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.
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.
['Meng|Xin|X|', 'Melo|Pedro|P|', 'Jones|Celine|C|', 'Ross|Caroline|C|', 'Mounce|Ginny|G|', 'Turner|Karen|K|', 'Child|Tim|T|', 'Coward|Kevin|K|']
D000328:Adult D000465:Algorithms D015415:Biomarkers D016022:Case-Control Studies D000066491:Clinical Decision-Making D003661:Decision Support Techniques D004624:Embryo Transfer D005260:Female D005298:Fertility D006801:Humans D007248:Infertility, Male D008297:Male D054315:Oocyte Retrieval D009865:Oocytes D010062:Ovulation Induction D054801:Phosphoinositide Phospholipase C D011247:Pregnancy D018873:Pregnancy Rate D020554:Sperm Injections, Intracytoplasmic D013094:Spermatozoa D016896:Treatment Outcome
Artificial oocyte activation calcium ionophore oocyte activation deficiency phospholipase C zeta and PLCζ deficiency