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Background: The Mayer-Rokitansky-Küster-Hauser syndrome, MRKHS, is a rare (orphan) disease characterized by the aplasia or hypoplasia of the uterus and the vagina. In women's health research, little is known as to how much care provision for patients with MRKHS takes into account their socio-demographic together with their clinical characteristics. This work examines the patients' socio-demographic characteristics, highlighting issues of inappropriate and deficient provision of care., Methods: The study was carried out as part of the larger TransCareO project and included a group of N=129 MRKHS patients who underwent surgery between 2008 and 2012. Using a specially developed questionnaire, we analyzed MRKHS patients' data found both in the clinical documentation of the Department for Women's Health, University Hospital of Tübingen and the patient surveys of the Center for Rare Genital Malformations (CRGM/ ZSGF). Patients who took part in interviews were compared with non-respondents., Results: Patient respondents and non-respondents did not differ as to the parameters of interest. In most cases, primary amenorrhea was reported as an admission reason. In 24% of patients, a medical intervention (hymenal incision or hormone treatment) already occurred before admission to the Center in Tübingen and proper diagnosis of MRKHS. About one third received in advance inappropriate treatment. During the therapy, more than half of the patients were in a solid partnership. 10% of the family anamneses documented the occurrence of urogenital malformations., Conclusions: Care provision for MRKHS patients is largely characterized by delayed proper diagnosis and in part, by inappropriate treatment attempts; there are also indications of regional differences. Anamnestic clues such as an asymptomatic amenorrhea or renal abnormalities of unclear origin still fail to result early enough in referral to a center on the basis of suspected MRKHS diagnosis. Urogenital malformations in the family are more common in patients than in the general population. For patients, a wide range of burdens are associated with the diagnosis. Abnormalities compared to their female peers occur, for instance, in the partnership status: MRKHS patients have more rarely a partner.

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Küster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation., (© 2019 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists/.)

Objective: To report our experience with the screening and selection of potential recipients and living donors of our uterus transplantation (UTx) program., Design: Part of an observational program., Setting: University hospital., Patient(s): Patients with absolute uterine factor infertility (AUFI)., Intervention(s): Screening by e-mail and telephone, selection during surgical consultation, and preoperative investigations according to a multistep procedure for living donation., Main Outcome Measure(s): Age, cause of AUFI, exclusion reasons, and preoperative workup., Result(s): A total of 212 potential recipients expressed interest in participation. Among the 46 potential recipients and 49 directed donors were 4 potential recipients, each with 2 directed donors. Mean (range) age of potential recipients was 29.6 (19-41) years. Of the potential recipients, 39 (84.8%) had congenital AUFI and 7 (17.3%) had acquired AUFI. Ultimately, 15 potential recipients with 16 directed donors were selected for participation, with 1 potential recipient having 2 directed donors. Mean age of included potential recipients was 28.9 (22-35) years, and mean donor age was 51.3 (37-62) years. Fourteen potential recipients (93.3%) had congenital AUFI, and one potential recipient (6.7%) had undergone hysterectomy for obstetric complications., Conclusion(s): The number of potential candidates for UTx is not inconsiderable, with congenital AUFI being the leading cause of AUFI in our cohort. However, our findings highlight that large numbers of AUFI patients need to be screened, considering our exclusion rates were >50%, owing to ABO incompatibility, unavailability of a directed donor, and self-withdrawal. Moreover, meticulous preoperative screening, including in-depth psychological assessment, is mandatory to maximize living donor safety and UTx success., (Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Purpose: This study aimed to analyze the hormone profiles, to detect the rate of hyperandrogenemia and to investigate the potential effect of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) on ovarian reserve, as reflected by the serum Anti-Mullerian hormone (AMH) levels. Clinical implications were analyzed by including our own experiences with three patients after ovarian stimulation in preparation for uterus transplantation., Methods: Serum samples of 100 patients with MRKHS (50 patients with MRKHS type 1 and 50 with type 2) were analyzed and compared to 50 individually age-matched healthy controls. Blood samples for hormone analyses were collected routinely during the clinical visit., Results: The mean age was 20.0 years for MRKHS type 1, MRKHS type 2 and healthy controls. Compared to healthy controls, there was no significant difference in AMH values in the MRKH patients. As shown in previous studies, the proportion of hyperandrogenemia without clinical symptoms was significantly higher in MRKHS type 1 (52%; p < 0.001) and type 2 (56%; p < 0.001) patients when compared to age-matched controls. In preparation for uterus transplantation, three patients were stimulated with FSH/hMG for mean 14.2 days and the mean number of aspirated oocytes was 13.2 (3-22), while 8.3 (2-10) oocytes could be fertilized and cryopreserved. The mean fertilization rate was 51.2% (30-67%)., Conclusion: The rate of hyperandrogenemia was significantly higher in MRKH patients compared to healthy age-matched controls. Though, ovarian reserve (AMH level) was not reduced compared to controls. Future studies are needed to identify optimal ovarian stimulation protocols as well as to implement a systematic multicenter reporting system.

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., (© 2017 Society for Reproduction and Fertility.)

Objective: To analyze the histologic and immunohistochemical structure of uterine rudiments focusing on the endometrium in a representative group of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome compared with a control group., Design: Prospective comparative study., Setting: University hospital., Patient(s): Forty-two patients with MRKH syndrome and 13 control subjects., Intervention(s): Representative biopsies or whole uterine rudiments were removed during surgery and processed by a standardized procedure including immunohistochemical staining and analysis., Main Outcome Measure(s): Histologic structure, tissue types, hormone receptor expression, endometrial proliferative capacity, and type in correlation with cycle phase., Result(s): Twenty-two of the uterine rudiments showed a duct-like structure or small cavity, 17 of which contained endometrial epithelium and CD10-positive stroma. All rudiments contained an intact myometrial layer. Tubal epithelium and stroma were found in three rudiment samples. No significant differences were observed with regard to estrogen receptor (ER) or progesterone receptor (PR) expression in endometrium or myometrium. Interestingly, patients showed predominantly basalis-like endometrium with specific lack of CD90 expression and significantly lower proliferation compared with controls., Conclusion(s): All typical uterine tissues can be found in uterine rudiments of patients with MRKH syndrome. Expression of hormonal receptors in the latter and controls did not differ significantly. Endometrium shows predominantly basalis-like features in uterine rudiments., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The prevalence of müllerian malformations is 1 in 200, or 0.5%. A third of the anomalies are septate, a third bicornuate uteri, 10% arcuate uterus, 10% didelphis and unicornuate uterus, and < 5% uterine and vaginal aplasia. Correct diagnosis of the malformation is most important but often very difficult. Correct treatment can only be performed if the malformation is clear. Longitudinal vaginal septums have to be removed due to potential obstetric problems. Transverse vaginal septums can cause hematocolpos and pain and have to be incised crosswise and excised so as not to shorten the vagina at the same time. Congenital vaginal agenesis occurs in Mayer-Rokitansky-Kuster-Hauser syndrome patients and in androgen insensitivity syndrome. The first choice for surgical treatment should be the new laparoscopic-assisted creation of a neovagina. Septate uterus has to be distinguished from a bicornuate uterus. Even if it is not proven to be a cause for infertility, the chance of miscarriage can be diminished by performing hysteroscopic metroplasty. Repair of a uterine septum in infertility patients often improves pregnancy rates. In contrast, surgical repair of a bicornuate uterus requires an abdominal metroplasty. This should only be performed if the patient has recurrent fetal loss due to the uterine structural defect. In a unicornuate uterus it is most important to determine if there is a second uterine horn that can cause cyclic pain if it has functioning endometrium. The only surgical option in these cases is to remove the rudimentary uterus with endometrium and hematometra, respectively., (© Thieme Medical Publishers.)

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Küster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation. [ABSTRACT FROM AUTHOR]