Ovarian stimulation for IVF: mild approaches

Item does not contain fulltextIn contrast to current approaches, the aim of mild stimulation is to develop safer and more patient-friendly protocols in which the risks of the treatment as a whole are minimized. Mild stimulation is defined as the method when exogenous gonadotropins are administered at lower doses, and/or for a shorter duration in GnRH antagonist co-treated cycles, or when oral compounds (antiestrogens, aromatase inhibitors) are used for ovarian stimulation for IVF, with the aim of limiting the number of oocytes obtained to fewer than eight. In this chapter we discuss the relevant physiology of follicle development, the development of milder stimulation protocols, the implications of mild stimulation, the current state of affairs, and future developments

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques

BACKGROUND:Zika virus (ZIKV; Flaviviridae, Flavivirus) was declared a public health emergency of international concern by the World Health Organization (WHO) in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV. METHODOLOGY/PRINCIPAL FINDINGS:Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form. CONCLUSIONS/SIGNIFICANCE:An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of vaccine protection, i.e., any Asian ZIKV immunogen that protects against homologous challenge will likely confer protection against all other Asian ZIKV strains