Paternal factors contributing to embryo quality

Abstract

Purpose: Advancing maternal and paternal age leads to a decrease in fertility, and hence, many infertile couples opt for assisted reproductive technologies [ART] to achieve biological parenthood. One of the key determinants of achieving a live outcome of ART, embryo quality, depends on both the quality of the oocyte and sperm that have created the embryo. Several studies have explored the effect of oocyte parameters on embryo quality, but the effects of sperm quality on the embryo have not been comprehensively evaluated.

Method: In this review, we assess the effect of various genetic factors of paternal origin on the quality and development of the embryo.

Results: The effects of sperm aneuploidy, sperm chromatin structure, deoxyribonucleic acid [DNA] fragmentation, role of protamines and histones, sperm epigenetic profile, and Y chromosome microdeletions were explored and found to negatively affect embryo quality.

Conclusion: We propose that careful assessment of spermatozoal parameters is essential to achieve embryo development and a healthy live birth. However, the heterogeneity in test results and the different approaches of assessing a single sperm parameter highlight the need for more research and the development of standardized protocols to assess the role of sperm factors affecting embryo quality.

Keywords: DNA fragmentation; Embryo; Histone; Methylation; Paternal factors; Protamines; Sperm chromatin; Sperm epigenetics; Y chromosome microdeletions.

Fig. 1

Genetic defects identified in spermatozoa

Fig. 2

Genetic factors of paternal origin that impact embryo quality. Images a to e depict the stages in human embryonic development. a Structural defects of sperm chromatin can decrease the fertilization capacity of sperm. b The rate at which the sperm fertilizes the oocyte can be affected by sperm chromatin defects, alterations in the protamine ratios, and the [Azoospermia factor c] AZFc microdeletions in the Y chromosome. c At the 4 cell stage, the zygotic genome is activated and dependence on maternal genome is eliminated. Embryonic development may be arrested at this stage if the P1/P2 ratio is unbalanced. d The morula stage [16–32 cells] is characterized by a series of cleavage events that successively generate smaller cells. Structural chromatin defects and an increased level of histones can decelerate the cleavage rate with the presence of Y chromosome microdeletions can increase the cleavage rate. e The blastocyst stage that is characterized by the presence of the trophectoderm and the inner cell mass. A skewed histone to protamine ration [HPR] can decrease blastocyst formation rates, poor embryonic development is seen when the embryo is fertilized by sperm carrying chromatin defects and altered P1/P2 ratios. Poor quality embryos are noted when there is an altered protamine 1/protamine 2 ratio and the paternal Y chromosome harbors and AZFc microdeletions. In ART, embryo transfer is performed at this stage of embryonic development. f The growth of the fetus after implantation into the endometrium of the uterus. Presence of altered P1/P2 ratios can cause implantation failure while fertilization by aneuploid sperm, altered protamine ratios, and sperm epigenetic defects can lead to failure to establish pregnancy