Anne-Bine Skytte

Purpose This study assessed the attitudes of (would-be) recipients of donor sperm and interested persons toward worldwide donor family quota, ideal and acceptable family numbers, reasons for supporting or opposing limits, and willingness to pay for restricted donors. Methods A cross-sectional online survey was conducted between August and September 2025. Univariate and multinomial logistic regression analyses were performed to identify demographic predictors of attitudes toward a worldwide family limit. Results Overall, 70.3% of respondents supported a worldwide donor family quota, 21.6% opposed it, and 7.7% were uncertain. Support was significantly associated with older age, higher education, higher income, European residence, and being a mother of a donor-conceived child. In multinomial analyses, respondents in heterosexual relationships and those living outside Europe were significantly more likely to oppose a worldwide limit. The most frequently cited reason for supporting a limit was concern about accidental romantic relationships between donor half-siblings, followed by concerns about genetic disease transmission and psychosocial harm associated with large donor-sibling groups. Those opposing a worldwide limit most commonly cited reduced access to donor sperm, longer waiting times, and the absence of compelling reasons for a global cap. Five families was the most commonly preferred limit, whereas 15–25 families were more often considered acceptable. Willingness to pay increased as family limits decreased. Conclusion Most respondents supported a worldwide donor family limit, although the principal reasons cited—consanguinity and genetic disease risks—are not supported by current scientific evidence. Policymakers should balance concerns about large same-donor offspring groups against the potential consequences of stricter limits, including reduced access to donor sperm, higher costs, longer waiting times, and diminished reproductive choice.

Purpose: The demand for sperm donation is increasing, yet only a small percentage of applicants are accepted, and little attention has been given to those who are rejected. The application process may reveal new medical or genetic information with potential personal and emotional consequences. The aim of this study was to explore how men experience rejection as sperm donors, including how they cope with the rejection and integrate potential new information into their lives. Methods: We conducted qualitative, in-depth interviews with 19 men rejected as sperm donors. Data was analyzed using thematic analysis. Results: Some men received new medical information that raised significant concerns, particularly regarding their health, fertility, and family. However, for most it was not the reason for rejection that affected them most, but the rejection itself. They had begun to identify as donors, and being turned down felt like a blow to their sense of self. Over time, participants used different coping strategies: information seeking, actionable reasoning, positive reframing, normalizing, and postponing. Although the experience was personally and emotionally challenging for many, it ultimately did not have a lasting negative impact on their lives. Conclusions: Sperm donation is not only a medical act but also tied to social identity, with rejection having personal and emotional consequences. For men whose rejection is based on new medical information that causes significant concerns, sperm banks should support rejected donors and help them exit the process positively. Further research is warranted to find out how this can be done.

The study intended to find out whether sperm and egg donors hold different views on identifiability, information about donor offspring, genetic testing, and extended carrier screening. An online questionnaire was sent to accepted sperm (n = 70) and egg donors (n = 39) from the same gamete bank in the United States 3 years apart (2020 and 2023). Only questions that were identical for both groups were included in the analysis. There were no differences in the donors' reasons for donating: both groups were mainly motivated by the wish to help childless couples, to earn money or a combination of the two. The study was performed in a setting where donors could choose between identity (ID) release or non-ID release donation. Egg donors were equally likely to opt for ID release (69.2%) as sperm donors (73.7%). The only significant difference was that egg donors were more likely than sperm donors to want to know whether the donation resulted in a pregnancy or birth (89.7% vs. 68.4%, p = 0.02). No differences were found in the information they wanted to receive about the offspring. They were also equally likely to be open about their donor status with other people and their own children. Both groups were in favour of genetic testing (92.6% and 82%, respectively) and positive about extended carrier screening (87.2 and 76.3%, respectively). There were few differences in the views and attitudes of egg and sperm donors regarding identity release, information about donor offspring, and extended genetic testing.

Mutations that accumulate in the human male germline with age are a major driver of genetic diversity and contribute to genetic diseases. However, aging-related male germline mutation rates have not been measured directly in germline cells (sperm) at the level of individuals. We developed a study design in which we recalled 23 sperm donors with prior banked samples to provide new sperm samples. The old and new sequential sperm samples were separated by long timespans, ranging from 10 to 33 years. We profiled these samples by high-fidelity duplex sequencing and demonstrate that direct high-fidelity sequencing of sperm yields cohort-wide mutation rates and patterns consistent with prior family-based (trio) studies. In every individual, we detected an increase in sperm mutation burden between the two sequential samples, yielding individual-specific measurements of germline mutation rate. Deep whole-genome sequencing of sequential sperm samples from two individuals followed by targeted validation measured remarkably stable mosaicism of clonal mutations that likely arose during embryonic and germline development, suggesting that age did not substantially impact the diversity of spermatogonial stem cell pools in these individuals. Our application of high-fidelity and deep whole-genome sequencing to sequential sperm samples provides insight into aging-related mutation processes in the male germline.

Mutations accumulate in the genome of every cell of the body throughout life, causing cancer and other diseases^1,2. Most mutations begin as nucleotide mismatches or damage in one of the two strands of the DNA before becoming double-strand mutations if unrepaired or misrepaired^3,4. However, current DNA-sequencing technologies cannot accurately resolve these initial single-strand events. Here we develop a single-molecule, long-read sequencing method (Hairpin Duplex Enhanced Fidelity sequencing (HiDEF-seq)) that achieves single-molecule fidelity for base substitutions when present in either one or both DNA strands. HiDEF-seq also detects cytosine deamination—a common type of DNA damage—with single-molecule fidelity. We profiled 134 samples from diverse tissues, including from individuals with cancer predisposition syndromes, and derive from them single-strand mismatch and damage signatures. We find correspondences between these single-strand signatures and known double-strand mutational signatures, which resolves the identity of the initiating lesions. Tumours deficient in both mismatch repair and replicative polymerase proofreading show distinct single-strand mismatch patterns compared to samples that are deficient in only polymerase proofreading. We also define a single-strand damage signature for APOBEC3A. In the mitochondrial genome, our findings support a mutagenic mechanism occurring primarily during replication. As double-strand DNA mutations are only the end point of the mutation process, our approach to detect the initiating single-strand events at single-molecule resolution will enable studies of how mutations arise in a variety of contexts, especially in cancer and ageing.

Has there been variation in semen quality among men applying to be sperm donors (i.e. donor candidates) in Denmark in recent years (2017–2022)? The motile sperm concentration and total motile sperm count (TMSC) in ejaculates—both measures of sperm quality—declined by as much as 22% from 2019 to 2022. Questions remain about whether human semen quality has declined in recent years. Whilst some studies provide evidence for a decline in human semen quality, these findings have been disputed owing to potential biases in the populations studied or in the methods used to measure semen quality. Resolution of this issue has important implications for human fertility, as well as for those involved in the recruitment of sperm donors for use in medically assisted reproduction. We obtained data on the semen quality of ejaculates previously collected from 2017 to 2022 at sperm bank locations in four cities in Denmark: Aarhus, Aalborg, Copenhagen, and Odense. Our study focuses on the single semen samples provided by 6758 donor candidates aged between 18 and 45 years old to determine whether their sperm quality met a minimum criterion for them to be accepted as sperm donors. All ejaculates were analyzed within 1 hour of production. Semen volume (ml) was estimated by weight and both the concentration (10⁶/ml) of sperm as well as the concentration of motile sperm (World Health Organization grades a and b) were measured using the same protocols and computer-assisted semen analysis system across all years at each site. Statistical analyses of the semen variables were controlled for age and donation site, as well as the average monthly high temperature when the ejaculate was produced. From 2017 to 2019, semen volume, sperm concentration, and total sperm count in the ejaculates of donor candidates increased by 2–12%. Then, from 2019 to 2022, sperm concentration and total sperm count changed by 0.1–5% from year to year, but none of those changes were statistically significant. In contrast, both motile sperm concentration and TMSC declined significantly, by 16% and 22%, respectively, between 2019 and 2022. Thus, the concentration of motile sperm in donor candidates declined from 18.4 [95% CL: 17.0, 20.0] million/ml in 2019 to 15.5 [14.4, 16.7] million/ml in 2022, and TMSC declined from 61.4 [55.8, 67.5] million per ejaculate in 2019 to 48.1 [44.1, 52.4] million in 2022. We cannot determine from the available data the causes of the decline in semen quality of donor candidates from 2019 to 2022. However, as this period coincides with lockdowns and changes in work patterns during the coronavirus disease 2019 pandemic, it is possible that changes in motile sperm concentration and TMSC were the result of changes in the lifestyles of the men whose semen was analyzed. Men providing initial semen samples at sperm banks, when applying to be sperm donors, are a useful population in which to monitor changes in human semen quality over time. Our results have implications for human fertility and the recruitment of sperm donors for medically assisted reproduction, where motile sperm concentration is an essential selection criterion because it influences fertility. We suggest that gathering health and lifestyle data on donor candidates at sperm banks might help to identify causal factors for the decline of sperm quality that could be addressed and intervention, if desired, could be personalized for each accepted donor. No external funding was obtained for this study. E.L. and A.-B.S. are employees of Cryos International. AP reports paid consultancy for Cryos International, Cytoswim Ltd, Exceed Health, and Merck Serono in the last 2 years of this study, but all monies were paid to the University of Sheffield (former employer). AP is also an unpaid trustee of the Progress Educational Trust (Charity Number 1139856). RM declares support from Cryos International to present results of this research at ESHRE 2023. None of the authors were directly involved in the collection or physical analysis of semen samples. N/A.

Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules (‘single duplexes’) to discern the true mutations on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than duplex sequencing. CODEC revealed mutation frequencies of 2.72 × 10⁻⁸ in sperm of a 39-year-old individual, and somatic mutations acquired with age in blood cells. CODEC detected genome-wide, clonal hematopoiesis mutations from single DNA molecules, single mutated duplexes from tumor genomes and liquid biopsies, microsatellite instability with 10-fold greater sensitivity and mutational signatures, and specific tumor mutations with up to 100-fold fewer reads. CODEC enables more precise genetic testing and reveals biologically significant mutations, which are commonly obscured by NGS errors.

People are becoming parents later in life and with increased parental age adverse reproductive outcomes are increased. Cryopreservation of gametes enables men and women to protect, prolong and seemingly preserve their fertility. Social freezing is an increasingly popular way of cryopreservation. During the COVID-19 pandemic, the gamete bank Cryos International experienced an increased influx of men wanting to deposit their sperm. A questionnaire-based study was initiated to investigate their motivations for doing so. The results showed that the men chose to deposit mainly due to medical indications (e.g. cancer and sex change), and that the COVID-19 pandemic had no significant influence on the reason for banking their sperm. Investigations into the altruistic reasons for depositing sperm (i.e. caring for reproductive masculinity) could shed new light onto the sparsely studied topic of male reproductive journeys.