Abstract
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.
Highlights
Advanced maternal age (AMA) is a critical social and clinical issue
The misperception about the resolutive effect of IVF is due to both a lack of knowledge and its growing popularity. This trend is challenging for fertility specialists who are witnessing an increase in the number of women seeking a pregnancy who are older than 35 year, namely the cut-off age to consider a patient of AMA [4]
An accurate estimation of the ovarian reserve, the optimization of the ovarian response and the collection of a consistent number of oocytes represent the ideal workflow to compensate for the reduced competence of the female gametes in AMA patients
Summary
Advanced maternal age (AMA) is a critical social and clinical issue. Currently, the proportion of women delaying childbearing until the late 3rd–early 4th decade of life has greatly increased, especially in Western societies [1, 2]. The misperception about the resolutive effect of IVF is due to both a lack of knowledge and its growing popularity This trend is challenging for fertility specialists who are witnessing an increase in the number of women seeking a pregnancy who are older than 35 year, namely the cut-off age to consider a patient of AMA [4]. The chance of producing a chromosomally-normal blastocyst might be even lower than 5% in women older than 43 year [7, 8] This can be attributed, on the one hand to the gradual depletion of the ovarian reserve, and on the other hand to the progressive decrease in oocyte/embryo competence, defined as the ability to produce a live birth [9,10,11]. The aim of this review is to focus on current and emerging experimental therapeutic approaches for AMA patients undergoing IVF (for a summary see Figure 1)
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