Sperm selection in natural conception: what can we learn from Mother Nature to improve assisted reproduction outcomes?

Abstract

Background: In natural conception only a few sperm cells reach the ampulla or the site of fertilization. This population is a selected group of cells since only motile cells can pass through cervical mucus and gain initial entry into the female reproductive tract. In animals, some studies indicate that the sperm selected by the reproductive tract and recovered from the uterus and the oviducts have higher fertilization rates but this is not a universal finding. Some species show less discrimination in sperm selection and abnormal sperm do arrive at the oviduct. In contrast, assisted reproductive technologies (ART) utilize a more random sperm population. In this review we contrast the journey of the spermatozoon in vivo and in vitro and discuss this in the context of developing new sperm preparation and selection techniques for ART.

Methods: A review of the literature examining characteristics of the spermatozoa selected in vivo is compared with recent developments in in vitro selection and preparation methods. Contrasts and similarities are presented.

Results and conclusions: New technologies are being developed to aid in the diagnosis, preparation and selection of spermatozoa in ART. To date progress has been frustrating and these methods have provided variable benefits in improving outcomes after ART. It is more likely that examining the mechanisms enforced by nature will provide valuable information in regard to sperm selection and preparation techniques in vitro. Identifying the properties of those spermatozoa which do reach the oviduct will also be important for the development of more effective tests of semen quality. In this review we examine the value of sperm selection to see how much guidance for ART can be gleaned from the natural selection processes in vivo.

Keywords: Fallopian tube; sperm selection; spermatozoa; uterine tube; uterus; vagina.

Figure 1

A comparison of sperm passage in nature versus different assisted reproductive technologies (ART). The key events encountered by sperm as they travel from the testes to the egg are highlighted on the left. The comparison between what the sperm encounters during natural conception and the different ART is shown on the right. The dashed lines represent the missing steps when comparing the different in vitro assisted reproduction process with the steps encountered by the sperm during natural conception. The more complex the ART procedure the greater the length of the dashed lines. IUI, intrauterine insemination.

Figure 2

A schematic representation of how and where current sperm selection techniques focus on removing spermatozoa with individual issues in relation to nature. Four current sperm selection techniques are likened to those steps in spermatogenesis, sperm transport or egg interaction they impact. (1) Apoptosis marker proteins (e.g. Annexin with magnetic activated cell sorting) deselect spermatozoa that express apoptotic markers on the membrane after spermatogenesis. (2) Intracytoplasmic morphologically selected sperm injection (IMSI) removes sperm with abnormal morphology that arise after spermatogenesis. (3) Swim up, density gradients and new technologies such as microfluidics and electrophoresis separate spermatozoa based largely on their density or motility characteristics. (4) Spermatozoa that express a normal array of membrane receptors after spermatogenesis are selected based on their ability to bind to the cumulus cells or zona pellucida. One example is the Hyaluronan binding assay. ROS, reactive oxygen species.

Figure 3

A schematic representing the hypothetical relative contributions of the egg, sperm and uterus to a successful live birth. The relative contribution of the sperm to a successful live birth can be hypothesized to be 10–15%. Aneuploidy and maternal age studies show that overall the egg's contribution is greater and could be hypothesized to be 70–80%, however when the paternal component is abnormal (red) it can drastically affect the ability of an embryo to reach the blastocyst stage and/or a fetus to develop and result in a live birth.