Low androgen signaling rescues genome integrity with innate immune response by reducing fertility in humans.

Development of the gonads under complex androgen regulation is critical for germ cells specification. In this work we addressed the relationship between androgens and genomic integrity determining human fertility. We used different study groups: individuals with Differences of Sex Development (DSD), including Complete Androgen Insensitivity Syndrome (CAIS) due to mutated androgen receptor (AR), and men with idiopathic nonobstructive azoospermia. Both showed genome integrity status influenced by androgen signaling via innate immune response activation in blood and gonads. Whole proteome analysis connected low AR to interleukin-specific gene expression, while compromised genome stability and tumorigenesis were also supported by interferons. AR expression was associated with predominant DNA damage phenotype, that eliminated AR-positive Sertoli cells as the degeneration of gonads increased. Low AR contributed to resistance from the inhibition of DNA repair in primary leukocytes. Downregulation of androgen promoted apoptosis and specific innate immune response with higher susceptibility in cells carrying genomic instability.

Telehealth Care in a Pediatric and Adolescent Gynecology Clinic During the COVID-19 Pandemic.

BACKGROUND: Since the onset of the COVID-19 pandemic, health care systems have increased their telehealth services to meet the changing public health needs. Before the pandemic, telehealth was used primarily in surgical specialties for postoperative visits and rural medicine. However, out of necessity, nearly all medical and surgical subspecialties incorporated this virtual technology to improve patient health care access in a short time. Few studies have addressed telehealth in pediatric and adolescent gynecology (PAG) to date. STUDY OBJECTIVE: To describe the large-scale utilization of telehealth visits, assess patient experience, and improve access to care in a large academic ambulatory gynecology PAG clinic METHODS: This retrospective, cross-sectional quality improvement study was performed by administering patient surveys and compiling aggregate data from the EPIC electronic health record in the Division of Pediatric and Adolescent Gynecology clinics at a single children's hospital between March 2020 and March 2021. Patient demographic characteristics, payer characteristics, visit type and purpose, and patient experience were reviewed. INTERVENTIONS: Wider expansion of telehealth in PAG clinics at a single institution RESULTS: A total of 6159 telehealth appointments were performed, involving 6 clinic sites and 9 providers. Telehealth visits constituted 50% of the total ambulatory volume (12,527). Most patients were located within the institution's state (99.5%), and the remaining called into their telehealth visits from a neighboring state. Most patients were 18 years of age or younger (73%). Video visits lasted 15-30 minutes and included routine follow-up (66.3%), new/consult visits (28.4%), postoperative visits (1.6%), and urgent follow-up (0.2%). The patient population was ethnically diverse by self-identification: 61.4% White, 38.4% Hispanic, 16% Black, 4.4% Asian, and 0.4% Native Hawaiian/American Indian/Alaska Native. Payer mix included self-pay (45.5%), private payer (32.2%), and Medicaid/CHIP (22.3%). Conditions seen ranged from menstrual management (71%) and routine preventive or acute gynecologic concerns (21%) to surgical evaluation for congenital anomalies, endometriosis, fertility preservation, and genital concerns or pelvic masses (8%). Telehealth visits met patient expectations for 87.3% of respondents. Patient-reported opportunities for improvement included improving set-up instructions and more consistent audio/video connections. Challenges identified by providers included difficulty utilizing interpreters, technology limitations, and privacy constraints during HEADSS examination. CONCLUSIONS: This study demonstrates how a large, diverse volume of patients with PAG needs received appropriate care through a telehealth format during the COVID-19 pandemic. Patients were satisfied with the services, but opportunities for improvement were elicited to allow for continued refining of this health care delivery tool in the future.

Robotic-Assisted Laparoscopic Approach to Removal of Müllerian Remnants.

BACKGROUND: Robotic-assisted laparoscopy (RAL) is an alternative to traditional laparoscopic surgery that might increase a surgeon's ability to offer minimally invasive removal of Müllerian remnants (MR) to patients with complex anatomy. We report on 2 cases of RAL resection of MR. CASES: RAL allowed for adequate resection of MR without complications in 2 cases. Case 1 was a 13 year-old female adolescent with VACTERL and uterine remnant close to the ureter of her ipsilateral single kidney. Case 2 was a 16 year-old female adolescent with cloacal exstrophy and omphalocele with remnant hindgut and cervical remnant deep in the pelvis close to the ileal conduit. SUMMARY AND CONCLUSION: In 2 adolescents with complex anatomy and surgical history, RAL allowed for successful removal of MR.

Implications of Ehlers-Danlos Syndrome in a Patient With Mayer-Rokitansky-Küster-Hauser Syndrome.

BACKGROUND: Ehlers-Danlos syndromes (EDS) are a heterogenous group of connective tissue disorders characterized by defective collagen production. Patients with EDS have lax and fragile connective tissue in their joints, skin, blood vessels, and hollow organs. This can lead to, among other complications, joint hypermobility, aneurysms, organ prolapse, and musculoskeletal chronic pain. Given that patients with vaginal agenesis, which occurs with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, often require vaginal dilation as part of their treatment, tissue elasticity and fragility are important considerations. This case report aims to describe the intersection of MRKH and EDS and its impact on vaginal dilation. CASE: A 16-year-old girl with joint hypermobility and type III EDS presented with primary amenorrhea and a karyotype of 46 XX. Magnetic resonance imaging confirmed an absent uterus, cervix, and upper vagina. Physical examination showed Tanner V breasts and Tanner IV pubic hair, and an external genital examination revealed a blind-ending, 1-cm vaginal dimple. The patient was diagnosed with MRKH. Following her diagnosis, she received vaginal dilation instruction and returned for follow-up 2 months later, having quickly progressed to the largest vaginal dilator without symptoms of bleeding, pain, or dysuria. In that timeframe, her vaginal dimple had increased from 1 cm to 7-8 cm in depth, a rate much faster than is typically seen. Because of this rapid progress, a urogenital examination was performed. There was no evidence of urethral abnormality, perforation, or vaginal prolapse. SUMMARY AND CONCLUSION: Recognition of EDS in patients with Müllerian anomalies has important implications for safe and effective vaginal dilation. All patients using vaginal dilation to lengthen the vagina require education on the technique. This need is heightened in patients with EDS in order to prevent accidental dilation of the urethra due to their tissue elasticity, to avoid tissue prolapse, and to prevent the theoretical risk of vaginal perforation.

Differences in bleeding phenotype and provider interventions in postmenarchal adolescents when compared to adult women with bleeding disorders and heavy menstrual bleeding.

INTRODUCTION: Due to lack of patient/health care provider awareness causing delayed diagnosis, the bleeding phenotype and provider interventions in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD) may be different when compared to adults. AIM: The aim of this study was to compare/characterize bleeding phenotype and provider interventions in postmenarchal adolescents < 18 years and premenopausal adults ≥ 18 years with HMB and BD. METHODS: Patient demographics, BD, and provider interventions/therapy details for HMB were compared between both age groups enrolled in the Centers for Disease Control and Prevention (CDC) Female Universal Data Collection (UDC) surveillance project in United States hemophilia treatment centres. Cross-sectional descriptive analyses including frequency distributions, summary statistics, bivariate and logistic regression analyses were performed. RESULTS: Of 269 females (79 adolescents; median age 16 years, interquartile range (IQR) = 2; 190 adults; median age 27 years, IQR = 13) evaluated, BD distribution was similar in both groups. Compared to adolescents, adults more often had family history of bleeding (Adjusted odds ratios [AOR] = 2.6, 1.3-5.6), delay in diagnosis (AOR = 2.5, 1.2-4.9), bleeding with dental procedures (AOR = 2.0, 1.0-4.0), gastrointestinal bleeding (AOR = 4.6, 1.0-21.9), anaemia (AOR = 2.7, 1.4-5.2), utilized desmopressin less often (AOR = 0.4, 0.2-0.8) and underwent gynaecologic procedure/surgery more frequently (AOR = 5.9, 1.3-27.3). CONCLUSION: Bleeding phenotypes of adolescents and adults with HMB and BD were different with more frequent bleeding complications, anaemia, gynaecologic procedures/surgeries, less desmopressin use and more delay in diagnosing BD in adults. Longitudinal studies are needed to determine whether improved patient/provider awareness and education will translate to early diagnosis and timely management of BD/HMB in adolescents that may prevent/reduce future haematologic/gynaecologic complications.

Crohn's Disease and Gynecologic Manifestations in Young Women.

STUDY OBJECTIVE: The purpose of this study was to describe the reproductive and gynecological concerns of young women with Crohn's disease. DESIGN, SETTING, AND PARTICIPANTS: Retrospective chart review of young women with Crohn's disease and gynecologic concerns at a large, urban tertiary children's hospital. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Documentation of abnormal bleeding, pelvic pain, genital fistula, ulcer, or abscess. RESULTS: Most of the patients (85.7%) had menstrual concerns reported as abnormal bleeding patterns or chronic pelvic pain. Genital complaints (fistula, ulcer, or abscess) were present in 75% of patients who ultimately required immune modulators or antibiotics to control their Crohn's disease. Genital complaints were present in only 1 of 3 patients who did not have a history of immune modulator use for Crohn's disease related flare. CONCLUSION: There is a paucity of information available on gynecological concerns occurring in patients with Crohn's disease. Providers should be aware of gynecological manifestations that might appear concurrently with Crohn's colitis, including vulvovaginal pain, vulvar infections, rectovaginal or rectovestibular fistulas, pelvic pain, and menstrual irregularities.

The female reproductive tract: congenital concerns.

The incidence and prevalence of conditions of the reproductive tract varies. This is related to both the complexity and spectrum of underlying and associated conditions. In some cases, only retrospective or case data are available, and likely under-reporting occurs, contributing to a lower than expected prevalence. Given the complex nature in which the reproductive tract develops in the fetus, it is important to understand the embryology, especially in situations of congenital anatomic differences. It is interesting to note not only patterns of conditions, but patterns of concurrent conditions or anomalies such as those occurring with isolated Müllerian anomalies, in conjunction with disorders of sexual differentiation or with cloacal malformations. This review will address typical presentation of these conditions, highlights of management and point to areas of research need, including clinical outcomes and genetic implications.

Diagnostic challenges in patients with bleeding phenotype and von Willebrand exon 28 polymorphism p.D1472H.

Exon 28 polymorphism p.D1472H is associated with significantly lower von Willebrand Ristocetin cofactor activity (VWF:RCoF) to von Willebrand antigen (VWF:Ag) ratio compared to normal, but has been reported as not conferring haemorrhagic risk. The impact of this polymorphism while assessing symptomatic patients for von Willebrand disease (VWD) has not been previously analysed. We retrospectively reviewed charts of children with clinically significant bleeding and abnormal VW panel who underwent VW exon 28 analysis. Twenty-three of 63 patients studied had p.D1472H. Of these 23 patients, 6 with borderline low VWF:RCo were given provisional diagnosis of VWD type 1 by treating physicians, which could be alternatively explained as due to the effect of p.D1472H. None of the patients with low VWF:RCo, decreased VWF:RCo/VWF:Ag ratio and p.D1472H had VWD type 2M mutations identified. This study illustrates the challenge in diagnosing VWD using ristocetin-based VW assay in symptomatic patients with p.D1472H.

Use of the Lumitex MD Lightmat® Surgical Illuminator for pediatric genital trauma cases: a retrospective case series.

STUDY OBJECTIVES: To review the literature regarding repair of pediatric female genital trauma. To review our experience with the use of a lighted retractor at the time of repair of genital trauma in an operating room setting. STUDY DESIGN: Retrospective case series. SETTING: Texas Children's Hospital. PARTICIPANTS: Patients with genital trauma requiring repair in an operating room setting where the Lumitex MD Lightmat Surgical Illuminator (LM) was utilized. INTERVENTIONS: Use of the LM in pediatric gynecology patients. RESULTS: Of the 16 cases where the LM lighted retractor was utilized, 12 were found to be performed secondary to genital trauma, resulting from straddle injury or coital trauma. Four patients were identified as having either congenital reproductive tract anomalies or foreign body. Patients ranged in age from 1-21 years with a mean age of 9 ± 4.91 years at the time of their vaginal repair. The mean operative time was 82 ± 47 minutes, with cases ranging from 37-182 minutes, with a median blood loss of 7 mL and an average hospital stay of 1.2 days. There were no surgical complications. CONCLUSION: Neurosurgeons and otolaryngologists have been optimizing safe visualization of small areas during surgery for years with the use of the LM. In cases of pediatric deep genital trauma, the LM can be used safely for easy visualization, allowing for direct visualization in cases of deep genital trauma.

Platelet function defects in adolescents with heavy menstrual bleeding.

Platelet function defects (PFD) are reported to occur frequently in adult women with heavy menstrual bleeding (HMB). Few studies on adolescent HMB report varying incidence rates (2-44%) for PFD. We reviewed our institutional experience in detecting and managing PFD in adolescent HMB. Postmenarchial girls and adolescents with HMB seen at our institution undergo a comprehensive bleeding disorder work-up by paediatric haematology and paediatric gynaecology providers. Whole blood platelet aggregometry (WBPA) is performed as a second tier test after excluding thrombocytopaenia, coagulation factor deficiencies and Von Willebrand disease (VWD). We retrospectively reviewed the medical records of adolescents with HMB seen between June 2009 and November 2010, as approved by the Institutional Review Board. Patient demographics, clinical features, laboratory results, therapy details and patient outcome information were analysed. Overall, 114 postmenarchial girls and adolescents with HMB were evaluated; 68 patients (59%) had WBPA study performed. Nineteen patients (28%) had at least one aggregation or secretion defect; 12 (18%) had two or more such defects. Treatment included hormonal therapy (13/19; 68%), antifibrinolytic agents (8/19; 42%) and intra-nasal DDAVP (3/19; 16%). Thirteen patients (81%) had improved outcome (median follow-up--15.6 months; range of 1-66 months). In this study, PFD were identified in nearly one-third of girls with HMB, with the majority of these having two or more defects as identified by WBPA. Further prospective studies are needed to better define the prevalence and address appropriate management of HMB and other bleeding complications of PFD in adolescents.

The utility of ultrasound and magnetic resonance imaging versus surgery for the characterization of müllerian anomalies in the pediatric and adolescent population.

STUDY OBJECTIVE: To evaluate the utility of transabdominal ultrasound and magnetic resonance imaging in the evaluation of American Society for Reproductive Medicine (†)(ASRM)-classified müllerian anomalies compared to surgical findings in the pediatric and adolescent population. DESIGN: Retrospective chart review. SETTING: Tertiary academic center. PARTICIPANTS: Thirty-eight patients with müllerian anomalies seen in our pediatric and adolescent gynecology clinic were identified both on the basis of ICD-9 codes and having magnetic resonance imaging at Texas Children's Hospital between 2004 and 2009. INTERVENTIONS: None. MAIN OUTCOMES MEASURE: Correlation among transabdominal ultrasound and magnetic resonance imaging findings with surgical findings. RESULTS: Mean age was 12.2 (± 4.1) years. Twenty-eight patients underwent magnetic resonance imaging and required surgical intervention, and 88.5% demonstrated correlative consistency with surgical findings. Twenty-two patients underwent ultrasound, magnetic resonance imaging, and surgery, which revealed consistency among ultrasound and surgical findings (59.1%) and consistency among magnetic resonance imaging and surgical findings (90.9%). In ASRM diagnoses evaluated by magnetic resonance imaging, surgical findings correlated in 92% (Pearson 0.89). Overall, 55.2% of patients had a renal malformation. CONCLUSIONS: Magnetic resonance imaging is the gold standard imaging modality for müllerian anomalies and is an effective technique for noninvasive evaluation and accurate classification of the type of anomaly in the pediatric and adolescent population. Magnetic resonance imaging should be considered as an adjunct to transabdominal ultrasound to evaluate müllerian anomalies.

Use of misoprostol for management of unsatisfactory colposcopy in the adolescent: a case report and review of the literature.

STUDY OBJECTIVE: To document the ability to use a prostaglandin analogue to achieve satisfactory colposcopy in a patient with cervical stenosis and unsatisfactory colposcopy. DESIGN: Case report. RESULTS: Satisfactory colposcopy was achieved by using 100mg of Misoprostol orally, administered the night before the planned colposcopic evaluation. CONCLUSION: In the presence of persistent atypia in an adolescent female with an unsatisfactory colposcopy, consider using a prostaglandin analogue for adequate evaluation of the endocervix, prior to proceeding with an ablative or excisional therapy.

Didelphic uterus and obstructed hemivagina with renal agenesis: case report and review of the literature.

Congenital disorders of development are more common than previously reported and the correct diagnosis is frequently missed leading to suboptimal treatment. Eight cases of uterus didelphys with obstructed hemivagina referred to the Gynecology service at Baylor College of Medicine over a 2-year period were reviewed. Initial presenting symptoms and signs were followed by an incorrect diagnosis by the referring physician 100% of the time. MRI, the most sensitive imaging modality for congenital anomalies (Kublik, RA: Female pelvis. Eur Radiol 1999; 9:1715), was utilized in only 50% of the cases. In this group of patients, hematocolpos and pyocolpos were discovered in equal numbers upon exploration. Ipsilateral renal anomalies were present 100% of the time, while coexisting contralateral anomalies were present 50% of the time. Resection of the vaginal septum was required for abatement of symptoms in all cases presented here. Laparoscopy provided additional information beyond radiologic tests regarding pelvic and urological anatomy. In two cases, resection of the ipsilateral uterine horn was required. These cases demonstrate the difficulty in diagnosis, heterogeneity in presentation, and need for expertise not only in this rare congenital anomaly but also all the other disorders of development of the female genital tract.

Altered skin elastic fibers in hypothyroid myxedema and pretibial myxedema.

Elastic fibers account for 2% of dermal volume and are responsible for normal skin resiliency. We investigated a disorder of the dermal elastic component as the mechanism for the decreased elasticity of skin in myxedema. Skin biopsy specimens were obtained from patients with thyroid diseases and normal subjects matched for age, sex, and biopsy location. Elastic fiber concentration, determined by computerized morphometric analysis of Verhoeff-van Gieson-stained sections, was significantly lower than normal in hypothyroid and pretibial myxedema. The decreased elastin concentration was not a consequence of the glycosaminoglycan infiltration. Ultrastructural studies of myxedematous skin showed wide variability of elastic fiber diameter and decreased microfibrils. Myxedema (hypothyroid and pretibial) is consistently associated with quantitative and qualitative defects of dermal elastic fibers.

Histochemical characterization of the cutaneous involvement of acromegaly.

We evaluated the pathogenesis of skin thickening in three patients with acromegaly. Growth hormone levels were normal in one patient and were elevated in two patients. Skin biopsy specimens were obtained from the forearm. Hematoxylineosin staining showed slight epidermal thinning and, in two of the patients, a small increase in the number of fibroblasts. Selective stains for collagen, elastic, and reticular fibers disclosed normal connective tissue. The most striking abnormality was increased glycosaminoglycan deposition on the slides stained with colloidal iron. Glycosaminoglycan infiltration occurred mostly in the papillary and upper reticular dermis and was not directly related to the simultaneous growth hormone levels. Tissue digestion with specific enzymes identified hyaluronic acid, chondroitin-4- and 6-sulfate, and dermatan sulfate as the most prominent glycosaminoglycans in the dermis. The skin ultrastructure appeared to be preserved on electron microscopy. We conclude that cutaneous mucinoses is the main cause for the thickening of the skin in acromegaly.