Abstract
Study question
Does the impact of sperm DNA fragmentation (SDF) on Intracytoplasmic sperm injection (ICSI) outcomes depend on the presence of oocyte dimorphisms?
Summary answer
There is a significant influence of oocyte quality on the impact of SDF on pregnancy outcomes.
What is known already
Sperm DNA fragmentation has been associated with ICSI outcomes. DNA damage is commonly encountered in human spermatozoa and it has been widely accepted that the oocyte assumes responsibility for the repair and remodelling of both the maternal and paternal genomes during the oocyte-embryo transition. Indeed, spermatozoa with DNA damage can fertilise oocytes and still lead to embryo development due to the oocyte DNA repair capacity. Considering the vital role played by the oocyte in the developmental process, it could be hypostatised that the oocyte quality, translated as oocyte morphology, would influence the machinery responsible for sperm DNA repair after fertilization.
Study design, size, duration
This cohort study included 3,035 oocytes from 525 patients undergoing ICSI cycles in a university-affiliated IVF-center, between June/2016 and July/2019. Oocytes were split into groups according to the SDF index of the sample used for ICSI: low-fragmentation (<30% SDF, n = 2,277) and high-fragmentation (≥30% SDF, n = 758). Oocytes were evaluated before sperm injection and the dimorphisms were recorded. The influence of SDF index on ICSI outcomes, depending on the presence of oocytes dimorphisms was evaluated.
Participants/materials, setting, methods
Data was evaluated using generalized linear models (GZLM) followed by Bonferroni post hoc. The results are expressed as mean ± standard error for continuous variables or percentages for dichotomous variables, and p-values. The sample size calculation suggested that a sample of at least 504 subjects had 95% power to detect a 20% effect with a significance level of 5% (α). The study was performed in a private university–affiliated in vitro fertilization (IVF) center.
Main results and the role of chance
The association of both factors: the presence of oocyte dimorphisms (dark cytoplasm, vacuoles in the ooplasm, and resistant membrane) and high SDF index resulted in the lowest fertilization rate among groups, while oocytes free of these dimorphisms injected with samples with <30% SDF had the highest fertilization rate (p = 0.05, p < 0.01 and p < 0.01 for dark cytoplasm, vacuoles in the ooplasm and resistant membrane respectively). The impact of SDF index on high quality embryos rate on cleavage stage was also influence by the presence smooth endoplasmic reticulum clusters and resistant membrane oocytes (p = 0.013 and p = 0.018). As for the clinical outcomes, the impact of SDF index on the implantation rate was influenced by the presence of vacuoles in the ooplasm (p < 0.01), smooth endoplasmic reticulum clusters (p < 0.01), large perivitelline space (p < 0.01), resistant membrane (p < 0.01), and non-resistant membrane (p < 0.01), while the influence of SDF index on the pregnancy rate was influenced by the presence large perivitelline space (p < 0.01), resistant membrane (p = 0.018) and non-resistant membrane (p < 0.01). The effect of SDF on the miscarriage rate was also increased in the presence of large perivitelline space (p = 0.045), non-resistant membrane (0.037) and centrally located cytoplasmic granular area (p = 0.025).
Limitations, reasons for caution
The retrospective nature is a limitation. It could be argued that using samples with high SDF index does not necessarily mean that a sperm cell with a fragmented DNA was injected, however, the higher the SDF index, the higher the chance of selecting one with fragmented DNA.
Wider implications of the findings
The findings presented here highlight the crucial role of male and female factors when facing assisted reproduction. The association of low oocyte quality and high SDF index may lead to impaired results. As the oocyte defect cannot be modified, in vivo upgrading of spermatozoa before the treatment should be encouraged.
Trial registration number
Not applicable
Role of Oocyte Morphological Abnormality Rates on the Embryo Development and Implantation