N. Banks

The Estimated Annual Cost of Uterine Leiomyomata in the United States

OBJECTIVE The purpose of this study was to estimate the total annual societal cost of uterine fibroid tumors in the United States, based on direct and indirect costs that include associated obstetric complications. STUDY DESIGN A systematic review of the literature was conducted to estimate the number of women who seek treatment for symptomatic fibroid tumors annually, the costs of medical and surgical treatment, the amount of work time lost, and obstetric complications that are attributable to fibroid tumors. Total annual costs were converted to 2010 US dollars. A sensitivity analysis was performed. RESULTS The estimated annual direct costs (surgery, hospital admissions, outpatient visits, and medications) were

Is FMR1 CGG repeat length a predictor of in vitro fertilization stimulation response or outcome

4.1-9.4 billion. Estimated lost work-hour costs ranged from

Endometriosis and Fertility Preservation.

1.55-17.2 billion annually. Obstetric outcomes that were attributed to fibroid tumors resulted in a cost of

Whole-Exome Sequencing for Diagnosis of Turner Syndrome: Toward Next-Generation Sequencing and Newborn Screening

238 million to

Mechanisms of Primary Ovarian Insufficiency

7.76 billion annually. Uterine fibroid tumors were estimated to cost the United States

Pregnancy in autosomal recessive polycystic kidney disease

5.9-34.4 billion annually. CONCLUSION Obstetric complications that are associated with fibroid tumors contributed significantly to their economic burden. Lost work-hour costs may account for the largest proportion of societal costs because of fibroid tumors.

Fertility Preservation for Women with Sickle Cell Disease (SCD)

OBJECTIVE To study a broad range of FMR1 CGG repeat lengths and assisted reproduction technology (ART) outcomes. DESIGN Retrospective cohort study. SETTING Private ART practice. PATIENT(S) Fresh autologous ART stimulation cycles. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Oocyte yield, live birth. RESULT(S) We screened 14,088 fresh autologous ART cycles from 2012 to 2015, of which 4,690 cycles in 3,290 patients met the inclusion criteria. The FMR1 repeat length was statistically significantly but weakly associated with oocyte yield and other markers of ovarian response. The receiver operating characteristic curve analysis suggested extremely limited predictive ability. Moreover, the FMR1 repeat length was not statistically significantly associated with outcomes in multivariable models, including other markers of ovarian reserve. The FMR1 repeat length was not associated with embryo quality or live birth. Only patient age had a strong ability to predict live birth. CONCLUSION(S) The FMR1 repeat length is associated with ART response, but only weakly. It provides no incremental predictive ability beyond the conventionally used predictors, including patient age, antimüllerian hormone concentration, antral follicle count, and follicle-stimulating hormone level. These data suggest a possible role of the FMR1 repeat length within the normal range in ovarian response but demonstrate no clinically relevant indication for testing FMR1 as a predictor of ART outcomes.

Phenotypic diversity amongst patients with an isodicentric y chromosome

Endometriosis is common, affecting 5% to 10% of reproductive age women. Nearly half of women with surgical evidence of endometriosis fail to achieve spontaneous pregnancy. Surgical treatment of endometriosis can be detrimental to ovarian reserve. In the absence of surgical intervention, ovarian reserve may still be negatively impacted over time. Fertility preservation was developed for women requiring gonadotoxic treatments. Improved methods have led to greater consideration of offering these services to women with other disease processes that threaten ovarian reserve. This chapter will present the debate regarding use of fertility preservation in management of endometriosis, and outline the need for further studies.

Epigenetics and Assisted Reproductive Technology

Context: Turner syndrome (TS) is due to a complete or partial loss of an X chromosome in female patients and is not currently part of newborn screening (NBS). Diagnosis is often delayed, resulting in missed crucial diagnostic and therapeutic opportunities. Objectives: This study sought to determine if whole-exome sequencing (WES) as part of a potential NBS program could be used to diagnose TS. Design, Setting, Patients: Karyotype, chromosomal microarray, and WES were performed on blood samples from women with TS (n = 27) enrolled in the Personalized Genomic Research study at the National Institutes of Health. Female control subjects (n = 37) and male subjects (n = 27) also underwent WES. Copy number variation was evaluated using EXCAVATOR2 and B allele frequency was calculated from informative single nucleotide polymorphisms. Simulated WES data were generated for detection of low-level mosaicism and complex structural chromosome abnormalities. Results: We detected monosomy for chromosome X in all 27 TS samples, including 1 mosaic for 45,X/46,XX and another with previously unreported material on chromosome Y. Sensitivity and specificity were both 100% for the diagnosis of TS with no false-positive or false-negative results. Using simulated WES data, we detected isochromosome Xq and low-level mosaicism as low as 5%. Conclusion: We present an accurate method of diagnosing TS using WES, including cases with low-level mosaicism, isochromosome Xq, and cryptic Y-chromosome material. Given the potential use of next-generation sequencing for NBS in many different diseases and syndromes, we propose WES can be used as a screening test for TS in newborns.

FMR1 CGG repeat length and ovarian function in a donor population

Premature loss of ovarian follicles can occur due to several basic underlying causes: (1) Inadequate initial complement of follicles due to defects in germ cell location, proliferation, or retention prior to attainment of maximum follicle numbers in fetal life; (2) excessive loss of a normal complement of follicles due to pathological processes, genetic causes, or environmental toxins; and (3) iatrogenic destruction of ovarian follicles either through surgery, chemotherapy, or other causes. Recent advances in genetics have led to the discovery of a number of unique mutations that cause primary ovarian insufficiency (POI). Each individual mutation is relatively rare, but they have revealed important information about the processes of early ovarian development and follicle maintenance. New knowledge about the environmental effects of cigarette smoking and other potential endocrine-disrupting chemicals may also provide information about the etiology of some cases of POI. Finally, underlying infectious and invasive processes such as pelvic inflammatory disease and endometriosis, which can require repeated ovarian surgeries, also carry risks of premature loss of ovarian follicles. This chapter will review the current state of the science.