Paternal contribution to aneuploidy in preimplantation embryos

Abstract

The association between sperm indices and the chromosomal status of preimplantation embryos was assessed in 230 couples with a female partner younger than 36 years undergoing 295 cycles of preimplantation diagnosis for aneuploidy: 105 cycles had normozoospermic samples, 134 cycles presented with oligoasthenoteratozoospermia (OAT), while the remaining cycles had spermatozoa retrieved from the seminal tract due to obstructive (29 cycles) or non-obstructive azoospermia (NOA, 27 cycles). One blastomere was biopsied from day-3 embryos and analysed for chromosomes XY, 13, 15, 16, 17, 18, 21, and 22. From the testing of 1549 embryos, the proportion of chromosomally abnormal embryos was significantly lower in normozoospermic patients (55%) than in OAT (62%, P < 0.025) and NOA patients (69%, P < 0.005). Complex abnormalities were the most frequent defect in NOA (68%), which also demonstrated the highest incidence of gonosomal aneuploidy (12%). From the re-analysis of all blastomeres in 493 non-transferred embryos, 95% of NOA embryos were chaotic mosaics. In conclusion, a severe male infertility condition could contribute to the generation of chromosomal abnormalities in the resulting embryos. This might occur especially in NOA patients in which the high incidence of chromosomal abnormalities is mainly due to mosaicism and gonosomal aneuploidy.

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

“…It is believed that at the blastocyst stage (reached at the 5th or 6th day after fertilization) that three-quarters of embryos of a 30-yr-old woman will be normal; however, at 40 years of age, only 40% are normal (109). The centrosome, responsible for the subsequent spindle and microtubule development within the embryo, is derived from the sperm, hence men with significant impairment in spermatogenesis, and oligospermia, may be responsible for higher rates of aneuploidy (the gain or loss of whole chromosomes) within the subsequent embryo (209,339). However, the most common cause of embryo aneuploidy is related to female age as the oocyte has been in a stage of arrested meiotic development in prophase since early fetal life, hence as a woman ages and is exposed to reactive oxygen species within the environment, there is a progressive loss of cohesion molecules that hold sister chromatids together, the incidence of aneuploidy increases exponentially (114), particularly the chiasmata proximal to the telomere (208).…”

Euploidy Rates in Donor Egg Cycles Significantly Differ Between Fertility Centers

“…Using SNP array analysis of embryos, most embryonic meiotic aneuploidies have been found to be maternal in origin (Treff et al, 2010;Rabinowitz et al, 2012;Konstantinidis et al, 2015), and although male factor infertility can increase chromosome abnormality rates in embryos (Silber et al, 2003;Dubey et al, 2008;Magli et al, 2009;Sánchez-Castro et al, 2009;Rodrigo et al, 2010), male factor was described as a diagnosis in only 9.5% of the cycles in this study. Euploidy rate for these cycles was not significantly different from the incidence expected for the entire donor pool.…”

Aneuploidy in the Human Cleavage Stage Embryo

“…Males with non-obstructive azoospermia produced embryos 95% of which were chaotic mosaics, a frequency significantly higher than found in embryos from others with severe male infertility [Magli et al, 2009].…”