title: In vitro and in vivo effects of ulipristal acetate on fertilization and early embryo development in mice.
abstract: OBJECTIVE
  Does ulipristal acetate (UPA), a selective progesterone receptor modulator used for emergency contraception (EC), interfere with fertilization or early embryo development in vitro and in vivo?
  
  
  CONCLUSIONS
  At doses similar to those used for EC, UPA does not affect mouse gamete transport, fertilization or embryo development.
  
  
  BACKGROUND
  UPA acts as an emergency contraceptive mainly by inhibiting or delaying ovulation. However, there is little information regarding its effects on post-ovulatory events preceding implantation.
  
  
  METHODS
  This was an in vitro and in vivo experimental study involving the use of mouse gametes and embryos from at least three animals in each set of experiments.
  
  
  METHODS
  For in vitro fertilization experiments, mouse epididymal spermatozoa capacitated in the presence of different concentrations of UPA (0-1000 ng/ml) were used to inseminate cumulus-intact or cumulus-free eggs in the presence or absence of UPA during gamete co-incubation, and the percentage of fertilized eggs was determined. For in vivo fertilization experiments, superovulated females caged with proven fertile males were injected with UPA (40 mg/kg) or vehicle just before or just after mating and the percentage of fertilized eggs recovered from the ampulla was determined. To investigate the effect of UPA on embryo development, zygotes were recovered from mated females, cultured in the presence of UPA (1000 ng/ml) for 4 days and the progression of embryo development was monitored daily.
  
  
  RESULTS
  In vitro studies revealed that the presence of UPA during capacitation and/or gamete co-incubation does not affect fertilization. Whereas the in vivo administration of UPA at the same time as hCG injection produced a decrease in the number of eggs ovulated compared with controls (vehicle injected animals, P < 0.05), no effects on fertilization were observed when UPA was administered shortly before or after mating. No differences were observed in either the percentage of cleaved embryos or the cleavage speed when UPA was present during in vitro embryo culture.
  
  
  CONCLUSIONS
  Considering the ethical and technical limitations inherent to the use of human gametes for fertilization studies, the mouse model was used as an approach for exploring the potential effects of UPA on in vivo sperm transport and fertilization. Nevertheless, the extrapolation of these results to humans requires further investigation.
  
  
  CONCLUSIONS
  This study presents new evidence on the lack of effect of UPA on gamete interaction and embryo development, providing new insights into the mechanism of action of UPA as an emergency contraceptive method with potential clinical implications. These new findings could contribute to increase the acceptability and proper use of UPA as an emergency contraceptive method.
  
  
  BACKGROUND
  This study was partially supported by a National Agency of Scientific and Technological Promotion (ANPCyT), Argentina grants PICT 2011-061 to D.J.C. and PICT 2011-2023 to P.S.C. None of the authors has any competing interests to declare.
authors.affiliation: Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.
authors.forename: Matías D
authors.initials: MD
authors.lastname: Gómez-Elías
authors.affiliation: Laboratory of Reproductive Studies, School of Biochemical and Pharmaceutical Sciences, National University of Rosario, Rosario, Argentina.
authors.forename: María J
authors.initials: MJ
authors.lastname: Munuce
authors.affiliation: Department of Obstetrics and Gynaecology, School of Medicine, University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Luis
authors.initials: L
authors.lastname: Bahamondes
authors.affiliation: Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Cuasnicú
authors.affiliation: Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina dcohen@ibyme.conicet.gov.ar.
authors.forename: Débora J
authors.initials: DJ
authors.lastname: Cohen
mesh_terms: D000818:Animals; D044363:Contraception, Postcoital; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005307:Fertilization in Vitro / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009649:Norpregnadienes / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000187:drug effects*; D013084:Sperm-Ovum Interactions / Q000187:drug effects*
chemical_list: D009649:Norpregnadienes; D011980:Receptors, Progesterone; C555622:ulipristal acetate
keywords: embryo development; emergency contraception; fertilization; sperm; ulipristal acetate