From a single child to family planning: determinants of returning to ART to build the desired family in a monocentric Italian cohort

Abstract STUDY QUESTION What factors are associated with couples' returning to have ART after having a first ART-conceived child? SUMMARY ANSWER Among returning couples, return was independently associated with younger maternal age, a singleton rather than twin first birth, and the availability of cryopreserved embryos and/or oocytes. WHAT IS KNOWN ALREADY Long-term family-building trajectories after an initial ART birth remain poorly characterized, despite being essential for counselling couples aiming to achieve their intended family size in the context of declining fertility rates and delayed parenthood in high-income countries. Age-related biological constraints, limited fertility awareness, and overestimation of ART effectiveness contribute to unrealized reproductive intentions; nevertheless, the determinants of couples’ return to ART after a first live birth and their association with subsequent live births remain largely unexplored. STUDY DESIGN, SIZE, DURATION Monocentric retrospective cohort study of 5,852 couples achieving a first ART-conceived live birth (index birth) from cycles initiated between 2010 and 2020, with follow-up through December 2024 to evaluate return to ART for further family building and subsequent live birth outcomes. As data were retrieved from a complete institutional database, no loss to follow-up occurred. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples achieving a first ART-conceived live birth between 2010 and 2020 at a single fertility center in Italy were included. Donor cycles and PGT were excluded. Participants were followed until December 2024. Couples were classified as returners or non-returners and stratified according to cryopreserved oocyte and/or embryo storage status. Outcomes of interest were return to ART for further family building and live birth achievement among returning couples. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 1,978 couples (33.8%) returned for further ART cycles; among returners, a second live birth was achieved by 49.3%. Return was significantly higher among couples with cryopreserved reproductive material compared with those without stored embryos or oocytes (41.0% vs 23.3%, p < 0.001), particularly among couples with cryopreserved embryos only or with both embryos and oocytes stored (41.6% and 44.3%, respectively). At multivariable analysis, independent predictors of return included lower maternal age (aOR 0.93 per year increase), male-factor infertility (aOR 1.26), singleton rather than twin first live birth (aOR 0.12 for twins), presence of cryopreserved material (aOR 2.21), and higher gestational age at delivery (aOR 1.03). Among couples who returned, the proportion achieving a second live birth varied markedly by cryopreservation status, ranging from 39.5% in couples without stored material to 64.6% in those with both embryos and oocytes available (p < 0.001). Few couples returned after a second live birth; however, the live birth proportion for a third child exceeded 50% when both embryos and oocytes were present. LIMITATIONS, REASONS FOR CAUTION Psychosocial and economic determinants potentially influencing non-returners were not assessed, data on spontaneous pregnancies were unavailable, and cross-centre migration could not be excluded. In addition, this monocentric study was conducted in Italy, where regulatory and cultural aspects of ART may influence treatment access and reproductive decision-making, potentially limiting generalizability. WIDER IMPLICATIONS OF THE FINDINGS ART counselling may benefit from being tailored to couples’ long-term reproductive goals. Treatment strategies aimed at increasing the number of embryos and/or oocytes cryopreserved at younger ages can facilitate their use at more advanced reproductive ages. This may help couples achieve their desired family size. FUNDING This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors, and was supported by institutional resources from the Division of Gynecology and Reproductive Medicine, Department of Gynecology, Fertility Center, IRCCS Humanitas Research Hospital, Rozzano. Milan, Italy. DISCLOSURES The authors declare no competing interests. TRIAL REGISTRATION NUMBER NCT07458165