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1.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

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.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
2.
Front Cell Dev Biol ; 8: 572281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072755

RESUMO

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue. In order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome. Differential and co-expression analyses of the data identified cellular processes and candidate genes that converge on a core network of interconnected regulators that emerge as pivotal for the perturbed expression space. With these results and browsable access to the rich data through an online tool we seek to accelerate research to unravel the underlying biology of the syndrome.

3.
J Clin Med ; 9(8)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756295

RESUMO

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer-Rokitansky-Küster-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.

4.
Eur J Contracept Reprod Health Care ; 25(1): 72-75, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31852274

RESUMO

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


Assuntos
Doenças Autoimunes/epidemiologia , Insuficiência Ovariana Primária/imunologia , Adolescente , Adulto , Doenças Autoimunes/complicações , Feminino , Humanos , Prevalência , Estudos Prospectivos , Adulto Jovem
5.
Arch Gynecol Obstet ; 299(3): 747-754, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30726553

RESUMO

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


Assuntos
Parto Obstétrico/métodos , Demografia/métodos , Trabalho de Parto/fisiologia , Adulto , Feminino , Humanos , Gravidez , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco
6.
Fertil Steril ; 111(1): 186-193, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30611405

RESUMO

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.


Assuntos
Infertilidade Feminina/cirurgia , Doadores Vivos , Transplantados , Útero/transplante , Adulto , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Doadores Vivos/psicologia , Pessoa de Meia-Idade , Transplante de Órgãos/métodos , Transplante de Órgãos/psicologia , Seleção de Pacientes , Transplantados/psicologia
7.
Arch Gynecol Obstet ; 299(2): 371-384, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30467635

RESUMO

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


Assuntos
Cesárea/estatística & dados numéricos , Educação a Distância/métodos , Pessoal de Saúde/normas , Mães/psicologia , Adulto , Estudos de Coortes , Tomada de Decisões , Parto Obstétrico , Feminino , Humanos , Internet , Gravidez , Gestão de Riscos , Inquéritos e Questionários
8.
Health Care Women Int ; 39(11): 1295-1315, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30362901

RESUMO

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


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/psicologia , Síndrome de Resistência a Andrógenos/psicologia , Anormalidades Congênitas/psicologia , Infertilidade/psicologia , Mães/psicologia , Ductos Paramesonéfricos/anormalidades , Adulto , Atitude , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
Lancet Diabetes Endocrinol ; 6(10): 771-780, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30075954

RESUMO

BACKGROUND: Women with complete androgen insensitivity syndrome (CAIS) after gonadectomy have complained about reduced psychological wellbeing and sexual satisfaction. The aim of this study was to compare the effectiveness of hormone-replacement therapy with either androgen or oestrogen in women with 46,XY karyotype and CAIS after gonadectomy. METHODS: This national, multicentre, double-blind, randomised crossover trial was performed at three university medical centres and three specialised treatment institutions in Germany. Eligible participants were women aged 18-54 years with 46,XY karyotype, genetically diagnosed CAIS, and removed gonads. Participants were randomly assigned (14:12) by a central computer-based minimisation method to either oestradiol 1·5 mg/day for 6 months followed by crossover to testosterone 50 mg/day for 6 months (sequence A) or to testosterone 50 mg/day for 6 months followed by crossover to oestradiol 1·5 mg/day for 6 months (sequence B). Participants also received oestradiol or testosterone dummy to avoid identification of the active substance. All participants received oestradiol 1·5 mg/day during a 2 months' run-in phase. The primary outcome was mental health-related quality of life, as measured with the standardised German version of the SF-36 questionnaire. Secondary outcomes were psychological wellbeing, as measured with the Brief Symptom Inventory (BSI), sexual function, as measured with the Female Sexual Function Index (FSFI), and somatic effects, such as signs of virilisation and effects on metabolic blood values. The primary analysis included all patients who were available at least until visit 5, even if protocol violations occurred. The safety analysis included all patients who received at least oestradiol during the run-in phase. This trial is registered with the German Clinical Trials Register, number DRKS00003136, and with the European Clinical Trials Database, number 2010-021790-37. FINDINGS: We enrolled 26 patients into the study, with the first patient enrolled on Nov 7, 2011, and the last patient leaving the study on Jan 23, 2016. 14 patients were assigned to sequence A and 12 were assigned to sequence B. Ten participants were withdrawn from the study, two of whom attended at least five visits and so could be included in the primary analysis. Mental health-related quality of life did not differ between treatment groups (linear mixed model, p=0·794), nor did BSI scores for psychological wellbeing (global severity index, p=0·638; positive symptom distress index, p=0·378; positive symptom total, p=0·570). For the FSFI, testosterone was superior to oestradiol only in improving sexual desire (linear mixed model, p=0·018). No virilisation was observed, and gonadotrophin concentrations remained stable in both treatment groups. Oestradiol and testosterone concentrations changed substantially during the study in both treatment groups. 28 adverse events were reported for patients receiving oestradiol (23 grade 1 and five grade 2), and 38 adverse events were reported for patients receiving testosterone (34 grade 1, three grade 2, and one grade 3). One serious adverse event (fibrous mastopathy) and 20 adverse events (16 grade 1 and four grade 2) were reported during the run-in phase, and 12 adverse events during follow-up (nine grade 1 and three grade 2). INTERPRETATION: Testosterone was well tolerated and as safe as oestrogen for hormone-replacement therapy. Testosterone can be an alternative hormone substitution in CAIS, especially for woment with reduced sexual functioning. FUNDING: German Federal Ministry of Education and Research.


Assuntos
Síndrome de Resistência a Andrógenos/tratamento farmacológico , Androgênios/uso terapêutico , Castração/efeitos adversos , Estradiol/uso terapêutico , Terapia de Reposição Hormonal , Testosterona/uso terapêutico , Adulto , Síndrome de Resistência a Andrógenos/etiologia , Síndrome de Resistência a Andrógenos/psicologia , Método Duplo-Cego , Terapia de Reposição de Estrogênios , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orgasmo/efeitos dos fármacos , Resultado do Tratamento , Adulto Jovem
10.
Womens Health (Lond) ; 14: 1745506518778992, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29806554

RESUMO

Previous publications suggest a reduction in the ovarian reserve following ovarian surgery. The influence of the underlying disease, histology, size of the ovarian cyst and type of procedure remains unclear. The aim of this study was to investigate the influence of an ovarian operation on the ovarian reserve, based on the anti-Müllerian hormone levels. The anti-Müllerian hormone values were determined by means of a standardized enzyme-linked immunosorbent assay. In total, 52 patients with one or more ovarian cysts of different histologic entities treated at the Department of Women's Health at the Women's University Hospital in Tübingen were included in the study. Anti-Müllerian hormone was determined before and after surgery. The patients were 28 (range = 18-40) years old on average. There was a statistically significant decrease in anti-Müllerian hormone from 3.94 ± 3.18 to 3.14 ± 2.57 ng/mL (p = 0.001). In 80.8%, the cysts were unilateral, and in over 90.4%, a complete cyst extirpation was performed. A statistically significant reduction was seen in follicular cysts (4.72 ± 3.84 to 3.76 ± 2.91 ng/mL; p = 0.039) and endometriosis cysts (2.55 ± 1.87 to 1.72 ± 1.39 ng/mL; p = 0.024). Also, the size of the cysts had an influence on the ovarian reserve, only larger ovarian cysts with a diameter of 5 cm or more showed a statistically significant reduction in anti-Müllerian hormone. Our data showed a significant decrease in anti-Müllerian hormone levels after surgery on the ovaries. If this results in a long-term reduced ovarian reserve or is merely a short-term reaction to the procedure needs to be clarified. However, concerning young women, the indication of surgery should be given cautiously as-at least temporarily-a reduction in the ovarian reserve can occur.


Assuntos
Hormônio Antimülleriano/sangue , Cistos Ovarianos/sangue , Cistos Ovarianos/cirurgia , Reserva Ovariana , Adulto , Feminino , Alemanha , Humanos , Laparoscopia , Tratamentos com Preservação do Órgão , Ovário/fisiopatologia , Adulto Jovem
11.
Acta Obstet Gynecol Scand ; 97(7): 830-837, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29603118

RESUMO

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


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Anormalidades Congênitas/cirurgia , Imagem por Ressonância Magnética , Ductos Paramesonéfricos/anormalidades , Estruturas Criadas Cirurgicamente , Vagina/diagnóstico por imagem , Feminino , Humanos , Laparoscopia , Ductos Paramesonéfricos/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Vagina/anormalidades , Vagina/cirurgia , Adulto Jovem
12.
Arch Gynecol Obstet ; 297(6): 1473-1481, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29549434

RESUMO

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


Assuntos
Anormalidades Congênitas/classificação , Genitália Feminina/anormalidades , Ductos Paramesonéfricos/anormalidades , Anormalidades Urogenitais/classificação , Adulto , Anormalidades Congênitas/diagnóstico , Feminino , Ginecologia , Humanos , Rim/anormalidades , Estudos Retrospectivos , Sociedades Médicas , Anormalidades Urogenitais/diagnóstico , Útero/anormalidades , Vagina/anormalidades
13.
Arch Gynecol Obstet ; 297(3): 675-684, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29270725

RESUMO

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.


Assuntos
Rejeição de Enxerto , Doadores Vivos , Útero/anormalidades , Útero/transplante , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Gravidez , Coleta de Tecidos e Órgãos , Falha de Tratamento , Anormalidades Urogenitais , Útero/fisiopatologia , Adulto Jovem
14.
Geburtshilfe Frauenheilkd ; 77(11): 1182-1188, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29200474

RESUMO

Introduction: Currently, almost every third child in Germany is delivered by caesarean section. Apart from straightforward and clear indications for caesarean section which account for approx. 10%, the large proportion of relative indications in particular needs to be critically reviewed if the current C-section rate is to be effectively lowered. It is more than doubtful, however, whether this can be a realistic goal in Germany, especially in the context of international developments. All studies on this topic demonstrate that the personal attitude of the obstetric team has a considerable influence on the pregnant woman's personally preferred mode of delivery. Therefore, in the first part of the DECISION study, the personal preferences of urogynaecologists were evaluated regarding the best suitable mode of delivery. Material and Methods: All 432 delegates at the 9th German Urogynaecology Congress in Stuttgart in April 2017 were invited to participate in an online questionnaire study. The questionnaire was developed especially for this study. Results: Of the 432 registered delegates, 189 (43.8%) participated in the survey. 84.7% (n = 160) of the study participants would prefer a vaginal delivery, in an otherwise uncomplicated pregnancy. Only 12.2% (n = 23) opted for an elective caesarean section. The main reasons stated for this decision were concerns about incontinence (87.5%) and pelvic floor trauma (79.2%). Amongst the study participants, 83.6% would like to be part of a risk stratification system presented in the questionnaire which, with the aid of specific parameters, is intended to allow early identification of a population with a high risk of developing pelvic floor disorders. There was also great interest in postpartum pelvic floor recovery (97.8%) and an associated optional pessary therapy (64.4%). The type of delivery already experienced (vaginal delivery vs. primary caesarean section) and parity also reveals to have a significant influence on the personal preferred mode of delivery as well. Conclusions: Urogynaecologists prefer vaginal delivery for themselves. There is a great interest to participate in a risk stratification process in order to approach childbirth in an individualized and risk-adapted manner.

15.
PLoS One ; 12(4): e0174031, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28426677

RESUMO

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.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/terapia , Anormalidades Congênitas/terapia , Genitália Feminina/anormalidades , Acesso aos Serviços de Saúde , Ductos Paramesonéfricos/anormalidades , Transtornos 46, XX do Desenvolvimento Sexual/psicologia , Adolescente , Anormalidades Congênitas/psicologia , Feminino , Humanos
16.
Cell Physiol Biochem ; 41(3): 1083-1097, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28245469

RESUMO

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


Assuntos
Endométrio/anormalidades , Ductos Paramesonéfricos/anormalidades , Células Estromais/patologia , Vagina/anormalidades , Transtornos 46, XX do Desenvolvimento Sexual/metabolismo , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Adolescente , Adulto , Anormalidades Congênitas/metabolismo , Anormalidades Congênitas/cirurgia , Endométrio/metabolismo , Endométrio/cirurgia , Estradiol/farmacologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Ductos Paramesonéfricos/metabolismo , Ductos Paramesonéfricos/cirurgia , Cultura Primária de Células , Progesterona/farmacologia , Prolactina/biossíntese , Prolactina/genética , Estudos Prospectivos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Vagina/metabolismo , Vagina/cirurgia
17.
Reproduction ; 153(5): 555-563, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28246310

RESUMO

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.


Assuntos
Anormalidades Congênitas/fisiopatologia , Hiperandrogenismo/etiologia , Hiperprolactinemia/etiologia , Anormalidades Urogenitais/complicações , Útero/anormalidades , Vagina/anormalidades , Adulto , Feminino , Humanos , Hiperandrogenismo/diagnóstico , Hiperprolactinemia/diagnóstico , Prognóstico , Síndrome
18.
Orphanet J Rare Dis ; 11(1): 152, 2016 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-27852280

RESUMO

INTRODUCTION: In health services research, there is a special emphasis on the transition from adolescence into adulthood. During this transition period, adolescents change from pediatric to adult medical care. This process must be carefully structured, particularly when special medical care is required. Challenges and difficulties become apparent particularly in the case of rare diseases. This is increasingly so when the rare disease affects the adolescence-specific development of patients, such as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS), also known as Müllerian agenesis. METHODS: A systematic literature review identified the care requirements of girls and young women with MRKHS, as well as studies of medical care during the adolescent transition period for various other diseases. This investigation was carried out in the years 2012 and 2013, and was updated in 2014/2015. In addition, the reference lists of the identified studies were reviewed. RESULTS: Nine publications on MRKHS and ten publications on the transition from adolescence to adulthood were included. Medical care requirements and measures were identified for the following areas: diagnosis during adolescence and organization of medical care, reactions to the diagnosis, functional infertility, psychological stress and threat to self-image, contact with others, and dealing with MRKHS coping strategies. DISCUSSION: There is still a great demand for research in the area of care during the transition period from adolescence into adulthood, particularly for rare diseases. The recommendations for treating MRKHS patients derived from the literature should be implemented and evaluated with regard to their effectiveness.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/psicologia , Anormalidades Congênitas/psicologia , Ductos Paramesonéfricos/anormalidades , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Adolescente , Anormalidades Congênitas/cirurgia , Feminino , Humanos , Ductos Paramesonéfricos/cirurgia , Autoimagem , Adulto Jovem
19.
J Sex Res ; 53(1): 109-24, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26133743

RESUMO

The perception of gender development of individuals with complete androgen insensitivity syndrome (CAIS) as unambiguously female has recently been challenged in both qualitative data and case reports of male gender identity. The aim of the mixed-method study presented was to examine the self-perception of CAIS individuals regarding different aspects of gender and to identify commonalities and differences in comparison with subfertile and infertile XX-chromosomal women with diagnoses of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and polycystic ovary syndrome (PCOS). The study sample comprised 11 participants with CAIS, 49 with MRKHS, and 55 with PCOS. Gender identity was assessed by means of a multidimensional instrument, which showed significant differences between the CAIS group and the XX-chromosomal women. Other-than-female gender roles and neither-female-nor-male sexes/genders were reported only by individuals with CAIS. The percentage with a not exclusively androphile sexual orientation was unexceptionally high in the CAIS group compared to the prevalence in "normative" women and the clinical groups. The findings support the assumption made by Meyer-Bahlburg ( 2010 ) that gender outcome in people with CAIS is more variable than generally stated. Parents and professionals should thus be open to courses of gender development other than typically female in individuals with CAIS.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/psicologia , Identidade de Gênero , Disgenesia Gonadal 46 XY/psicologia , Infertilidade/psicologia , Síndrome do Ovário Policístico/psicologia , Sexualidade/psicologia , Adulto , Feminino , Humanos
20.
Photomed Laser Surg ; 33(9): 481-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26332918

RESUMO

OBJECTIVE: Evaluation of safety, feasibility, and possibilities of the thulium laser, Vela(®), with a wavelength of 1.9 µm for laser treatment of the portio, vagina, and/or vulva. BACKGROUND DATA: Laser techniques have been used for many years in the gynecological setting for the treatment of cervical, vaginal, and vulval intraepithelial neoplasias (CIN, VAIN, VIN) and also for the treatment of condylomas. To date, the most commonly used laser for this treatment is the CO2 laser. METHODS: After indication was made for laser treatment, the patients were treated using the thulium laser, Vela. Follow-up examination usually took place after 1-2 weeks, 3 months, and 6 months, when colposcopy and, where necessary, a cytological smear were performed. RESULTS: During the period from January 2012 to January 2014, 18 patients were treated using the thulium laser. Three patients had a CIN I, 12 had condylomas, two had CIN I and condylomas, and one had CIN II and condylomas. During the follow-up, 40% (n = 6) of patients had a relapse of condylomas. No relapse occurred in cases of CIN. Itching, burning, pain, bleeding, discharge, and skin irritation were listed as side effects of the procedure. CONCLUSIONS: This feasibility study shows that the use of the thulium laser for the treatment of cervical neoplasias and condylomas offers a good alternative to the standard treatment using a CO2 laser.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Condiloma Acuminado/cirurgia , Terapia a Laser , Neoplasias do Colo do Útero/cirurgia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Lasers , Pessoa de Meia-Idade , Medição da Dor , Recidiva , Túlio
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