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Objective: To explore how women with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome experience dilation or surgical vaginal lengthening treatment, and their current sexual well‐being. Design: A qualitative interview study. Setting: Denmark. Population: Women aged ≥25 years diagnosed with MRKH syndrome. Methods: Semi‐structured video interviews were conducted with 18 women. Interviews lasted a median of 92 min and were digitally recorded, transcribed and anonymised. Data were analysed using thematic analysis. Main Outcome Measures: A qualitative analysis of women's experiences. Results: The analysis identified three themes. Firstly, Experiences with dilation treatment revealed dilation as an awkward routine, especially for adolescents living with parents and yet to sexually debut. While some experienced successful vaginal lengthening, others faced treatment failure leading to frustration and self‐blame. Secondly, Experiences with neovaginal surgery described the procedure as extremely painful but resulting in a 'normal size' vagina. Some women felt that the procedure had negatively impacted their self‐confidence, and all underscored the importance of maturity before opting for surgery. Lastly, Current sex life and sexual well‐being indicated a well‐functioning sex life for many women, but with reported low sexual confidence and genital self‐image due to the perceived 'deviance' of their genitalia. Conclusions: For women with MRKH syndrome, vaginal lengthening treatment, whether through dilation or surgery, may result in a 'normal size' vagina. However, according to the women's experiences, vaginal lengthening treatment does not adequately foster positive sexual esteem and genital self‐image. This article includes Author Insights, a video abstract available at: https://1drv.ms/v/c/426d88d9eb0a10fb/ERqbdfeTFeFLkp24xVb9n7ABTZ5VS3f6yxoHlXT7BUPs6A?e=y41xwc. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to find out what proportion of women with MRKHS have decided to become mothers and have children or would like to have children and consider various options for motherhood. Additionally, the survey aimed at identifying factors that might influence the women's decisions and opinions regarding adoption, gestational surrogacy (GS) and uterus transplantation (UTx). Material and methods: The study group consisted of 100 adult women with MRKHS who filled out questionnaires consisting of 56 questions. The survey was self-administered and anonymous. Results: Most of the study participants were under 30, lived in large cities (> 150 000 inhabitants) and declared to be heterosexuals in a steady relationship (p < 0.05). While 11 participants had children, 66 out of 89 childless women (74%) expressed a desire for motherhood, but as many as 80 surveyed women have felt pressured to have children. The number of participants for whom a biological relationship with offspring was significant and insignificant respectively equaled (p = 1.000). The majority of the study participants supported the process of legalizing GS in Poland (95 vs 4) yet would opt for commercial rather than altruistic GS (64 vs 31) (p < 0.05). Most respondents stated that UTx is consistent with their faith and conscience (91 vs 4) and found UTx ethical (88 vs 4) (p < 0.0001). Conclusions: The majority of Polish women with MRKHS express the need to become a mother, but only one in ten has a child. The women's interest in biological motherhood is significant. [ABSTRACT FROM AUTHOR]

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by agenesis/aplasia of the uterus and upper part of the vagina in females with normal external genitalia and a normal female karyotype (46,XX). Patients typically present during adolescence with complaints of primary amenorrhea where the diagnosis is established with significant implications including absolute infertility. Most often cases appear isolated with no family history of MRKH syndrome or related anomalies. However, cumulative reports of familial recurrence suggest genetic factors to be involved. Early candidate gene studies had limited success in their search for genetic causes of MRKH syndrome. More recently, genomic investigations using chromosomal microarray and genome-wide sequencing have been successful in detecting promising genetic variants associated with MRKH syndrome, including 17q12 (LHX1, HNF1B) and 16p11.2 (TBX6) deletions and sequence variations in GREB1L and PAX8, pointing towards a heterogeneous etiology with various genes involved. With uterus transplantation as an emerging fertility treatment in MRKH syndrome and increasing evidence for genetic etiologies, the need for genetic counseling concerning the recurrence risk in offspring will likely increase. This review presents the advancements in MRKH syndrome genetics from early familial occurrences and candidate gene searches to current genomic studies. Moreover, the review provides suggestions for future genetic investigations and discusses potential implications for clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Contradictory findings on sexual health in women with Mayer-Rokitansky-Kuester-Hauser syndrome (MRKHS) after vaginal reconstruction point toward the need for more profound assessment of this subject, particularly as it is still unclear what constitutes sexual well-being, especially genital self-image or sexual self-esteem, in women with MRKHS and neovagina. Aim The aim of this qualitative study was to assess individual sexual health and sexual well-being in the context of MRKHS after vaginal reconstruction, with an emphasis on genital self-image, sexual self-esteem, sexual satisfaction, and coping with MRKHS. Methods Qualitative semistructured interviews were conducted with women with MRKHS after vaginal reconstruction (n = 10) with the Wharton-Sheares-George surgical method and a matched control group without MRKHS (n = 20). Women were surveyed about their previous and current sexual activities, perception of and attitudes toward their genitals, disclosure to others, coping with the diagnosis, and perception of surgery. Data were analyzed through qualitative content analysis and compared with the control group. Outcomes The primary outcomes of the study were major categories, such as sexual satisfaction, sexual self-esteem, genital self-image, and dealing with MRKHS, as well as subcategories related to the content analysis. Results Although half the women in the present study indicated that they were coping well with their condition and were satisfied with sexual intercourse, most felt insecure about their neovagina, were cognitively distracted during intercourse, and showed low levels of sexual self-esteem. Clinical Implications A better understanding of expectations and uncertainties regarding the neovagina might help professionals to support women with MRKHS after vaginal reconstruction to increase sexual well-being. Strengths and Limitations This is the first qualitative study focusing on individual aspects of sexual well-being, especially sexual self-esteem and genital self-image, in women with MRKHS and neovagina. The qualitative study indicates good interrater reliability and data saturation. The limitations of this study include the inherent lack of objectivity resulting from the method but also the fact that all the patients had a particular surgical technique, consequently resulting in limited generalizability of these findings. Conclusions Our data indicate that integrating the neovagina into the genital self-image is a prolonged process that is essential for sexual well-being and should thus be the focus of sexual counseling. [ABSTRACT FROM AUTHOR]

Introduction Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a difference (disorder) of sex development that results from Müllerian duct aplasia in 46,XX females. The diagnosis of MRKHS is usually established in late adolescence. The purpose of the study was to assess the impact of congenital absence of uterus and vagina (CAUV) on a patient’s psychosexual functioning. Participants and procedure Thirty-two women with MRKHS (mean age 22.9 years) and 32 matched healthy controls (mean age 24.75 years) completed three study questionnaires: the Sexual Self-Esteem Inventory for Women, the Rosenberg Self-Esteem Scale, and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Statistical analysis was performed by IBM SPSS Statistics 22. Results There was no difference in global self-esteem between the two study groups. MRKHS females had lower sexual self-esteem and experienced higher intensity of some psychological functioning characteristics (paranoia, psychasthenia, schizophrenia) than their peers. Correlations between sexual self-esteem and results on depression, psychopathic deviate, schizophrenia, social introversion and anxiety scales were observed in patients with MRKHS. Global self-esteem and schizophrenia results were significant predictors of sexual self-esteem in the clinical group. Higher global self-esteem and lower results in the schizophrenia scale were associated with higher sexual self-esteem in patients with MRKHS. Conclusions Psychological and medical counseling of women with MRKHS should address their impaired sexual self-esteem, especially sexual skills and experiences. While the number of diagnostic responses indicating the presence of specific symptoms in MRKHS females is statistically significantly different, the level of scores obtained does not exceed the threshold of clinical pathology.

BACKGROUND Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a difference (disorder) of sex development that results from Müllerian duct aplasia in 46, XX females. The diagnosis of MRKHS is usually established in late adolescence. The purpose of the study was to assess the impact of congenital absence of uterus and vagina (CAUV) on a patient's psychosexual functioning. PARTICIPANTS AND PROCEDURE Thirty-two women with MRKHS (mean age 22.9 years) and 32 matched healthy controls (mean age 24.75 years) completed three study questionnaires: the Sexual Self-Esteem Inventory for Women, the Rosenberg Self-Esteem Scale, and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Statistical analysis was performed by IBM SPSS Statistics 22. RESULTS There was no difference in global self-esteem between the two study groups. MRKHS females had lower sexual selfesteem and experienced higher intensity of some psychological functioning characteristics (paranoia, psychasthenia, schizophrenia) than their peers. Correlations between sexual self-esteem and results on depression, psychopathic deviate, schizophrenia, social introversion and anxiety scales were observed in patients with MRKHS. Global self-esteem and schizophrenia results were significant predictors of sexual self-esteem in the clinical group. Higher global self-esteem and lower results in the schizophrenia scale were associated with higher sexual self-esteem in patients with MRKHS. CONCLUSIONS Psychological and medical counseling of women with MRKHS should address their impaired sexual self-esteem, especially sexual skills and experiences. While the number of diagnostic responses indicating the presence of specific symptoms in MRKHS females is statistically significantly different, the level of scores obtained does not exceed the threshold of clinical pathology. [ABSTRACT FROM AUTHOR]

Abstract Background Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX). Main body The diagnosis is often made during adolescence following investigations for primary amenorrhea and has an estimated prevalence of 1 in 5000 live female births. MRKH syndrome is classified as type I (isolated uterovaginal aplasia) or type II (associated with extragenital manifestations). Extragenital anomalies typically include renal, skeletal, ear, or cardiac malformations. The etiology of MRKH syndrome still remains elusive, however increasing reports of familial clustering point towards genetic causes and the use of various genomic techniques has allowed the identification of promising recurrent genetic abnormalities in some patients. The psychosexual impact of having MRKH syndrome should not be underestimated and the clinical care foremost involves thorough counselling and support in careful dialogue with the patient. Vaginal agenesis therapy is available for mature patients following therapeutical counselling and education with non-invasive vaginal dilations recommended as first-line therapy or by surgery. MRKH syndrome involves absolute uterine factor infertility and until recently, the only option for the patients to achieve biological motherhood was through gestational surrogacy, which is prohibited in most countries. However, the successful clinical trial of uterus transplantation (UTx) by a Swedish team followed by the first live-birth in September, 2014 in Gothenburg, proofed the first available fertility treatment in MRKH syndrome and UTx is now being performed in other countries around the world allowing women with MRKH syndrome to carry their own child and achieve biological motherhood. Conclusion Several advances in research across multiple disciplines have been made in the recent years and this kaleidoscopic review provides a current status of various key aspects in MRKH syndrome and provides perspectives for future research and improved clinical care.

Although it has been clearly stated that vaginal dilation must be considered the first-line treatment for clinical conditions characterized by an absent or hypoplastic vagina, mainly Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a great number of scientific papers on surgical vaginal reconstructions are reported every year. This wide variety of surgical techniques (more than 10) are recognized and performed worldwide, making it difficult to compare results and define an evidence-based approach. Standardized treatment should be considered even more important in the pediatric and adolescent population for the implications offered by the uterus transplantation scenario. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

To summarize the self-reported sexual experiences of women with vaginal agenesis before treatment and discuss the clinical implications. A retrospective review of pretreatment baseline sexuality data and medical records of women with vaginal agenesis seeking vaginal construction. A specialist multidisciplinary center for women with genital differences associated with diverse sex development. One hundred thirty-seven women with untreated vaginal agenesis associated with Mayer-Rokitansky-Küster-Hauser Syndrome and complete androgen insensitivity syndrome aged 15 to 41 years (mean age, 20 years). Gynecological examination and completion of questionnaires. (1) Sexual Experiences Questionnaire; (2) Multidimensional Sexuality Questionnaire; (3) Vaginal Self-Perceptions; and (4) vaginal length. A sizable proportion of women reported having had sexually intimate experiences before any medical intervention on the vagina. Vaginal length, which ranged from dimple to 7 cm and averaged 2.7 cm for the cohort, was unrelated to the range of sexual experiences. Most women perceived their vagina as being too small, but less than half believed that a sexual partner would notice this. Two-thirds of the cohort subsequently completed the dilation program, which was not predicted by pretreatment vaginal length or sexual experience. Contrary to the assumption that a vagina of certain dimensions is a prerequisite for women to "have sex," many women with Mayer-Rokitansky-Küster-Hauser syndrome and complete androgen insensitivity syndrome reported having experienced genital and nongenital sexual activities with no medical interventions. It is recommended that treatment providers affirm women's capacity for sexual intimacy, relationships, and enjoyment before they introduce the topic of vaginal construction as a non-urgent choice. [ABSTRACT FROM AUTHOR]

Fusion anomalies of the Müllerian ducts are associated with an increased risk for miscarriage and premature labor. In most cases polygenic‐multifactorial inheritance can be assumed but autosomal‐dominant inheritance with reduced penetrance and variable manifestation should be considered. We performed array‐comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with Müllerian fusion anomalies. In 8 patients we detected microdeletions and microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and 7q31.1. The rearrangement in 17q12 including LHX1 and HNF1β as well as in 22q11.21 have already been observed in MRKHS (Mayer‐Rokitansky‐Küster‐Hauser syndrome). In summary, we (1) detected causative micro‐rearrangements in patients with Müllerian fusion anomalies, (2) show that Müllerian fusion anomalies and MRKHS may have a common etiology, and (3) identified new candidate genes for Müllerian fusion anomalies. [ABSTRACT FROM AUTHOR]

Mayer-Rokitansky-Küster-Hauser syndrome ( MRKHS) is a well-known malformation pattern of the Müllerian ducts ( MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b-/- mice show a MRKHS-like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model. [ABSTRACT FROM AUTHOR]

Objective To identify genetic causes of malformations of the müllerian ducts. Design Retrospective laboratory study. Setting University hospital. Patient(s) A total of 167 patients with disorders of the müllerian ducts: 116 patients with Mayer-Rokitansky-Küster-Hauser syndrome and 51 patients with fusion disorders of the müllerian ducts. The control group was composed of 94 fertile women with at least one child. Intervention(s) Sequential analysis of RBM8A and TBX6 in a group of 167 clinically well-defined patients with disorders of the müllerian ducts. Main Outcome Measure(s) Identification of rare variants in RBM8A and TBX6 . Result(s) In total, we detected four RBM8A variants in 13 patients with disorders of the müllerian ducts and two heterozygous TBX6 variants in 5 of 167 patients. Conclusion(s) Mutations of RBM8A and TBX6 are associated with disorders of the müllerian ducts. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study was to assess self-reported depressive and anxiety symptoms in adolescents with polycystic ovary syndrome (PCOS) and those with the rare Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKHS), compared with healthy adolescents. Material and methods. The participants were 49 adolescent girls, of whom 27 were patients with confirmed menstrual disorder, 22 with PCOS and 5 with MRKHS; and 22 were healthy eumenorrheic adolescents (control group) matched by age and school grade. The Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI-Gr) were used to measure depression and anxiety, respectively. Results. The results showed that it was 1.08 times more likely for the PCOS group (p = 0.043) and 1.12 times more likely for the MRKHS group (p = 0.039) to have higher scores than healthy adolescents on the anxiety scale. The MRKHS group was 1.40 times more likely to have a higher number of depressive symptoms (p = 0.040) than the control group. Conclusions. These findings, although based on a small sample, suggest a relationship between PCOS and MRKHS and the presence of psychological problems, such as anxiety and depressive symptoms in adolescents. This study is among the first to examine psychological difficulties in adolescents with such a rare menstrual syndrome as MRKHS. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma with extended vaginal intraepithelial neoplasia (VAIN) in a patient with Müllerian Agenesis (Mayer-Rokitansky-Kuster-Hauser Syndrome MRKHS) 41 yrs after construction of a neovagina Case Report A 57yr old patient with MRKHS presented with vaginal bleeding and dyspareunia 41yrs after construction of a neovagina by interposition of a small bowel loop On gynaecological examination a narrow vagina and moderate bleeding were found. A fixed nodule was palpable 3cm above the introitus in the anterior wall. On ultrasound a nodule of 1,7cm, distinct from the bladder, was visible. (pic 1) A biopsy showed a moderately differentiated squamous cell carcinoma of basaloid subtype, With an extended associated VAIN III, HPV high risk positive. (pic 2) A MRT showed a nodule of 2,4cm in the vault of the vagina, not clearly separeted from the bladder wall. No free fluid or enlarged Lymph nodes were noted. A cystoscopy showed no infiltration of the bladder wall. The interdisciplinary tumor board decided on a combined radio-chemotherapy. The patient received a total of 64 Gray (pic 3) and Cisplatin 40mg weekly for 5 weeks. At the end of the radiotherapy a mild local reaction with reness of the vaginal epithelium was present, which regressed. No nodule was palpable anymore. Results MRT control after 6 and 12 months showed no residual tumor or tumor progression (pic 3) Discussion and Conclusion Malignomas in a neovagina are rare, but cases have been reported. There are various techniques of constructing a neovagina, and squamous cell carcinomas are most commonly described in skin grafts and adenocarcinomas after interposition of bowel. Squamous cell carcinomas in a bowl graft are extremely rare. MRKHS can present as hypoplasia or as agenesis. In hypoplasia a malignant transformation of the residual vaginal tissue is possible. In bowel graft a metaplastic transformation of the bowel mucosa into physiological and anatomical squamous cell epithelium, resembling initial vaginal epithelium, is taking place. In most cases of squamous cell carcinomas of the neovagina a positive HPV result is present. Therefore these patients should be offered a routine screening programm. Therapeutic options include surgery or radio-chemotherapy. In this case the interdisciplinary tumor board decided on a radio-chemotherapy. The 1yr follow-up showed no residual tumor and the patient is symptom-free. [ABSTRACT FROM AUTHOR]