Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report

The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-zeta) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca2+) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro. 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- zeta protein by Western blot analysis and immunofluorescence and PLC-zeta bioactivity by an in vitro model of Ca2+ release. A second IVF cycle was performed using Ca2+ ionophore with ICSI to enhance Ca2+-induced oocyte activation of oocytes matured in vitro. Sperm PLC-zeta protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-zeta bioactivity using an in vitro model of Ca2+ release. Nevertheless, with this sperm and supplementation of Ca2+ 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. Deficiency of PLC-zeta in normal-appearing human sperm is associated with impaired Ca2+-dependent oocyte activation during ICSI. Under this condition, use of Ca2+ ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca2+-dependent mechanisms governing fertilization and preimplantation embryogenesis.