Obstructive anomalies of the gynecologic tract.

PURPOSE OF REVIEW: This review discusses current diagnosis, management and outcomes of obstructive anomalies of the gynecologic tract. RECENT FINDINGS: In this review, we will discuss the clinical presentation of obstructive anomalies, surgical management and reproductive outcomes following surgical intervention. SUMMARY: Identification of obstructive anomalies of the gynecologic tract is crucial when evaluating patients presenting with or without menses and cyclical pain. Surgical management is often the preferred modality for treatment, although menstrual suppression is recommended in certain circumstances.

Efficacy of ultrasound-indicated cerclage in twin pregnancies.

OBJECTIVE: We sought to compare the perinatal outcomes in twin pregnancies with short cervical length (CL) with ultrasound-indicated cerclage (UIC) vs no cerclage (control). STUDY DESIGN: This was a retrospective cohort study of asymptomatic twin pregnancies with transvaginal ultrasound (TVU) CL ≤25 mm at 16-24 weeks from 1995 through 2012 at 4 separate institutions. Exclusion criteria were: genetic or major fetal anomaly, multifetal reduction >14 weeks, monochorionic-monoamniotic placentation, or medically indicated preterm birth (PTB). Primary outcome was spontaneous PTB (SPTB) <34 weeks. Secondary outcome was SPTB <28, <32, and <37 weeks. We also planned to evaluate primary and secondary outcome for the subgroup of twin pregnancies with CL ≤15 mm. RESULTS: In all, 140 women with twin pregnancy and TVU-CL ≤25 mm were managed with either UIC (n = 57) or no cerclage (n = 83). Demographic characteristics were not significantly different except women who underwent UIC presented at an earlier gestational age (GA) at diagnosis of short CL. After adjusting for GA at presentation, there were no differences in GA at delivery or SPTB <28 weeks: 12 (21.2%) vs 20 (24.1%) (adjusted odds ratio [aOR], 0.3; 95% confidence interval [CI], 0.68-1.37), <32 weeks: 22 (38.6%) vs 36 (43.4%) aOR, 0.34; 95% CI, 0.1-1.13), or <34 weeks: 29 (50.9%) vs 53 (63.9%) (aOR, 0.37; 95% CI, 0.16-1.1). In the subgroup of women with CL ≤15 mm (32 with UIC and 39 controls) the interval between diagnosis to delivery was significantly prolonged by 12.5 ± 4.5 vs 8.8 ± 4.6 weeks (P < .001); SPTB <34 weeks was significantly decreased: 16 (50%) vs 31 (79.5%) (aOR, 0.51; 95% CI, 0.31-0.83) as was admission to neonatal intensive care unit: 38/58 (65.5%) vs 63/76 (82.9%) (aOR, 0.42; 95% CI, 0.24-0.81) when the UIC group was compared with the control group, respectively. CONCLUSION: UIC in asymptomatic twin pregnancies with TVU-CL ≤25 mm was not associated with significant effects on perinatal outcomes compared to controls. However, in the planned subgroup analysis of asymptomatic twin pregnancies with TVU-CL ≤15 mm before 24 weeks, UIC was associated with a significant prolongation of pregnancy by almost 4 more weeks, significantly decreased SPTB <34 weeks by 49%, and admission to neonatal intensive care unit by 58% compared with controls.

Adverse Events Related to Direct-To-Consumer Sequential Aligners-A Study of the MAUDE Database.

Background-Direct-to-consumer (DTC) sequential aligners promote "teeth straightening" at a low cost and with added patient convenience. DTC sequential aligners have risen in popularity among the general public and sparked debate among dental professionals. Dental professionals argue that using these aligners without an in-person diagnosis and treatment planning protocol set by a licensed dentist or orthodontist may lead to adverse effects on teeth and surrounding structures. The objective of this study is to describe adverse clinical events associated with the use of DTC sequential aligners as reported in the Food and Drug Administration's Manufacturer and User Facility Device Experience (FDA MAUDE) database. Methods-We searched the MAUDE database from 1 January 2010 to 31 December 2020 for the product code of 'NXC' (sequential aligners). The year, type of adverse event, reporter occupation, and event description were noted. Results-651 reports associated with sequential aligners were found, of which 104 were related to DTC sequential aligners. Fifty-four adverse events were reported in 2019. From the event description, 41.3% comprised bite problems, 29.8% comprised orofacial pain, and 26.6% of patients had some form of periodontal sequelae. Furthermore, 69.2% of the patients followed up after an adverse event with a dentist not associated with DTC aligners. Conclusions-The use of DTC sequential aligners without dental supervision has led to oral health problems, as documented in the MAUDE database. Commonly reported adverse events include bite problems, pain, sensitivity, and periodontal disease, and some adverse events are irreversible.

Effects of Ovarian Tissue Cryopreservation on Primary Ovarian Insufficiency in Girls Undergoing Bone Marrow Transplantation.

OBJECTIVE: To determine if removing an ovary for ovarian tissue cryopreservation (OTC) increased rates of primary ovarian insufficiency (POI) in girls undergoing bone marrow transplantation (BMT). Institutional review board approval was obtained from all 3 clinical sites. DESIGN: Multicenter retrospective cohort study SETTING: Academic children's hospitals PATIENTS: Females aged 2-21 who underwent BMT with or without OTC from 2010 to 2017. INTERVENTIONS: None MAIN OUTCOME MEASURES: Rates of POI in girls who underwent OTC vs those who underwent BMT alone as determined by serum markers, presence of menses, or clinical diagnosis. RESULTS: A total of 142 patients were identified, 43 who had OTC and 99 with BMT alone. The rate of POI in girls undergoing OTC was 65% vs 41.8% in those who underwent BMT alone (P = .26). CONCLUSIONS: Although this study was not powered to detect a lack of difference, it is reassuring that there does not seem to be a clinically significant increase in POI in patients undergoing OTC.

Gastrointestinal effects of the addition of ascorbic acid to aspirin.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been associated with the damage to the gastrointestinal tract. One proposed mechanism of injury to the gastrointestinal mucosa by NSAIDs is oxygen radical-dependent microvascular injury. There is reasonable evidence to support the benefit of the addition of ascorbic acid, an ingredient with antioxidant properties, to moderate the adverse gastrointestinal (GI) effects of aspirin. Pharmacokinetic data have demonstrated that aspirin and ascorbic acid combination therapy can assist in mitigating the decrease in levels of ascorbic acid secondary to aspirin monotherapy. Endoscopic evaluation has demonstrated that the addition of ascorbic acid to aspirin significantly improves Lanza scores and rates of blood loss when compared to aspirin administration alone. When taken with ascorbic acid, the patient-reported tolerability of aspirin has been shown to be comparable to paracetamol and placebo. The existing body of evidence is relevant to short-term therapy with analgesic aspirin doses, and extrapolation to long-term therapy with low-dose aspirin is not appropriate. The purported benefit of an aspirin and ascorbic acid combination is a local observance and is not suspected to influence the adverse GI effects experienced as a result of systemic prostaglandin inhibition. Nevertheless, ascorbic acid may be a viable addition to the strategies employed to improve the gastrointestinal tolerability of aspirin.

Recent lessons learned from population pharmacokinetic studies of mycophenolic acid: physiological, genomic, and drug interactions leading to the prediction of drug effects.

INTRODUCTION: Mycophenolic acid (MPA) is a widely used immunosuppressant in transplantation and autoimmune disease. Highly variable pharmacokinetics have been observed with MPA, but the exact mechanisms remain largely unknown. AREAS COVERED: The current review provided a critical, comprehensive update of recently published population pharmacokinetic/dynamic models of MPA (n = 16 papers identified from PubMed and Embase, inclusive from January 2017 to August 2021), with specific emphases on the intrinsic and extrinsic factors influencing the pharmacology of MPA. The significance of the identified covariates, potential mechanisms, and comparisons to historical literature have been provided. EXPERT OPINION: While select covariates affecting the population pharmacokinetics of MPA are consistently observed and mechanistically supported (e.g. cyclosporine and post-transplant time on MPA clearance), some variables have not been regularly reported and/or lacked mechanistic explanation (e.g. diarrhea and several genetic polymorphisms). Very few pharmacodynamic models were available, pointing to the need to extrapolate pharmacokinetic findings. Ideal models of MPA should consist of: i) utilizing optimal sampling points to allow the characterizations of absorption, re-absorption, and elimination phases; ii) characterizing unbound/total MPA, MPA metabolites, plasma/urinary concentrations, and genetic polymorphisms to facilitate mechanistic interpretations; and iii) incorporating actual outcomes (e.g. rejection, leukopenia, infections) and pharmacodynamic data (e.g. inosine-5'-monophosphate dehydrogenase activities) to establish clinical relevance. We anticipate the field will continue to expand in the next 5 to 10 years.

Turner Syndrome with Y Chromosome: Spontaneous Thelarche, Menarche, and Risk of Malignancy.

STUDY OBJECTIVE: Girls with Turner syndrome with Y-chromosome material (TS + Y) are assumed to have nonfunctional gonads with increased tumor risk, therefore prophylactic gonadectomy is recommended at diagnosis. In this study we aimed to determine rates of spontaneous thelarche (ST) and spontaneous menarche (SM), and prevalence of gonadal tumor and malignancy in girls with TS + Y, to further inform discussions about gonadectomy. DESIGN: Retrospective review of clinical and pathology data. SETTING: Multicenter study involving 4 United States children's hospitals. PARTICIPANTS: Patients included those with a genetically proven diagnosis of TS + Y and phenotypically female genitourinary exam. INTERVENTIONS: Demographic characteristics, pubertal development, and gonadal pathology data were abstracted from clinical records. Data for ST were analyzed for patients aged 13 years and older and SM for patients older than 15 years. MAIN OUTCOME MEASURES: ST, SM, prevalence of gonadal tumor, and malignancy. RESULTS: Forty-four patients met inclusion criteria. Nineteen patients were 13 years or older; 8/19 (42%) had ST and reached Tanner stages 2-4 and 2 (11%) had normal ovarian pathology. Nineteen patients were 15 years or older; 2/19 (11%) had SM. Thirty-seven patients underwent gonadectomy; 35 had available pathology results. Gonadoblastoma was identified in 35/7 patients (19%), 1 in situ germ cell neoplasia, and 1 dysgerminoma (3%). One patient with bilateral gonadoblastoma had ST and SM. CONCLUSION: In this multicenter cohort, 42% of girls with TS + Y entered puberty spontaneously and 11% had SM, supportive of gonadal function. Risk of tumor was similar to previous reports. To achieve informed decision-making, discussions about gonadectomy should incorporate potential for gonadal function and tumor risk.

Providers' Experiences with Vaginal Dilator Training for Patients with Vaginal Agenesis.

STUDY OBJECTIVE: To examine providers' experiences with vaginal dilator training for patients with vaginal agenesis. DESIGN AND SETTING: Anonymous electronic survey. PARTICIPANTS: Members of the North American Society for Pediatric and Adolescent Gynecology. INTERVENTIONS AND MAIN OUTCOME MEASURES: How providers learn about vaginal dilator training, common techniques, and methods used for patient training, assessment of patient readiness, common patient complaints, issues leading to early discontinuation. RESULTS: There were a total of 55 completed survey responses of which 31 respondents (56%) had been in practice for more than 10 years. Forty-nine were gynecologists (89%), 20 had completed a fellowship in pediatric and adolescent gynecology (36%), and 6 were reproductive endocrinologists (11%). Thirty-one respondents had first learned about vaginal dilator training through lectures (56%) whereas only 9 through mentorship and fellowship (16%). According to respondents, the most common issue leading to early discontinuation was lack of patient motivation and readiness (n = 42; 76%). The most common complication was pain or discomfort (n = 45; 82%). More than half of respondents determined dilator therapy was successful when patients reported comfortable sexual intercourse (n = 30; 55%) and 65% (n = 35) did not delineate any restrictions to initiation of sexual intercourse. Most respondents (87%) requested further vaginal dilator training at either a clinical meeting (n = 26; 47%) or with a training video (n = 22; 40%). CONCLUSION: Our study in an experienced cohort of pediatric gynecology providers highlights the need for further research and training on vaginal dilation education.

Venous Thromboembolism in Female Adolescents: Patient Characteristics.

STUDY OBJECTIVE: Our goal was to describe the period prevalence of venous thromboembolism (VTE) and characterize adolescent female patients diagnosed with VTE by describing their age, race, and number of comorbidities. Female adolescents with estrogen exposure were of particular interest because estrogen-containing contraceptives increase the risk of VTE. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: We queried the Pediatric Health Information System database for International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification codes to identify female patients aged 12-18 years diagnosed with a VTE or pulmonary embolism from April 2006 to March 2016 in the United States. Patient demographic characteristics and comorbidities were also analyzed. We divided our study population into two five-year groups and calculated the change in period prevalence of VTE between those groups. MAIN OUTCOME MEASURES: Primary diagnosis of VTE in the extremities, or pulmonary embolism. RESULTS: The period prevalence of VTE increased from 2.3 female adolescents per 10,000 hospitalized children (group 1) to 3.3 per 10,000 (group 2), representing a statistically significant increase of 0.010% (P < .001). Caucasian and black individuals were most commonly affected. The number of girls affected increased steadily from ages 12 to 16 years and a large percentage (59.6%) had four or more comorbidities. In patients (n = 32) with estrogen exposure, more than 96% had one or more comorbidity in addition to estrogen exposure. CONCLUSION: Pediatric health care providers should be aware that the period prevalence of VTEs in female adolescents is increasing. Those with a history of estrogen exposure rarely develop VTEs from estrogen alone and they typically have multiple comorbidities.

Noncytotoxic-Related Primary Ovarian Insufficiency in Adolescents: Multicenter Case Series and Review.

STUDY OBJECTIVE: Primary ovarian insufficiency (POI) in adolescents not due to cytotoxic therapy has not been well studied. Causes of POI have been described in adults, but adolescents might represent a unique subset necessitating a targeted approach to diagnosis, workup, and treatment. We sought to better characterize adolescent POI through a descriptive multicenter study. DESIGN: Case series of patients with POI. SETTING: Six tertiary care institutions. PARTICIPANTS: Patients presenting from 2007 to 2014 aged 13-21 years diagnosed with noncytotoxic POI, with exclusions for those who received gonadotoxic therapy, with 46XY gonadal dysgenesis, or lack of evidence of hypergonadotropic hypogonadism on chart review. INTERVENTIONS: Review and data extraction of records identified according to International Classification of Diseases Ninth or Tenth Revision codes. MAIN OUTCOME MEASURES: Data were analyzed for signs and symptoms, workup, and treatments. Complete workup was on the basis of American College of Obstetricians and Gynecologists guidelines. Characteristics of patients with POI who presented with delayed puberty/primary amenorrhea vs secondary amenorrhea were compared. RESULTS: One hundred thirty-five records were identified. Those who had received cytotoxic therapy (n = 52), 46XY gonadal dysgenesis (n = 7), or on review did not have POI (n = 19) were excluded. Of 57 remaining cases, 16 were 45X, 2 had galactosemia, and 4 had X-chromosome abnormalities. Most did not undergo full etiologic evaluation. Girls diagnosed after primary amenorrhea/delayed puberty were less symptomatic and more likely to receive an estrogen patch than those diagnosed after secondary amenorrhea. CONCLUSION: Noncytotoxic POI in adolescents is an uncommon condition with, to our knowledge, only 64 cases in 6 institutions over 7 years. These patients might not undergo complete etiological workup. Aside from 45X, the most common etiologies were X-chromosome abnormalities or galactosemia.

Timing of Gonadectomy in Patients with Complete Androgen Insensitivity Syndrome-Current Recommendations and Future Directions.

This review highlights the controversy regarding timing of gonadectomy in patients with complete androgen insensitivity syndrome (CAIS). We will review the published literature regarding frequency of gonadal malignancy and summarize historical findings. Recent research suggests that gonadectomy may be deferred until adulthood due to the low risk of malignancy. An algorithm is also provided to help guide clinicians in management of patients with complete androgen insensitivity syndrome who have deferred gonadectomy.