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Purpose To limit the burden of long-term immunosuppression (IS) after uterus transplantation (UTx), removal of the uterine allograft is indicated after maximum two pregnancies. Hitherto this has required graft hysterectomy by laparotomy. Our objective was to demonstrate, as a proof of concept, the feasibility of less traumatic transplantectomy by total laparoscopic hysterectomy (TLH). Patient A 37-year-old woman with uterovaginal agenesis due to Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS) who had undergone neovaginoplasty at age 19 years prior to living-donor (LD) UTx in 10/2019 at age 35 years gave birth to a healthy boy by primary cesarean section in 06/2021. During pregnancy, she developed impaired renal function, with bilateral hydronephrosis, necessitating early allograft removal in 09/2021 to prevent chronic kidney disease, particularly during a potential second pregnancy. Methods Transplantectomy by TLH essentially followed standard TLH procedures. We paid meticulous attention to removing as much donor tissue as possible to prevent postoperative complications from residual donor tissue after stopping IS, as well as long-term vascular damage. Results TLH was performed successfully without the need to convert to open surgery. Surgical time was 90 min with minimal blood loss. No major complications occurred intra- or postoperatively and during the subsequent 9-month follow-up period. Kidney function normalized. Conclusions To our knowledge, we report the first successful TLH-based removal of a uterine allograft in a primipara after LD UTx, thus demonstrating the feasibility of TLH in uterus recipients with MRKHS.

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.Die Diagnose des Mayer-Rokitansky-Küster-Hauser Syndroms (MRKHS), eine seltene Variante der weiblichen Geschlechtsentwicklung, wird meist in der Pubertät gestellt. Die Verunsicherung im Selbstbild, die Unmöglichkeit schwanger zu werden führen häufig zu deutlicher Belastung. Obwohl eine psychosomatische Begleitung in der Literatur konsistent empfohlen wird gibt es bislang nur wenige Studien zu psychischen Aspekten von MRKHS. Ziel dieser Studie ist es, die Lebensqualität und Belastung von Frauen mit MRKHS bei der operativen Anlage einer Neovagina zu untersuchen und andererseits Effekte einer Intervention zur Vorbereitung und Unterstützung während der Behandlung zu evaluieren. Methoden An einem überregionalen Zentrum zur Neovaginaanlage wurde im Rahmen einer explorativen quasi-experimentellen Prä-Post-Untersuchung allen Patientinnen eine psychosomatische Intervention angeboten (Interventionsgruppe IG, n=23) und vor Operation (t0) sowie sechs Monate danach (t1) die sexuelle Funktion (FSFI), psychische Belastung (PHQ-D) und gesundheitsbezogene Lebensqualität (SF-12) erhoben. Diese wurden mit den Daten einer zuvor sowie im Anschluss an den Interventionszeitraum erhobenen Stichprobe verglichen (Vergleichsgruppe VG, n=30). Ergebnisse Während die körperliche Lebensqualität (SF-12) beider Gruppen zu beiden Zeitpunkten unauffällig war, zeigte sich eine signifikante Beeinträchtigung in der psychischen Lebensqualität. Beide Gruppen (IG, VG) verbesserten sich von t0 zu t1 in ihrer sexuellen Funktion (FSFI) und zeigten niedrigere Depressionswerte (PHQ-D). Die im Rahmen dieser Studie entwickelte Kurzintervention wurde von den Betroffenen gut akzeptiert und als hilfreich bewertet. Diese subjektiv empfundene Wirksam-keit der Intervention zeigte sich jedoch nicht durch eine Verbesserung auf der Lebensqualitätsskala (SF-12) und Depressionsskala (PHQ-D). Schlussfolgerung Die Betroffenen zeigen eine deutliche, klinisch relevante Belastung (SF-12), die sich aber nicht in Form psychischer Komorbidität (PHQ-D) abbildet. Diese scheinbare Diskrepanz weist auf psychisch stabile Frauen mit akuter Belastung durch die Diagnose der Variante der Geschlechtsentwicklung hin. Für sie scheint ein niederschwelliges Unterstützungsangebot mit supportivem Charakter zur Begleitung während der operativen Behandlung notwendig und hilfreich. Die rekonstruktive Therapie zur Anlage einer Neovagina scheint die psychische Lebensqualität positiv zu beeinflussen. Dass eine Schwangerschaft aufgrund des fehlenden Uterus weiterhin nicht möglich ist könnte ein Grund für das Nicht-Erreichen der Lebensqualität der Durchschnittsbevölkerung sein.

The risk of gonadal germ cell tumors is increased over the lifetime of patients with XY-disorders of sex development (XY-DSD). The aim of this study was to evaluate clinical features and histopathological outcome after gonadectomy in patients with XY-DSD to assess the risk of malignant transformation to gonadal germ cell tumors. Thirty-five women treated for XY-DSD at our hospital between 2003 and 2020 were enrolled in this study. Twenty-seven (77%) underwent prophylactic gonadectomy, 10 (29%) at our department and 17 (48%) at external hospitals. Eight (23%) patients didn’t receive gonadectomy. Of the patients who underwent a surgical procedure at our hospital, two patients were diagnosed with a unilateral seminoma, one patient with a bilateral and one patient with a unilateral Sertoli cell adenoma. According to these findings, preventive gonadectomy in patients with XY-DSD should be taken into consideration. Guidelines concerning the necessity of gonadectomy to avoid malignant transformation are still lacking. The risk of malignant germ cell tumors from rudimentary gonads has not been investigated sufficiently to date, as it is mostly based on case series due to the rarity of the condition. In our study we retrospectively analyzed patients who partly underwent bilateral gonadectomy, aiming to fill this gap. Concerning the ideal point of time for gonadectomy, further studies with a higher number of patients are needed.

Introduction The complication of tape erosion in the urethra following placement of a retropubic (TVT) or transobturator (TOT) tension-free suburethral vaginal sling or an accidental iatrogenic transurethral tape position can result in the formation of a urethrovaginal or vesicovaginal fistula. The objective of the investigation is the evaluation of the management of such rare complications. Patients and Methods Retrospective analysis of 14 patients who were treated for a urethral lesion or urethrovaginal fistula formation status post TVT/TOT placement between June 2011 and February 2018 in the Tübingen University Department of Gynaecology. Results As surgical therapy, 57.1% (n = 8) cases underwent vaginal fistula closure using a Martius flap of the labium majus and in 21.4% (n = 3) using a vaginal rotation skin flap. In 21.4% (n = 3), exclusively vaginal suture reconstruction of the urethra following excision of the tape running transurethrally or tape erosion was performed. 50% (n = 7) of the patients had lasting continence postoperatively without any further need for therapy. In 28.6% (n = 4), there was ongoing stress urinary incontinence, in 21.4% (n = 3) mixed urinary incontinence. Six of the 7 patients with persistent incontinence underwent new placement of a tension-free suburethral retropubic sling (TVT) an average of 8.8 months (5 – 13 months) postoperatively which was uncomplicated in all patients and achieved satisfactory continence. The 3 patients with mixed urinary incontinence and persistent urgency components additionally received anticholinergic medication. During the time period investigated, there were no long-term complications, in particular no recurrent fistulas. Conclusion The rare but relevant complications of a urethral erosion, transurethral tape position or urethrovaginal fistula formation status post TVT/TOT placement can be successfully managed via vaginal surgery. Persistent postoperative urinary incontinence with the need for a two-phase repeat TVT placement following sufficient wound healing must be preoperatively clarified.

To contribute to establishing donor selection criteria based on our experience with two successful living-donor human uterus transplantations (UTx) and an aborted attempt. 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. 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. 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. ClinicalTrials.gov Identifier: NCT03048396.

Introduction Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as the cause for MRKHS has existed, supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature. Material and methods DNA sequence analysis of the oxytocin receptor (OXTR) and estrogen receptor-1 gene (ESR1) was performed in a group of 93 clinically well-defined patients with uterovaginal aplasia (68 with the isolated form and 25 with associated malformations). Results In total, we detected three OXTR variants in 18 MRKHS patients with one leading to a missense mutation, and six ESR1 variants in 21 MRKHS patients, two of these causing amino acid changes and therefore potentially disease. Conclusions The identified variants on DNA level might impair receptor function through different molecular mechanisms. Mutations of ESR1 and OXTR are associated with MRKHS. Thus, we consider these genes potential candidates associated with the manifestation of MRKHS.

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 ofWNT4mutations 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 ofWNT4,WNT5A,WNT7AandWNT9Bdemonstrated 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.

The Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is defined as a congenital aplasia of the vagina and the uterus with normal female chromosomes and normal functioning ovaries. The creation of a neovagina with a sufficient vaginal length is not only the premise for a normal sexual life of these patients but also a precedent condition when thinking about uterus transplantation as a treatment for absolute uterine infertility. The non-surgical dilation is recommended as the first-line treatment for creation of a neovagina. Alternatively, there are different options of vaginal reconstruction methods. The well-established surgical approaches can be distinguished into three techniques: intestinal vaginoplasty, graft methods, and stretching techniques. The laparoscopically assisted creation of a neovagina in a modified Vecchietti-based technique seems to be the first-choice surgical option for MRKH patients, especially when aiming for a uterus transplantation in the future. The procedure should be performed in a specialized center by experienced surgeons and patients need to be treated in a holistic approach.

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Kuster-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.

Als weibliche genitale Fehlbildungen werden angeborene Anomalien des inneren oder auseren Genitale unterschiedlicher Ursache bezeichnet. Sie sind im Kindesalter haufig inapparent und werden erst mit dem Einsetzen der Menarche, der sexuellen Aktivitat oder einem unerfullten Kinderwunsch symptomatisch und konnen ursachlich fur eine Sterilitat oder Infertilitat sein. Aufgrund der Seltenheit, der breiten Varianz und der Komplexitat von weiblichen genitalen Fehlbildungen sind neben einer akkuraten Diagnostik eine optimale Aufklarung, operative Versorgung und Nachsorge sowie eine interdisziplinare Betreuung in einem spezialisierten Zentrum essenziell, um Fehldiagnosen und daraus resultierende verzogerte oder falsche Therapien zu vermeiden.

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer&ndash, Rokitansky&ndash, K&uuml, ster&ndash, Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to standardizing recipient/donor selection, UTx surgery, and postoperative treatment, and their implementation in routine settings. We descriptively analyzed prospectively collected observational data from our four uterus recipients, all with MRKHS, their living donors, and the two newborns born to two recipients, including 1-year postnatal follow-ups. Analysis included only living-donor/recipient pairs with completed donor/recipient surgery. Two recipients, both requiring ovarian restimulation under immunosuppression after missed pregnancy loss in one case and no pregnancy in the other, each delivered a healthy boy by cesarean section. We conclude that parameters crucial to successful transplantation, pregnancy, and childbirth include careful selection of donor/recipient pairs, donor organ quality, meticulous surgical technique, a multidisciplinary team approach, and comprehensive follow-up. Surgery duration and blood vessel selection await further optimization, as do the choice and duration of immunosuppression, which are crucial to timing the first embryo transfer. Data need to be collected in an international registry due to the low prevalence of MRKHS.

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.

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. 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. 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-Mullerian anomalies, most frequently renal (20.9%) and skeletal (9.1%) malformations. 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.

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.

Objective The main objectives of our study were to demonstrate that laparoscopic supracervical hysterectomy (LSH) or total laparoscopic hysterectomy (TLH) can be performed safely even in patients with a uterine weight ≥ 500 g, to analyze the rate of conversions to laparotomy due to uterine size and to estimate the incidence and type of intraoperative and long-term postoperative complications. Study Design Retrospective open, single-center, comparative interventional study of LSH and TLH. Results The present study comprised a total of 138 patients that underwent laparoscopic hysterectomy with a uterine weight ≥ 500 g; 109 patients (79.0 %) underwent LSH and 29 patients (21.0 %) underwent TLH. Median uterine weight across the entire cohort was 602 g, with the largest uterus weighing 1860 g. A total of 24 cases (17.4 %) among the 138 hysterectomies were converted to a laparotomy due to lack of adequate intraabdominal space and size of the uterus. Mean uterine weight of the patients in the LSH group that underwent conversion was 883 g (SD 380 g, n = 13) and 757 g (SD 371 g, n = 11) in the TLH group. The rate of conversion to laparotomy due to the uterine weight was significantly lower in the LSH group (11.9 %) compared to the TLH group (37.9 %) (p = 0.002). Intraoperative complications requiring laparotomy for other reasons but uterine size occurred in 6 patients of the study cohort (6/138; 4.3 %). Long-term postoperative complications occurred in 2 patients (2/138, 1.4 %), both patients from LSH group had to be re-operated on due to adhesions. Conclusions Our study adds further insight in the limited data set of laparoscopic hysterectomy for increased uterine weight and shows that LSH and TLH are safe and feasible even in patients with very large uteri (≥ 500 g).