Ethynylestradiol feminizes gene expression partly in testis developing as ovotestis and disrupts asymmetric Müllerian duct development by eliminating asymmetric gene expression in Japanese quail embryos.

In avian embryos, xenoestrogens induce abnormalities in reproductive organs, particularly the testes and Müllerian ducts (MDs). However, the molecular mechanisms remain poorly understood. We investigated the effects of ethynylestradiol (EE2) exposure on gene expression associated with reproductive organ development in Japanese quail embryos. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis revealed that the left testis containing ovary-like tissues following EE2 exposure highly expressed the genes for steroidogenic enzymes (P450scc, P45017α, lyase, and 3ß-HSD) and estrogen receptor-ß, compared to the right testis. No asymmetry was found in these gene expression without EE2. EE2 induced hypertrophy in female MDs and suppressed atrophy in male MDs on both sides. RNA sequencing analysis of female MDs showed 1,366 differentially expressed genes between developing left MD and atrophied right MD in the absence of EE2, and these genes were enriched in Gene Ontology terms related to organogenesis, including cell proliferation, migration and differentiation, and angiogenesis. However, EE2 reduced asymmetrically expressed genes to 21. RT-qPCR analysis indicated that genes promoting cell cycle progression and oncogenesis were more highly expressed in the left MD than in the right MD, but EE2 eliminated such asymmetric gene expression by increasing levels on the right side. EE2-exposed males showed overexpression of these genes in both MDs. This study reveals part of the molecular basis of xenoestrogen-induced abnormalities in avian reproductive organs, where EE2 may partly feminize gene expression in the left testis, developing as the ovotestis, and induce bilateral MD malformation by canceling asymmetric gene expression underlying MD development.

Managing pronounced hematocolpos in Herlyn-Werner-Wunderlich syndrome: A comprehensive case report.

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare and complex congenital anomaly of the genitourinary system characterized by uterus didelphys, an obstructed hemivagina, and ipsilateral renal agenesis. It is the result of the maldevelopment of both the Mullerian and Wolffian ducts. Clinical manifestations of dysmenorrhea, dysuria, and urinary retention appear after menarche due to the accumulation of menstrual blood and distention of the obstructed hemivagina. Diagnosis of this anomaly is often delayed, and the obstructive nature of the condition is missed due to cyclic menstruation from the one canalized hemivagina. This case report represents a typical form of HWW syndrome to highlight the importance of considering this rare entity in an adolescent girl presenting with signs of dysmenorrhea and urinary complaints. A 13-year-old patient was presented at the obstetrics and gynecology clinic due to low abdominal pain and urinary retention on the fifth day of menstruation. For the last 6 months, the patient suffered progressive cyclic low abdominal pain associated with menstruation. Inspection of the external genitalia was unremarkable, and the hymenal membrane had a normal oval opening. An ultrasound examination revealed the sonographic features of the didelphys uterus and was suggestive of a right obstructed hemivagina with hematocolpos. Magnetic resonance imaging and computed tomography urography showed evidence of didelphys uterus, right blind obstructed hemivagina associated with huge hematocolpos, and ipsilateral renal agenesis. The diagnosis of HWW syndrome was established. Surgical resection of the vaginal septum was undertaken without delay, and the patient was discharged the following days.

Wharton-Sheares-George vaginoplasty: a safe and efficient technique in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION AND HYPOTHESIS: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition with an underdeveloped or absent vagina and uterus due to embryological growth failure of the Müllerian ducts. Many techniques have been described to construct a neovagina with an acceptable depth that allows penetrative intercourse. This is a step-by-step video tutorial on the Wharton-Sheares-George surgical technique for vaginoplasty in patients with MRKH syndrome. METHOD: With Wharton-Sheares-George vaginoplasty, the rudimentary Müllerian ducts are incrementally dilated by pushing Hegar dilators in the direction of the pelvic axis, and the resulting median raphe is then intersected using diathermy. As a result, a neovagina is created and an estriol-coated vaginal mold is inserted for 3 days. The patient receives comprehensive discharge instructions, a self-dilation program three times a day, and a monthly follow-up. RESULTS: A 3-month follow-up showed a high subjective degree of satisfaction with surgery and sexual satisfaction in both patients. CONCLUSION: Wharton-Sheares-George vaginoplasty is a safe and efficient technique for creating a neovagina for patients with MRKH syndrome.

In ovo o,p'-DDT exposure induces malformation of reproductive organs and alters the expression of genes controlling sexual differentiation in Japanese quail embryo.

In ovo exposure to o,p'-dichloro-diphenyl-trichloroethane (o,p'-DDT) impairs reproduction by inducing malformation of the reproductive organs in birds, although the mechanism remains unclear. Here, we examined the effects of o,p'-DDT on the development of the reproductive organs, the expression of genes controlling sexual differentiation, and the plasma concentrations of testosterone and estradiol in Japanese quail embryos. o,p'-DDT-containing sesame oil was injected into the yolk sac on Embryonic Day (E) 3 at a dose of 500, 2,000, or 8,000 µg per egg. On E15, the reproductive organs were observed; the gonads and Müllerian ducts (MDs) were sampled to measure the mRNA of steroidogenic enzymes, sex steroid receptors, anti-Müllerian hormone (AMH), and AMH receptor 2 (AMHR2); blood samples were collected to assay plasma testosterone and estradiol levels; and the gonads were used for histological analysis. o,p'-DDT dose-dependently increased the prevalence of hypertrophic MDs in females and residual MDs in males. In female MDs, o,p'-DDT dose-dependently decreased estrogen receptor (ER) α, ERß, and AMHR2 mRNA expression. o,p'-DDT dose-dependently induced left-biased asymmetry of testis size, and ovary-like tissue was found in the left testis after exposure to 8,000 µg per egg o,p'-DDT, although asymmetric gene expression did not occur. o,p'-DDT did not affect ovarian tissue but did decrease 17α-hydroxylase/C17-20 lyase mRNA expression and dose-dependently increased ERß mRNA expression. o,p'-DDT decreased plasma testosterone concentrations in females. These findings suggest that o,p'-DDT induces hypertrophy of the MDs and ovarian tissue formation in the left testis. Abnormal MD development may be linked to altered gene expression for sensing estrogens and AMH signals.

The Need for Earlier Diagnosis of Obstructed Hemivagina and Ipsilateral Renal Agenesis/Anomaly (OHVIRA) Syndrome in Case of Renal Agenesis in Girls-Case Report and Review of the Literature.

Obstructed hemivagina and ipsilateral renal agenesis/anomaly (OHVIRA) syndrome is a very rare condition affecting girls. The time of diagnosis varies, from cases of prenatal diagnosis up to adulthood, including pregnancy or delivery. Most commonly, it is recognised during puberty and usually as an acute condition. We present a case report of an adolescent girl who underwent the treatment because of acute abdominal pain. The case is interesting due to a previous diagnosis of one-side renal agenesis. It appears to be useful to perform a diagnostic pelvic imaging at the time of diagnosis of renal agenesis or to plan to perform it at the beginning of puberty, to prevent the need for urgent surgery. This management may allow the planning of proper follow-up, minimising the risk of possible complications.

Variante incomum da síndrome de Herlyn- -Werner-Wunderlich: relato de caso / Unsual Herlyn-Werner-Wunderlich syndrome: case report

Malformações müllerianas correspondem a variações anatômicas do trato repro- dutor feminino. Comumente assintomáticas, o diagnóstico e a verdadeira incidên- cia são difíceis de determinar. A síndrome de Herlyn-Werner-Wunderlich, clas- sicamente descrita pela tríade útero didelfo, hemivagina cega e agenesia renal ipsilateral também pode ter variações diferentes. Em virtude da mesma origem embrionária dos tratos genital e urinário, anomalias renais devem ser investigadas nesses casos, sendo a mais comum a agenesia renal. Este artigo relata o caso de uma paciente de 18 anos, do sexo feminino, com história de piocolpo por cinco anos. Em propedêutica complementar, foi identificado útero com septação com- pleta associado a hemissepto de terço superior de vagina, formação de piocolpo e agenesia renal à direita. Apesar de não ser a definição clássica, o quadro está incluído nos casos de síndrome de Herlyn-Werner-Wunderlich.

Mullerian malformations correspond to anatomical variations of the female repro- ductive tract. Commonly asymptomatic, the diagnosis and true incidence are difficult to determine. The Herlyn-Werner-Wunderlich syndrome, classically described by the triad: uterus didelphus, blind hemivagina and ipsilateral renal agenesis, can also have different variations. Due to the same embryonic origin of the genital and urinary tracts, renal anomalies must be investigated in these cases, the most common being renal agenesis. This article reports the case of an 18-year-old female patient with a 5-year history of pyocolpus. In complementary exams, a uterus with complete septa- tion was identified, associated with a hemiseptum in the upper third of the vagina, formation of pyocolpus and renal agenesis on the right side. Despite not being the classic definition, it is included in the cases of Herlyn-Werner-Wunderlich syndrome.

Mullerian ducts anomaly of 2 divergent uterine horns with cervicovaginal hypoplasia: Is it considered unclassified or under the spectrum of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome?

The Mullerian ducts give rise to the upper part of the female reproductive system, including the uterus, cervix, upper two-thirds of the vagina, and fallopian tubes, which undergo specific processes of development, fusion, and resorption. Any failure in this process will lead to Mullerian duct anomaly (MDA). We present a unique and complex case of MDA, signifying the wide variability and simultaneous existence of combined abnormalities in 1 patient, which do not always fit under a single or particular class from the known classification systems. Therefore, subclassifications may be necessary for each part alone (uterus, cervix, and vagina) or incorporating more than 1 class for a single case. It also shows the role of imaging in the diagnosis; considering that magnetic resonance imaging (MRI) is the standard modality for a detailed description of the reproductive system and its anomalies.

Herlyn-Werner-Wunderlich syndrome: A fertility-sparing approach to a rare mullerian anomaly.

The Herlyn-Werner-Wunderlich syndrome (HWWS) is characterized by the triad of uterus didelphys, obstructed hemivagina, and renal agenesis. The typical clinical presentation involves chronic pelvic pain, dysmenorrhea, and palpable abdominal mass, related to hematocolpos/hematometra. It is a rare disease, with a challenging clinical and radiological diagnosis. Surgery is the definitive treatment. Complications such as endometriosis, infertility and chronic pelvic pain occur more frequently and severely when diagnosis and treatment are delayed. This is a case report of a twelve-year-old patient admitted to the Gynecology Department of the Federal University of Rio de Janeiro's General Hospital (HUCFF/UFRJ), in March 2021, with progressive symptoms of dysmenorrhea and abdominal distention due to palpable abdominal mass. She had a previous history of congenital solitary kidney. Magnetic Resonance Imaging (MRI) showed a double uterus with hematometra and hematocolpos on the left side, pelvic endometriosis and left renal agenesis. Conservative clinical treatment with inhibition of the hypothalamic-pituitary-ovarian (H-P-O) axis was initiated while a definitive surgical approach was being defined. In June 2022, the patient underwent left hemi-hysterectomy and salpingectomy, achieving full remission of symptoms. Given the rarity of this syndrome and its potential complications, our report aims to familiarize clinicians with it, mostly those who work with children and adolescents, so that more patients have access to early diagnosis and adequate treatment. Consequently, future fertility can be effectively preserved.

Clinical profile and cytogenetic correlations in females with primary amenorrhea.

OBJECTIVE: This study was conducted to investigate chromosomal abnormalities and their correlations with clinical and radiological findings in females with primary amenorrhea (PA). METHODS: Detailed forms were recorded for 470 females, including the construction of three-generation pedigrees. Peripheral venous blood was drawn, with informed consent, for cytogenetic analysis. RESULTS: An abnormal karyotype was found in 16.38% of participants. The incidence of structural abnormalities (6.8%) exceeded that of numerical abnormalities (6.15%). Turner syndrome represented 45% of all numerical abnormalities. Furthermore, the Y chromosome was detected in 5% of females with PA. Among the structural chromosomal abnormalities detected (n=32) were mosaicism (25%), deletions (12.5%), isochromosomes (18.75%), fragile sites (3.12%), derivatives (3.12%), marker chromosomes (3.12%), and normal variants (29.125%). An examination of secondary sexual characteristics revealed that 29.6% of females had a complete absence of breast development, 29.78% lacked pubic hair, and 36.88% exhibited no axillary hair development. Radiological findings revealed that 51.22% of females had a hypoplastic uterus and 26.66% had a completely absent uterus. Abnormal ovarian development, such as the complete absence of both ovaries, absence of one ovary, one absent and other streak, or both streak ovaries, was observed in 69.47% of females with PA. Additionally 43.1%, 36.1%, 67.4%, and 8% of females had elevated levels of serum follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and prolactin, respectively. CONCLUSION: This study underscores the importance of karyotyping as a fundamental diagnostic tool for assessing PA. The cytogenetic correlation with these profiles will aid in genetic counseling and further management of the condition.

Pubertal sexual development and endpoints for disrupted spermatogenesis in the model Xenopus tropicalis.

Peripubertal models to determine effects of anti-androgenic endocrine disrupting chemicals are needed. Using the toxicological model species Xenopus tropicalis, the aims of the study were to 1) provide data on sexual maturation and 2) characterise effects of short-term exposure to an anti-androgenic model substance. Juvenile (2.5 weeks post metamorphosis old) X. tropicalis were exposed to 0, 250, 500 or 1000 µg flutamide/L (nominal) for 2.5 weeks. Upon exposure termination, histology of gonads and Müllerian ducts was characterised in detail. New sperm stages were identified: pale and dark spermatogonial stem cells (SSCs). The testes of control males contained spermatozoa, indicating pubertal onset. The ovaries were immature, and composed of non-follicular and pre-vitellogenic follicular oocytes. The Müllerian ducts were more mature in females than males indicating development/regression in the females and males, respectively. In the 500 µg/L group, the number of dark SSCs per testis area was decreased and the number of secondary spermatogonia was increased. No treatment effects on ovaries or Müllerian ducts were detected. To conclude, our present data provide new knowledge on spermatogenesis, and pubertal onset in X. tropicalis. New endpoints for evaluating spermatogenesis are suggested to be added to existing assays used in endocrine and reproductive toxicology.

Herlyn-Werner-Wunderlich syndrome also known as obstructed hemivagina and ipsilateral renal anomaly: A case report and a comprehensive review of literature.

Herlyn-Werner-Wunderlich syndrome, also known as obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), is a Müllerian duct anomaly. It is a rare clinical condition consisting of a duplicated uterus with an oblique vaginal septum that causes partial genital tract outflow obstruction. A urinary tract anomaly, most commonly renal agenesis, is usually present on the obstructed side. The diagnosis of genital tract outflow obstruction is often delayed due to the normal functioning of the unaffected side. The most frequent complications are dysmenorrhea, chronic pelvic pain, infection, infertility and endometriosis. This report describes a 17-year-old G0P0 patient with a history of severe dysmenorrhea and left-sided renal agenesis, who was admitted for complaints of foul vaginal discharge over the past 3 months that was unsuccessfully treated with antibiotics. Transrectal ultrasound revealed the presence of 2 separate hemicavities on transverse and longitudinal views. A cystic lesion with ground-glass opacities was detected between the bladder and a normal-appearing cervix, which was determined to be hematocolpos. The diagnosis of OHVIRA was made. This case highlights the importance of excluding a Müllerian anomaly in the presence of renal system abnormalities. Being aware of the type of anomalies, combinations and variants is crucial to determine the diagnosis and the best surgical approach. Ultrasound was an invaluable imaging exam to determine the type of anomaly and its complexity. Awareness of this syndrome and its variants will prevent misdiagnosis and will help to define the appropriate treatment for these patients.

Genome Sequencing and Transcriptome Profiling in Twins Discordant for Mayer-Rokitansky-Küster-Hauser Syndrome.

To identify potential genetic causes for Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), we analyzed blood and rudimentary uterine tissue of 5 MRKH discordant monozygotic twin pairs. Assuming that a variant solely identified in the affected twin or affected tissue could cause the phenotype, we identified a mosaic variant in ACTR3B with high allele frequency in the affected tissue, low allele frequency in the blood of the affected twin, and almost absent in blood of the unaffected twin. Focusing on MRKH candidate genes, we detected a pathogenic variant in GREB1L in one twin pair and their unaffected mother showing a reduced phenotypic penetrance. Furthermore, two variants of unknown clinical significance in PAX8 and WNT9B were identified. In addition, we conducted transcriptome analysis of affected tissue and observed perturbations largely similar to those in sporadic cases. These shared transcriptional changes were enriched for terms associated with estrogen and its receptors pointing at a role of estrogen in MRKH pathology. Our genome sequencing approach of blood and uterine tissue of discordant twins is the most extensive study performed on twins discordant for MRKH so far. As no clear pathogenic differences were detected, research to evaluate other regulatory layers are required to better understand the complex etiology of MRKH.

Treatment of Urethral Intercourse and Impact on Female Sexual Function.

BACKGROUND: Urethral intercourse is a very rare entity which usually presents as urinary incontinence during and after intercourse and is most commonly seen in patients with vaginal agenesis (Mayer-Rokitansky-Hauser Syndrome) or hypoplasia, or other rear vaginal anomalies. AIM: To evaluate management and outcomes for vaginal and urethral consequences of urethral intercourse, including urinary incontinence. METHODS: Between February 2006 and March 2021, 8 women aged from 17 to 22 years underwent genital and urethral reconstruction due to consequences of urethral sexual intercourse. Vaginal reconstruction included sigmoid vaginoplasty and introitoplasty with division of the vaginal septum in cases of vaginal agenesis (5 cases) and vaginal duplication (3 cases), respectively. Incontinence was treated by sling procedures in 5 women with longer history of urethral coitus and evident bladder neck prolapse. OUTCOMES: Sexual and psychosexual outcomes assessment was based on the Female Sexual Function Index and standardized questionnaires. RESULTS: Follow-up ranged from 9 to 188 months (mean 78 months). Good esthetical and functional results were achieved in all 8 women. All patients reported satisfactory sexual intercourse. All 5 incontinent women who had underwent sling procedure were continent. In one of 3 nontreated cases, additional sling treatment was indicated 6 months after vaginal reconstruction with satisfactory outcome. One patient with vaginal duplication reported a successful pregnancy with a Caesarean section delivery. CLINICAL IMPLICATIONS: Urinary incontinence with megalourethra in young women, along with the presence of Mullerian anomalies should raise suspicion of urethral coitus. Surgical treatment includes correction of vaginal anomalies and management of consequences. STRENGTHS AND LIMITATIONS: This study represents one of the largest series for urethral intercourse, with assessment of psychosexual outcome. The limitation is the lack of statistical analysis due to small sample size. CONCLUSION: Urethral intercourse is very rare, but it can cause severe consequences. It is important to recognize this occurrence and treat it by well-known vaginal or urethral reconstructive procedures. Djordjevic ML, Bizic M, Stojanovic B, et al. Treatment of Urethral Intercourse and Impact on Female Sexual Function. Sex Med 2022;10:100534.

Endometrial organoids derived from Mayer-Rokitansky-Küster-Hauser syndrome patients provide insights into disease-causing pathways.

The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focuses on DNA-sequencing efforts and, so far, has been unable to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully hormone responsive. Transcriptome analyses, however, identified an array of dysregulated genes that point to potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.

The Herlyn-Werner-Wunderlich (HWW) syndrome - A case report with radiological review.

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly of female urogenital tract involving combined mullerian duct anomalies and mesonephric duct malformation characterized by uterus didelphys, obstructed hemi-vagina and ipsilateral renal agenesis which is also known as OHVIRA syndrome. It can be classified based on a completely or incompletely obstructed hemivagina. It presents soon after menarche or shows delayed presentation depending on the type. The most common presentation is lower abdominal pain, dysmenorrhea, and abdominal mass in the lower abdomen secondary to hematometra or hematocolpos. We present a 15-year-old unmarried patient with an unusual case of OHVIRA syndrome suffering from dysmenorrhea and painful mass in suprapubic region. We described the role of imaging modalities in diagnosis of the Herlyn-Werner Wunderlich syndrome with a review of literature. On USG and MRI, she had right renal agenesis with compensatory hypertrophy of the left kidney, didelphic uterus with an obstructed hemi-vagina on right side which led to marked distention of ipsilateral cervix and proximal vagina in the form of hematometrocolpos. OHVIRA syndrome can present early or late, depending on the type. In patients with uterine and vaginal abnormalities, a work-up for associated renal anomalies should be performed. The choice imaging modalities for the diagnosis of OHVIRA syndrome are ultrasound and MRI. Knowing the imaging findings of this rare condition is crucial for early diagnosis in order to prevent complications which may lead to endometriosis and infertility.

Embarazo ectópico en cuerno rudimentario izquierdo de útero unicorne con embarazo de 15 semanas: reporte de un caso / Ectopic pregnancy in rudimentary left horn of unicorne uterus with pregnancy of 15 weeks: a case report

INTRODUCCIÓN: El embarazo ectópico en el cuerno rudimentario de un útero unicorne tiene una incidencia de 1 en 76.000 embarazos. La aproximación diagnóstica se realiza con la ecografía y como estudio complementario con la resonancia magnética. El diagnóstico temprano con tratamiento oportuno es fundamental para la prevención de la morbimortalidad materna asociada. El objetivo es describir el diagnóstico y el tratamiento temprano de un caso de embarazo ectópico de 15 semanas en cuerno rudimentario no comunicante de útero unicorne. CASO CLÍNICO: Mujer de 38 años con embarazo de 15 semanas, asintomática, que ingresa al servicio de urgencias referida desde el servicio de ecografía por sospecha de embarazo ectópico. Se realizan ecografía y resonancia magnética que muestran embarazo con feto único de 15 semanas en cuerno uterino izquierdo rodeado de miometrio, sin comunicación con la cavidad endometrial. Con impresión diagnóstica de embarazo ectópico cornual en paciente con malformación mülleriana, se realizó manejo quirúrgico que confirmó útero unicorne con embarazo ectópico en cuerno rudimentario no comunicante. CONCLUSIONES: El embarazo ectópico en un cuerno rudimentario de útero unicorne es infrecuente y presenta un alto riesgo de rotura, con aumento de la morbimortalidad obstétrica. El tratamiento estándar, al igual que la confirmación diagnóstica, es la escisión quirúrgica completa.

INTRODUCTION: Ectopic pregnancy in the rudimentary horn of a unicornuate uterus has an incidence of 1 in 76,000 pregnancies; the diagnostic approach is carried out with ultrasound and magnetic resonance imaging as a complementary study; Early diagnosis with timely treatment is essential for the prevention of associated maternal morbidity and mortality. The objective is to describe the early diagnosis and treatment of a case of 15-week ectopic pregnancy in a rudimentary non-communicating horn of the unicornuate uterus. CASE REPORT: A 38-year-old patient with an asymptomatic 15-week pregnancy was admitted to the emergency department, referred to the ultrasound service for suspected ectopic pregnancy. Ultrasound and magnetic resonance imaging were performed with pregnancy with a single fetus of 15 weeks in the left uterine horn surrounded by myometrium, without communication with the endometrial cavity. With a diagnostic impression of cornual ectopic pregnancy in a patient with a Müllerian malformation, a surgical management was performed where a unicornuate uterus with a rudimentary non-communicating ectopic horn was confirmed. CONCLUSIONS: Ectopic pregnancy in rudimentary horn of the unicornuate uterus is rare, it presents a high risk of rupture with increased obstetric morbidity and mortality. The standard treatment as well as the diagnostic confirmation is complete surgical excision.

The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser Syndrome: Genetics and Environmental Factors.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical presentations seems consistent with an inheritance pattern characterized by incomplete penetrance and variable expressivity. Mutations of several candidate genes have been proposed as possible causes based on genetic analyses of human patients and animal models. In addition, studies of monozygotic twins with discordant phenotypes suggest a role for epigenetic changes following potential exposure to environmental compounds. The spectrum of clinical presentations is consistent with intricate disruptions of shared developmental pathways or signals during early organogenesis. However, the lack of functional validation and translational studies have limited our understanding of the molecular mechanisms involved in this condition. The clinical management of affected women, including early diagnosis, genetic testing of MRKH syndrome, and the implementation of counseling strategies, is significantly impeded by these knowledge gaps. Here, we illustrate the embryonic development of tissues and organs affected by MRKH syndrome, highlighting key pathways that could be involved in its pathogenesis. In addition, we will explore the genetics of this condition, as well as the potential role of environmental factors, and discuss their implications to clinical practice.

Herlyn-Werner-Wunderlich syndrome: Case report / Síndrome de Herlyn-Werner-Wunderlich. Reporte de caso

Abstract Introduction: Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital malformation of the urogenital tract characterized by the triad of uterine didelphys, obstructed hemivagina, and ipsilateral renal agenesis, which is usually diagnosed after menarche. It is treated by resecting the vaginal septum and draining the obstructed hemivagina and has a favorable postoperative prognosis. Case presentation: This is the case of 22-year-old woman with a 9-year history of dysmenorrhea, pelvic pain, and irregular menstrual cycles that started after she had her first menstruation, who visited the gynecology service of a secondary care hospital in Sogamoso, Boyacá (Colombia). The patient reported having visited multiple specialists and being treated with vitamin E, metformin, and contraceptives, without experiencing an improvement of symptoms and signs. After being assessed, and taking into account ultrasound and MRI findings, she was diagnosed with HWW syndrome. She underwent a colpotomy plus resection of right paracervical mass of approximately 60x60mm and vaginal septum, achieving complete resolution of symptoms. Finally, 10 months after the surgery, she reported being pregnant without complications. Conclusion: HWW syndrome is a rare malformation that should be considered as a differential diagnosis in women of any age with paramesonephric duct anomalies, pelvic pain, dysmenorrhea, and presence of masses in the genital tract, since its early diagnosis and timely treatment considerably improve the quality of life of these patients by reducing the severity of symptoms, decreasing the incidence of complications, and improving obstetric prognosis.

Resumen Introducción. El síndrome de Herlyn-Werner-Wunderlich (SHWW) es una malformación congénita rara del tracto urogenital que se caracteriza por la triada útero didelfo, hemivagina obstruida y anomalía renal ipsilateral, y que suele diagnosticarse después de la menarquia. Su tratamiento consiste en resección del tabique vaginal y drenaje de la hemivagina obstruida, con un buen pronóstico postquirúrgico. Presentación del caso. Mujer de 22 años con un cuadro clínico de 9 años de evolución que inició cuando tuvo su primera menstruación, consistente en dismenorrea, dolor pélvico y ciclos menstruales irregulares, quien asistió al servicio de ginecología de un hospital de segundo nivel en Sogamoso, Boyacá (Colombia). La paciente reportó haber visitado múltiples especialistas y recibido tratamiento con vitamina E, metformina y anticonceptivos, sin mejoría de los síntomas y signos. Luego de ser valorada, y teniendo en cuenta los hallazgos en ecografía y resonancia magnética, fue diagnosticada con SHWW, por lo que se le realizó colpotomía más resección de masa paracervical derecha de aproximadamente 60x60mm y de tabique vaginal, lográndose la resolución completa de los síntomas. Finalmente, 10 meses después de la cirugía, la joven refirió encontrarse en estado de embarazo, sin presentar complicaciones. Conclusión. El SHWW es una malformación poco común que debe considerarse como diagnóstico diferencial en mujeres de cualquier edad con anomalías de los conductos paramesonéfricos, dolor pélvico, dismenorrea y masa en el tracto genital, pues su diagnóstico temprano y un tratamiento oportuno mejoran considerablemente la calidad de vida de estas pacientes al reducir la severidad de los síntomas, disminuir la incidencia de complicaciones y mejorar el pronóstico obstétrico.

Síndrome de Herlyn-Werner-Wunderlich: reporte de caso y revisión de la literatura / Herlyn-Werner-Wunderlich syndromne: case review and report of the literatura

RESUMEN Objetivo: Presentar un reporte de caso de síndrome de Herlyn Werner Wunderlich (SHWW) y hacer una revisión de la literatura para determinar los hallazgos clínicos e imagenológicos en estas pacientes. Materiales y métodos: Se presenta el caso de una mujer de 16 años que consultó, en un hospital de las fuerzas militares en Bogotá, por dolor pélvico recurrente, su diagnostico final fue SHWW. Se realizó una búsqueda sistemática de la literatura en las diferentes bases de datos, revisiones sistemáticas, cohortes, series de casos y reportes de casos en pacientes con diagnóstico de SHWW en cualquier edad, se obtuvo información sobre las características de presentación clínica, y las tecnologías diagnósticas más frecuentemente utilizadas. Se hace resumen narrativo de los hallazgos. Resultados: Se incluyeron 77 publicaciones, un total de 676 pacientes. Los síntomas más frecuentes fueron dismenorrea (63,9 %), seguido de dolor pélvico (35,2%). Las tecnologías diagnósticas más utilizadas fueron el ultrasonido pélvico en un 92,1% y la resonancia magnética nuclear en un 74,6% de los casos. La histeroscopia y laparoscopia son poco utilizados en el diagnóstico. Conclusión: El SHWW es una entidad poco frecuente, debe hacer parte del estudio complementario de la agenesia renal del paciente pediátrico y del diagnóstico diferencial de la dismenorrea primaria en pacientes en la adolescencia. Se requiere evaluar con estudios de cohorte más grandes la utilidad de la histeroscopia en estas pacientes.

ABSTRACT Objective: To report a case of Herlyn-Werner-Wunderlich syndrome (HWWS) and conduct a review of the literature to determine clinical and imaging findings in these patients. Material and methods: A 16-year-old female patient who presented to a military hospital in Bogota complaining of recurrent pelvic pain, receiving a final diagnosis of HWWS. A systematic search was conducted in the different databases of systematic reviews, cohort studies, case series and case reports of patients of any age diagnosed with HWWS. Clinical presentation characteristics and the most frequent diagnostic technologies used were obtained. A narrative summary of the findings is presented. Results: Overall, 77 publications with a total of 676 patients were included. The most frequent symptom was dysmenorrhea (63.9%), followed by pelvic pain (35.2%). The most frequently used diagnostic technologies were pelvic ultrasound in 92.1% of cases and nuclear magnetic resonance in 74.6%. Hysteroscopy and laparoscopy are seldom used for diagnosing this condition. Conclusion: HWWS is an infrequent disease condition. It must be part of the work-up for renal agenesis in pediatric patients and of the differential diagnosis in primary dysmenorrhea in adolescence. The role of hysteroscopy in this condition must be further assessed in larger cohort studies.