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Context: Adolescent males with hypogonadotropic hypogonadism (HH) have traditionally been treated with exogenous testosterone (T) or human chorionic gonadotropin (hCG) to produce virilization; however, those modalities do not result in growth of the testes and may promote premature maturation and terminal differentiation of Sertoli cells prior to their proliferation, which may impact future fertility. Another option is to use gonadotropins in those individuals to induce testicular growth, proliferation and maturation of Sertoli cells, and production of endogenous T with consequent virilization. Objective: We examined the efficacy and safety of corifollitropin alfa (CFA) combined with hCG for the induction of testicular growth and pubertal development in adolescent boys with HH. Methods: This was a 64-week, multicenter, open-label, single-group study of CFA in adolescent boys, aged 14 to younger than 18 years, with HH. Seventeen participants initiated a 12-week priming period with CFA (100 μg if weight ≤ 60 kg, or 150 μg if weight > 60 kg) given subcutaneously once every 2 weeks, after which they entered a 52-week combined treatment period with CFA, once every 2 weeks, and subcutaneous hCG, twice-weekly (hCG dose adjusted between 500 IU and 5000 IU to keep total T and estradiol levels within protocol-specified ranges). The primary efficacy end point was change from baseline in testicular volume (TV), measured as the sum of volumes of left and right testes by ultrasound. Results: After 64 weeks of therapy with CFA/CFA combined with hCG, geometric mean fold increase from baseline in TV was 9.43 (95% CI, 7.44-11.97) (arithmetic mean of change from baseline at week 64, 13.0 mL). Hormonal, Tanner stage, and growth velocity changes were consistent with initiation and progression of puberty. Treatment was generally well tolerated. No participant developed anti-CFA antibodies. Conclusion: Treatment of adolescent boys with HH with CFA alone for 12 weeks followed by CFA combined with hCG for 52 weeks induced testicular growth accompanied by pubertal progression, increased T, and a pubertal growth spurt (EudraCT: 2015-001878-18). [ABSTRACT FROM AUTHOR]

MicroRNAs influence hematopoietic differentiation, but little is known about their effects on the stem cell state. Here, we report that the microRNA processing enzyme Dicer is essential for stem cell persistence in vivo and a specific microRNA, miR-125a, controls the size of the stem cell population by regulating hematopoietic stem! progenitor cell (HSPC) apoptosis. Conditional deletion of Dicer revealed an absolute dependence for the multipotent HSPC population in a cell-autonomous manner, with increased HSPC apoptosis in mutant animals. An evolutionarily conserved microRNA cluster containing miR-99b. let-7e, and miR-125a was preferentially expressed in long-term hematopoietic stem cells. MicroRNA miR-125a alone was capable of increasing the number of hematopoietic stem cells in vivo by more than 8-fold. This result was accomplished through a differentiation stage-specific reduction of apoptosis in immature hematopoietic progenitors, possibly through targeting multiple proapoptotic genes. Bak1 was directly down-regulated by miR-125a and expression of a 3'UTR-less Bak1 blocked miR-125a-induced hematopoietic expansion in vivo. These data demonstrate cell-state- specific regulation by microRNA and identify a unique microRNA functioning to regulate the stem cell pool size. [ABSTRACT FROM AUTHOR]

Roughly 11% of induced abortions in the United States are performed after 14 weeks of gestation, most commonly by dilation and evacuation (D&E). For a D&E procedure, the cervix must be dilated sufficiently to allow passage of operative instruments and products of conception without injuring the uterus or cervical canal. Preoperative preparation of the cervix reduces the risk of cervical laceration and uterine perforation. The cervix may be prepared with osmotic dilators, prostaglandin analogues, or both. Osmotic dilators currently available in the United States include Dilapan-S, Lamicel, and laminaria. Laminaria tents are made from dehydrated seaweed and require 12-24 h to achieve greatest dilation. The synthetic products, Dilapan-S and Lamicel, achieve maximum effect within 6 h. Dilapan-S achieves greater dilation than the others and, thus, requires fewer dilators to be placed but may be more difficult to remove. For same day procedures, Dilapan-S and Lamicel are preferable to laminaria. A single set of one to several dilators is usually adequate for D&E before 20 weeks of gestation. Additional sets over 1-2 days may be needed in challenging cases. Misoprostol, a prostaglandin analogue, is sometimes used instead of osmotic dilators; however, the data to support such use are limited. Misoprostol is inferior to overnight dilation with laminaria for cervical priming prior to D&E. Misoprostol use as an adjunct to overnight osmotic dilation is only marginally beneficial for priming beyond 16 weeks and does not truly demonstrate any benefit before 19 weeks of gestation. Limited data demonstrate the safety of misoprostol prior to D&E in patients with a uterine scar. The Society of Family Planning recommends preoperative cervical preparation to decrease the risk of complications when performing a D&E prior to 20 weeks of gestation. The three currently available osmotic dilators (laminaria, Lamicel, and Dilapan-S) are safe and effective for this use. Since no single protocol has been found to be superior, clinical judgment is warranted when selecting a method of preoperative cervical preparation.