Infertility is a growing global phenomenon affecting millions of individuals and is characterized by multifactorial causes, including both lifestyle and environmental factors. These include smoking, chronic exposure to environmental pollutants, stress, excessive caffeine or alcohol intake, drug use, improper eating habits and physical inactivity. The potential to modify these behaviors has gained increasing interest due to its impact on reproductive health and its role in mitigating infertility. Preconception counseling has also emerged as a fundamental strategy, providing education and risk assessments to improve pregnancy outcomes. Among lifestyle factors, nutrition, body composition and physical activity significantly influence female fertility, emphasizing the strong connection between metabolism and reproductive function. Supplementation with anti-inflammatory nutrients, such as omega-3 polyunsaturated fatty acids (n-3 PUFAs), a key component of the Mediterranean diet, may offer benefits for female fertility, partially through the modulation of gene expression in reproductive tissues. However, the specific mechanisms linking diet and fertility remain unclear. The primary objective of this review is to explore how the modification of selected lifestyle factors, with particular reference to dietary habits, may positively influence the female reproductive system and improve fertility and pregnancy-related outcomes.

Expanded carrier screening (ECS) has emerged as a cornerstone of reproductive genetics, enabling the identification of couples at risk of transmitting autosomal recessive and X-linked disorders. Advances in next-generation sequencing and the increasing adoption of exome- and genome-based strategies have greatly expanded its clinical scope. However, despite existing national and international recommendations, substantial heterogeneity remains in gene panel composition, inclusion criteria, and interpretation frameworks. A key novelty of the current genomic era is the availability of large, publicly accessible human genome datasets encompassing broader ancestral diversity. These resources are transforming our understanding of variant frequencies and disease penetrance across populations, supporting the development of evidence-based and ancestry-informed gene panels. In parallel, recent studies investigating the genetic contribution of pathogenic variants to euploid pregnancy losses are opening new perspectives for ECS. Incorporating genes associated with lethal conditions in utero may enhance the predictive power of screening and deepen our understanding of reproductive outcomes, while also demanding careful consideration of clinical validity and counseling implications. This mini-review synthesizes current evidence on ECS, examines ongoing interpretive and implementation challenges, and discusses how population-scale genomic resources and emerging data on reproductive lethality are shaping the next generation of evidence-based carrier screening.

To evaluate the cost-effectiveness of including embryos derived from atypically-pronucleated zygotes (APZs) in IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A), compared with standard use of only typically fertilised (2PN) embryos. Model-based cost-effectiveness analysis using retrospective clinical data. Data were derived from two clinical embryology datasets from a private IVF centre in Italy, comprising 8,334 intracytoplasmic sperm injection (ICSI) cycles with PGT-A (2015-2022) and 826 ICSI cycles with time-lapse monitoring (2013-2020). A decision-tree model compared two IVF strategies over up to two treatment cycles: (1) standard selection of euploid blastocysts derived exclusively from 2PN zygotes and (2) inclusion of PGT-A-confirmed euploid blastocysts derived from APZs (1PN or ≥3PN) in addition to 2PN embryos. The primary effectiveness outcome was the probability of achieving at least one live birth per treatment pathway, and costs reflected patient out-of-pocket expenses. Incremental cost-effectiveness ratios (ICERs) were calculated against a patient-derived willingness-to-pay (WTP) threshold of €422.25 per 1% absolute increase in live-birth probability. Deterministic (±20% parameter variation) and probabilistic (10,000 Monte Carlo simulations) sensitivity analyses evaluated parameter uncertainty and the robustness and transferability of results across clinical and economic settings, with subgroup analyses by maternal age and embryo availability. Inclusion of APZ-derived euploid blastocysts increased cumulative live-birth probability from 0.7294 to 0.7436 (absolute increase 1.42%) while marginally reducing mean treatment cost (€12,737.92 vs €12,749.49), resulting in a cost saving of €11.57 per couple. Across all sensitivity analyses and subgroups, the APZ-inclusive strategy consistently demonstrated higher effectiveness with lower costs or favourable ICERs, remaining economically dominant or cost-effective within the predefined WTP threshold. Notably, higher treatment costs further enhanced the relative cost-effectiveness of APZ utilisation by increasing the economic value of incremental gains in live-birth probability. Inclusion of PGT-A-confirmed euploid APZ-derived blastocysts improves IVF live-birth outcomes at lower or comparable cost and remains cost-effective across diverse clinical and economic scenarios. This is particularly relevant in healthcare systems with higher IVF and PGT-A costs, supporting routine integration of APZ-derived embryos as a generalisable and economically efficient approach.

Background: Polygenic embryo screening (PES) has recently become available to in-vitro fertilization (IVF) patients, allowing them to evaluate the genetic risk of each of their embryos for polygenic conditions such as heart attack or diabetes. Initial modeling predicted that transferring the embryo with the lowest genetic risk for one or more diseases would substantially reduce prevalence in the next generation, with relative risk reductions up to 50%. However, these models assumed the availability of a prespecified number of embryos and that the embryo with the most favorable polygenic risk is born once transferred to the uterus. In reality, a large percentage of embryo transfers do not lead to live births, and IVF frequently results in no or only a single live birth. Methods: To quantify the expected risk reduction in the context of IVF, we used two datasets: 6944 ovarian stimulation cycles from 4452 Italian infertility patients and 2138 stimulation cycles of egg donors. In both datasets, we simulated the hypothetical application of PES in these cycles by assigning patients and their embryos randomly drawn polygenic risk scores for a given disease, assuming that embryos have been transferred in increasing order of their risk, and tracing their birth outcomes. We then compared the risk of the embryo born after hypothetical PES to the risk of an embryo born without PES. We either considered only completed cycles or integrated over possible birth outcomes of non-transferred embryos in incomplete cycles. Results: In stimulation cycles in infertility patients in which all embryos have been transferred and at least one child was born, we estimate that PES will result in relative risk reductions of just ≈1-3%. In an intention-to-screen analysis of all completed cycles (regardless of birth outcomes), relative risk reductions are under 0.5%. The risk reductions increase, as expected, with more euploid blastocysts and with younger maternal age. Including incomplete cycles (in which not all embryos have been transferred) increases risk reductions to ≈2-5%, due to the availability of more euploid blastocysts and a higher live birth rate per transfer in these cycles. Pooling all embryos from all cycles of the same patient increases risk reductions to ≈5-10%. Relative risk reductions in egg donor cycles reach ≈20% even with a single stimulation cycle per donor. Conclusions: With the exception of particularly good-prognosis patients or cycles, typical infertility patients would benefit little from PES. In fertile patients, as represented by egg donors, PES is predicted to achieve greater relative risk reductions. However, even though these reductions are still substantially lower than prior estimates that did not account for realistic live birth rates. Ethical, social, and clinical issues associated with offering PES in the general population should be prioritized in future research.