Heterozygous TP63 pathogenic variants in isolated primary ovarian insufficiency.

PURPOSE: Our study aimed to identify the genetic causes of non-syndromic primary ovarian insufficiency (POI) in female patients. METHODS: We performed whole exome sequencing in females suffering from isolated POI and in their available family members. Copy number variations were validated by long-range PCR and Sanger sequencing, and conservation analysis was used to evaluate the impact of sequence variants on protein composition. RESULTS: We detected two pathogenic TP63 heterozygous deleterious single nucleotide variants and a novel TP63 intragenic copy number alteration in three unrelated women with isolated POI. Two of these genetic variants are predicted to result in loss of transactivation inhibition of p63, whereas the third one affects the first exon of the ΔNp63 isoforms. CONCLUSION: Our results broaden the spectrum of TP63-related disorders, which now includes sporadic and familial, isolated, and syndromic POI. Genomic variants that impair the transactivation inhibitory domain of the TAp63α isoform are the cause of non-syndromic POI. Additionally, variants affecting only the ΔNp63 isoforms may result in isolated POI. In patients with isolated POI, careful evaluation of genomic variants in pleiotropic genes such as TP63 will be essential to establish a full clinical spectrum and atypical presentation of a disorder.

Management of Hematometra and Hematocolpos in Obstructive Mullerian Anomalies by Image-Guided Drainage with Interventional Radiology: A Multi-Institutional Case Series.

STUDY OBJECTIVE: To describe cases of image-guided drainage of symptomatic hematometrocolpos from obstructive Müllerian anomalies as a temporizing measure to manage acute pain symptoms and delay definitive management of the obstructive Müllerian anomalies that require complex reconstruction METHODS: Institutional Review Board exemption from all included institutions was obtained. A retrospective case series from 3 academic children's hospitals of 8 females under the age of 21 with symptomatic hematometrocolpos due to obstructive Müllerian anomalies drained by image-guided percutaneous transabdominal vaginal or uterine drainage with interventional radiology was reviewed and described. RESULTS: Eight pubertal patients with obstructive Müllerian anomalies (6 patients with distal vaginal agenesis, 1 patient with an obstructed uterine horn, and 1 patient with a high obstructed hemi-vagina) and symptomatic hematometrocolpos are reported. All patients with distal vaginal agenesis had greater than 3 cm lower vaginal agenesis, which would usually require complex vaginoplasty and use of postoperative stents. Given their immaturity and inability to use stents or dilators postoperatively or medical complexity, they subsequently underwent ultrasound-guided drainage of hematometrocolpos with interventional radiology to relieve pain symptoms, followed by menstrual suppression. The patients with obstructed uterine horns had complex medical and surgical histories requiring perioperative planning; they also underwent ultrasound-guided drainage of hematometra as a temporizing measure to manage acute symptoms. CONCLUSION: Patients presenting with symptomatic hematometrocolpos due to obstructive Müllerian anomalies might not be psychologically mature enough to undergo definitive complex reconstruction, which requires vaginal stent or dilator use postoperatively to prevent stenosis and other complications. Image-guided percutaneous drainage of symptomatic hematometrocolpos serves as a temporizing measure by offering pain relief until patients are ready to undergo surgical management and/or to allow time for complex surgical planning.

Surgical considerations and challenges in the pediatric and adolescent gynecologic patient.

It is important for practitioners to recognize that there are special considerations when performing gynecologic surgery in a pediatric or adolescent patient. A provider must be familiar with differences in anatomy, physiology, surgical technique, and psychosocial concerns. This can be challenging for a provider who does not routinely operate on patients in this population. A minimally invasive surgical approach is preferred in the pediatric and adolescent patient whenever possible. While a good command of laparoscopy in the adult patient is certainly a useful skill when operating on pediatric and adolescent patients, there are technical adaptations and challenges to consider. This chapter reviews the pre-operative preparation, operative technique and challenges, and post-operative care of the surgical pediatric and adolescent gynecologic patient.

Teaching Trainees to Deliver Adolescent Reproductive Health Services.

STUDY OBJECTIVE: Delivery of reproductive services to adolescents varies according to specialty and has been linked to differences in clinical training. Few studies have explored how different specialties' graduate medical education (GME) programs prepare providers to deliver adolescent reproductive services. We explored the perceptions of resident physicians regarding their training in delivering adolescent reproductive health services. DESIGN: Between November 2008 and February 2009, 9 focus groups were conducted with graduate medical trainees in 3 specialties that routinely care for adolescents. The semistructured discussions were audio-recorded, transcribed, and analyzed using an inductive approach to content analysis. SETTING: Large, urban academic medical center in Pittsburgh, Pennsylvania. PARTICIPANTS: Fifty-four resident trainees in pediatrics, family medicine, and obstetrics/gynecology. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Trainees' perspectives regarding the didactic teaching and clinical training in providing adolescent reproductive services. RESULTS: Five themes emerged, reflecting trainees' beliefs regarding the best practices in which GME programs can engage to ensure that trainees graduate with the belief that they are competent and will be comfortable delivering adolescent reproductive services. Trainees believed programs need to: (1) provide didactic lectures and diverse inpatient and outpatient clinical experiences; (2) have faculty preceptors skilled in providing and supervising adolescent reproductive services; (3) teach skills for engaging adolescents in clinical assessments and decision-making; (4) train providers to navigate confidentiality issues with adolescents and caregivers; and (5) provide infrastructure and resources for delivering adolescent reproductive services. CONCLUSION: The 3 specialties differed in how well each of the 5 best practices were reportedly addressed during GME training. Policy recommendations are provided.