The overall success of human reproduction, either spontaneously or after IVF, is highly dependent upon maternal age. The main reasons for age-related infertility include reduced ovarian reserve and decreased oocyte/embryo competence due to aging insults, especially concerning an increased incidence of aneuploidies and possibly decreased mitochondrial activity. Age-related chromosomal abnormalities mainly arise because of meiotic impairments during oogenesis, following flawed chromosome segregation patterns such as non-disjunction, premature separation of sister chromatids, or the recent reverse segregation. In this review, we briefly discuss the main mechanisms putatively impaired by aging in the oocytes and the deriving embryos. We also report the main strategies proposed to improve the management of advanced maternal age women in IVF: fertility preservation through oocyte cryopreservation to prevent aging; optimization of the ovarian stimulation and enhancement of embryo selection to limit its effects; and oocyte donation to circumvent its consequences.
Advanced maternal age (AMA; >35 year) is associated with a decline in both ovarian reserve and oocyte competence. At present, no remedies are available to counteract the aging-related fertility decay, however different therapeutic approaches can be offered to women older than 35 year undergoing IVF. This review summarizes the main current strategies proposed for the treatment of AMA: (i) oocyte cryopreservation to conduct fertility preservation for medical reasons or “social freezing” for non-medical reasons, (ii) personalized controlled ovarian stimulation to maximize the exploitation of the ovarian reserve in each patient, (iii) enhancement of embryo selection via blastocyst-stage preimplantation genetic testing for aneuploidies and frozen single embryo transfer, or (iv) oocyte donation in case of minimal/null residual chance of pregnancy. Future strategies and tools are in the pipeline that might minimize the risks of AMA through non-invasive approaches for embryo selection (e.g., molecular analyses of leftover products of IVF, such as spent culture media). These are yet challenging but potentially ground-breaking perspectives promising a lower clinical workload with a higher cost-effectiveness. We also reviewed emerging experimental therapeutic approaches to attempt at restoring maternal reproductive potential, e.g., spindle-chromosomal complex, pronuclear or mitochondrial transfer, and chromosome therapy.
In vitro
generation of gametes is also an intriguing challenge for the future. Lastly, since infertility is a social issue, social campaigns, and education among future generations are desirable to promote the awareness of the impact of age and lifestyle habits upon fertility. This should be a duty of the clinical operators in this field.
The term “cryopreservation” refers to the process of cooling cells and tissues and storing them at subzero temperatures in order to stop all biological activity and preserve their viability and physiological competences for future use. Cooling to subzero temperatures is not a physiological condition for human cells; this is probably due to the high content of water in the living matter, whose conversion to ice crystals may be associated with severe and irreversible damage. Among reproductive cells and tissues, metaphase II oocytes are notably vulnerable to cryopreservation, mainly because of their large size, low surface area to volume ratio, relatively high water content and presence of the meiotic spindle. As human biological systems lack efficient internal defense mechanisms against chilling injuries, it is of the utmost importance to supply adequate external support, in terms of cryoprotectant additives, appropriate cooling/warming rates, and suitable long‐term storage. Over the years, scientists have proposed different cryopreservation strategies in the effort to achieve an optimized recipe ensuring cell survival and, at the same time, maintenance of the physiological functions and abilities necessary to continue life. However, despite the first success obtained in the 1980s with frozen oocytes, it was not until recently that notable improvements in the cryopreservation technique, thanks to the advent of vitrification, allowed a breakthrough of this fine procedure.
This failure modes and effects analysis describes the precautionary administrative measures, the additional personal protective equipment required, and the modifications of IVF laboratory settings and procedures required to reduce the risk of aerosol-mediated viral infections.
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