The Unfinished Journey:multifactorial analysis of untransferred cycles in IVF

The Unfinished Journey:multifactorial analysis of untransferred cycles in IVF | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Unfinished Journey:multifactorial analysis of untransferred cycles in IVF Qi Jin, Xiaohua Jiang, Shun Bai, Lu Zong, Shengxia Zheng, Limin Wu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7368769/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract In vitro fertilization (IVF) cycles that do not progress to embryo transfer—termed untransferred cycles—are frequently overlooked in outcome reporting, despite their potential clinical and psychosocial implications.This 14-year retrospective study analyzed 30,731 untransferred IVF cycles from a tertiary fertility center (2011–2025). Cycles were categorized by type (fresh vs. frozen-thawed) and by cause (medical vs. non-medical). Reasons included OHSS risk, no embryos or oocytes, failed fertilization, uterine abnormalities, and patient-level factors. Temporal trends were also examined.Of 81,723 IVF cycles, 37.6% were untransferred. Fresh cycles accounted for 98.1% of these, with 90.2% attributed to medical reasons. Frozen-thawed cycles showed a more balanced distribution of causes. Over time, OHSS-related cancellations declined, while uterine cavity issues and PGT-related interruptions increased. Personal, psychological, and social factors accounted for nearly 10% of untransferred cycles.The journey from IVF initiation to embryo transfer is influenced by biological, emotional, and social complexities. Recognizing and addressing these multidimensional barriers may reduce untransferred cycles, enhance patient-centered care, and prevent unnecessary resource loss. IVF cycle discontinuation Untransferred cycles Medical and non-medical reasons Assisted reproductive technology Trend analysis Figures Figure 1 Figure 2 Background Although embryo quality, implantation rate, and live birth rate are key metrics of concern in in vitro fertilisation (IVF) treatment, another equally important yet rarely discussed endpoint is the number of cycles that fail to reach the embryo transfer stage. These “non-transfer cycles”—including cases terminated for medical reasons and those voluntarily terminated by patients—are typically not included in treatment outcome metrics [ 1 ]. However, they represent cycle interruptions, cancellations within IVF programmes, potentially indicating critical attrition points in the treatment pathway and impacting clinical efficiency and patient experience. Recent studies suggest that demographic and systemic factors such as race, economic stress, and inadequate insurance coverage may lead to patients prematurely discontinuing IVF treatment [ 2 ]. Beyond individual burdens, IVF treatment discontinuation is also associated with reduced cumulative live birth rates, suggesting its significant negative impact on reproductive success rates at the population level [ 3 ]. Notably, early treatment discontinuations and unplanned freeze-all cycles are of particular concern. These events not only prolong the overall treatment timeline and entail substantial emotional stress and financial burdens for patients, but may also result in inefficient allocation of limited healthcare resources. Therefore, comprehensive knowledge of the multifactorial factors contributing to untransferred IVF cycles is thus crucial for informing more holistic and equitable clinical strategies, enhancing patient-centered interventions, and ultimately optimizing reproductive outcomes and healthcare resource efficiency. Methods Study design and setting This retrospective study was conducted over a 14-year period, from April 2011 to April 2025, at a single tertiary fertility center. The objective was to analyze all in vitro fertilization (IVF) cycles that were initiated but did not result in embryo transfer, defined herein as "untransferred cycles." Definition of untransferred cycles Untransferred cycles were defined as IVF treatment cycles in which couples completed the registration process and initiated clinical or laboratory procedures but ultimately did not proceed to embryo transfer. These cases were included regardless of whether the interruption occurred before or after oocyte retrieval. Classification of reasons for non-transfer Each untransferred cycle was classified based on two main criteria: the cycle type (fresh vs. frozen-thawed) and the underlying reason for non-transfer. Reasons were broadly grouped into two categories. Medical interruptions encompassed clinical conditions such as poor ovarian response, high risk of ovarian hyperstimulation syndrome (OHSS), failed fertilization, absence of oocytes or embryos, and contraindications to embryo transfer due to uterine or endometrial abnormalities. Non-medical withdrawals referred to patient-driven discontinuation, including personal reasons, psychological stress, socioeconomic pressures, or partner-related issues. Data validation and stratification To ensure accuracy, all classifications were independently reviewed by two experienced reproductive clinicians. Discrepancies were resolved through discussion and consensus. Further stratification of cases was performed to examine distributions across cycle types, specific interruption causes, and temporal trends spanning the 14-year period. The analysis aimed to describe patterns without hypothesis testing. Results Overall cycle analysis Out of 81,723 IVF cycles recorded during the study period, 30,731 cycles (37.6%) were identified as untransferred. Among these, 98.13% (n = 30,155) were fresh cycles, while only 1.87% (n = 576) involved frozen-thawed embryo transfers. This distribution reflects a higher susceptibility of fresh cycles to clinical or patient-related disruptions (Fig. 1). Fresh cycle outcomes In fresh IVF cycles, medical factors were the leading cause of cycle interruption, accounting for 90.21% (n = 27,202) of untransferred cases (Table 1). The most prevalent medical reasons included high OHSS risk (26.54%), the use of progesterone-primed ovarian stimulation (PPOS) protocols (20.8%), uterine cavity abnormalities (14.88%), and luteal phase stimulation (9.57%). Non-medical causes were less common, constituting 9.79% (n = 2,953), with personal reasons (82.15%) and social factors (10.9%) being the dominant subcategories. Temporal trends in fresh cycles Analysis of annual patterns revealed a decline in OHSS-related cancellations after 2019, suggesting improvements in ovarian stimulation safety and clinical monitoring. Conversely, uterine cavity abnormalities became increasingly prominent in recent years, likely due to more widespread hysteroscopic evaluations. The application of PPOS protocols rose steadily from 2014, replacing luteal-phase stimulation, which showed a marked decrease after 2016 before plateauing (Fig. 2A). Other trends included a drop in unusable embryos after 2021 and stabilization in cases of unusable oocytes, reflecting stable laboratory and retrieval practices. Interruptions linked to elevated serum progesterone levels began to rise from 2021 onward. Discontinuations due to preimplantation genetic testing (PGT) increased sharply starting in 2019 and accelerated further after 2022 (Fig. 2B). Frozen-thawed cycle outcomes Among the 576 untransferred frozen-thawed cycles (Table 2), 71.0% (n = 409) were due to medical factors, while 29.0% (n = 167) were attributed to non-medical causes. The primary medical issues were embryonic arrest (51.34%), uterine abnormalities (11.0%), and abnormal laboratory results (9.29%). Non-medical factors included upper respiratory infections (34.73%), personal reasons (28.14%), and COVID-19 infections (21.56%), which reflect broader social and public health influences on fertility treatment adherence during the pandemic years. Discussion Despite significant advancements in assisted reproduction,such as ovarian stimulation, laboratory techniques, and cycle monitoring, a significant proportion of IVF cycles are discontinued even before embryo transfer. Our findings highlight that medical factors continue to dominate the reasons for untransferred fresh cycles,temporal trend analysis reveals shifting clinical patterns over time.These shifts reflect both improvements in IVF safety and emerging challenges requiring targeted interventions. Our analysis demonstrates that the consistent decline in cycle cancellations due to OHSS highlights the efficacy of optimized stimulation protocols. Temporal trends further reflect the evolving landscape of clinical decision-making, including the widespread adoption of PPOS and luteal-phase stimulation protocols, supporting individualized and flexible cycle management.This progression aligns with global initiatives to enhance IVF safety[ 4 ], as evidenced by the ESHRE guidelines, which strongly recommend GnRH antagonist protocols rather than GnRH agonist protocols to improve safety in IVF practice[ 5 ]. Uterine-cavity factors accounted for 14.88% of fresh cycles without embryo transfer in our cohort, primarily involving polyps, adhesions, and chronic endometritis. This increasing detection is likely attributed to the routine application of hysteroscopy, which enables the identification of subtle endometrial abnormalities that might otherwise go unnoticed. Recent studies have shown that hysteroscopy plays an important role in managing repeated implantation failure (RIF) patients with adenomyosis and in diagnosing retained products of conception following early pregnancy loss after IVF [ 6 , 7 ]. Early hysteroscopic intervention for known intrauterine abnormalities before ovarian stimulation may help reduce the risk of cycle interruption and improve treatment continuity. We observed a sharp increase in PGT cycles, reflecting both advancements in reproductive genetics and rising patient demand for chromosomal and monogenic screening. However,studies have suggested that while PGT-A may benefit specific subgroups—such as women of advanced maternal age (≥ 38 years) or those with decreased ovarian reserve resulting in low oocyte yield (≤ 3 oocytes)—by improving clinical pregnancy rates per transfer, it does not significantly increase live birth rates[ 8 ]. Moreover, current evidence does not support the routine use of PGT-A as a standard adjunct to IVF for the general population[ 9 ]. The frequencies of no usable oocytes and embryos have remained within a relatively stable range over time, suggesting consistent performance in oocyte retrieval and laboratory procedures. Meanwhile, the upward trend in progesterone-related cancellations indicates the need for closer monitoring and management of luteal-phase hormonal profiles during stimulation. Beyond medical causes, nearly one in ten untransferred cycles are still attributable to personal, psychological, or social factors, underscoring the importance of holistic patient support throughout treatment. Psychosocial factors play a critical role in early treatment discontinuation, as evidenced by our finding that nearly 10% of untransferred fresh cycles cited personal and social reasons as a key reason. Recent studies highlight the complexity of infertility-related stress: Jin et al. [ 10 ]revealed that men and women experience and cope with this stress differently, underscoring the importance of couple-based psychological interventions.In the untransferred fresh cycles, it was reported that more women were emotionally affected by the waiting time from oocyte pick-up to embryo transfer. Additionally, women were generally more distressed than their partners[ 11 ]. These insights, along with Scognamiglio et al. [ 12 ], who found psychological distress often co-occurred with factors like dissatisfaction with medical staff or relational instability.Collectively, these findings underscore the necessity of integrating comprehensive psychosocial support and interventions to reduce early dropouts and improve overall patient engagement. Healthcare policy and financial support also significantly influence couples' decisions to pursue fertility treatment. Evidence from a large-scale survey in Eastern China shows that government subsidies can positively impact couples’intentions to continue treatment, particularly among those with financial concerns[ 13 ]. Similarly, a policy evaluation in Taiwan estimated substantial public economic gains following the 2021 expansion of IVF subsidies, indicating that well-designed financial interventions not only improve access but also generate societal benefits [ 14 ]. These findings suggest that reducing the economic burden through targeted subsidy programs could to some extent boost people’s fertility intentions. These findings underscore that the journey from cycle initiation to embryo transfer is not merely biological—it is governed with physiological, emotional, and social complexities. Recognizing and anticipating these multidimensional barriers may help reduce cycles cancellation, optimize clinical pathways, and better align reproductive care with patients’ lived realities. Moreover, minimizing non-medical interruptions and strengthening early intervention for medical factors could collectively help reduce the unnecessary consumption of valuable healthcare resources. Declarations Funding The authors acknowledge funding support from the National Natural Science Foundation of China (82471657, 82171599, and 82201792), as well as from the 2022 Anhui Provincial Social Science Innovation and Development Research Project (Grant No. 2022CX082). Conflicts of interest The authors declare no conflicts of interest. Ethics approval The study protocol was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of USTC on November 18, 2024 (Ethical approval No. 2024 KY 535). Consent to participate All participants provided written informed consent prior to inclusion in the study. The study protocol was reviewed and approved by the institutional ethics committee. Written Consent for publication Written consent for publication of anonymized data was obtained from all participants. Availability of data and material Data regarding any of the subjects in the study can be shared after reasonable request to the corresponding author. No identifying data will be provided. Code availability Not applicable Authors' contributions Q. J., X.J., and S.B. contributed equally to this work and share first authorship. Q.J. was responsible for sample collection, manuscript drafting, and revisions. X.J. constructed the figures and tables. S.B. and L.Z. performed the statistical analyses and interpreted the data. S.Z., L.W., and B.X. jointly supervised the study, contributed to the study design and critical revision of the manuscript, and share corresponding authorship. All authors read and approved the final version of the manuscript. References Kahn JL, Wu H, Gerber R, Shah T, Lieman H, Pollack SE, Singh M, Jindal S. Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13 000 autologous cycles reported to SART CORS. HUM REPROD 2024. Almquist RG, Barrera CM, Fried R, Boulet SL, Kawwass JF, Hipp HS. Impact of access to care and race/ethnicity on IVF care discontinuation. REPROD BIOMED ONLINE. 2022;44(6):1159–68. Smith A, Gromski PS, Rashid KA, Tilling K, Lawlor DA, Nelson SM. Population implications of cessation of IVF during the COVID-19 pandemic. REPROD BIOMED ONLINE. 2020;41(3):428–30. Prevention of moderate. and severe ovarian hyperstimulation syndrome: a guideline. FERTIL STERIL. 2024;121(2):230–45. Ovarian ST, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, La Marca A, Lainas G et al. ESHRE guideline: ovarian stimulation for IVF/ICSI(dagger). HUM REPROD OPEN 2020, 2020(2):hoaa9. Di Spiezio SA, Iorio GG, Guerra S, Isaacson K, Kafetzis D, Conforti A, De Angelis MC, Zizolfi B, Alviggi C. The role of hysteroscopy in patients with adenomyosis and infertility: bringing out the submerged. FERTIL STERIL. 2025;123(6):1140–2. George JS, Naert MN, Lanes A, Yin S, Bharadwa S, Ginsburg ES, Srouji SS. Utility of Office Hysteroscopy in Diagnosing Retained Products of Conception Following Early Pregnancy Loss After In Vitro Fertilization. OBSTET GYNECOL. 2023;142(5):1019–27. Ou Z, Liu N, Chen A, Li Q, Li J, Wen X, Huo J, Fang X, Du J, Lin X. Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes. FERTIL STERIL. 2025;123(6):991–8. Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. COCHRANE DB SYST REV. 2020;9(9):CD5291. Zhang X, Deng X, Mo Y, Li Y, Song X, Li H. Relationship between infertility-related stress and resilience with posttraumatic growth in infertile couples: gender differences and dyadic interaction. HUM REPROD. 2021;36(7):1862–70. Bergenheim S, Saupstad M, Colombo C, Moller JE, Bogstad JW, Freiesleben NC, Behrendt-Moller I, Praetorius L, Oxlund B, Nohr B, et al. Psychosocial and physical wellbeing in women and male partners undergoing immediate versus postponed modified natural cycle frozen embryo transfer after ovarian stimulation and oocyte pick-up: a sub-study of a randomized controlled trial. HUM REPROD. 2025;40(1):96–109. Scognamiglio C, Cirillo F, Ronchetti C, Secchi M, Busnelli A, Morenghi E, Alviggi C, Levi-Setti PE. From hope to hesitation: why couples fail to return for infertility treatment after the first consultation. HUM REPROD. 2025;40(5):919–25. Dong WH, Wang X, Yuan F, Wang L, Gu TM, Zhu BQ, Shao J. Will a government subsidy increase couples' further fertility intentions? A real-world study from a large-scale online survey in Eastern China. HUM REPROD OPEN 2024, 2024(4):hoae55. Chen MJ, Kotsopoulos N, Ming-Fang YA, Lin KT, Connolly MP. Estimating the public economic gains in Taiwan from in vitro fertilization (IVF) subsidy changes implemented in 2021. HUM REPROD. 2025;40(2):328–34. Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.xlsx Table2.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 17 Sep, 2025 Reviews received at journal 12 Sep, 2025 Reviewers agreed at journal 12 Sep, 2025 Reviewers invited by journal 10 Sep, 2025 Editor invited by journal 16 Aug, 2025 Editor assigned by journal 13 Aug, 2025 Submission checks completed at journal 13 Aug, 2025 First submitted to journal 13 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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These \u0026ldquo;non-transfer cycles\u0026rdquo;\u0026mdash;including cases terminated for medical reasons and those voluntarily terminated by patients\u0026mdash;are typically not included in treatment outcome metrics [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, they represent cycle interruptions, cancellations within IVF programmes, potentially indicating critical attrition points in the treatment pathway and impacting clinical efficiency and patient experience.\u003c/p\u003e\u003cp\u003eRecent studies suggest that demographic and systemic factors such as race, economic stress, and inadequate insurance coverage may lead to patients prematurely discontinuing IVF treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Beyond individual burdens, IVF treatment discontinuation is also associated with reduced cumulative live birth rates, suggesting its significant negative impact on reproductive success rates at the population level [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNotably, early treatment discontinuations and unplanned freeze-all cycles are of particular concern. These events not only prolong the overall treatment timeline and entail substantial emotional stress and financial burdens for patients, but may also result in inefficient allocation of limited healthcare resources. Therefore, comprehensive knowledge of the multifactorial factors contributing to untransferred IVF cycles is thus crucial for informing more holistic and equitable clinical strategies, enhancing patient-centered interventions, and ultimately optimizing reproductive outcomes and healthcare resource efficiency.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design and setting\u003c/h2\u003e\u003cp\u003eThis retrospective study was conducted over a 14-year period, from April 2011 to April 2025, at a single tertiary fertility center. The objective was to analyze all in vitro fertilization (IVF) cycles that were initiated but did not result in embryo transfer, defined herein as \"untransferred cycles.\"\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDefinition of untransferred cycles\u003c/h3\u003e\n\u003cp\u003eUntransferred cycles were defined as IVF treatment cycles in which couples completed the registration process and initiated clinical or laboratory procedures but ultimately did not proceed to embryo transfer. These cases were included regardless of whether the interruption occurred before or after oocyte retrieval.\u003c/p\u003e\n\u003ch3\u003eClassification of reasons for non-transfer\u003c/h3\u003e\n\u003cp\u003eEach untransferred cycle was classified based on two main criteria: the cycle type (fresh vs. frozen-thawed) and the underlying reason for non-transfer. Reasons were broadly grouped into two categories. Medical interruptions encompassed clinical conditions such as poor ovarian response, high risk of ovarian hyperstimulation syndrome (OHSS), failed fertilization, absence of oocytes or embryos, and contraindications to embryo transfer due to uterine or endometrial abnormalities. Non-medical withdrawals referred to patient-driven discontinuation, including personal reasons, psychological stress, socioeconomic pressures, or partner-related issues.\u003c/p\u003e\n\u003ch3\u003eData validation and stratification\u003c/h3\u003e\n\u003cp\u003eTo ensure accuracy, all classifications were independently reviewed by two experienced reproductive clinicians. Discrepancies were resolved through discussion and consensus. Further stratification of cases was performed to examine distributions across cycle types, specific interruption causes, and temporal trends spanning the 14-year period. The analysis aimed to describe patterns without hypothesis testing.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eOverall cycle analysis\u003c/h2\u003e\u003cp\u003eOut of 81,723 IVF cycles recorded during the study period, 30,731 cycles (37.6%) were identified as untransferred. Among these, 98.13% (n\u0026thinsp;=\u0026thinsp;30,155) were fresh cycles, while only 1.87% (n\u0026thinsp;=\u0026thinsp;576) involved frozen-thawed embryo transfers. This distribution reflects a higher susceptibility of fresh cycles to clinical or patient-related disruptions (Fig.\u0026nbsp;1).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eFresh cycle outcomes\u003c/h3\u003e\n\u003cp\u003eIn fresh IVF cycles, medical factors were the leading cause of cycle interruption, accounting for 90.21% (n\u0026thinsp;=\u0026thinsp;27,202) of untransferred cases (Table\u0026nbsp;1). The most prevalent medical reasons included high OHSS risk (26.54%), the use of progesterone-primed ovarian stimulation (PPOS) protocols (20.8%), uterine cavity abnormalities (14.88%), and luteal phase stimulation (9.57%). Non-medical causes were less common, constituting 9.79% (n\u0026thinsp;=\u0026thinsp;2,953), with personal reasons (82.15%) and social factors (10.9%) being the dominant subcategories.\u003c/p\u003e\n\u003ch3\u003eTemporal trends in fresh cycles\u003c/h3\u003e\n\u003cp\u003eAnalysis of annual patterns revealed a decline in OHSS-related cancellations after 2019, suggesting improvements in ovarian stimulation safety and clinical monitoring. Conversely, uterine cavity abnormalities became increasingly prominent in recent years, likely due to more widespread hysteroscopic evaluations. The application of PPOS protocols rose steadily from 2014, replacing luteal-phase stimulation, which showed a marked decrease after 2016 before plateauing (Fig.\u0026nbsp;2A). Other trends included a drop in unusable embryos after 2021 and stabilization in cases of unusable oocytes, reflecting stable laboratory and retrieval practices. Interruptions linked to elevated serum progesterone levels began to rise from 2021 onward. Discontinuations due to preimplantation genetic testing (PGT) increased sharply starting in 2019 and accelerated further after 2022 (Fig.\u0026nbsp;2B).\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eFrozen-thawed cycle outcomes\u003c/h2\u003e\u003cp\u003eAmong the 576 untransferred frozen-thawed cycles (Table\u0026nbsp;2), 71.0% (n\u0026thinsp;=\u0026thinsp;409) were due to medical factors, while 29.0% (n\u0026thinsp;=\u0026thinsp;167) were attributed to non-medical causes. The primary medical issues were embryonic arrest (51.34%), uterine abnormalities (11.0%), and abnormal laboratory results (9.29%). Non-medical factors included upper respiratory infections (34.73%), personal reasons (28.14%), and COVID-19 infections (21.56%), which reflect broader social and public health influences on fertility treatment adherence during the pandemic years.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eDespite significant advancements in assisted reproduction,such as ovarian stimulation, laboratory techniques, and cycle monitoring, a significant proportion of IVF cycles are discontinued even before embryo transfer. Our findings highlight that medical factors continue to dominate the reasons for untransferred fresh cycles,temporal trend analysis reveals shifting clinical patterns over time.These shifts reflect both improvements in IVF safety and emerging challenges requiring targeted interventions.\u003c/p\u003e\u003cp\u003eOur analysis demonstrates that the consistent decline in cycle cancellations due to OHSS highlights the efficacy of optimized stimulation protocols. Temporal trends further reflect the evolving landscape of clinical decision-making, including the widespread adoption of PPOS and luteal-phase stimulation protocols, supporting individualized and flexible cycle management.This progression aligns with global initiatives to enhance IVF safety[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], as evidenced by the ESHRE guidelines, which strongly recommend GnRH antagonist protocols rather than GnRH agonist protocols to improve safety in IVF practice[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eUterine-cavity factors accounted for 14.88% of fresh cycles without embryo transfer in our cohort, primarily involving polyps, adhesions, and chronic endometritis. This increasing detection is likely attributed to the routine application of hysteroscopy, which enables the identification of subtle endometrial abnormalities that might otherwise go unnoticed. Recent studies have shown that hysteroscopy plays an important role in managing repeated implantation failure (RIF) patients with adenomyosis and in diagnosing retained products of conception following early pregnancy loss after IVF [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Early hysteroscopic intervention for known intrauterine abnormalities before ovarian stimulation may help reduce the risk of cycle interruption and improve treatment continuity.\u003c/p\u003e\u003cp\u003eWe observed a sharp increase in PGT cycles, reflecting both advancements in reproductive genetics and rising patient demand for chromosomal and monogenic screening. However,studies have suggested that while PGT-A may benefit specific subgroups\u0026mdash;such as women of advanced maternal age (\u0026ge;\u0026thinsp;38 years) or those with decreased ovarian reserve resulting in low oocyte yield (\u0026le;\u0026thinsp;3 oocytes)\u0026mdash;by improving clinical pregnancy rates per transfer, it does not significantly increase live birth rates[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Moreover, current evidence does not support the routine use of PGT-A as a standard adjunct to IVF for the general population[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe frequencies of no usable oocytes and embryos have remained within a relatively stable range over time, suggesting consistent performance in oocyte retrieval and laboratory procedures. Meanwhile, the upward trend in progesterone-related cancellations indicates the need for closer monitoring and management of luteal-phase hormonal profiles during stimulation. Beyond medical causes, nearly one in ten untransferred cycles are still attributable to personal, psychological, or social factors, underscoring the importance of holistic patient support throughout treatment.\u003c/p\u003e\u003cp\u003ePsychosocial factors play a critical role in early treatment discontinuation, as evidenced by our finding that nearly 10% of untransferred fresh cycles cited personal and social reasons as a key reason. Recent studies highlight the complexity of infertility-related stress: Jin et al. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]revealed that men and women experience and cope with this stress differently, underscoring the importance of couple-based psychological interventions.In the untransferred fresh cycles, it was reported that more women were emotionally affected by the waiting time from oocyte pick-up to embryo transfer. Additionally, women were generally more distressed than their partners[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These insights, along with Scognamiglio et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], who found psychological distress often co-occurred with factors like dissatisfaction with medical staff or relational instability.Collectively, these findings underscore the necessity of integrating comprehensive psychosocial support and interventions to reduce early dropouts and improve overall patient engagement.\u003c/p\u003e\u003cp\u003eHealthcare policy and financial support also significantly influence couples' decisions to pursue fertility treatment. Evidence from a large-scale survey in Eastern China shows that government subsidies can positively impact couples\u0026rsquo;intentions to continue treatment, particularly among those with financial concerns[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Similarly, a policy evaluation in Taiwan estimated substantial public economic gains following the 2021 expansion of IVF subsidies, indicating that well-designed financial interventions not only improve access but also generate societal benefits [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. These findings suggest that reducing the economic burden through targeted subsidy programs could to some extent boost people\u0026rsquo;s fertility intentions.\u003c/p\u003e\u003cp\u003eThese findings underscore that the journey from cycle initiation to embryo transfer is not merely biological\u0026mdash;it is governed with physiological, emotional, and social complexities. Recognizing and anticipating these multidimensional barriers may help reduce cycles cancellation, optimize clinical pathways, and better align reproductive care with patients\u0026rsquo; lived realities. Moreover, minimizing non-medical interruptions and strengthening early intervention for medical factors could collectively help reduce the unnecessary consumption of valuable healthcare resources.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge funding support from the National Natural Science Foundation of China (82471657, 82171599, and 82201792), as well as from the 2022 Anhui Provincial Social Science Innovation and Development Research Project (Grant No. 2022CX082).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Medical Research Ethics Committee of the First Affiliated Hospital of USTC on November 18, 2024 (Ethical approval No. 2024 KY 535).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided written informed consent prior to inclusion in the study. The study protocol was reviewed and approved by the institutional ethics committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWritten Consent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent for publication of anonymized data was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData regarding any of the subjects in the study can be shared after reasonable request to the corresponding author. No identifying data will be provided.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQ. J., X.J., and S.B. contributed equally to this work and share first authorship. Q.J. was responsible for sample collection, manuscript drafting, and revisions. X.J. constructed the figures and tables. S.B. and L.Z. performed the statistical analyses and interpreted the data. S.Z., L.W., and B.X. jointly supervised the study, contributed to the study design and critical revision of the manuscript, and share corresponding authorship. All authors read and approved the final version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKahn JL, Wu H, Gerber R, Shah T, Lieman H, Pollack SE, Singh M, Jindal S. Protocol change improves live birth and recurrent cycle cancellation rates after a previous IVF cycle cancellation: an analysis of 13 000 autologous cycles reported to SART CORS. HUM REPROD 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlmquist RG, Barrera CM, Fried R, Boulet SL, Kawwass JF, Hipp HS. Impact of access to care and race/ethnicity on IVF care discontinuation. REPROD BIOMED ONLINE. 2022;44(6):1159\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmith A, Gromski PS, Rashid KA, Tilling K, Lawlor DA, Nelson SM. Population implications of cessation of IVF during the COVID-19 pandemic. REPROD BIOMED ONLINE. 2020;41(3):428\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePrevention of moderate. and severe ovarian hyperstimulation syndrome: a guideline. FERTIL STERIL. 2024;121(2):230\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOvarian ST, Bosch E, Broer S, Griesinger G, Grynberg M, Humaidan P, Kolibianakis E, Kunicki M, La Marca A, Lainas G et al. ESHRE guideline: ovarian stimulation for IVF/ICSI(dagger). \u003cem\u003eHUM REPROD OPEN\u003c/em\u003e 2020, 2020(2):hoaa9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDi Spiezio SA, Iorio GG, Guerra S, Isaacson K, Kafetzis D, Conforti A, De Angelis MC, Zizolfi B, Alviggi C. The role of hysteroscopy in patients with adenomyosis and infertility: bringing out the submerged. FERTIL STERIL. 2025;123(6):1140\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGeorge JS, Naert MN, Lanes A, Yin S, Bharadwa S, Ginsburg ES, Srouji SS. Utility of Office Hysteroscopy in Diagnosing Retained Products of Conception Following Early Pregnancy Loss After In Vitro Fertilization. OBSTET GYNECOL. 2023;142(5):1019\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOu Z, Liu N, Chen A, Li Q, Li J, Wen X, Huo J, Fang X, Du J, Lin X. Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes. FERTIL STERIL. 2025;123(6):991\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. COCHRANE DB SYST REV. 2020;9(9):CD5291.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang X, Deng X, Mo Y, Li Y, Song X, Li H. Relationship between infertility-related stress and resilience with posttraumatic growth in infertile couples: gender differences and dyadic interaction. HUM REPROD. 2021;36(7):1862\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBergenheim S, Saupstad M, Colombo C, Moller JE, Bogstad JW, Freiesleben NC, Behrendt-Moller I, Praetorius L, Oxlund B, Nohr B, et al. Psychosocial and physical wellbeing in women and male partners undergoing immediate versus postponed modified natural cycle frozen embryo transfer after ovarian stimulation and oocyte pick-up: a sub-study of a randomized controlled trial. HUM REPROD. 2025;40(1):96\u0026ndash;109.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eScognamiglio C, Cirillo F, Ronchetti C, Secchi M, Busnelli A, Morenghi E, Alviggi C, Levi-Setti PE. From hope to hesitation: why couples fail to return for infertility treatment after the first consultation. HUM REPROD. 2025;40(5):919\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDong WH, Wang X, Yuan F, Wang L, Gu TM, Zhu BQ, Shao J. Will a government subsidy increase couples' further fertility intentions? A real-world study from a large-scale online survey in Eastern China. \u003cem\u003eHUM REPROD OPEN\u003c/em\u003e 2024, 2024(4):hoae55.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen MJ, Kotsopoulos N, Ming-Fang YA, Lin KT, Connolly MP. Estimating the public economic gains in Taiwan from in vitro fertilization (IVF) subsidy changes implemented in 2021. HUM REPROD. 2025;40(2):328\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"IVF cycle discontinuation, Untransferred cycles, Medical and non-medical reasons, Assisted reproductive technology, Trend analysis","lastPublishedDoi":"10.21203/rs.3.rs-7368769/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7368769/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIn vitro fertilization (IVF) cycles that do not progress to embryo transfer\u0026mdash;termed untransferred cycles\u0026mdash;are frequently overlooked in outcome reporting, despite their potential clinical and psychosocial implications.This 14-year retrospective study analyzed 30,731 untransferred IVF cycles from a tertiary fertility center (2011\u0026ndash;2025). Cycles were categorized by type (fresh vs. frozen-thawed) and by cause (medical vs. non-medical). Reasons included OHSS risk, no embryos or oocytes, failed fertilization, uterine abnormalities, and patient-level factors. Temporal trends were also examined.Of 81,723 IVF cycles, 37.6% were untransferred. Fresh cycles accounted for 98.1% of these, with 90.2% attributed to medical reasons. Frozen-thawed cycles showed a more balanced distribution of causes. Over time, OHSS-related cancellations declined, while uterine cavity issues and PGT-related interruptions increased. Personal, psychological, and social factors accounted for nearly 10% of untransferred cycles.The journey from IVF initiation to embryo transfer is influenced by biological, emotional, and social complexities. Recognizing and addressing these multidimensional barriers may reduce untransferred cycles, enhance patient-centered care, and prevent unnecessary resource loss.\u003c/p\u003e","manuscriptTitle":"The Unfinished Journey:multifactorial analysis of untransferred cycles in IVF","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-17 11:11:27","doi":"10.21203/rs.3.rs-7368769/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"57082591363979319598361228224783632215","date":"2025-09-17T12:18:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-12T09:48:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"175339403780183083347469509047905710059","date":"2025-09-12T09:46:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-10T10:12:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-16T21:01:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-14T03:21:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-14T03:20:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2025-08-14T01:30:31+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f8009ec6-5c8a-4d3e-be97-93cfa193742f","owner":[],"postedDate":"September 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-17T11:11:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-17 11:11:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7368769","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7368769","identity":"rs-7368769","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}