Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability

Objective: To evaluate whether aberrant sperm P1/P2 ratios are predictive of abnormal fertilizing ability and are related to in vitro fertilization (IVF) outcome. Design: Prospective case-control study. Setting: University-based infertility and IVF clinic. Patient(s): Forty-three male infertility patients with an abnormally reduced P1/P2 ratio, 251 patients with a normal P1/P2 ratio, and 121 patients with an abnormally elevated P1/P2 ratio. Intervention(s): Human IVF, the sperm penetration assay (SPA), and sperm protamine quantification via nuclear protein extraction, gel electrophoresis, and densitometry analysis. Main Outcome Measure(s): Sperm P1/P2 ratios; P1 and P2 quantities; SPA scores; and IVF-fertilization, embryo-quality, pregnancy, delivery, and spontaneous-abortion rates. Result(s): Standard IVF fertilization rates and SPA scores were significantly reduced in patients with abnormally low and high P1/P2 ratios. In vitro fertilization embryo quality was comparable between these groups, but pregnancy rates were significantly reduced in patients with abnormally reduced P1/P2 ratios. Conclusion(s): The P1/P2 ratio has a significant relationship to sperm fertilization ability. The relationship between protamines and fertilization ability is not understood but may be either a reflection of generalized abnormalities during spermiogenesis or an indication of protamine deficiency acting as a regulator or checkpoint of spermatogenesis.