Systematic analysis of ICSI fertilization failure and coping strategy
I. Pathological mechanisms of ICSI fertilization failure Although ICSI (intracytoplasmic single sperm microinjection) technology can overcome severe male factor infertility (e.g., sperm concentration <1×10⁶/mL or motility <5%), Total Fertilization Failure (TFF) still occurs in 3%-5% of cycles. The core mechanism lies in defective egg activation and involves the following key components: Abnormal calcium oscillatory signaling: during normal fertilization, sperm-specific phospholipase C (PLCζ) triggers cyclic fluctuations in intracytoplasmic calcium ion concentration (0.1-1 μM for 2-4 hours) in the oocyte, which activates calmodulin-dependent kinase (CaMKII) and initiates embryonic development. If there is a mutation in the sperm PLCζ gene (e.g. c.1450G>T) or dysfunction of the oocyte calcium release channel (IP3 receptor), this will result in disruption of calcium signaling. Insufficient oocyte maturity: the cortical granules of GV-stage oocytes have not fully migrated to the subcellular membrane, which makes them susceptible to multiple fertilization; whereas the meiotic arrest of MI-stage oocytes, with reduced PLCζ sensitivity, results in a fertilization failure rate of 40%. Second, the technological breakthrough of assisted oocyte activation (AOA) To address the activation defects, the clinical use of Artificial Oocyte Activation (AOA) technology, which restores calcium oscillations through exogenous calcium ion carriers or chemical stimulation: Calcium ion carriers (Ionomycin): Mechanism of action: binds to oocyte membrane calcium channels and induces transient calcium inward flow (at concentrations up to 5 μM), mimicking physiologic calcium oscillations. Clinical data: 2017 Meta-analysis showed that AOA with Ionomycin resulted in an increase in fertilization rate from 12% to 72%, an increase in the rate of good quality embryos from 18% to 45%, and a 3-fold increase in live birth rate. Strontium Chloride (SrCl₂): Mechanism of action: triggers persistent calcium oscillations through TRPV3 channels, especially for patients with PLCζ defects. Scenario of application: in cases unresponsive to Ionomycin, SrCl₂ (10 mM treatment for 15 min) results in a fertilization rate of 65%. III. Precision pathway for…
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