Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management

Immunofluorescence analysis of PLCz in the sperm of men with previous fertilization failure can guide clinicians to identify candidates for intracytoplasmic sperm injection/artificial oocyte activation.

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Volume 114, Issue 1, Pages 163–174

Authors:

Xin Meng, M.Sc., Pedro Melo, M.Sc., Celine Jones, Caroline Ross, B.Sc. (Hons.), Ginny Mounce, M.Sc., Karen Turner, Ph.D., Tim Child, M.D., Kevin Coward, Ph.D.

Abstract:

Objective

To investigate the applicability of phospholipase C zeta (PLCζ) analysis in assisting the clinical decision-making process when considering artificial oocyte activation (AOA) for infertile males in assisted reproductive technology.

Design

Fifty-six males (43 infertile/13 fertile) were screened using our PLCζ assay.

Setting

Fertility unit/university laboratory.

Patient(s)

Infertile males with abnormal sperm morphology or total fertilization failure, low fertilization rate (<50%), or repeated fertilization failure in assisted reproductive technology.

Intervention(s)

We analyzed PLCζ levels in sperm from fertile and infertile males. Eligible patients subsequently underwent intracytoplasmic sperm injection (ICSI)/artificial oocyte activation (AOA) with calcimycin (GM508).

Main Outcome Measure(s)

PLCζ localization and level and the proportion of sperm expressing PLCζ. Thresholds of PLCζ deficiency, fertilization rates, pregnancy rates, and live birth rates of AOA and non-AOA cycles.

Result(s)

Compared with 13 fertile controls, 34 of the 43 infertile males had significantly lower levels of PLCζ and/or a significantly lower proportion of sperm exhibiting PLCζ. Of these 34 patients, 15 showed a significant PLCζ reduction in both parameters, which we termed “PLCζ deficiency.” Five PLCζ-deficient patients opted for AOA; all five achieved fertilization, and four achieved clinical pregnancies and live births. The fertilization rate improved significantly from 18.6% (ICSI) to 56.8% (ICSI/AOA). The clinical pregnancy rate and live birth rate with AOA were both 40% per initiated cycle. Youden index analysis revealed that the cutoffs below which infertile males were likely to benefit from AOA were 71% for the proportion of sperm expressing PLCζ and 15.57 arbitrary units for mean PLCζ level.

Conclusion(s)

PLCζ analysis is a useful diagnostic tool to determine patient eligibility for subsequent AOA treatment.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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