Age-Dependent in vitro Maturation Efficacy of Human Oocytes – Is There an Optimal Age?

Abstract

In vitro maturation of oocytes from antral follicles seen during tissue harvesting is a fertility preservation technique with potential advantages over ovarian tissue cryopreservation (OTC), as mature frozen and later thawed oocyte used for fertilization poses decreased risk of malignant cells re-seeding, as compared to ovarian tissue implantation. We previously demonstrated that in vitro maturation (IVM) performed following OTC in fertility preservation patients, even in pre-menarche girls, yields a fair amount of oocytes available for IVM and freezing for future use. We conducted a retrospective cohort study, evaluating IVM outcomes in chemotherapy naïve patients referred for fertility preservation by OTC that had oocyte collected from the medium with attempted IVM. A total of 133 chemotherapy naïve patients aged 1–35 years were included in the study. The primary outcome was IVM rate in the different age groups – pre-menarche (1–5 and ≥6 years), post-menarche (menarche-17 years), young adults (18–24 years) and adults (25–29 and 30–35 years). We demonstrate a gradual increase in mean IVM rate in the age groups from 1 to 25 years [4.6% (1–5 years), 23.8% (6 years to menarche), and 28.4% (menarche to 17 years)], with a peak of 38.3% in the 18–24 years group, followed by a decrease in the 25–29 years group (19.3%), down to a very low IVM rate (8.9%) in the 30–35 years group. A significant difference in IVM rates was noted between the age extremes – the very young (1–5 years) and the oldest (30–35 years) groups, as compared with the 18–24-year group (p < 0.001). Importantly, number of oocytes matured, percent of patients with matured oocytes, and overall maturation rate differed significantly (p < 0.001). Our finding of extremely low success rates in those very young (under 6 years) and older (≥30 years) patients suggests that oocytes retrieved during OTC prior to chemotherapy have an optimal window of age that shows higher success rates, suggesting that oocytes may have an inherent tendency toward better maturation in those age groups.

Fertility Preservation: How to Preserve Ovarian Function in Children, Adolescents and Adults

“…This was confirmed by a second study where success rates hardly reached 15.5% in premenarchal compared to 28.2% in young postmenarchal patients [66]. Another very recent study demonstrated that in vitro maturation rates peaked at 38.3% between the ages of 18 and 24, but dropped dramatically in patients ≤5 or ≥30 years of age (4.6% and 8.9%, respectively) [62]. This approach represents an add-on method to potentially increase the fertility opportunities for cancer patients, especially in young women with cancer where transplantation of cortical tissue may pose a risk of relapse, but the in vitro maturation approach is currently too inefficient to be the only method used for fertility preservation [63].…”

“…OTC can be coupled with collection of immature oocytes at the time of freezing. Immature oocytes can be isolated by puncture from visible antral follicles on the surface of the ovary [61], retrieved from the medium used for ovary preparation [62] or collected from surplus ovarian medullary tissue [63]. The immature oocytes are then matured in vitro, fertilized or not, depending on the partner status of the patient, and subsequently vitrified.…”

“…The immature oocytes are then matured in vitro, fertilized or not, depending on the partner status of the patient, and subsequently vitrified. Since the first live birth achieved from cryopreserved embryos issued from in vitro-matured oocytes in 2014 [64], there has been a growing interest in the technique [61,62]. Nevertheless, the success rate of in vitro maturation depends on the age of the patient.…”

Factors Influencing the In Vitro Maturation (IVM) of Human Oocyte

“…A cross-sectional study based on 58 women in an ICSI program also reported that the maturation rates of oocytes were significantly reduced in women over 30 years [ 133 ]. Similarly, a study based on 133 patients (aged 1–35 years) who underwent FP by ovarian tissue cryopreservation found that patients between menarche to 25 years could achieve the highest IVM rates, while women ≥30 years and pre-menarche girls (<6 years) obtained extremely low IVM rates (<10%) [ 134 ]. The changed oocyte maturation capacity in different ages may stem from the epigenetic changes [ 135 ] and differential gene expressions [ 136 , 137 ] of oocytes as they age.…”

In Vivo and In Vitro Matured Oocytes From Mice of Advanced Reproductive Age Exhibit Alternative Splicing Processes for Mitochondrial Oxidative Phosphorylation

“…However, previous studies have reported that maternal aging is associated with reduced IVM success rates and adverse events (8,9). IVM is an alternative option for ovarian tissue cryopreservation (OTC); however, the success rates for IVM can be very low when used to mature oocytes retrieved from females of advanced age during OTC (10). Therefore, there is an urgent need to identify the molecular mechanisms underlying IVM so that this technique can be become a driving force for the implementation of ART technology.…”