Male Age and Progressive Sperm Motility Are Critical Factors Affecting Embryological and Clinical Outcomes in Oocyte Donor ICSI Cycles

Male gametes are usually generated in millions and this biological process alone should indicate that not all spermatozoa are equally competent. We should, therefore, preclude from seeing semen analysis and sperm parameters as absolute numbers within or outside thresholds, but instead seek the cascade of sperm function that defines a positive reproductive outcome. The introduction and incorporation of the intra-cytoplasmic sperm injection (ICSI) in the available treatments through assisted reproduction technologies (ART) have significantly allowed more conceptions and births and especially in male factor infertility with severely affected spermatozoa population, motility, and morphology. Even though in ICSI cycles there is gamete isolation, optimization of reproductive conditions, and sperm selection for insertion directly to the oocyte, we do obtain unfertilized oocytes, poor developmental and qualitative states of the embryos, and negative events of implantation and pregnancy progression.

We should attempt to gain a better insight into the characteristics of the “successful” sperm and by establishing this we should gain a better view on the anticipated outcomes of ART to allow optimization of embryological methods and clinical results and to furthermore encourage patient-centered management. Even though novel potential biomarkers of male fertility tend to skew our scientific interests into new directions, it is indeed challenging to return to simplistic research questions and support that basic sperm parameters may exhibit a more complex role than the obvious, reflecting reproductive dynamics and capacity, in a setting that we so far thought that circumvented male factor such as ART and specifically ICSI.

On this basis, we designed a retrospective study with minimal female factor interference through an oocyte donation model, for the evaluation of the reproductive performance of variable and frequent male fertility states through ICSI; normozoospermia, oligozoospermia, asthenozoospermia, and oligoasthenozoospermia, as defined by the WHO 2010 criteria. Specifically, we analyzed and compared 339 OD-ICSI cycles based on their embryological outcomes (fertilization, blastocyst formation, top-quality embryo rate) as well as their clinical outcomes (biochemical pregnancy, clinical pregnancy, live birth, and miscarriage). In addition, we analyzed and compared all demographic data as well as male age that has been previously shown to influence spermatogenesis and ART embryological and clinical parameters.

The analysis clearly demonstrated a significant effect of initial sperm motility, sperm count, and paternal age on variable embryological and reproductive outcomes. More specifically, a compromised initial sperm sample motility demonstrated a strong effect on oocyte fertilization through ICSI and the resulting embryo quality, as also on implantation, clinical pregnancy, and live birth rates. Sperm count exhibited an effect on fertilization, embryo quality, and blastocyst formation, while male age was a significant factor for fertilization, biochemical and clinical pregnancy, and live birth. The incidence of miscarriage did not appear to be affected by any of the factors analyzed, neither sperm parameters nor paternal age. The roles of sperm motility and paternal age were pronounced by the level of their effect in the embryological and clinical results during ICSI procedures, only to state in a single sentence that with advancing paternal age and/or with reduced sperm motility in the initial sample, even when female factor is absent, we should expect a significantly lower performance on fertilization, embryo development, and quality, as well as a poorer prognosis in terms of embryo implantation and obtaining a clinical pregnancy through livebirth. There is a strong biological basis of the effect of both the “aged” and the “slow” sperm extensively discussed in our study and these results, along with their scientific background justification, are crucial candidates to consider when assessing male fertility potential and especially when pursuing personalized fertility treatments, even with ICSI where male age, sperm count and motility of the initial sample are not obviously challenged.

Written by: Evi Vogiatzi, BSc, MSc, DEA, PhD, Geneticist, Clinical Embryologist, Attikon University Hospital

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