{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:50:27Z","timestamp":1791348627439,"version":"4.3.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Does advanced paternal age affect miscarriage and\/or live birth outcomes following the first transfer attempt in oocyte donation cycles?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Paternal age has a gradual but cumulative effect that becomes apparent above 45\u2009years of age, where it evidently increases miscarriage rates and decreases live birth rates following the first transfer in oocyte donation cycles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS ALREADY KNOWN<\/jats:title>\n                    <jats:p>Donor oocyte cycles are becoming a common strategy for addressing female age-related infertility, offering high success rates (\u223c60% ongoing pregnancies) attributed to superior oocyte quality. However, male age-related effects on the success of ART have received less attention. In autologous cycles, advanced paternal age has been associated with poor clinical outcomes. However, disentangling its effects from female factors remains challenging. Oocyte donation cycles offer a useful model for studying the impact of male factors on ART outcomes, eliminating biases related to female age and underlying diagnoses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>Multicentric, retrospective study of 1606 first oocyte donation cycles performed between January 2019 and December 2023, across seven IVF centers. Only ICSI cycles with fresh donor oocytes, inseminated with partner sperm were included. Only the first single blastocyst transfers (fresh or frozen) were considered. Cycles with abnormal male karyotypes, sperm obtained from testicular biopsy, donor sperm, frozen oocytes, in vitro matured oocytes or preimplantation genetic testing (PGT) were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Paternal age was assessed as a continuous variable, in multiple age strata (&amp;lt;35, 35\u201340, 40\u201345, and &amp;gt;45\u2009years) and dichotomized into \u226445 and &amp;gt;45\u2009years. Fertilization rates, the number of usable blastocysts and blastocyst utilization rates were assessed. Clinical outcomes included clinical pregnancy, miscarriage, and live birth rates. P\u2009&amp;lt;\u20090.05 was considered statistically significant after univariate tests and a multivariable logistic analysis adjusting for recipient and oocyte age, male and recipient BMI, fresh\/frozen semen for insemination, number of mature (MII) oocytes injected, embryo morphology grade, and fresh\/frozen embryo transfer. An exploratory analysis comparing Kaplan\u2013Meier curves for subsequent embryo transfers was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Within the cohort of 1606 patients who underwent a first oocyte donation cycle, the mean female recipient age (\u00b1SD) was 43.2 (\u00b14.1) years, the mean oocyte donor age (\u00b1SD) was 26.2 (\u00b14.2) years, and the mean paternal age (\u00b1SD) was 43.1 (\u00b16.0). Paternal age as a continuous variable showed a modest but gradual reduction in live birth without a discrete transition at any specific age. Stratifying paternal age (&amp;lt;35, 35\u201340, 40\u201345, and &amp;gt;45\u2009years) showed a trend to reduced odds of live birth when comparing the &amp;gt;45\u2009years group to the &amp;lt;35\u2009years group (aOR = 0.66; 95% CI 0.43\u20131.02; P\u2009=\u20090.06). To explore cumulative effects of paternal age in ART outcomes, we decided to compare in more detail two groups: \u226445 and &amp;gt;45\u2009years. In the \u226445\u2009years group (n\u2009=\u20091031), the mean paternal age (\u00b1SD) was 39.7 (\u00b14.1) years, while in the &amp;gt;45\u2009years group (n\u2009=\u2009575), it was 49.1 (\u00b13.7). No differences were observed in oocyte donor age, number of oocytes fertilized, or number of blastocysts obtained among paternal age groups. Interestingly, miscarriage rate was 25.4% (67\/264) in the &amp;gt;45\u2009years group and 15.6% (81\/518) in the \u226445\u2009years group. The differences were statistically significant (P\u2009=\u20090.001). Consequently, the live birth rate was also reduced to 34.3% in &amp;gt;45\u2009years versus 42.4% in \u226445\u2009years (197\/575 vs 437\/1031; P\u2009=\u20090.001). These results were further confirmed in the adjusted analysis, where &amp;gt;45\u2009years of paternal age remained associated with a statistically significant higher miscarriage rate (aOR = 1.86, [95% CI: 1.25\u20132.76], P\u2009=\u20090.002) and a statistically significant lower live birth rate (aOR = 0.72, [95% CI: 0.57\u20130.91], P\u2009=\u20090.005). In an exploratory analysis, the &amp;gt;45\u2009years group also showed a lower probability of achieving a live birth in subsequent embryo transfers compared to the \u226445\u2009years old group (P\u2009=\u20090.003).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>This study is limited by its retrospective nature. No data on the chromosomal status of the blastocysts transferred was available. Caution is warranted when generalizing results to different embryo transfer strategies or other patient populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Our results indicate that paternal age can affect clinical outcomes in oocyte donation cycles. If confirmed in a larger cohort of patients, these results would suggest considering patient counseling in relation to advanced paternal age when delaying childbearing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>No funding was received from agencies in the public, commercial, or not-for-profit sectors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCLOSURES<\/jats:title>\n                    <jats:p>The authors declare no conflict of interest related to the current study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deag159","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:56:17Z","timestamp":1790164577000},"source":"Crossref","is-referenced-by-count":0,"title":["Advanced paternal age affects miscarriages and live birth outcomes in oocyte donation cycles"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2870-0140","authenticated-orcid":false,"given":"Juan J","family":"Fraire-Zamora","sequence":"first","affiliation":[{"name":"EUGIN Group, R&D , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Guglielmo","sequence":"additional","affiliation":[{"name":"Clinica EUGIN , Taranto,","place":["Italy"]},{"name":"Clinica EUGIN , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bartoli","sequence":"additional","affiliation":[{"name":"Clinica EUGIN , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Valerio","sequence":"additional","affiliation":[{"name":"Clinica EUGIN , Modena,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Maruccia","sequence":"additional","affiliation":[{"name":"Andrology Unit, Clinica EUGIN , Milano,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Romano","family":"Mignini Renzini","sequence":"additional","affiliation":[{"name":"Clinica EUGIN , Milano,","place":["Italy"]},{"name":"Clinica EUGIN , Modena,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"De Ponti","sequence":"additional","affiliation":[{"name":"Medical Physics Department, Fondazione IRCCS San Gerardo , Monza,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jos\u00e9","family":"Zamora","sequence":"additional","affiliation":[{"name":"Embryology Laboratory, Clinica EUGIN , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Lafuente","sequence":"additional","affiliation":[{"name":"Andrology Laboratory, Centro de Infertilidad y Reproducci\u00f3n Humana , Barcelona,","place":["Spain"]},{"name":"Andrology Unit, Clinica EUGIN , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Guillen","sequence":"additional","affiliation":[{"name":"EUDONA, Clinica EUGIN , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7030-8281","authenticated-orcid":false,"given":"Amelia","family":"Rodriguez-Aranda","sequence":"additional","affiliation":[{"name":"EUGIN Group, R&D , Barcelona,","place":["Spain"]},{"name":"EUGIN Group, Medical and Scientific Directorate , Barcelona,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5716-4127","authenticated-orcid":false,"given":"Mariabeatrice","family":"Dal Canto","sequence":"additional","affiliation":[{"name":"Clinica EUGIN , Milano,","place":["Italy"]},{"name":"Clinica EUGIN , Modena,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"2026100700013603600_deag159-B1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1093\/humupd\/dmac033","article-title":"Age-associated epigenetic changes in mammalian sperm: implications for offspring health and development","volume":"29","author":"Ashapkin","year":"2023","journal-title":"Hum Reprod Update"},{"key":"2026100700013603600_deag159-B2","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1007\/s10815-023-02714-1","article-title":"Does paternal age affect the live birth rate in donor oocyte cycles? 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