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.

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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.

The capability of human zona pellucida (ZP) to bind selectively to normal functional sperm with normal chromatin has been reported widely in the literature. The aim of this study was to evaluate whether ZP-binding sperm selection may represent a method to retrieve superior spermatozoa for intracytoplasmic sperm injection (ICSI). Patients were divided into two groups: a ZP-ICSI and a conventional ICSI group. In the ZP-ICSI group, spermatozoa for injection were selected after ZP-sperm incubation and spermatozoa that were tightly bound to the ZP were used for ICSI (ZP-ICSI). Clinical outcomes of ZP-ICSI were compared with the outcomes of traditional scientist-selected sperm injection (conventional ICSI). Results did not show any significant difference in fertilization, pregnancy, implantation and take-home-baby rates between conventional ICSI and ZP-ICSI. However, when data relative to patients who received ZP-ICSI were analyzed, an interesting result was observed: higher sperm concentration and morphology correlated with higher ZP-sperm binding. Additionally, patients with higher ZP-sperm binding seem to have improved pregnancy and take-home-baby rates. In conclusion, this study shows that ZP-ICSI is not a superior method compared with conventional ICSI. However, clinical ICSI outcomes were apparently improved in the presence of good ZP-sperm binding. We therefore speculate that sperm competence to ICSI could be reduced when the sperm's ability to bind the ZP is impaired.

Purpose The aim of the present randomized, comparative study was to evaluate the effect of reduced culture volumes on sibling human embryo development. Methods Firstly, sibling injected oocytes obtained from 88 out of 165 consenting couples undergoing infertility treatment were cultured either in large (35 μl) or in small drops (15 μl) of culture medium. Secondly, sibling injected oocytes from 77 couples were cultured either in large (35 μl) or in mini drops (7 μl). Embryo quality on day-2 and day-3 and blastocyst formation rate on day-5 were evaluated. Results No statistically significant difference in terms of embryo quality was detected comparing embryos cultured either in large (35 μl) or small (15 μl) drops until blastocyst stage. Similarly, no difference appeared between large (35 μl) or mini (7 μl) drops until day-3, however a significantly higher blastocyst formation rate was observed in mini (7 μl) drops on day-5. Conclusions Reduced culture volume seems not to influence early embryo development but a reduction of medium appears to positively affect blastocyst development. This supports the hypothesis that the pre-implantation embryo produces autocrine factors which exert a positive effect on embryo development when culture is performed in a reduced volume.

Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting a mutual association between nutrition and female fertility. Different “fertile” dietary patterns have been studied; however, in humans, conflicting results or weak correlations are often reported, probably because of the individual variations in genome, proteome, metabolome, and microbiome and the extent of exposure to different environmental conditions. In this scenario, “precision nutrition”, namely personalized dietary patterns based on deep phenotyping and on metabolomics, microbiome, and nutrigenetics of each case, might be more efficient for infertile patients than applying a generic nutritional approach. In this review, we report on new insights into the nutritional management of infertile patients, discussing the main nutrigenetic, nutrigenomic, and microbiomic aspects that should be investigated to achieve effective personalized nutritional interventions. Specifically, we will focus on the management of low-grade chronic inflammation, which is associated with several infertility-related diseases.