Update on Mayer-Rokitansky-Küster-Hauser syndrome.

This review presents an update of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome on its etiologic, clinical, diagnostic, psychological, therapeutic, and reproductive aspects. The etiology of MRKH syndrome remains unclear due to its intrinsic heterogeneity. Nongenetic and genetic causes that may interact during the embryonic development have been proposed with no definitive etiopathogenesis identified. The proportion of concomitant extragenital malformations varies in different studies, and the discrepancies may be explained by ethnic differences. In addition to physical examination and pelvic ultrasound, the performance of pelvic magnetic resonance imaging is crucial in detecting the presence of rudimentary uterine endometrium. MRKH syndrome has long-lasting psychological effects on patients, resulting in low esteem, poor coping strategies, depression, and anxiety symptoms. Providing psychological counseling and peer support to diagnosed patients is recommended. Proper and timely psychological intervention could significantly improve a patient's outcome. Various nonsurgical and surgical methods have been suggested for treatment of MRKH syndrome. Due to the high success rate and minimal risk of complications, vaginal dilation has been proven to be the first-line therapy. Vaginoplasty is the second-line option for patients experiencing dilation failure. Uterine transplantation and gestational surrogacy are options for women with MRKH syndrome to achieve biological motherhood.

Three-dimensional Printer Molds for Vaginal Agenesis: An Individualized Approach as Conservative Treatment.

OBJECTIVE: The aim of this study was to evaluate the use of vaginal molds, made with three-dimensional (3D) printing, for conservative treatment through vaginal dilation in patients with vaginal agenesis (VA). METHODS: A total of 16 patients with a diagnosis of VA (Mayer-Rokitansky-Küster-Hauser syndrome, total androgen insensitivity syndrome, and cervicovaginal agenesis) from the Federal University of São Paulo were selected. Device production was performed in a 3D printer, and the polymeric filament of the lactic polyacid (PLA) was used as raw material. A personalized treatment was proposed and developed for each patient. RESULTS: There were 14 patients who reached a final vaginal length of 6 cm or more. The initial total vaginal length (TVL) mean (SD) was 1.81(1.05) and the final TVL mean (SD) was 6.37 (0.94); the difference, analyzed as 95% confidence interval (95% CI) was 4.56 (5.27-3.84) and the effect size (95% CI) was 4.58 (2.88-6.28). CONCLUSION: The 3D printing molds for vaginal dilation were successful in 87.5% of the patients. They did not present any major adverse effects and offered an economical, accessible, and reproducible strategy for the treatment of VA.

OBJETIVO: O objetivo deste estudo foi avaliar o uso de moldes dilatadores vaginais, confeccionados com impressão tridimensional (3D), para tratamento conservador através da dilatação vaginal em pacientes com agenesia vaginal (AV). MéTODOS: Foram selecionadas 16 pacientes com diagnóstico de AV (síndrome de Mayer-Rokitansky-Küster-Hauser, síndrome de insensibilidade androgênica total e agenesia cervicovaginal), da Universidade Federal de São Paulo. A produção dos dispositivos foi realizada em uma impressora 3D e, como matéria-prima, foi utilizado o filamento polimérico do poliácido lático (PLA). Um tratamento personalizado foi proposto e desenvolvido para cada paciente. RESULTADOS: Quatorze pacientes atingiram um comprimento vaginal final (CVF) de 6 cm ou mais. A média inicial do CVF (DP) foi de 1,81 (1,05) e a média final do CVF (DP) 6,37 (0,94); a diferença (IC 95%) foi de 4,56 (5,27­3,84) e o tamanho do efeito (IC 95%) foi de 4,58 (2,88­6,28). CONCLUSãO: Os moldes de impressão 3D para dilatação vaginal obtiveram sucesso em 87,5% das pacientes. Como impacto secundário, não apresentaram efeitos adversos importantes e ofereceram uma estratégia econômica, acessível e reprodutível para o tratamento da AV.

The Sexuality of Adolescents and Young Women With MRKH Syndrome: A Qualitative Study.

BACKGROUND: Vaginal agenesis, most commonly referred as Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome, is mostly diagnosed as primary amenorrhea in teenage girls; although there is plenty of literature concerning the formation of a neovagina, limited research has focused on the psychological burden of this diagnosis to the girls. AIM: To enlighten health providers into the finer aspects of sexuality through the own words and experiences of girls with MRKH under our care. METHODS: Women currently undergoing vaginal dilation or who had completed vaginal dilation within the past year were recruited from February 2019 to January 2020. A gynecologist with training in Sexual Medicine conducted a semistructured interview, which was recorded and then transcribed to identify common themes among interviewees. OUTCOMES: The main outcome explored was the narrative experiences of women with MRKH. RESULTS: 7 women participated, with a mean age of 19.7 (range 17-22 years). None of the girls felt stigmatized, however one reported significant distress at diagnosis, stemming from the attitude of health care professionals and exacerbated by an earlier age at disclosure. All girls accepted that VDT was successful, when it was initiated after they had felt sexual interest and arousal. Exact quantification of the vaginal length at onset, worried 4 as they felt pressurized to achieve a specific length. A few girls reported anxiety over sharing the diagnosis with an intimate partner. All of them pretended at some point to have menses. Childbearing was an important issue for most of the interviewees, but it did not concern them for the time being. All girls had supporting families. However, 5 did not want to share information about VDT with them. One girl reported that openness in discussing genital anatomy, VDT and sexuality, helped her both in completing treatment and adapting in a sexual relationship. CLINICAL IMPLICATIONS: A multidisciplinary team should aim for age-appropriate disclosure and consultation and guide women through VDT and their sexual relations. STRENGTHS AND LIMITATIONS: This is a thorough account of women's perceptions regarding VDT and sexuality in MRKH. However, our conclusions may be limited by the small number of participants. CONCLUSION: Gradual provision of information at disclosure and adjusted timing at VDT may reduce stress in girls with MRKH. Tsitoura A, Michala L. The Sexuality of Adolescents and Young Women With MRKH Syndrome: A Qualitative Study. J Sex Med 2021;18:2012-2019.

Clinical Characteristics of 46,XX Males with Congenital Adrenal Hyperplasia

Objective: To retrospectively evaluate the follow-up data in patients with 46,XX congenital adrenal hyperplasia (CAH) who were raised male. Methods: A national database was created. The data of patients were asked to be recorded in the data form. Results: The median (range) age of diagnosis was three (0.1-18.3) years in 44 patients. Twenty nine cases were diagnosed after the age of two years. Most (95.4%) cases were stage 4-5 virilized. Hysterectomy and bilateral salpingoopherectomy, at a median age of 7.25 (2.4-25.3) years, was performed in 35 cases. Testicular prostheses were placed in 11 (25%) cases at a median age of 11.2 (2.8-17) years. The median final height was 149.2 (132.8-172) cms in 38 patients, including simple virilizing (n=18), salt-wasting (n=6), and 11-beta hydroxylase (n=12). Of the 16 patients above the age of eighteen, university education was completed in 25%. Conclusion: It was seen that most (65.9%) of the 46,XX CAH cases raised male were diagnosed after two years of age. In these cases, hysterectomy and bilateral salpingoopherectomy, genital corrective surgeries and testicular prosthesis operations were performed in a very wide age rage.

An alternative approach to vaginal dilation in patients with Meyer-Rokitanski-Küster-Hauser syndrome: two case reports.

Vaginal dilation, currently considered as the first-line therapy for vaginal aplasia in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is a safe and effective treatment that aims to create a functional neovagina. However, rigid vaginal dilators classically described in the literature usually cause physical discomfort and side effects that can lead to vaginal necrosis. Here, we present two cases of MRKH syndrome patients with vaginal agenesis whose main complaint was the inability to have sexual intercourse with their partners. Considering unavailability of acrylic dilators and previous studies reporting good responses with the use of silicone dilators in women with post-radiotherapy vaginal stenosis, the medical team and patients opted for creation of a neovagina through the daily use of silicone vaginal dilators. Patient 1 developed an 8-cm vagina after 6 months of treatment and had a satisfactory sex life with her partner. Patient 2 developed a 7-cm vagina and reported significant symptom improvement. None of the patients developed side effects after the treatment. The use of inexpensive and easily accessible silicone vaginal dilators may be an effective and noninvasive alternative with few side effects for women with vaginal agenesis, particularly in the developing countries.

Oocyte Retrieval during Laparoscopic Vaginoplasty to Reduce Invasiveness in the Treatment of Mayer-Rokitansky-Küster-Hauser Syndrome.

STUDY OBJECTIVE: To evaluate the treatment of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a combination of oocyte retrieval and surgical vaginoplasty in a single laparoscopic procedure. DESIGN: A case series. SETTING: The study was conducted at 2 tertiary referral facilities for MRKH syndrome in Milan, Italy, between July 2017 and September 2018. PATIENTS: Eleven patients presented with MRKH and required surgical vaginoplasty while expressing a desire for future fertility. INTERVENTIONS: Two experienced surgeons and an expert in assisted reproductive technology performed concomitant vaginoplasty according to the modified technique of Davydov and laparoscopic oocyte retrieval for gamete cryopreservation. MEASUREMENTS AND MAIN RESULTS: Before the procedure, patients underwent extensive counseling and gave written consent. At the start of surgery, 10.4 ± 4.4 (mean ± standard deviation [SD]) oocytes were retrieved laparoscopically, and 8.8 ± 3.1 (SD) mean mature oocytes were cryopreserved. After oocyte retrieval, the steps of the modified Davydov technique were followed. The total operative time was 116 ± 16 minutes (mean ± SD), and no intraoperative/postoperative complications were observed. CONCLUSION: This is the first report of combined oocyte retrieval and vaginoplasty for patients with MRKH syndrome. The approach was found to be feasible in patients with a desire for future fertility. It is our belief that physicians treating patients with MRKH should refer patients to centers with expertise in both vaginoplasty and assisted reproductive technology.

Four cases of Mayer-Rokitansky-Küster-Hauser syndrome treated via non-surgical vaginal reconstruction using uterine cervical dilators.

Vaginal creation is the standard treatment for Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Although non-surgical method is recommended as a first-line treatment in the American College of Obstetricians and Gynecologists guidelines for gynecological practice, it is not commonly performed in Japan. At our hospital, vaginal dilation using uterine cervical dilators (Hegar's dilator) is performed for patients with MRKH syndrome. We report four cases successfully treated with vaginal dilation. After the examination, patients were instructed to practice daily self-dilation at home. The initiation size was No. 13 with 10.5-mm diameter. After the vaginal cavity was dilated to a depth of 6 cm, the size of dilators was gradually increased until No. 30 with 25-mm diameter in a tip and 28-mm diameter in a trunk. The duration required to achieve the outcome was 5-22 months. All cases were successfully treated without any severe complication.

Child with '46, XX' disorder of sex development: clues to diagnose aromatase deficiency.

A diagnosis of congenital adrenal hyperplasia (CAH) in a '46, XX' newborn with ambiguous genitalia is like a 'knee jerk reaction' of the paediatrician because of its higher frequency and life-threatening consequences if remain undiagnosed and hence untreated. Aromatase deficiency (AD), a rare cause of '46, XX' disorder of sex development, mimics virilising CAH in many aspects; thus, the disease is often overlooked. Diagnosis of AD in women is much easier around puberty due to the presence of primary amenorrhoea, undeveloped breasts, androgen excess and tall stature with eunuchoid proportions. Diagnosing AD with confidence immediately after birth or during early childhood is a challenging task without genetic analysis. In resource-restricted settings, AD remains a diagnosis of exclusion particularly in this age group and history of maternal virilisation, non-progressive genital ambiguity, elevated gonadotrophins (follicle-stimulating hormone >>luteinising hormone), mildly delayed bone age with/without enlarged polycystic ovaries serve as important clues to the underlying AD.

Zinner and Mayer-Rokitansky-Küster-Hauser syndromes: when unilateral renal agenesis meets genital anomalies.

Congenital unilateral renal agenesis is a relatively frequent condition at birth diagnosed mostly incidentally. Despite the excellent prognosis, unilateral renal agenesis is associated with an increased risk of other structural abnormalities, including genital malformations. The authors present two cases of asymptomatic adolescents with known congenital unilateral renal agenesis and associated genital malformations solely diagnosed during puberty-a man with Zinner syndrome and a female with Mayer-Rokitansky-Küster-Hauser syndrome.

Clinical and genetic analysis in males with 46,XX disorders of sex development: A reproductive centre experience of 144 cases.

To explore the clinical features and assisted reproductive technology (ART) outcomes of 46,XX disorders of sex development (DSD) males, 144 males with 46,XX DSD were recruited in this retrospective study. The baseline information, clinical characteristics and ART outcomes of the participants were collected and analysed. The mean age was 29.06 ± 4.50 years. The mean volumes (95% CI) of left and right testicles were 2.16 (1.82-2.49) ml and 2.16 (1.83-2.49) ml, respectively. Cryptorchidism and/or hypospadias appeared in 19 patients (13.19%). Elevated levels of follicle-stimulating hormone (FSH) were found in 136 patients (95.10%) and increased luteinising hormone (LH) values were detected in 125 patients (92.59%). Eighty subjects (62.99%) had low testosterone values. Among 86 patients with status of sex-determining region Y (SRY)-gene and azoospermia factor (AZF) region available, fifteen (17.44%) patients were SRY-negative and AZF region was absent in every patient without exception. Additionally, fertility achieved in 87 patients through ART using donor spermatozoa. In conclusion, hypergonadotropic hypogonadism appeared as the main presentation of 46,XX DSD males regardless of the SRY status. The available fertility option proved to achieve live birth was limited to ART using donor spermatozoa.

Sexual satisfaction in patients with Mayer-Rokitansky-Küster-Hauser syndrome after surgical and non-surgical techniques: a systematic review.

INTRODUCTION AND HYPOTHESIS: The treatment and mental support of patients with Mayer-Rokitansky-Küster-Hauser syndrome are very important. Many of these patients seek treatment to improve their sexual relationships and the quality of their sexual life. This systematic review sought to evaluate the sexual satisfaction of patients with MRKH syndrome following various types of vaginoplasty and non-surgical procedures over the past 10 years. METHODS: A systematic review of studies published in English during 2008-2018 was performed. Electronic databases and valid sites, including PubMed, EMBASE, Science Direct, Cochrane Library, SCOPUS, Ovid, and ProQuest, were searched for articles published from the beginning of 2008 to February 2018. Literature restricted to women with Mayer-Rokitansky-Küster-Hauser syndrome who underwent vaginoplasty surgery or a non-surgical technique was reviewed. Of 195 papers identified, 45 articles were analyzed. All studies that reported sexual and functional outcomes following various vaginoplasty procedures and non-surgical procedures were selected. RESULTS: Greater vaginal length and higher sexual satisfaction were observed following surgical procedures than after non-surgical techniques. A range of complications was reported following the use of different surgical approaches. The Female Sexual Function Index (FSFI) was the most commonly applied tool to measure sexual satisfaction, but its results were not always in agreement with the findings of other research tools. Finally, women who underwent surgical techniques had higher sexual activity levels than those who received non-surgical procedures. CONCLUSION: The reviewed studies highlighted the need for further quantitative and qualitative research on the sexual performance and outcomes of patients with MRKH syndrome. REGISTRATION NUMBER: None.

Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAs in vitro.

STUDY QUESTION: Could human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) accelerate vaginal epithelium cell (VK2) growth? SUMMARY ANSWER: HucMSC-Ex play a significant role in promoting proliferation of VK2 cells by accelerating the cell cycle and inhibiting apoptosis through exosomal microRNAs in vitro. WHAT IS KNOWN ALREADY: Numerous studies have reported that MSC-Ex play an important role in tissue injury repair. STUDY DESIGN, SIZE, DURATION: hucMSC and exosomes isolated from their conditioned medium were used to treat a vaginal epithelial cell line (VK2). Normal human fibroblasts (HFF-1) were used as negative control to hucMSC. PARTICIPANTS/MATERIALS, SETTING, METHODS: VK2 cells were co-cultured with hucMSC whose paracrine effect on the viability, cell cycle and cell apoptosis of VK2 vaginal epithelial cells was further assessed by the CCK-8 assay and flow cytometry. HucMSC-Ex isolated from culture medium by ultracentrifuge were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blot. HucMSC-Ex at different concentrations and HFF-1 exosomes were used to treat VK2 cells. High-throughput RNA sequencing was utilized to reveal the profile of microRNAs in hucMSC, hucMSC-Ex, HFF-1 and HFF-1 exosomes and GO analysis was applied to demonstrate their functions. To evaluate the function of these specific microRNAs in hucMSC-Ex, VK2 cells were treated with RNA-interfered-hucMSC-Ex (RNAi-hucMSC-Ex) and their proliferation was measured by Label-free Real-time Cellular Analysis System. MAIN RESULTS AND THE ROLE OF CHANCE: The study showed that hucMSC stimulate VK2 cell growth possibly through a paracrine route by promoting cell cycle and inhibiting apoptosis. Compared with control and low dose groups, hucMSC-Ex of high concentration (more than 1000 ng/ml) significantly increased VK2's growth after treatment in a dose-depended manner (P < 0.05). HucMSC-Ex raised the proportion of cells in S-phase and reduced the percentage of apoptotic cells in VK2 cells in comparison with the HFF-1 exosomes and control groups (P < 0.05). microRNAs, including miR-100 (16.92%), miR-146a (9.21%), miR-21 (6.67%), miR-221 (6.39%) and miR-143 (4.63%), were found to be specifically enriched (P < 0.05) in hucMSC-Ex and their functions concentrated on cell cycle, development and differentiation. Collectively, our findings indicate that hucMSC-Ex may play a significant role in accelerating VK2's proliferation by promoting cell cycle and inhibiting apoptosis through exosomal microRNAs in vitro. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Our study did not confirm the function of hucMSC-Ex or specifically enriched exosomal microRNAs in vivo. miR-100 and miR-146a are well-known immunomodulatory miRNAs that participate in the regulation of inflammatory disorders and may enhance the therapeutic effect of hucMSC-Ex by promoting the surgical injury repair after vaginal reconstruction. But whether it acts through anti-inflammatory responses needs further study. WIDER IMPLICATIONS OF THE FINDINGS: This finding supports the potential use of hucMSC-Ex as a cell-free therapy of Meyer-Rokitansky-Küster-Hauser syndrome (MRKHS) after vaginoplasty. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Chinese National Nature Sciences Foundation (grant number 91440107, 81471416 and 81771524) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19040102). All authors state that there is no conflict of interest to disclose.

Treatment of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome in Denmark: a nationwide comparative study of anatomical outcome and complications.

OBJECTIVE: To compare the long-term anatomical outcome and complications in treatments of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. DESIGN: A historical comparative follow-up study using medical chart reviews. SETTING: Public hospitals. PATIENT(S): A nationwide cohort of patients diagnosed with MRKH syndrome (n = 168). INTERVENTION(S): McIndoe vaginoplasty (n = 54), self-dilation (n = 60), coital dilation (n = 20), Baldwin vaginoplasty (n = 4), Williams vaginoplasty (n = 3), Davydov vaginoplasty (n = 2), or no treatment (n = 29). MAIN OUTCOME MEASURES(S): Mean vaginal depth at follow-up, anatomical treatment success rates at levels of ≥6 cm, ≥7 cm, and ≥8 cm, complications, and resurgery. RESULT(S): Mean vaginal depths were 7.4 cm (95% confidence interval [CI] 6.8-8.1 cm), 7.3 cm (95% CI 6.7-7.9 cm), and 8.7 cm (95% CI 7.9-9.5 cm) at follow-up in patients treated by McIndoe vaginoplasty, self-dilation, and coital dilation, respectively. Overall complication rates in the three groups were 35/54 (65%), 21/52 (35%), and 1/20 (5%), respectively. Eighteen (33%) of the patients who underwent McIndoe vaginoplasty needed resurgery. CONCLUSION(S): Our findings support the current recommendations of dilation therapy as the first-line treatment of vaginal agenesis and emphasize the relevance of coital dilation in patients able to regularly engage in coital activity. However, further studies of functional outcome and patient satisfaction are needed.

Surgery is not superior to dilation for the management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome: a multicenter comparative observational study in 131 patients.

BACKGROUND: Vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome can be managed either by various surgeries or dilation. The choice still depends on surgeon's preferences rather than on quality comparative studies and validated protocols. OBJECTIVE: We sought to compare dilation and surgical management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome, in terms of quality of life, anatomical results, and complications in a large multicenter population. STUDY DESIGN: Our multicenter study included 131 patients >18 years, at least 1 year after completing vaginal agenesis management. All had an independent gynecological evaluation including a standardized pelvic exam, and completed the World Health Organization Quality of Life instrument (general quality of life) as well as the Female Sexual Function Index and Female Sexual Distress Scale-Revised (sexual quality of life) scales. Groups were: surgery (N = 84), dilation therapy (N = 26), and intercourse (N = 20). One patient was secondarily excluded because of incomplete surgical data. For statistics, data were compared using analysis of variance, Student, Kruskal-Wallis, Wilcoxon, and Student exact test. RESULTS: Mean age was 26.5 ± 5.5 years at inclusion. In all groups, World Health Organization Quality of Life scores were not different between patients and the general population except for lower psychosocial health and social relationship scores (which were not different between groups). Global Female Sexual Function Index scores were significantly lower in the surgery and dilation therapy groups (median 26 range [2.8-34.8] and 24.7 [2.6-34.4], respectively) than the intercourse group (30.2 [7.8-34.8], P = .044), which had a higher score only in the satisfaction dimension (P = .004). However, the scores in the other dimensions of Female Sexual Function Index were not different between groups. The Female Sexual Distress Scale-Revised median scores were, respectively, 17 [0-52], 20 [0-47], and 10 [10-40] in the surgery, dilation therapy, and intercourse groups (P = .38), with sexual distress in 71% of patients. Median vaginal depth was shorter in dilatation therapy group (9.6 cm [5.5-12]) compared to surgery group (11 cm [6-15]) and intercourse group (11 cm [6-12.5]) (P = .039), but remained within normal ranges. One bias in the surgery group was the high number of sigmoid vaginoplasties (57/84, 68%), but no differences were observed between surgeries. Only 4 patients achieved vaginas <6.5 cm. Delay between management and first intercourse was 6 months (not significant). Seventy patients (53%) had dyspareunia (not significant), and 17 patients all from the surgery group had an abnormal pelvic exam. In the surgery group, 34 patients (40.5%) had complications, requiring 20 secondary surgeries in 17 patients, and 35 (42%) needed postoperative dilation. In the dilation therapy group, 13 (50%) needed maintenance dilation. CONCLUSION: Surgery is not superior to therapeutic or intercourse dilation, bears complications, and should therefore be only a second-line treatment. Psychological counseling is mandatory at diagnosis and during therapeutic management.

Sexual response in women with Mayer-Rokitansky-Küster-Hauser syndrome with a nonsurgical neovagina.

BACKGROUND: Sexual dysfunction is prevalent in women with Mayer-Rokitansky-Küster-Hauser syndrome after the creation of a neovagina. Insight into the physiologic response of the neovagina during sexual arousal is lacking, although this would help in the understanding of sexual function of these patients. The physiologic sexual response of the vagina can be measured objectively by vaginal photoplethysmography to assess vaginal blood flow. OBJECTIVE: Testing whether the physiologic and subjective sexual response in women with Mayer-Rokitansky-Küster-Hauser syndrome with a neovagina differs from the response in women with a natal vagina. STUDY DESIGN: Vaginal blood flow (vaginal pulse amplitude) and subjective sexual responses during neutral and erotic film viewing were assessed in premenopausal women with Mayer-Rokitansky-Küster-Hauser syndrome with a nonsurgically created neovagina (n=15) and were compared with responses of an age-matched control group (n=21). RESULTS: All women with Mayer-Rokitansky-Küster-Hauser syndrome had created their neovagina themselves by dilation. Women with Mayer-Rokitansky-Küster-Hauser syndrome showed a significantly smaller vaginal pulse amplitude compared with control subjects during neutral film viewing (P=.002). In both groups, vaginal pulse amplitude increased significantly during erotic film viewing, but this increase was significantly smaller in the Mayer-Rokitansky-Küster-Hauser syndrome group (P<.005). Levels of subjective sexual arousal did not significantly differ between the 2 groups (P>.2). CONCLUSION: Women with Mayer-Rokitansky-Küster-Hauser syndrome with a nonsurgically created neovagina showed a weaker vaginal blood flow response during visual sexual stimulation and poorer basal blood flow compared with control subjects. The differences in vaginal blood flow may be related to less vascularization and innervation of the neovagina compared with the natal vagina. The weaker vaginal sexual response can play a role in sexual dysfunction; however, despite the weaker vaginal response, women with Mayer-Rokitansky-Küster-Hauser syndrome did not differ in their level of subjective sexual arousal. Future studies may compare vaginal blood flow and subjective sexual response of women with Mayer-Rokitansky-Küster-Hauser syndrome with nonsurgically and surgically created vaginas.

Intensive vaginal dilation using adjuvant treatments in women with Mayer-Rokitansky-Kuster-Hauser syndrome: retrospective cohort study.

AIMS: To evaluate the effect of adjuvants during intensive vaginal dilator therapy for functional and anatomical neovagina creation in women with Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). METHODS: This retrospective cohort study included 75 women with MRKH undergoing intensive vaginal dilator treatment between 2000 and 2014. One specialist nurse performed non-surgical vaginal dilation aided by adjuvants, during inpatient admissions for several dilation sessions per day. Following discharge, women continued dilation at home and were advised to attend fortnightly follow-up appointments. RESULTS: Outcomes from 68 women were analysed. The median age of starting treatment was 18 years (range: 13-36). There was a mean of 3 days per admission (range 1-5) with a median of 10 dilation sessions per admission. Adjuvant treatment was used by 48/68 (71%) women: oestriol cream 29/68 (43%), 50:50 nitrous oxide and oxygen 44/68 (65%), diazepam 8/68 (12%), lidocaine ointment 26/68 (39%), paracetamol 35/68 (51%) and naproxen 2/68 (3%). There were no statistically significant differences for changes in vaginal parameters. Women receiving adjuvants had a median increase of 4.5 cm (0.5-7 cm) in neovaginal length compared with women not receiving adjuvants who had a median increase of 3.25 cm (0-7 cm) during intensive treatment. Women who received adjuvants tolerated more dilation sessions per day (10 vs 6.5 median sessions respectively) than those who did not (P < 0.001). Of those with documented length at discharge, 42/56 (75%) women had an anatomical neovagina of 7 cm or greater length. CONCLUSIONS: Vaginal dilation delivered by intensive treatment and supplemented by adjuvant treatments in a multi-disciplinary centre is a rapid and effective method for creation of a neovagina in women with MRKH.

[Mayer-Rokitansky-Küster-Hauser syndrome].

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital anomaly characterized by uterovaginal agenesis in females with normal secondary sex characteristics and normal karyotype (46,XX). The prevalence of MRKH syndrome is one in 5,000 live female births as recently confirmed by a nationwide population-based study in Denmark. This review kaleidoscopically summarizes the current knowledge of the history, genetics, diagnostics, treatment of vaginal agenesis, psychosexual aspects, and fertility options in MRKH syndrome.

Information ranks highest: Expectations of female adolescents with a rare genital malformation towards health care services.

BACKGROUND: Access to highly specialized health care services and support to meet the patient's specific needs is critical for health outcome, especially during age-related transitions within the health care system such as with adolescents entering adult medicine. Being affected by an orphan disease complicates the situation in several important respects. Long distances to dedicated institutions and scarcity of knowledge, even among medical doctors, may present major obstacles for proper access to health care services and health chances. This study is part of the BMBF funded TransCareO project examining in a mixed-method design health care provisional deficits, preferences, and barriers in health care access as perceived by female adolescents affected by the Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), a rare (orphan) genital malformation. METHODS: Prior to a communicative validation workshop, critical elements of MRKHS related care and support (items) were identified in interviews with MRKHS patients. During the subsequent workshop, 87 persons involved in health care and support for MRKHS were asked to rate the items using a 7-point Likert scale (7, strongly agree; 1, strongly disagree) as to 1) the elements' potential importance (i.e., health care expected to be "best practice", or priority) and 2) the presently experienced care. A gap score between the two was computed highlighting fields of action. Items were arranged into ten separate questionnaires representing domains of care and support (e.g., online-portal, patient participation). Within each domain, several items addressed various aspects of "information" and "access". Here, we present the outcome of items' evaluation by patients (attended, NPAT = 35; respondents, NRESP = 19). RESULTS: Highest priority scores occurred for domains "Online-Portal", "Patient participation", and "Tailored informational offers", characterizing them as extremely important for the perception as best practice. Highest gap scores yielded domains "Tailored informational offers", reflecting perceived lack of disease-related information for affected persons, medical experts, and health insurance companies, "Online-Portal" (with limited information available on specialist clinics and specialized doctors), and regarding insufficient support offers (e.g., in school and occupational settings). Conversely, lowest gap scores were found with group offers for MRKHS patients ("Transition programs") and MRKHS self-help days ("Patient participation"), suggesting satisfaction or good solutions in place. DISCUSSION: The importance assigned to disease-related information indicates that informational deficits are perceived by patients as barriers, hindering proper access to health care, especially in an orphan disease. Access to health-related information plays a role for all persons seeking help and care. However, the overwhelmingly high scores attributed to these elements in the context of an orphan disease reveal that here improved information policies are crucial, demanding for institutionalized solutions supported by the health care system. IMPLICATIONS FOR PRACTICE: The disparity between experience of care and attribution as best practice detected describes areas of action in all domains involved, highlighting information related fields. New concepts and structures for health care in orphan diseases could draw upon these patient-oriented results a) regarding orphan-disease specific elements demanding institutionalized reimbursement, b) essential elements for center care and corresponding networks, and c) elements reflecting patients´ participation in the conception of centers for rare diseases.

Assessing the Experience of Vaginal Dilator Use and Potential Barriers to Ongoing Use among a Focus Group of Women with Mayer-Rokitansky-Küster-Hauser Syndrome.

STUDY OBJECTIVE: To assess the experience of dilator use for neovagina creation in women diagnosed with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and identify barriers affecting patient compliance with dilator use. DESIGN AND SETTING: This was a qualitative study using a structured questionnaire to investigate perception and identify barriers regarding vaginal dilator use. A questionnaire was administered after participants viewed a 2-minute patient educational video to additionally examine the usefulness of a patient education video tool as an adjunct to counseling in clinic on vaginal dilator use. PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We enrolled 13 adolescent girls and women diagnosed with MRKH, aged 14-48 years, recruited from clinic and during a conference geared toward women affected by MRKH. RESULTS: The mean age of participants was 26 (±11.4) years with most diagnosed between the ages of 12 and 18 years. Of all participants, 69% (9/13) reported ever being sexually active with a mean age of coitarche of 16 (±2.6) years. Seventy-seven percent (10/13) reported current or past use of vaginal dilators, and most had some previous education on dilator use. Only 15% (2/13) reported no previous exposure to an educational tool. After viewing the 2-minute educational video, all participants rated it very helpful using a Likert scale (strongly agree to strongly disagree). Major themes that emerged as perceived barriers to dilator use included viewing dilation as a negative experience, uncertainty about success, and lack of motivation. CONCLUSION: Education is an integral part of improving compliance with vaginal dilator use among adolescent girls and women affected by MRKH. Technology can be used to reinforce face-to-face counseling in the clinic. To our knowledge, this is the first study to specifically investigate patient experience with dilator use and opinion regarding the use of video technology to demonstrate self-directed neovagina creation in an MRKH population. The barriers identified in this study provide new insights to inform future research and clinical management of dilator use.

[CONSERVATIVE TREATMENT OF MAYER-ROKITANSKY-KÜSTER-HAUSER SYNDROME. REVIEW OF LITERATURE AND OUR EXPERIENCE].

Mayer-Rokitansky-Küster-Hauser syndrome is a part of the group of abnormalities known as "Anomalies of the fusion of the Müllerian ducts". It is characterized by normal development of breasts and hairs, normal appearance of external genitalia, normal feminine genotype (46XX), normal FSH, LH, E2 and Test. levels, normal ovaries and congenital absence of uterus and the whole or the upper two thirds of the vagina. It is observed in about 15% of the cases with primary amenorrhea and the incidence is about 1:4500-6000. Etiologycal factors such as lack of estrogen/gestagen receptors, deletions or mutations of genes that stop the fusion, as well as the activation of anti-Müllerian hormone (AMH), are considered. The etiology is being explored but there is no consensus yet. The diagnosis is confirmed during a clinical examination, which takes place because of a primary amenorrhea (often happening at the age of 16), and the absence of a uterus and vagina is proved. The therapy should be handled by a multidisciplinary team including obstetrician, trained midwife, psychologist, specialist in imaging and psycho-sexual counseling. The idea for surgical creation of vagina (neovagina) dates many years ago. The first known documents date back to 1817 and over the years a variety of methods are offered usage of amnion, dura mater, peritoneum, skin grafts, different parts of the intestine, cellulose, etc. The first method of non-surgical treatment is offered by the Czech gynecologist Frank. His ambition was to build a vagina by gradual dilatation of the tissue while applying dilatators with successively increasing length and thickness. The method was further developed by Ingram (1981) and nowadays by Edmonds (2012). He reported about 245 patients treated during the last 12 years by his team. 232 of them had a success in anatomic aspect (95%), 13 did not complete the treatment due to psychological or cultural problems. The experts from American College of Obstetricians and Gynecologists include in their "Committee Opinion" from May 2013 the following lines: "Non-surgical creation of the vagina is the appropriate first line approach in most patients". Briefly is presented our experience in this field--14 girls at the age of 16-18, successfully treated with dilatation in the III Gynecology Clinic in University hospital "Maichin dom", Sofia, Bulgaria.