) and their sexual function (FSFI), psychological distress (PHQ-D) and health-related quality of life (SF-12) were assessed before surgery (t0) and six months after (t1). These were compared with data from a sample collected before and after the intervention period (comparison group VG, n=30). Results While the physical quality of life (SF-12) of both groups was unremarkable at both time points, there was a significant impairment in the psychological quality of life. Both groups (IG, VG) improved from t0 to t1 in their sexual function (FSFI) and showed lower depression scores (PHQ-D). The specific intervention developed was well accepted by those affected and rated as helpful. However, this subjectively perceived effectiveness of the intervention was not reflected by improvement on the quality of life scale (SF-12) and depression scale (PHQ-D). Conclusion Those affected show a clear, clinically relevant distress (SF-12), but this is not reflected in the form of psychological comorbidity (PHQ-D). This apparent discrepancy points to psychologically stable women with acute distress due to the diagnosis of variant sex de-evolution. For them, a low-threshold support service with a supportive character seems to be necessary and helpful during the surgical treatment. The reconstructive therapy for the creation of a neovagina seems to have a positive influence on the psychological quality of life. The fact that pregnancy is still not possible due to the missing uterus could be a reason for not reaching the quality of life of the average population.

Prevalence of autoimmune disease in women with premature ovarian failure.

Objective: The aim of the study was to investigate the relationship between premature ovarian failure and autoimmune disease.Methods: This interdisciplinary prospective study included 52 consecutively recruited women with premature ovarian failure, aged 18-40 years. Diagnosis of premature ovarian failure was defined as amenorrhoea lasting more than 4 months and anti-Müllerian hormone levels below the age-appropriate range. Women with an abnormal karyotype or Fragile X syndrome were excluded from the study. All participants were screened by a rheumatologist for the presence of underlying autoimmune disease.Results: The average age at first diagnosis of premature ovarian failure was 29.5 years; 92.3% of participants (n = 48) presented with a secondary amenorrhoea, while only 7.7% (n = 4) had primary amenorrhoea. Of all 52 participants, 40.4% (n = 21) had at least one confirmed autoimmune disease, including Hashimoto's disease, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Crohn's disease, polyglandular autoimmune syndrome and coeliac disease. Response rates for hormonal stimulation therapy were low and the presence of autoimmune disease was associated with poor infertility treatment outcome.Conclusions: We found a high prevalence of autoimmune disease in women with premature ovarian failure. Screening for autoimmune diseases should be offered to all women with premature ovarian failure.

Demographic changes and effects on the mode of delivery: a retrospective analysis of a large birth registry containing 27,729 singleton deliveries in a level I center.

PURPOSE: To characterize and understand the demographics (age and body mass index, BMI) of a cohort of women who delivered at a single institution over an 11-year period. The purpose of this analysis is to look for effects over time of demographic characteristics on mode of delivery. METHODS: Retrospective analysis of singleton deliveries between 2004-2014, n = 27,729; level 1 perinatal center, university hospital setting. Data were extracted from the digital birth registry. All statistical analyses were done using R version 3.5.1. Variables analyzed were: age, BMI, and mode of delivery (in the current and any prior pregnancies). RESULTS: Mean age increased from 31.1 ± 5.2 years in 2004 to 31.5 ± 5.0 years in 2014 (p < 0.001, eta2 = 0.0006). Mean BMI before pregnancy increased from 23.7 ± 4.5 to 24.7 ± 5.2 kg/m2. Mean BMI at delivery increased from 28.5 ± 4.7 to 29.6 ± 5.2 kg/m2 (p < 0.001, eta2 = 0.0049). Regarding maternal age, patients with elective Cesarean section (CS) (32.5 ± 5.3 years), emergency CS (31.6 ± 5.6 years) and CS in labor (31.4 ± 5.3 years) were older compared to those with spontaneous (31.0 ± 5.2 years) or instrument-assisted vaginal delivery such as vacuum (31.0 ± 5.0 years) and forceps (30.2 ± 5.4 years). Among the multiparous patients, the mode of delivery in prior pregnancies is the variable with the greatest effect on the mode of delivery in any subsequent pregnancies. The mode of delivery was: spontaneous (55.5%), vaginal operative including vacuum and forceps (8.8%), and Cesarean section (35.7%). CONCLUSIONS: Increase of age and BMI over years is significant, but very small and in a range which seems not clinically relevant. Previous births have the strongest effects on mode of delivery in the current pregnancy.

The preferred mode of delivery of medical professionals and non-medical professional mothers-to-be and the impact of additional information on their decision: an online questionnaire cohort study.

PURPOSE: It was the aim to evaluate the personal preference of mode of delivery and to analyze differences between medical professionals and non-medical professionals. Interest in participating in a risk stratification system was evaluated. We hypothesized that gaining information about risk stratification provided in the survey could potentially change participants' decision regarding the preferred mode of delivery; therefore, subjects were asked twice (before and after providing information). METHODS: Five cohorts [four professionals (MP) including participants of the German Urogynecology Congress 2017, employees of two major university hospitals in Germany, and members of the German Society of Gynecology and Obstetrics, and one non-professional group (NP) including pregnant women] were invited online to participate in this survey. RESULTS: Vaginal delivery was the preferred mode of delivery in both groups (MP 90.4% vs. NP 88.8%; p = 0.429). MP are more likely to opt for CS due to concerns regarding pelvic floor disorders (MP 56.6% vs. NP 9.1%; p < 0.001). Likewise, parity and prior experienced CS (pCS) had a significant impact on the decision towards vaginal delivery (parity MP OR 7.5 95% CI 4.6-12.3, NP OR 9.3 95% CI 1.9-44.2; (pCS) MP OR 0.12 95% CI 0.07-0.19, NP OR 0.05 95% CI 0.01-0.25). There is great interest in participating in risk stratification systems in the majority of participants (68.9%). CONCLUSIONS: MP and NP prefer vaginal birth for themselves or their partners. Within the group that opted for CS, MP were significantly more often concerned about pelvic floor disorders. Future prevention aspects might include education about pelvic floor disorders.

Magnetic resonance imaging of vaginal support structure before and after Vecchietti procedure in women with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION: It is unclear how pelvic floor supporting structures might be affected by the absence of the vagina. It was the aim of this prospective study to analyze the magnetic resonance imaging morphology of pelvic support prior and after a Vecchietti procedure in women suffering Mullerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome). MATERIAL AND METHODS: 26 women with a diagnosis of Mayer-Rokitansky-Küster-Hauser syndrome associated vaginal agenesis were recruited prospectively prior to the laparoscopic creation of a neovagina according to the Vecchietti procedure. The primary outcome measure was the magnetic resonance imaging morphology of supporting structures. Secondary outcome measures were anatomical and functional vaginal length. Follow up was conducted six months after surgery. RESULTS: Twenty-six women were analyzed. Mean age was 19.8 ± 4.4 years (±SD) and mean body mass index was 23.7 ± 4.3 kg/m2 (±SD). All were Caucasian. Supporting structures consistent with cardinal and uterosacral ligaments were visible on magnetic resonance imaging in all cases (100%). There were no levator ani defects. The vaginal apex could be visualized postoperatively in 12 women (46.2%) reaching up to Level I. The vagina was visible in both Level II and III with normal relations to the pelvic walls in all cases. On gynecological examination, vaginal length was 8.8 ± 2.1 cm (mean ± SD) anatomically and 10.2 ± 2.2 cm (mean ± SD) functionally. CONCLUSIONS: The preoperative presence of pelvic support structures into which the vagina is lengthened by the surgery likely explains the uncommon occurrence of vaginal prolapse in women who had the Vecchietti procedure.

Female genital tract congenital malformations and the applicability of the ESHRE/ESGE classification: a systematic retrospective analysis of 920 patients.

PURPOSE: Several classification systems for female genital tract anomalies exist but are of limited use in clinical practice. We, therefore, assessed the applicability and ease of use of the new ESHRE/ESGE classification, using only patient records. METHODS: This retrospective, single-center, proof-of-principle study systematically analyzed the surgical reports and other hospital records of 920 inpatients and outpatients treated for confirmed female genital tract congenital malformations at a major German university hospital during 2003-2013. Using only this information, a non-expert (medical student) assigned patients to an ESHRE/ESGE class, rating ease of classification based on the time and the number of additional medical records required. Results were verified by an expert gynecologist, who also classified any malformations previously left unclassified. Data analysis used descriptive statistics. RESULTS: The non-expert successfully classified 859/920 patients (93.4%), rating classification as "easy" for 836/859 (90.9%) and "moderately difficult" for 23/859 (2.5%) patients. The expert gynecologist successfully classified 60 (60/920, 6.5%) of the remaining 61 patients rated as "difficult" by the non-expert, but was unable to accurately subclassify 1 patient (1/920, 0.1%) because the operative report lacked the relevant details. 251/920 (27.3%) patients had associated non-Müllerian anomalies, most frequently renal (20.9%) and skeletal (9.1%) malformations. CONCLUSIONS: The ESHRE/ESGE classification provides a generally applicable, comprehensive, and adequately specific classification of female genital tract congenital malformations. It offers an efficient basis for communication between non-experts and experts in the field and is, therefore, useful in clinical management and treatment planning.

Selecting living donors for uterus transplantation: lessons learned from two transplantations resulting in menstrual functionality and another attempt, aborted after organ retrieval.

PURPOSE: To contribute to establishing donor selection criteria based on our experience with two successful living-donor human uterus transplantations (UTx) and an aborted attempt. METHODS: This interventional study included three patients with uterine agenesis, aged 23, 34, and 23 years, scheduled for UTx, and their uterus-donating mothers, aged 46, 61, and 46 years, respectively. Interventions included preoperative investigations, donor surgery, back-table preparation, and recipient surgery. Preoperative imaging, surgical data, histopathology, menstrual pattern, and uterine blood flow were the main outcome measures. RESULTS: In the first case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 12.12/5.95 h. Regular spontaneous menstruations started 6-week post-transplantation, continuing at 24-28-day intervals throughout the 6-month observation period. Repeated follow-up cervical biopsies showed no signs of rejection. In the second case (61-year-old donor), surgery lasted 13.10 h; attempts to flush the retrieved uterus failed due to extreme resistance of the left uterine artery (UA) and inability to perfuse the right UA. Transplantation was aborted to avoid graft vessel thrombosis or insufficient blood flow during potential pregnancy. Histopathology revealed intimal fibrosis and initial sclerosis (right UA), extensive intimal fibrosis (parametric arterial segments), and subtotal arterial stenosis (myometrial vascular network). In the third case (46-year-old mother/23-year-old daughter), donor/recipient surgery took 9.05/4.52 h. Menstruations started 6-week post-transplantation. Repeated cervical biopsies showed no signs of rejection during the initial 12-week follow-up period. CONCLUSIONS: Meticulous preoperative evaluation of potential living uterus donors is essential. This may include selective contrast-enhanced UA angiograms and limitation of donor age, at least in donors with risk factors for atherosclerosis. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03048396.

Living with permanent infertility: A German study on attitudes toward motherhood in individuals with Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS).

In this study the authors examined the issue of permanent infertility in two diagnoses of the diverse sex developments (DSD) spectrum: Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-KÏster-Hauser Syndrome (MRKHS). The participants with CAIS (n = 12) was older, showed a lower wish for a child and was less distressed about their infertility compared to participants with MRKHS (n = 49). Our data indicated an "indifferent" attitude toward motherhood in CAIS and an "ambivalent" attitude in MRKHS. Depression was frequent in both. Infertility is a source of distress. However, the two groups seem to cope in different ways. Comprehensive medical information and psychological support should be provided.

Decidualization is Impaired in Endometrial Stromal Cells from Uterine Rudiments in Mayer-Rokitansky-Küster-Hauser Syndrome.

BACKGROUND/AIMS: Uterine rudiments from patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) contain all tissues typically found in the uterus. Endometrium from the rudiments predominantly exhibits basalis-like features, and endometrial proliferative capacity in patients' epithelium and stroma is significantly lower. METHODS: This single-center, prospective study conducted at a major German university hospital compared in-vitro decidualization in cultured ESCs from MRKHS patients and hysterectomy controls. Primary ESC cultures were established from both sources. Hormone-induced prolactin and IGFBP-1 secretion served as a measure of their ability to undergo decidualization in response to hormonal stimulation. Expression levels of 8 key marker genes of decidualization were also determined. RESULTS: At day 9, mean secretion of prolactin and IGFBP-1 was significantly reduced by 89.0% and 99.5%, respectively, in MRKHS ESCs vs. hysterectomy controls, both indicating impaired decidualization of MRKHS ESCs. Key decidual markers confirmed impaired decidualization in MRKHS patients. CONCLUSION: Our results indicate that the ESCs from MRKHS patients lack hormone responsiveness as a potential sign of dysfunctional hormone receptor function, which may also play a role in the onset of MRKHS. Further studies are needed to corroborate our findings, directly address receptor function, and elucidate the role of other potential determinants of uterine development and adult function.

Hyperandrogenemia and high prolactin in congenital utero-vaginal aplasia patients.

Patients with the Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) have a congenital utero-vaginal cervical aplasia, but normal or hypoplastic adnexa and develop with normal female phenotype. Some reports mostly demonstrated regular steroid hormone levels in small MRKH cohorts including single MRKH patients with hyperandrogenemia and a clinical presentationof hirsutism and acne has also been shown. Genetically a correlation of WNT4 mutations with singular MRKH patients and hyperandrogenemia was noted. This study analyzed the hormone status of 215 MRKH patients by determining the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, 17-OH progesterone, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and prolactin to determine the incidence of hyperandrogenemia and hyperprolactinemia in MRKH patients. Additional calculations and a ratio of free androgen index and biologically active testosterone revealed a hyperandrogenemia rate of 48.3%, hyperprolactinemia of 9.8% and combined hyperandrogenemia and hyperprolactinemia of 4.2% in MRKH patients. The rates of hirsutism, acne and especially polycystic ovary syndrome (PCOS) were in the normal range of the population and showed no correlation with hyperandrogenemia. A weekly hormone assessment over 30 days comparing 5 controls and 7 MRKH patients revealed high androgen and prolactin, but lower LH/FSH and SHBG levels with MRKH patients. The sequencing of WNT4, WNT5A, WNT7A and WNT9B demonstrated no significant mutations correlating with hyperandrogenemia. Taken together, this study shows that over 52% of MRKH patients have hyperandrogenemia without clinical presentation and 14% hyperprolactinemia, which appeals for general hormone assessment and adjustments of MRKH patients.

Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany.

Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2+ (CIN2+), including 43 women with CIN3+. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2+ (P = 0.180) or CIN3+ (P = 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (

Acne and PCOS are less frequent in women with Mayer-Rokitansky-Küster-Hauser syndrome despite a high rate of hyperandrogenemia: a cross-sectional study.

BACKGROUND: Acne is a very common skin condition during adolescence and adulthood. Patients with uterovaginal agenesis (Mayer-Rokitansky-Küster-Hauser syndrome, MRKH) treated at the Tübingen University Center for Rare Female Genital Malformations, however, clinically appeared to be less frequently affected by acne. The etiology of MRKH syndrome remains unknown. The only known MRKH-associated mutations are located within the WNT4 gene and lead to an atypical form of MRKH syndrome associated with clinical and biochemical hyperandrogenism. Our study aimed to assess the frequency, severity, and self-evaluation of acne in MRKH patients and to correlate the clinical findings with hormone analyses. METHODS: As part of a cross-sectional longterm follow-up study after laparoscopic assisted creation of a neovagina a questionnaire was sent to 149 MRKH patients aged 16-44 years comprising 26 items concerning prevalence and self-evaluation of acne, and the effects of acne on quality of life. The questionnaire was derived from one used in a former epidemiological study of acne in 4,000 women. Blood for hormone analyses was collected routinely during the clinical visit. RESULTS: Fully completed, evaluable questionnaires were returned by 69/149 (46%) women. Of these respondents, 42 (60.1%) showed hyperandrogenemia without other clinical signs of virilization but only 17 (24.6%) reported acne (8 (11.6%) had physiological acne and 9 (13.0%) clinical acne) and only 10 (14.5%) reported receiving medical treatment for their acne. Effects of acne on quality of life were minor. Only 4 patients (5.8%) with PCOS were identified, among them one with physiological acne, the other three within the acne-free group. CONCLUSIONS: Although hyperandrogenemia is common, acne is significantly less frequent in women with MRKH than reported in the literature for non-MRKH women, and is seldom treated medically. Patients in this study appeared resistant to acne to some extent, possibly due to the sebaceous glands in the acne regions being less sensitive to androgens compared to the normal population. A WNT4 mutation is unlikely to be the main cause of MRKH syndrome in our hyperandrogenemic patients.

Sexual life and sexual wellness in individuals with complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS).

INTRODUCTION: Sexual wellness depends on a person's physical and psychological constitution. Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS) can compromise sexual well-being. AIMS: To compare sexual well-being in CAIS and MRKHS using multiple measures: To assess sexual problems and perceived distress. To gain insight into participants' feelings of inadequacy in social and sexual situations, level of self-esteem and depression. To determine how these psychological factors relate to sexual (dys)function. To uncover what participants see as the source of their sexual problems. METHODS: Data were collected using a paper-and-pencil questionnaire. Eleven individuals with CAIS and 49 with MRKHS with/without neovagina treatment were included. Rates of sexual dysfunctions, overall sexual function, feelings of inadequacy in social and sexual situations, self-esteem and depression scores were calculated. Categorizations were used to identify critical cases. Correlations between psychological variables and sexual function were computed. Sexually active subjects were compared with sexually not active participants. A qualitative content analysis was carried out to explore causes of sexual problems. MAIN OUTCOME MEASURES: An extended list of sexual problems based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, by the American Psychiatric Association and related distress. Female Sexual Function Index (FSFI), German Questionnaire on Feelings of Inadequacy in Social and Sexual Situations (FUSS social scale, FUSS sexual scale), Rosenberg Self-Esteem Scale (RSE), Brief Symptom Inventory (BSI) subscale depression. Open question on alleged causes of sexual problems. RESULTS: The results point to a far-reaching lack of sexual confidence and sexual satisfaction in CAIS. In MRKHS apprehension in sexual situations is a source of distress, but sexual problems seem to be more focused on issues of vaginal functioning. MRKHS women report being satisfied with their sex life. CONCLUSION: Different conditions can affect individuals in diagnosis-specific ways despite some shared clinical features. Professionals should adopt an interdisciplinary approach and provide custom-made care in order to promote sexual well-being in patients.

The rectovaginal septum: visible on magnetic resonance images of women with Mayer-Rokitansky-Küster-Hauser syndrome (Müllerian agenesis).

INTRODUCTION AND HYPOTHESIS: Ongoing debate exists about whether the rectovaginal septum (Denonvilliers' fascia) is myth or reality. This study evaluates magnetic resonance images (MRI) of women with Müllerian agenesis for the presence of fascial layers between the rectum and the bladder to test the hypothesis that this layer exists in the absence of the vagina. METHODS: This is a secondary analysis of a study describing MRI aspects in women with vaginal agenesis before and after laparoscopic Vecchietti procedure. Study participants (n =16) had a multiplanar pelvic MR scan. Images were evaluated independently by two investigators (MH, JOLD) for the appearance of layers separate from the bladder and rectum in the area of interest, with characteristic anatomical features of the septum. RESULTS: Participants' mean age was 19.4±2.6 years ± standard deviation (SD). In 12 of 16 patients (75 %) a distinct layer between rectum and bladder was identified in either the axial(4/16; 25 %) or sagittal (12/16; 75 %) scan or both. Characteristic anatomical features included lateral attachment to the levator ani muscle, cranial fusion to the cul-de-sac peritoneum,and caudal insertion into the perineal body.Conclusions Three quarters of women with Müllerian agenesis have a visible layer between bladder and rectum. As none of the participants had a vagina, these results support the existence of a rectovaginal septum, separate from a vaginal adventitia.

A Cohort of 469 Mayer-Rokitansky-Küster-Hauser Syndrome Patients-Associated Malformations, Syndromes, and Heterogeneity of the Phenotype.

The Mayer-Rokitansky-Küster-Hauser syndrome is characterized by aplasia of the uterus and upper two-thirds of the vagina. While it can appear as an isolated genital malformation, it is often associated with extragenital abnormalities, with little still known about the pathogenetic background. To provide an overview of associated malformations and syndromes as well as to examine possible ties between the rudimentary tissue and patient characteristics, we analyzed a cohort of 469 patients with MRKHS as well as 298 uterine rudiments removed during surgery. A total of 165 of our patients (35.2%) had associated malformations (MRKHS type II). Renal defects were the most common associated malformation followed by skeletal abnormalities. Several patients had atypical associated malformations or combined syndromes. Uterine rudiments were rarer in patients with associated malformations than in patients without them. Rudiment size ranged from 0.3 cm3 to 184.3 cm3 with a mean value of 7.9 cm3. Importantly, MRKHS subtype or concomitant malformations were associated with a different frequency of uterine tissue as well as a different rudiment size and incidence of endometrial tissue, thereby indicating a clear heterogeneity of the phenotype. Further research into the associated molecular pathways and potential differences between MRKHS subtypes is needed.

[A questionnaire for the assessment of women's perception of their own femininity: a study on women with Mayer-Rokitansky-Kuster-Hauser-syndrome and women with polycystic ovary syndrome]. / Fragebogen zum Erleben der eigenen Weiblichkeit (FB-W): Ergebnisse von Frauen mit Mayer-Rokitansky-Küster-Hauser Syndrom und Frauen mit polyzystischem Ovarsyndrom.

Women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) or polycystic ovary syndrome (PCOS) experience substantial changes in female body characteristics. It was investigated how this is associated with changes concerning the experience of one's own femininity. A questionnaire was developed to measure the experience of one's own femininity. The question-naire assesses how important several aspects are to women for their experience of their own femininity. Data from 49 women with MRKHS and 55 women with PCOS were compared to a non-clinical sample (932 women). The experience of their own femininity differed between the clinical groups as well as in comparison to the control sample. Diagnosis-specific characteristics emerged, which should be considered in the treatment of affected women. The developed questionnaire proved to be suitable for measuring differences in the experience of one's own femininity between groups of gynecological -patients.

Can Classifications Adequately Represent Genital Malformations?: EVA Study ( E SHRE/ESGE | V CUAM | A FS) - A Prospective Multicenter Study to Evaluate the Current Female Genital Malformation Classifications.

Introduction Genital malformations are a common clinical occurrence that can be represented using different classifications. Reproducibility is an essential quality characteristic for a classification, and it plays an important role, especially in consultations and the treatment of infertile patients and in obstetric management. The aim of this study is to demonstrate the reproducibility and clinical practicality of three commonly used classifications: the ESHRE/ESGE (European Society of Human Reproduction and Embryology/ European Society for Gynecological Endoscopy), VCUAM (Vagina Cervix Uterus Adnex-associated Malformation), and AFS (American Fertility Society) classifications. Materials and Methods Sixty-five patients with female genital malformations were included in this prospective, multicenter, exploratory, observational study. All participants underwent a clinical examination and a medical interview. The investigators were instructed to classify the presenting malformations according to the ESHRE/ESGE, VCUAM, and AFS classifications using a structured questionnaire. Investigators were asked whether the malformation could be reproducibly classified (yes/no) and about the grade (grade 1-5 from "very good" to "deficient") they would assign to each classification. Classification assessment was queried for vagina, cervix, uterus, adnexa, and associated malformations and was scored from 1 to 5. Results Reproducibility was rated as 80% (n = 52/65), 92.3% (n = 60/65), and 56.9% (n = 37/65) for the ESHRE/ESGE, VCUAM, and AFS classification, respectively. ESHRE/ESGE, VCUAM and AFS were rated as "very good" or "good" for 83.3%, 89.2%, and 10.8% of vaginal malformations; for 75.8%, 87.5%, and 24.2% of cervical malformations; and for 89.7%, 89.5%, and 86.2% of uterine malformations, respectively. VCUAM was rated as "very good" or "good" for 77.8% and 69.6% of adnexal malformations and associated malformations, respectively. ESHRE/ESGE and AFS were rated as "sufficient" or "deficient" for 100% and 75% of adnexal malformations and for 77.3% and 69.6% of associated malformations, respectively. Conclusion The prospective multicenter EVA ( E SHRE/ESGE | V CUAM | A FS) study revealed that the organ-based ESHRE/ESGE and VCUAM classifications of female genital malformations perform better in terms of reproducibility as well as in the assessment of individual compartments than the non-organ-based AFS classification.