Müllerian Agenesis in a patient with Rubinstein-Taybi Syndrome: A Case Series and Review of the Overlapping Developmental Biologic Pathways.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multi-system neurodevelopmental condition caused by deficiency of CREBBP (16p13.3) or EP300 (22q13.2). Müllerian agenesis, or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is defined as congenital agenesis of the uterus, cervix, and upper vagina without a definite genetic cause. INDEX CASE AND CASE SERIES: We present a 14-year-old female with RSTS type 1 (CREBBP, c.4395-2A>C) and MRKH, the first documented in the literature. Following presentation to Gynecology for anticipatory guidance regarding future menstrual suppression and follow-up of previously diagnosed labial adhesions, exam under anesthesia revealed a single urogenital opening with cystoscopy demonstrating a normal urethra and bladder. Laboratory evaluation was consistent with peripubertal female gonadotropins and estradiol, 46,XX karyotype, and normal microarray, and a pelvic MRI confirmed Müllerian agenesis. Given this case, we assessed our cohort of females with RSTS and found that 4 of 12 individuals also had Müllerian anomalies. CONCLUSION: Gynecologic evaluation should be a part of medical care for females with RSTS, particularly in individuals with delayed menarche or abnormal menstrual history, on the basis of the observed association between RSTS and Müllerian anomalies in this case series. Although several candidate genes and copy number variants are associated with MRKH, no candidate genes in close proximity to the 16p13.3 region have been identified to explain both RSTS and MRKH in the index patient. Due to the regulatory nature of CREBBP during embryonic development, we theorize that CREBBP may play a role in the migration of Müllerian structures during embryogenesis.

A Retrospective Comparison of Time to Cessation of Acute Heavy Menstrual Bleeding in Adolescents Following Two Dose Regimens of Combined Oral Hormonal Therapy.

STUDY OBJECTIVE: Although multiple hormonal treatment strategies are effective in decreasing heavy menstrual bleeding (HMB) in adolescents, few studies have compared the relative effectiveness of hormone therapy on the basis of dose. DESIGN: Retrospective chart review SETTING: Urban tertiary care institution PARTICIPANTS: Adolescents aged 9-19 years with acute HMB and anemia in 2008-2018 INTERVENTIONS: We used billing codes to identify encounters for acute HMB with hemoglobin less than 12 mg/dl and reviewed initial treatment and time until resolution of acute HMB. We excluded patients who had previously used gonadal steroids or did not complete follow-up. We then compared patients who received combined oral ethinyl estradiol with progestin (EE/P) in standard dosing (EE ≤35 mcg/day) vs taper dosing (EE >35mcg/day in any step-down regimen). MAIN OUTCOME MEASURES: Time until patient-reported resolution of acute HMB, measured in days from initial treatment RESULTS: Of 207 patients with vaginal bleeding and anemia, 90 met the criteria for review of therapy type and dose. Users of combined EE/P were hormone-naïve in 28/33 (84.8%) of those who initiated standard EE/P and 22/32 (68.8%) who initiated taper dosing. Bleeding duration was available for 15/28 (53.6%) and 18/22 (81.8%). Resolution of HMB occurred in 0-9 days with standard dosing (mean ±SD 2.1 ± 2.3 days) versus 1-15 days for taper dosing (4.9 ± 4.7; p = 0.04). Excluding six outliers of zero or more than 10 days, HMB ceased by 2.6 and 3 days (n = 12 and 15; p = 0.62). CONCLUSION: Currently recommended higher dose combined hormonal regimens do not appear to shorten the time to resolution of acute HMB in adolescents.

Changes in uptake and cost of long-acting reversible contraceptive devices following the introduction of a new low-cost levonorgestrel IUD in Utah's Title X clinics: a retrospective review.

OBJECTIVE: The objective was to assess changes in long-acting reversible contraceptive (LARC) method uptake at Utah's Title X clinics before and after introduction of a new, low-cost levonorgestrel (LNG) 52mg IUD (Liletta®). STUDY DESIGN: We conducted a retrospective medical record review of LARC visits occurring at seven Title-X family planning clinics in Utah before the introduction of the low-cost LNG IUD (preintroduction period: 01/01/2014-04/30/2015) and after (postintroduction period: 05/01/2015-03/31/2016). We ran segmented, interrupted time series ordinary least squares regression models using Newey-West standard errors to assess both the change in numbers of women initiating any LARC method and the average payment amount per LARC method. We evaluated both the low-cost LNG IUD and all LARC methods. RESULTS: At the outset of preintroduction period, there were 29.2 [95% confidence interval (CI): 20.1-38.4] monthly LNG IUD insertions. Immediately postintroduction, there was a significant level of increase of 14.4 LNG IUD insertions the first month (95% CI: 2.0-26.8) followed by a significant trend increase each month of 2.4 additional LNG IUD insertions (95% CI: 0.32-4.47). Postintroduction, there was a significant level of remitted-payment decrease from all sources of -$240.43 per LNG IUD (95% CI: -311.02 to 168.87) followed by a significant monthly trend decrease of -$23.01 per LNG IUD (95% CI: -32.02 to -13.98). There were minimal changes in uptake and payment of other LARC methods following the introduction of the low-cost LNG IUD. CONCLUSIONS: Following introduction of a low-cost LNG IUD at Title X clinics, LNG IUD initiation increased and average payment for the method decreased. IMPLICATIONS: Reducing the cost of LARC methods, both to clinics and to patients, is essential to expanding access. Additional efforts to develop and provide access to low-cost copper IUDs and subdermal implants as well as novel LARC methods should be continued.