Effect of women’s age on embryo morphology, cleavage rate and competence—A multicenter cohort study

Abstract

This multicenter cohort study on embryo assessment and outcome data from 11,744 IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of women’s age on oocyte, zygote, embryo morphology and cleavage parameters, as well as cycle outcome measures corrected for confounding factors as center, partner’s age and referral diagnosis. Cycle outcome data confirmed the well-known effect of women’s age. Oocyte nuclear maturation and proportion of 2 pro-nuclear (2PN) zygotes were not affected by age, while a significant increase in 3PN zygotes was observed in both IVF and ICSI (p<0.0001) with increasing age. Maternal age had no effect on cleavage parameters or on the morphology of the embryo day 2 post insemination. Interestingly, initial hCG value after single embryo transfer followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and ICSI (p = 0.001) cycles. For the first time, we show that a woman’s age does impose a significant footprint on early embryo morphological development (3PN). In addition, the developmentally competent embryos were associated with increased initial hCG values as the age of the women increased. Further studies are needed to elucidate, if this increase in initial hCG value with advancing maternal age is connected to the embryo or the uterus.

The impact of age and BMI on oocyte maturation and embryo development

“…Some studies shows that there is a significant effect of age on the expression of genes involved in cell cycle regulation (e.g. microtubule-based processes, chromatin assembly, M-phase of the meiosis) in oocytes in metaphase II (MII) from women undergoing IVF or ICSI treatment, these findings supported that meiosis and cell cycle regulation mechanisms may be affected by increasing age of the woman [13]. In addition, at various developmental stages, follicles behave differently in response to factors promoting follicular cell proliferation, growth, differentiation and apoptosis and very few reach ovulation [14].…”

“…It is well recognized that the fertility potential of women decreases with increasing age. The decline in female reproductive capacity with increasing age has two main causes: Gradual depletion of oocytes from the ovary, and a decrease in oocyte quality [3].…”

“…A fully developmentally competent oocyte is an oocyte that through oogenesis achieves the ability to resume meiosis, become fertilized with a single spermatozoa, decondense the sperm head, create two pronuclei (PN), pass cleavage stages, undergo maternal to embryonic transition, reach the blastocyst stage, hatch, and establish a pregnancy that results in the birth of a healthy baby [3].…”

Nuclear sperm quality in total polymorphic teratozoospermia and its impact on intracytoplasmic sperm injection outcome

“…Furthermore, as a limitation for our study, the mean age of women who had an ICSI cycle was relatively high (36 years). But a recent study of Grondahlet al, , demonstrated that oocyte nuclear maturation and the proportion of 2 pro‐nuclear (2PN) zygotes were not precious by age. In addition, maternal age had no effect neither on cleavage parameters nor on the morphology of the embryo day 2 after insemination (Grondahl et al, ).…”

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“…It has been found that there was an increment in the prevalence of infertility from 1% to 55% at age 25 years and 45 years respectively (9). This effect of age on fertility potential and ART's outcomes could be explained by several aspects including increasing aneuploidy, decreasing ovarian reserve, decreasing oocyte quantity and quality and decreasing availability of competent embryos for transfer in IVF cycles (13,14). On the other hand, no such effect is observed regarding duration of infertility (Table 1); where there was no significant deference in duration of infertility between pregnant and non-pregnant cases.…”