Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies

In recent years, postponement of marriage and childbearing in women of reproductive age has led to an increase in the incidence of age‐related infertility. The reproductive aging process in women is assumed to occur due to a decrease in both the quantity and quality of the oocytes, with the ultimate result being a decline in fecundity. This age‐related decline in fecundity is strongly dependent on oocyte quality, which is critical for fertilization and subsequent embryo development. Aged oocytes display increased chromosomal abnormality and dysfunction of cellular organelles, both of which factor into oocyte quality. In particular, mitochondrial dysfunction has been suggested as a major contributor to the reduction in oocyte quality as well as to chromosomal abnormalities in aged oocytes and embryos. Participation of oxidative stress in the oocyte aging process has been proposed because oxidative stress has the capacity to induce mitochondrial dysfunction and directly damage many intracellular components of the oocytes such as lipids, protein, and DNA. In an attempt to improve mitochondrial function in aged oocytes, several therapeutic strategies have been investigated using both animal models and assisted reproductive technology. Here, we review the biological mechanisms and present status of therapeutic strategies in the female reproductive aging field and indicate possible future therapeutic strategies.     

Oocyte cryopreservation beyond cancer: tools for ethical reflection

Purpose

This article offers physicians a tool for structured ethical reflection on challenging situations surrounding oocyte cryopreservation in young healthy women.

Methods

A systematic literature review offers a comprehensive overview of the ethical debate surrounding the practice. Ethical Counseling Methodology (ECM) offers a practical approach for addressing ethical uncertainties. ECM consists of seven steps: (i) case presentation; (ii) analysis of possible implications; (iii) presentation of ethical question(s); (iv) explanation of ethical terms; (v) presentation of the ethical arguments in favor of and against the procedure; (vi) examination of the individual patient’s beliefs and wishes; and (vii) conclusive summary.

Results

The most problematic aspects in the ethical debate include the distinction between medical and non-medical use of oocyte cryopreservation, safety and efficiency of the procedure, and marketing practices aimed at healthy women. Female empowerment and enhanced reproductive choices (granted oocyte cryopreservation is a safe and efficient technique) are presented as ethical arguments supporting the practice, while ethical reservations towards oocyte cryopreservation are based on concerns about maternal and fetal safety and wider societal implications.

Conclusions

Oocyte cryopreservation is gaining popularity among healthy reproductive age women. However, despite promised benefits it also involves risks that are not always properly communicated in commercialized settings. ECM offers clinicians a tool for structured ethical analysis taking into consideration a wide range of implications, various ethical standpoints, and patients’ perceptions and beliefs.     

Epigenetics of pregnancy: looking beyond the DNA code

Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.