Abstract
Study question
Are the morphological parameters and development of in vitro cultured embryos, and intracytoplasmic sperm injection (ICSI) outcomes influenced by maternal and paternal ageing?
Summary answer
The slopes of maternal age on blastulation, blastocyst quality, and implantation, pregnancy and miscarriage rates significantly changed (worsened) for every year increase in paternal age.
What is known already
Due to the vast literature demonstrating that female age interferes with intracytoplasmic sperm injection (ICSI) outcomes, there is an imposition, in numerous countries, regarding maternal age limit for assisted reproduction. Despite several studies have underscored the negative impact of paternal age and lifestyle factors on reproductive health, the influence of paternal age on ICSI outcomes is still a matter of debate. The aim of this study was to investigate if the effect of paternal age on embryo development differs at different values of maternal age, thus creating a rationale for the data to reach physicians, patients, and public health recommendations.
Study design, size, duration
This historical cohort study included 3837 couples undergoing their first ICSI cycle from January/2014 to October/2020. A total of 21960 oocytes were injected and embryos were evaluated until day 5 of development. The main effects of maternal and paternal ages, as well as the effect of their product (interaction term) on embryo growth and development, and on pregnancy outcomes were investigated taking into account clustering of data (multiple embryos per cycle), using generalized mixed models.
Participants/materials, setting, methods
The study was performed in a private university-affiliated in vitro fertilization center. Zygotes were morphologically evaluated 17h post ICSI. For days 2 and 3 of development, the number of blastomeres, blastomere symmetry, percentage of fragmentation and presence of multinucleation were recorded. On day 5 of development, successful blastulation, and inner cell mass and trophectoderm qualities were recorded. Pregnancy was calculated per transfer, and miscarriage was defined as pregnancy loss before 20 weeks gestation.
Main results and the role of chance
The coefficients for the interaction term were statistically significant for blastocyst development (B: - 0.005, OR: 0.995, CI: 0.994 – 0.996, p < 0.001), top-quality blastocyst (B: - 0.003, OR: 0.997, CI: 0.996 – 0.999, p < 0.001), implantation rate (B: - 0.041, OR: 0.960, CI: 0.947 – 0.973, p < 0.001), pregnancy rate (B: - 0.004, OR: 0.996, CI: 0.995 – 0.997, p < 0.001), and miscarriage rate (B: 0.011, OR: 1.012, CI: 1.005 – 1.018, p = 0.001). These values describe the changes in slopes such that, the slope of one independent variable (e.g. maternal age) on the dependent variable (e.g. implantation rate) changes by the value of B (- 0.041) for every unit change on the other independent variable (e.g. paternal age). No significant results were observed for the influence of the interaction term on embryo morphological features on days 1, 2 and 3 of development. Two post hoc power analyses were calculated, given α of 5%, sample size of 21960 zygotes and 3315 ICSI cycles with embryo transfer and effect sizes for blastulation and pregnancy outcomes, respectively. The achieved power was superior to 99% in both analyses.
Limitations, reasons for caution
The retrospective and monocentric nature of the study are its major limitations.
Wider implications of the findings
Our results underscore the importance of both maternal and paternal ages for blastulation and successful pregnancy. Main effects of paternal and maternal ages should no longer be interpreted as the relationship between each independent variable and a given outcome, but rather be conditional on the values of the interaction term.
Trial registration number
Not applicable
The effect of paternal age on pregnancy outcomes in ovum donation cycles
