Síndrome de Herlyn-Werner Wünderlich: reporte de dos casos / Herlyn-Werner-Wünderlich syndrome: Two case report

El síndrome de Herlyn-Werner Wünderlich, también llamado OHVIRA por sus siglas en inglés (obstructed hemivagina and ipsilateral renal anomaly), es una anomalía congénita mülleriana poco frecuente que se caracteriza por la asociación entre útero didelfo, hemivagina obstruida y agenesia renal ipsilateral. La presentación clínica más común es la masa abdominal secundaria a hematocolpos, dolor y dismenorrea. Se asocia a infertilidad, endometriosis, alteraciones menstruales y obstétricas. La ecografía es la técnica de elección para la evaluación inicial, mientras que la resonancia magnética sigue siendo el método más exacto para el diagnóstico. La septotomía vaginal es el tratamiento recomendado. Se describen 2 casos clínicos con el objetivo de destacar la importancia del diagnóstico temprano para evitar las posibles complicaciones futuras.

Herlyn-Werner-Wunderlich syndrome, also known as obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), is a rare, congenital Müllerian duct anomaly characterized by the association of septate uterus, obstructed hemivagina, and ipsilateral renal agenesis. The most common clinical presentation is an abdominal mass secondary to hematocolpos, pain, and dysmenorrhea. It is associated with infertility, endometriosis, and menstrual and obstetric alterations. The ultrasound is the technique of choice for the initial assessment, while the magnetic resonance imaging remains the most accurate method for diagnosis. The resection of the vaginal septum is the recommended treatment. Here we describe 2 clinical cases to highlight the importance of an early diagnosis to prevent potential complications in the future.

Recent trends in AI applications for pelvic MRI: a comprehensive review.

Magnetic resonance imaging (MRI) is an essential tool for evaluating pelvic disorders affecting the prostate, bladder, uterus, ovaries, and/or rectum. Since the diagnostic pathway of pelvic MRI can involve various complex procedures depending on the affected organ, the Reporting and Data System (RADS) is used to standardize image acquisition and interpretation. Artificial intelligence (AI), which encompasses machine learning and deep learning algorithms, has been integrated into both pelvic MRI and the RADS, particularly for prostate MRI. This review outlines recent developments in the use of AI in various stages of the pelvic MRI diagnostic pathway, including image acquisition, image reconstruction, organ and lesion segmentation, lesion detection and classification, and risk stratification, with special emphasis on recent trends in multi-center studies, which can help to improve the generalizability of AI.

CD38/cADPR-mediated calcium signaling in a human myometrial smooth muscle cell line, PHM1.

Cyclic ADP-ribose (cADPR) has emerged as a calcium-regulating second messenger in smooth muscle cells. CD38 protein possesses ADP-ribosyl cyclase and cADPR hydrolase activities and mediates cADPR synthesis and degradation. We have previously shown that CD38 expression is regulated by estrogen and progesterone in the myometrium. Considering hormonal regulation in gestation, the objective of the present study was to determine the role of CD38/cADPR signaling in the regulation of intracellular calcium upon contractile agonist stimulation using immortalized pregnant human myometrial (PHM1) cells. Western blot, immunofluorescence, and biochemical studies confirmed CD38 expression and the presence of ADP-ribosyl cyclase (2.6 ± 0.1 pmol/mg) and cADPR hydrolase (26.8 ± 6.8 nmoles/mg/h) activities on the PHM1 cell membrane. Oxytocin, PGF2α, and ET-1 elicited [Ca2+]i responses, and 8-Br-cADPR, a cADPR antagonist significantly attenuated agonist-induced [Ca2+]i responses between 20% and 46% in average. The findings suggest that uterine contractile agonists mediate their effects in part through CD38/cADPR signaling to increase [Ca2+]i and presumably uterine contraction. As studies in humans are limited by the availability of myometrium from healthy donors, PHM1 cells form an in vitro model to study human myometrium.

Potential anatomical determinants of retrograde menstruation: a comprehensive narrative review.

A century ago, Sampson identified three uterine anatomical structures that may determine the amount of retrograde menstruation and the likelihood of the development of endometriosis: the cervix, the intramural portion of the fallopian tubes, and the myometrium. Critical appraisal was undertaken of data published over the last 40 years on the potential effect of the characteristics of these three anatomical variables on the risk of endometriosis. There is some evidence to support the pathogenic role of the diameter of the cervical canal, stenosis of internal or external orifices, and stiffness of cervical tissue. One study showed a significant association between the morphology of the intramural tubal tract and the frequency of endometriosis. A large body of evidence points to abnormalities of the myometrial structure as the anatomical aberration most consistently associated with endometriosis. These abnormalities have largely been interpreted as signs of early-onset adenomyosis, which may precede endometriosis and even lead to its development by increasing the amount of retrograde menstruation. Future research should aim to verify whether a positive relationship exists between the substantially increased number of ovulatory menses occurring in the decade following menarche, the development of anatomical myometrial abnormalities, changes in the amount of retrograde menstruation over time, and the risk of endometriosis.

Comparison of preoperative diagnostic performance between dual-energy CT, conventional CT, and MRI in endometrial cancer.

Purpose: To compare the diagnostic performance of virtual monoenergetic imaging (VMI), computed tomography (CT), and magnetic resonance imaging (MRI) in patients with endometrial cancer (EC). Material and methods: This retrospective study analysed 45 EC patients (mean age: 62 years, range: 44-84 years) undergoing contrast-enhanced CT with dual-energy CT (DECT) and MRI between September 2021 and October 2022. Dual-energy CT generated conventional CT (C-CT) and 40 keV VMI. Quantitative analysis compared contrast-to-noise ratio (CNR) of tumour to myometrium between C-CT and VMI. Qualitative assessment by 5 radiologists compared C-CT, VMI, and MRI for myometrial invasion (MI), cervical invasion, and lymph node metastasis. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were calculated and compared for each diagnostic parameter. Results: Virtual monoenergetic imaging showed significantly higher CNR than C-CT (p < 0.001) and a higher sensitivity for MI than C-CT (p = 0.027) and MRI (p = 0.011) but lower specificity than MRI (p = 0.018). C-CT had a higher sensitivity and AUC for cervical invasion than MRI (p = 0.018 and 0.004, respectively). Conclusions: The study found no significant superiority of MRI over CT across all diagnostic parameters. VMI demonstrated heightened sensitivity for MI, and C-CT showed greater sensitivity and AUC for cervical invasion than MRI. This suggests that combining VMI with C-CT holds promise as a comprehensive preoperative staging tool for EC when MRI cannot be performed.

Impact of Heat Stress on Oocyte Developmental Competence and Pre-Implantation Embryo Viability in Cattle.

Rectal and vaginal temperatures are utilised in both in vivo and in vitro models to study the effects of heat stress on oocyte competence and embryo viability in cattle. However, uterine temperature increases by only 0.5 °C in heat-stressed cows, significantly lower than simulated increases in in vitro models. Temperature variations within oviducts and ovarian follicles during heat stress are poorly understood or unavailable, and evidence is lacking that oocytes and pre-implantation embryos experience mild (40 °C) or severe (41 °C) heat stress inside the ovarian follicle and the oviduct and uterus, respectively. Gathering detailed temperature data from the reproductive tract and follicles is crucial to accurately assess oocyte competence and embryo viability under realistic heat stress conditions. Potential harm from heat stress on oocytes and embryos may result from reduced nutrient availability (e.g., diminished blood flow to the reproductive tract) or other unidentified mechanisms affecting tissue function rather than direct thermal effects. Refining in vivo stress models in cattle is essential to accurately identify animals truly experiencing heat stress, rather than assuming heat stress exposure as done in most studies. This will improve model reliability and aid in the selection of heat-tolerant animals.

Dysmorphic Uterus: More Questions than Answers.

A T-shaped uterus is a rare uterine malformation that is classically associated with diethylstilbesterol (DES) exposure. Surprisingly, the prevalence of T- and Y-shaped uterus has increased in recent years despite the absence of a diagnostic consensus and a correlation with the reproductive outcomes has been observed. A systematic electronic database search for all English-language studies published on reproductive outcomes associated with dysmorphic uteri over the past 10 years using PubMed, Google Scholar, and Scopus was performed. This uterine malformation is associated with impaired reproductive outcomes, including primary infertility, miscarriage, ectopic pregnancy, and preterm birth. Hysteroscopic metroplasty is a simple surgical procedure that could potentially improve outcomes in subfertile women, but the data are not robust. Studies reported significant improvements in implantation and pregnancy rates after corrective metroplasty in women undergoing in vitro fertilization. However, multicenter, prospective, randomized, and controlled trials are needed to validate these findings and to help define clear diagnostic criteria, surgical indications, and appropriate follow-up of reproductive outcomes after the procedure.

Effect of Obesity on Aquaporin5 Expression in Human Placental and Uterus Tissues.

Background: Obesity and overweight are also becoming more prevalent among women of childbearing age and pregnant women. In maternal obesity, the activation of metabolic, inflammatory, and oxidative stress pathways is proven, which appears to be a key step in the pathological changes observed in placental and uterine function. Several recent studies have evidenced that aquaporins (AQPs) are critical players in adipose tissue biology and are involved in the onset of obesity. Methods: Our studies aimed to investigate the changes in placental volume and vascularization and measure the AQP5 expression and total antioxidant capacity (TAC) in the placenta and uterus tissues in obese and typical-weight mothers. We also aim to measure the AQP5 plasma concentration. Results: We found AQP5 dominance in the uterus and plasma at 34 weeks of normal pregnancy. The placental volume increased and the vascularization decreased in obese mothers compared to the control. The AQP5 expression increased in the uterus of the obese group and did not change in the placenta. The TAC decreased in the plasma of overweight mothers. Conclusions: We hypothesize that increased AQP5 expression prolongs the length of pregnancy and inhibits the onset of contractions. Based on our findings, we can develop diagnostic tests and provide new targets for tocolytic drug development.

Is Hysteroscopic Metroplasty Advisable for U2bC2V1 Malformation?

A complete uterine septum, with a double cervix and vaginal septum, is a complex and rare congenital genital tract anomaly. The diagnosis is difficult and often challenging, requiring complex imaging investigations and diagnostic hysteroscopy. The benefit of hysteroscopic metroplasty for this uterine malformation is still the subject of dispute. However, the potential benefits of obtaining pregnancies and reducing the rate of abortions make this surgical method a desirable one. We present a series of three cases with U2bC2V1 malformation that were diagnosed via magnetic resonance imaging (MRI), in which hysteroscopic removal of the uterine septum and resection of the longitudinal vaginal septum were performed, with the preservation of the two cervixes. All patients became pregnant after the hysteroscopic intervention and reported an improvement in dyspareunia and dysmenorrhea.

Carcinoma Endometrium Coexisting in Huge Procidentia.

Surgery remains the gold standard treatment for endometrial cancer. Vaginal approach is suitable for candidates with low risk for lymph node metastasis or in elderly females with extensive comorbidities, especially when surgery is done for palliative purpose only. We herein describe a case of cancer endometrium in huge procidentia, managed by vaginal hysterectomy followed by hormonal therapy.

Automatic segmentation of high-risk clinical target volume and organs at risk in brachytherapy of cervical cancer with a convolutional neural network.

PURPOSE: This study aimed to design an autodelineation model based on convolutional neural networks for generating high-risk clinical target volumes and organs at risk in image-guided adaptive brachytherapy for cervical cancer. MATERIALS AND METHODS: A novel SERes-u-net was trained and tested using CT scans from 98 patients with locally advanced cervical cancer who underwent image-guided adaptive brachytherapy. The Dice similarity coefficient, 95th percentile Hausdorff distance, and clinical assessment were used for evaluation. RESULTS: The mean Dice similarity coefficients of our model were 80.8%, 91.9%, 85.2%, 60.4%, and 82.8% for the high-risk clinical target volumes, bladder, rectum, sigmoid, and bowel loops, respectively. The corresponding 95th percentile Hausdorff distances were 5.23mm, 4.75mm, 4.06mm, 30.0mm, and 20.5mm. The evaluation results revealed that 99.3% of the convolutional neural networks-generated high-risk clinical target volumes slices were acceptable for oncologist A and 100% for oncologist B. Most segmentations of the organs at risk were clinically acceptable, except for the 25% sigmoid, which required significant revision in the opinion of oncologist A. There was a significant difference in the clinical evaluation of convolutional neural networks-generated high-risk clinical target volumes between the two oncologists (P<0.001), whereas the score differences of the organs at risk were not significant between the two oncologists. In the consistency evaluation, a large discrepancy was observed between senior and junior clinicians. About 40% of SERes-u-net-generated contours were thought to be better by junior clinicians. CONCLUSION: The high-risk clinical target volumes and organs at risk of cervical cancer generated by the proposed convolutional neural networks model can be used clinically, potentially improving segmentation consistency and efficiency of contouring in image-guided adaptive brachytherapy workflow.

Navigating the complexities of a forgotten double J stent.

Double-J (DJ) stents are most commonly used urological tools these days. Serious complications may occur when stents are left in place for longer duration. We present a case of a woman in her 40s with a forgotten DJ stent for 4 years, leading to complications such as encrustations, bladder and renal stone formation. The patient underwent a comprehensive endourological approach, including endoscopic cystolithotomy and left-sided percutaneous nephrolithotomy. The case highlights the importance of timely stent removal to prevent complications such as encrustations and stone formation. Patient education and counselling are crucial to avoid poor compliance and the associated risks of forgotten stents. This case underscores the significance of a multidisciplinary approach and emphasises the need for proactive measures to prevent such complications, including the implementation of a stent placement registry.

Gene Regulatory Network Analysis of Decidual Stromal Cells and Natural Killer Cells.

Human reproductive success relies on the proper differentiation of the uterine endometrium to facilitate implantation, formation of the placenta, and pregnancy. This process involves two critical types of decidual uterine cells: endometrial/decidual stromal cells (dS) and uterine/decidual natural killer (dNK) cells. To better understand the transcription factors governing the in vivo functions of these cells, we analyzed single-cell transcriptomics data from first-trimester terminations of pregnancy, and for the first time conducted gene regulatory network analysis of dS and dNK cell subpopulations. Our analysis revealed stromal cell populations that corresponded to previously described in vitro decidualized cells and senescent decidual cells. We discovered new decidualization driving transcription factors of stromal cells for early pregnancy, including DDIT3 and BRF2, which regulate oxidative stress protection. For dNK cells, we identified transcription factors involved in the immunotolerant (dNK1) subpopulation, including IRX3 and RELB, which repress the NFKB pathway. In contrast, for the less immunotolerant (dNK3) population we predicted TBX21 (T-bet) and IRF2-mediated upregulation of the interferon pathway. To determine the clinical relevance of our findings, we tested the overrepresentation of the predicted transcription factors target genes among cell type-specific regulated genes from pregnancy disorders, such as recurrent pregnancy loss and preeclampsia. We observed that the predicted decidualized stromal and dNK1-specific transcription factor target genes were enriched with the genes downregulated in pregnancy disorders, whereas the predicted dNK3-specific targets were enriched with genes upregulated in pregnancy disorders. Our findings emphasize the importance of stress tolerance pathways in stromal cell decidualization and immunotolerance promoting regulators in dNK differentiation.

(-)-Carvone Inhibits Oxytocin-induced Writhing Via Uterine Relaxation in Rodents.

(-)-Carvone, a ketone monoterpene, is the main component of essential oils from several medicinal plants and has been reported to have anti-arthriric, anticonvulsive, antidiabetic, anti-inflammatory, anticancer, and immunomodulatory effects. Therefore, this study aimed to investigate the spasmolytic activity of (-)-carvone in rodent models. The isolated virgin rat uterus was mounted in an organ bath apparatus, and the relaxing effect of ( -)-carvone and its mechanism of action were evaluated in tonic contractions induced by carbachol, KCl, PGF2α, or oxytocin. The animal model of primary dysmenorrhea was replicated with the injection of estradiol benzoate in female mice for three consecutive days, followed by intraperitoneal administration of oxytocin. Non-clinical acute toxicity evaluation was also performed. (-)-Carvone potency and effectiveness were larger in carbachol (pEC50 = 5.41 ± 0.14 and Emax = 92.63 ± 1.90% at 10-3 M) or oxytocin (pEC50 = 4.29 ± 0.17 and Emax = 86.69 ± 1.56% at 10-3 M) contractions. The effect of ( -)-carvone was altered in the presence of 4-aminopyridine, glibenclamide, L-NAME, or methylene blue. Mice pre-treated with (-)-carvone at a dose of 100 mg/kg showed a significant reduction in the number of writhing after oxytocin administration. No toxicity was observed after oral administration of 1 g/kg ( -)-carvone. Taken together, we showed that (-)-carvone reduced writhing by a spasmolytic effect, probably through the participation of KV and KATP channels and the nitric oxide pathway.

Influence of Cesarean Section Scar on the Mean Pulsatility Index of the Uterine Artery Doppler between 20 and 34 Weeks of Gestation.

Objective: The aim of this study was to assess the influence of the cesarean section scars on the mean pulsatility index (PI) of the uterine artery Doppler between 20 and 34 weeks of gestation. A secondary objective was to assess the association between previous cesarean section and adverse maternal/perinatal outcomes. Methods: A retrospective cohort study was conducted with pregnant women who had their deliveries between March 2014 and February 2023. PI of the uterine arteries Doppler was performed transvaginally between 20-24 weeks and transabdominally between 28-34 weeks. The following variables were considered adverse perinatal outcomes: birth weight < 10th percentile for gestational age, preeclampsia, premature birth, placental abruption, perinatal death, postpartum hemorrhage, neonatal intensive care unit (NICU) admission. Results: A total of 479 pregnant women were included in the final statistical analysis, being that 70.6% (338/479) had no (Group I) and 29.4% (141/479) had at least one previous cesarean section (Group II). Pregnant women with a previous cesarean had higher median of mean PI (1.06 vs. 0.97, p = 0.044) and median MoM of mean PI uterine arteries Doppler (1.06 vs. 0.98, p = 0.037) than pregnant women without previous cesarean section at ultrasound 20-24 weeks. Pregnant women with a previous cesarean section had higher median of mean PI (0.77 vs. 0.70, p < 0.001) and mean MoM PI uterine arteries Doppler (1.08 vs. 0.99, p < 0.001) than pregnant women without previous cesarean section at ultrasound 28-34 weeks. Pregnant women with ≥ 2 previous cesarean sections had a higher median of mean PI uterine arteries Doppler than those with no previous cesarean sections (1.19 vs. 0.97, p = 0.036). Group II had a lower risk of postpartum hemorrhage (aPR 0.31, 95% CI 0.13-0.75, p = 0.009) and composite neonatal outcome (aPR 0.66, 95% CI 0.49-0.88, p = 0.006). Group II had a higher risk of APGAR score at the 5th minute < 7 (aPR 0.75, 95% CI 1.49-51.29, p = 0.016). Conclusion: The number of previous cesarean sections had a significant influence on the mean PI uterine arteries Doppler between 20-24 and 28-34 weeks of gestation. Previous cesarean section was an independent predictor of postpartum hemorrhage and APGAR score at the 5th minute < 7. Pregnancy-associated arterial hypertension and number of previous deliveries influenced the risk of composite neonatal outcome, but not the presence of previous cesarean section alone.

IL-2/JES6-1 antibody complex expands the maternal T regulatory cell pool and alleviates fetal loss in abortion-prone mice.

Regulatory T (Treg) cells are essential for immune tolerance of embryo implantation and insufficient Treg cells are implicated in early pregnancy loss. An abortion-prone mouse model was utilized to evaluate the utility of IL-2 complexed with JES6-1 anti-IL-2 antibody (IL-2/JES6-1) to boost uterine Treg cells and improve reproductive success. IL-2/JES6-1 but not IL-2/IgG control administered in the peri-conception phase to CBA/J females mated with DBA/2 males elicited a >2-fold increase in the proportion of CD4+ T cells expressing FOXP3, and an increase in the ratio of FOXP3+ Treg cells to FOXP3- T conventional cells, in the uterus and its draining lymph nodes at embryo implantation that was sustained into mid-gestation. An attenuated phenotype was evident in both thymic-derived and peripheral Treg cells with elevated CTLA4, CD25, and FOXP3 indicating improved suppressive function, as well as increased proliferative marker Ki67. IL-2/JES6-1 treatment reduced fetal loss from 31% to 10%, but this was accompanied by a 6% reduction in late gestation fetal weight, despite comparable placental size and architecture. Similar effects of IL-2/JES6-1 on Treg cells and fetal growth were seen in CBA/J females with healthy pregnancies sired by BALB/c males. These findings show that expanding the uterine Treg cell pool through targeting IL-2 signaling is a strategy worthy of further investigation for mitigating immune-mediated fetal loss.

A new treatment for Robert's uterus with adenomyosis: a case report and review of the literature.

PURPOSE: To provide a method for the differential diagnosis of Robert's uterus with adenomyosis, a rare uterine malformation, and determine the best course of treatment. METHODS: A patient who had Robert's uterus with adenomyosis was admitted to our hospital in December 2022. We analyzed and summarized her case . RESULTS: Our patient complained of progressively worsening primary dysmenorrhea over the course of 3 years and lower abdominal pain lasting for 2 days. Her carbohydrate antigen 125 (CA125) level was 372.10 U/mL. Examinations conducted by several hospitals indicated that she had a single-horned uterus and a residual horned uterus, and our hospital's examination identified Robert's uterus. This malformation was corrected by open abdominal surgery. For the procedure, pelvic adhesions were first isolated, after which the closed uterine cavity and adenomyosis were resected. Subsequently, the left ovarian endometriosis cyst was resected and right tubal ligation was performed. After surgery, three injections of gonadotropin-releasing hormone A (GnRH-A) were administered, which lowered the patient's CA125 level to 14 U/mL and normalized her condition. CONCLUSION: We pioneered a new therapeutic approach for the treatment of Robert's uterus with adenomyosis. Some valuable references are provided for clinical practice.

Comparative Analysis of Total Laparoscopic Hysterectomy Versus Non-descent Vaginal Hysterectomy for Benign Uterine Pathologies in Women: A Systematic Review.

Hysterectomy, which can be conducted through abdominal or vaginal routes, is one of the most common gynecological procedures performed worldwide. When the patient is not able to undergo a vaginal hysterectomy due to contraindications involving a narrow pelvis or endometriosis and technical difficulties, laparoscopic removal of the uterus is the recommended method over abdominal hysterectomy. Additionally, the type of surgery depends on the expertise of the surgeon. Therefore, this systematic review aimed to evaluate different measures related to total laparoscopic (TLH) versus non-descent vaginal hysterectomy (NDVH) in women with benign uterine pathologies. ScienceDirect, PubMed, and Google Scholar databases were searched from 2019 to 2023 for a literature review using keywords including "Non-descent Vaginal Hysterectomy," AND "Total Laparoscopic Hysterectomy," AND "Benign Uterine Pathologies." This systematic review includes five studies based on the selection criteria. The data were extracted and a quality assessment of the studies was performed. The review concluded that NDVH has an advantage over TLH as a scarless surgery performed in a very short period and with minimum blood loss with fewer complications and in terms of cost-effectiveness. However, the postoperative parameters and satisfaction with the TLH technique were better than the NDVH technique, but the procedure was much more time-consuming and needed laparoscopic surgical expertise. The duration of hospitalization in NDVH and TLH was nearly the same. Furthermore, both techniques could be employed for salpingo-oophorectomy or when there are adnexal masses and adhesions present; however, TLH may be the best course of action.