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

  • Gamete Biology
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

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 (Ca2+) 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 Ca2+ release. A second IVF cycle was performed using Ca2+ ionophore with ICSI to enhance Ca2+-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 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.

Conclusions

Deficiency of PLC-ζ 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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of California Los Angeles, 10833 Le Conte Ave, Room 22-178 CHS, Los Angeles, CA, 90095, USA

    Zahabiya H. Chithiwala & Daniel A. Dumesic

  2. Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, 01003, USA

    Hoi Chang Lee & Rafael Fissore

  3. ART Reproductive Center, 450 North Roxbury Drive Suite 520, Beverly Hills, CA, 90210, USA

    David L. Hill

  4. 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

    Teru Jellerette-Nolan & Daniel Grow

Authors
  1. Zahabiya H. Chithiwala
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  2. Hoi Chang Lee
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  3. David L. Hill
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  4. Teru Jellerette-Nolan
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  5. Rafael Fissore
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  6. Daniel Grow
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  7. Daniel A. Dumesic
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Corresponding author

Correspondence to Daniel A. Dumesic.

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Capsule

In an IVF couple with impaired oocyte fertilization during ICSI from deficient PLC-ζ in normal-appearing sperm, Ca2+ ionophore use following ICSI of oocytes matured in vitro improved oocyte competence, leading to the birth of a healthy term female offspring.

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Chithiwala, Z.H., Lee, H.C., Hill, D.L. et al. Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report. J Assist Reprod Genet 32, 1415–1419 (2015). https://doi.org/10.1007/s10815-015-0531-1

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  • DOI: https://doi.org/10.1007/s10815-015-0531-1

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