title: Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report.
abstract: OBJECTIVE
  The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca(2+)) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro.
  
  
  METHODS
  An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC- ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca(2+) release. A second IVF cycle was performed using Ca(2+) ionophore with ICSI to enhance Ca(2+)-induced oocyte activation of oocytes matured in vitro.
  
  
  RESULTS
  Sperm PLC-ζ protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-ζ bioactivity using an in vitro model of Ca(2+) release. Nevertheless, with this sperm and supplementation of Ca(2+) ionophore following ICSI, fertilization of four of six oocytes matured in vitro was obtained. In addition, four embryos underwent cleavage and two of them reached the blastocyst stage. Transfer of these blastocysts into the uterus led to a single pregnancy and live birth.
  
  
  CONCLUSIONS
  Deficiency of PLC-ζ in normal-appearing human sperm is associated with impaired Ca(2+)-dependent oocyte activation during ICSI. Under this condition, use of Ca(2+) ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca(2+)-dependent mechanisms governing fertilization and preimplantation embryogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, University of California Los Angeles, 10833 Le Conte Ave, Room 22-178 CHS, Los Angeles, CA, 90095, USA.
authors.forename: Zahabiya H
authors.initials: ZH
authors.lastname: Chithiwala
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
authors.forename: Hoi Chang
authors.initials: HC
authors.lastname: Lee
authors.affiliation: ART Reproductive Center, 450 North Roxbury Drive Suite 520, Beverly Hills, CA, 90210, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Hill
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Baystate Medical Center, Western Campus of Tufts University School of Medicine, 280 Chestnut Street, Springfield, MA, 01199, USA.
authors.forename: Teru
authors.initials: T
authors.lastname: Jellerette-Nolan
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, 01003, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fissore
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Baystate Medical Center, Western Campus of Tufts University School of Medicine, 280 Chestnut Street, Springfield, MA, 01199, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grow
authors.affiliation: Department of Obstetrics and Gynecology, University of California Los Angeles, 10833 Le Conte Ave, Room 22-178 CHS, Los Angeles, CA, 90095, USA. danieldumesic@aol.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dumesic
mesh_terms: D000328:Adult; D015153:Blotting, Western; D004624:Embryo Transfer; D005260:Female; D005306:Fertilization / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007231:Infant, Newborn; D007246:Infertility / Q000201:enzymology / Q000209:etiology*; D008297:Male; D009865:Oocytes / Q000166:cytology* / Q000502:physiology; D010062:Ovulation Induction; D054801:Phosphoinositide Phospholipase C / Q000172:deficiency*; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*; D013094:Spermatozoa / Q000502:physiology*; D017211:Treatment Failure
chemical_list: C499235:PLCZ1 protein, human; D054801:Phosphoinositide Phospholipase C
keywords: Assisted reproductive technology (ART); Calcium ionophore; In vitro maturation; Oocyte activation; Phospholipase C-zeta; Sperm