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Abstract Background The AZFc region of the human Y chromosome is a highly recombinogenic locus containing multi-copy male fertility genes located in repeated DNA blocks (amplicons). These AZFc gene families exhibit slight sequence variations between copies which are considered to have functional relevance. Yet, partial AZFc deletions yield phenotypes ranging from normospermia to azoospermia, thwarting definite conclusions on their real impact on fertility. Results The amplicon content of partial AZFc deletion products was characterized with novel amplicon-specific sequence markers. Data indicate that partial AZFc deletions are a male infertility risk [odds ratio: 5.6 (95% CI: 1.6–30.1)] and although high diversity of partial deletion products and sequence conversion profiles were recorded, the AZFc marker profiles detected in fertile men were also observed in infertile men. Additionally, the assessment of rearrangement recurrence by Y-lineage analysis indicated that while partial AZFc deletions occurred in highly diverse samples, haplotype diversity was minimal in fertile men sharing identical marker profiles. Conclusion Although partial AZFc deletion products are highly heterogeneous in terms of amplicon content, this plasticity is not sufficient to account for the observed phenotypical variance. The lack of causative association between the deletion of specific gene copies and infertility suggests that AZFc gene content might be part of a multifactorial network, with Y-lineage evolution emerging as a possible phenotype modulator.

Aim: Several factors have been proposed to influence human embryo freeze/thaw cryodamage, as well as the outcome of frozen embryo transfers (FET). At our center, the interesting observation that embryos thawed on the same day of transfer resulted in higher pregnancy rate lead us to retrospectively evaluate the influence of the post-thaw culture period on the implantation and developmental potential of cleavage stage embryos. Method: In this study, 265 FET cycles were allocated to one of two study groups, depending on the post-thaw culture period: (1) the long (18-24 h), or (2) the short (2-5 h) culture group. Groups were compared regarding implantation rate (IR) and live birth rate per embryo transferred (LBR/E). This statistical comparison was adjusted to possibly biasing factors such as: maternal age at oocyte pick-up, number of transferred embryos, developmental day at freezing, blastomere survival after thawing, catheter used for transfer and year of procedure. The importance of post-thaw mitosis assessment was also evaluated. Results: IR and LBR/E were inversely related to the post-thaw culture period, as the FET outcome after a short post-thaw culture period is significantly higher than after a long period (IR: 10.9% vs 4.9%, OR = 2.321, p = 0.039; LBR/E: 9.6% vs 2.9%, OR = 2.963, p = 0.035). This difference was not influenced by the possibly confounding factors mentioned above. Additionally, no advantage was found if only embryos with observed mitotic activity were transferred in comparison to transfers where mitotic resumption was not evaluated (IR: 6.5% vs 11.5%, OR = 1.985, p = 0.197; LBR/E: 5.2% vs 10.0%, OR = 1.966, p = 0.262). Conclusion: In this study we identified an association between a long post-thaw culture period and a loss of implantation and developmental potential of cleavage stage human embryos. Moreover, this study raises the interesting proposal that, in order to maintain acceptable post-thaw developmental potential, extending embryo culture should be avoided, even to document mitotic resumption. [ABSTRACT FROM AUTHOR]

Study Question: What are the current national medically assisted reproduction (MAR) data collection systems across EU Member States, and how can these countries contribute to a unique, cycle-by-cycle registry for the European Monitoring of Medically Assisted Reproduction (EuMAR) project?, Summary Answer: The study identified significant variation in MAR data collection practices across Member States, with differences in data types, collection methods, and reporting requirements; the EuMAR project emerges as an opportunity to enhance data standardization and improve MAR data collection in the EU., What Is Known Already: There is a need for new approaches in MAR data collection that include long-term and cross border follow-up. The EuMAR project intends to establish a unified, cycle-by-cycle registry of data on MAR treatments in EU countries, from which accurate cumulative outcomes can be calculated., Study Design, Size, Duration: This cross-sectional study involved a survey and interviews with stakeholders from 26 EU Member States conducted in 2023 over a period of seven months., Participants/materials, Setting, Methods: Representatives from national competent authorities and professional associations involved in MAR data collection in EU countries were invited to complete the survey and interviewed to assess current data flows, information requirements, and their interest in the EuMAR project., Main Results and the Role of Chance: Half of the participating countries reported having a national MAR registry with cycle-by-cycle data (n = 13), while 31% reported having a national registry with aggregated data (n = 8) and 19% reported having no national registry (n = 5). Of the countries with a national cycle-by-cycle registry, eight countries collect identifiable data, five countries collect pseudonymized data, and one country collects fully anonymized data. Informed consent is required in 10 countries. The main advantages that participants expected from a European registry like EuMAR were the possibility of obtaining national statistics in the absence of a national registry and improving the calculation of cumulative outcomes., Limitations, Reasons for Caution: The results of the study are based on self-reported data, which may be subject to bias, however, the validity of the collected information was verified with different means, including follow-up calls for clarifications and sharing final transcript reports. The feasibility of the proposed data flow models will be tested in a pilot study., Wider Implications of the Findings: Despite the heterogeneity of data collection practices across EU countries, the results show that stakeholders have high expectations of the benefits that the EuMAR registry can bring, namely the improvement of data consistency, cross-border comparability, and cumulative live birth rates, leading to better information for patients, health care providers and policy makers., Study Funding/competing Interest(s): The EuMAR project was co-founded by ESHRE and the European Commission (101079865-EuMAR-EU4H-2021-PJ2). No competing interests were declared., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)