Towards the identification of a subset of unexplained infertility A sperm proteomic approach

Altered sperm proteome was observed with respect to poor blastocyst development and in vitro fertilization outcome in donor oocyte cycles despite normal sperm testing parameters.

Susanna McReynolds, Ph.D., Monika Dzieciatkowska, Ph.D., John Stevens, B.S., Kirk C. Hansen, Ph.D., William B. Schoolcraft, M.D., Mandy Katz-Jaffe, Ph.D.

Volume 102, Issue 3, Pages 692-699


To investigate the male gamete proteome and its relation to blastocyst development and reproductive success.

Experimental study.

Research laboratory.

Male infertility patients (n = 12) with no known male factor infertility, donated motile sperm after intracytoplasmic sperm injection during an oocyte donor in vitro fertilization cycle.


Main Outcome Measure(s):
Proteomic profiles of sperm from normozoospermic males.

Patients were grouped based on day-5 embryo development: group A = good blastocyst development (>35% ≥ grade 3 BB) and group B = poor blastocyst development (<15% ≥ grade 3 BB). No differences between the groups were observed for sperm concentration, motility, or Kruger morphology. The in vitro fertilization outcome was statistically significantly different with higher viable implantation rates observed for group A (A = 80% vs. B = 48%). Proteomic analysis of the motile sperm samples revealed 49 proteins with statistically significantly differential abundance in relation to blastocyst development (>1.5-fold). Twenty-nine proteins showed decreased abundance for group B, including several proteins involved in spermatogenesis, and 20 proteins showed increased abundance for group B, including several heat shock proteins.

An altered sperm proteome was observed with respect to poor blastocyst development and in vitro fertilization outcome in donor oocyte cycles despite normal sperm testing parameters. These data could represent a novel subset of male factor infertility. Ongoing investigation into the male factor contribution to idiopathic infertility may result in improved patient care and enhanced outcomes.

  • Proteomics is the future of fertility assessment. Although semen analysis is currently the mainstay of an initial male evaluation it only scratches the surface of male infertility. It is not able to explain why men with normal parameters cannot cause a pregnancy and why men with abnormal parameters can cause a pregnancy. As additional proteomes are identified and associated with specific conditions and pathologies, hopefully we can offer a more tailored approach to each couple’s infertility.

  • msamplaski

    It is increasingly obvious that the basic semen parameters are only a superficial view of sperm function. A growing body of knowledge supports that proteomics plays a role in sperm function, which will likely translate into live birth outcomes. Obviously these findings will need to be confirmed in larger numbers of patients, particularly in couples with standardized female factors. It would be helpful to perform this study in couples with a young female partner, but these are couples that are not seeking medical assistance with fertility. In addition, it would be interesting to compare proteomics among “normospermic” men and men with asthenospermia or severe oligospermia. Regardless, these results likely represent the tip of the iceberg for proteomics and male fertility.

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