Optimizing family building in women of advanced reproductive age: a Faster-Fewer-and-Finished approach

Although female fertility starts to decline significantly after the age of 35 years, further increments in fertility decline can occur between 40 to 43 years and again at >44 years ( 8 ). Accordingly, conventional treatment approaches in ARA women risks preventable delays, cumulative treatment burden, and may result in failure in women for whom time is the most critical determinant of success. We propose that treatment recommendations should, therefore, be based on a more nuanced categorization across different age ranges while also considering the desired ideal family size. In our opinion, the key to addressing this requires the minimization of avoidable delays in current strategies for assessment and treatment and minimizing delays between cycles, while still ensuring timely, optimized, and outcome-focused care. A personalized treatment plan based on an individual’s circumstances and preferences can then be adopted. Such a plan should be fully informed by the prospect that any delay in treatment may further reduce the chances of having a first baby with MAR, and potentially having a second baby in the future ( 30 ). In light of this, we propose the hypothesis-generating Faster-Fewer-and-Finished (3F) approach as an extension of the One-and-Done approach that is a more tailored and realistic option for ARA women ( Figure 1 ). Key features of the One-and-Done and Faster-Fewer-and-Finished approaches.

There is a global trend towards delayed parenthood, with the average age of first-time mothers rising steadily. In 2020, women in many Asia–Pacific countries, including Australia, Singapore, South Korea, Japan and New Zealand, had their first child at an average age of 30 years or older ( 1 ). In the European Union, the average age increased from 29.0 years in 2001 to 31.1 years in 2022 ( 2 ), with Italy and Spain reporting the oldest first-time mothers ( 3 ). Similarly, in the United States the average age increased from 21.4 in 1970 to 27.1 in 2020 ( 4 ). The global rise in delayed parenthood is driven by societal shifts, such as the increased participation of women in higher education and the workforce, greater access to contraception, evolving societal norms, and economic factors ( 5 ). As a result, a growing number of individuals are entering advanced reproductive age (ARA), typically defined for women as ≥35 years of age. This age threshold is clinically significant as time to pregnancy (TTP) is inherently age dependent, and female reproductive potential declines significantly from this age ( 6 , 7 ), with notable increments in fertility decline occurring between 40 to 43 years and again at >44 years ( 8 ). The progressive decline in fertility is due to decreased ovarian reserve and, more critically, declining oocyte quality driven by increased aneuploidy rates and impaired cytoplasmic maturation ( 9 , 10 ). This places ARA women at a considerably high risk of adverse reproductive outcomes, including infertility, pregnancy loss, fetal anomalies, obstetric complications, or stillbirth ( 11 ). Consequently, delaying childbearing can lead to challenges in conceiving and increased infertility rates ( 12 ). Recent data have shown that ~63% of in-vitro fertilization (IVF) cycles in North America ( 13 ) and ~56% of cycles in Europe ( 14 ) are undertaken in ARA women. However, this population faces suboptimal outcomes from medically assisted reproduction (MAR) interventions compared with younger women ( 15 ), as MAR success rates also decline with age ( 16 ). This contributes to the stress and financial burden for individuals looking to build a family using this option ( 17 ) and the high levels of dropout ( 18 ). Despite this, the decision to postpone family building is frequently underinformed and the ability of ART to overcome age-related fertility decline is overestimated ( 19 – 23 ). Current treatment guidelines include sections on ARA women, with the European Society of Human Reproduction and Embryology (ESHRE) guideline providing detailed, evidence-graded recommendations on specific areas such as fertility preservation ( 24 ), whereas the American Society for Reproductive Medicine guideline focusses on risk-benefits and ethical considerations of late-age family building ( 25 ). In this Perspectives article, we set out a conceptual, hypothesis-generating framework to reduce the time to live birth in ARA women—the Faster-Fewer-and-Finished (3F) approach— developed through author discussion following a symposium and based on expert opinion informed by the published literature. This refreshed paradigm of care aims to maximize pregnancy potential with each ART cycle, resulting in fewer stimulation cycles and shorter time to achieve the desired outcome of family building, and is informed by patient autonomy, emotional preparedness and individual desires with respect to ideal family size. The “Finished” component is a patient-defined endpoint that may, on one hand, reflect achievement of the patient’s desired family-building goal. On the other hand, following shared decision-making, it may also reflect the decision to stop, pause or change strategy because of prognosis, previous treatment response, medical or obstetric risk, emotional burden, financial or access constraints, changing personal priorities, or a preference for donor gametes or another family-building pathway. We envisage these combined approaches may help clinicians to better support ARA women.

As time is the most critical factor in ARA women, current interventions need to be re-examined to reduce the time to live birth. To achieve this, the patient journey may generally be adapted in several ways ( Supplementary Figure 1 ), including advice on timely intervention, comprehensive evaluation, early diagnosis and intervention, personalized treatment plans, and by adopting a psychosocial, multidisciplinary approach. Collaborations with other specialists, such as andrologists or obstetricians, should be considered for pre-pregnancy assessment. Although recognized preventive measures, such as smoking cessation and losing weight, may still be beneficial for ARA women, this population could also benefit from clear information that helps them make rapid, well-informed decisions on when or whether to start MAR treatment. However, there are only few high-quality guidelines that address counselling on age-related fertility decline, and the existing guidance is inconsistent ( 23 ).

The hypothesis-generating 3F approach concept presented here recognizes the importance of tailored and realistic approaches in fertility care for the growing sub-population of ARA women seen at our clinics. In particular, it considers the specific challenges faced by ARA women, such as declining ovarian reserve and increased aneuploidy rates, while minimizing the overall impact of fertility treatments, as an achievable and time-efficient strategy for MAR in this population. Decreased oocyte quantity and quality are hallmark features of ovarian aging and have a significant negative impact on clinical outcomes in ARA women ( 94 ). This highlights the urgent need for research focused on understanding the underlying mechanisms of ovarian aging and, particularly, how changes in oocyte-intrinsic pathways and the ovarian environment both drive ovarian aging ( 95 ). Developing novel models and identifying future therapeutic strategies that extend reproductive longevity and overall health is an urgent priority in this field. The validity of the 3F approach in clinical practice will now need to be assessed, in the first instance, in prospective studies that assess patient-relevant outcomes, including cumulative live birth and time to live birth, miscarriage, number of stimulation cycles and procedures, adverse events, emotional burden and treatment discontinuation. Cost-effectiveness studies will also need to be conducted to ensure that any potential financial implications do not impede its wider implementation.

A retrospective, single-center, cohort modelling study including 16,474 IVF cycles showed that it was possible to achieve 1 or ≥2 live births from a single retrieval cycle followed by use of all embryos in subsequent frozen cycles (the One-and-Done approach). With current MAR practices, over one-quarter of women could complete their family by achieving at least two live births from a single ovarian stimulation (OS), assuming that all retrieved embryos have equal potential to achieve a live birth ( 26 ). The success of the One-and-Done approach is influenced by the patient’s age, ovarian reserve status, and oocyte quality. As a higher number of retrieved oocytes is associated with a higher number of high-quality embryos ( 27 ), younger patients with good ovarian reserve are more likely to benefit from this strategy, as they are likely to produce more euploid embryos from a given oocyte yield compared with ARA women ( 28 ). Thus, its effectiveness may diminish with advancing reproductive age. The One-and-Done approach may, therefore, be a more realistic option for women aged <35 years, in whom the ideal 15–20 oocytes ( 29 ) can be retrieved from a single fresh OS cycle. Nevertheless, data suggest that with 10–14 oocytes retrieved, around 10% of women between 38–40 years of age could still achieve at least two live births ( 26 ).

The 3F concept is designed to minimize the number of stimulation cycles needed to achieve the optimal number of oocytes, giving the best chance of achieving their ideal family size. This can be accomplished by following safe and efficient protocols that optimize both oocyte quantity and quality over the shortest possible timeframe, aligned according to age category and family expectations ( Supplementary Figure 2 ). A key consideration is to understand the ideal family size of each woman (i.e., do they see their family as being complete with one child or more than one child) ( Table 1 ). Meeting these expectations will require further tailoring of the treatment protocols. Although elective family preservation and third-party reproduction are adjacent and important options, our focus in this Perspectives article is on women presenting for MAR with the immediate goal of building their family. The 3F treatment strategy encompassing ARA age categories and desired family size. Recommendations based on one pregnancy; the number of back-to-back cycles required to bank the requisite number of euploid blastocysts will depend on the completed family size. *Number of MII oocytes needed at age of vitrification giving ≥90% probability of ≥1 euploid blastocysts calculated using the Merck Oocyte Number Estimator ONE using retrospective cohort data ( 31 , 32 ). †Estimates of minimum number of MII oocytes needed by age at vitrification giving ≥99% probability of ≥3 euploid blastocysts based on population-level counselling estimates derived from a published prediction model based on retrospective cohort data ( 33 ). Oocyte yield and modelled euploid-blastocyst yield are intermediate outcomes and do not guarantee live birth or completion of the patient’s family-building goal. The actual number of oocytes and cycles required (achieved through multiple cycles and banking of oocytes) will vary according to ovarian reserve, prior ovarian response, laboratory performance, sperm-related factors and other individual characteristics. These data were obtained from cycles with PGT-A and intracytoplasmic sperm injection of MII oocytes and should be interpreted accordingly. Based on EHSRE 2025 Guidelines for OS ( 34 ) and informed by Conforti 2021 and Bielfeld 2023. Based on Lensen 2018 ( 84 ) and Ngwenya 2024 ( 85 ). Within cycle dose adjustments are probably not recommended, according to the latest ESHRE Guidelines (2025). **Based on EHSRE 2025 guidelines for OS ( 34 ) and depending on patient characteristics (e.g., very low reserve, urgent need to bank oocytes), although there is no evidence that it improves live birth rates in ARA women. Within the 3F approach, ‘Finished’ is defined operationally as the point at which (i) the woman’s pre-specified desired family size has been achieved with a live birth or live births, or (ii) the next age threshold is reached at which the benefit–risk balance shifts materially (40 years for the 35–39 group; 44 years for the 40–43 group), at which point the strategy and prognosis should be revisited with the patient. The rationale for an age-anchored stop is the steep age-related decline in euploid blastocyst yield per stimulation cycle and the parallel rise in obstetric and perinatal risk, rather than a fixed numerical cap on cycles. Women aged >35 years should not be considered as a homogenous group, and treatment recommendations should be considered according to specific age categories as well as their desired family size. We propose separate treatment protocols for women who fall within three age categories (35–39 years, 40–43 years and 44–50 years) ( 8 ). These proposed age categories are pragmatic counselling strata intended to prompt reassessment and individualization, rather than absolute treatment thresholds, and are based on fertility status, potential for obstetric complications with increasing age, and whether their family would be complete with one child or more than one child ( Table 1 ). Furthermore, treatment decisions within each age category should also take account of factors such as ovarian reserve, previous treatment response, semen-related factors, relevant comorbidities and pregnancy risk, patient-defined reproductive goals, emotional readiness, access and cost. Given the age-related decline in fertility and time pressure, we recommend that all women ≥35 years should receive expedited evaluation and treatment after 6–12 months of failed conception attempts, or earlier if clinically indicated. Time can be optimized by smart streamlining clinical workflows: fast-tracking appointments, particularly the first one, based on age; expediting the diagnostic process; and focusing on essential evidence-based assessments that confirm prognosis. We acknowledge that prioritizing rapid access to MAR for ARA women must be balanced with equitable access for all eligible patients within finite service capacity, and that local pathway implementation will require careful service-level planning to ensure that fast-tracking by age does not disadvantage other patient groups. Thorough assessment for male infertility is also an essential, although frequently overlooked, part of the evaluation. Age-related decline in male fertility can contribute to a longer time to conception, higher miscarriage rates, reduced sperm quality, and increased genetic risks ( 35 ). In addition to conventional analysis of sperm parameters, such as sperm count, morphology, motility and volume, the assessment should also include paternal age, endocrine function, quality of sperm DNA, lifestyle influences and environmental determinants ( 36 – 42 ). For women in the 40–43 age bracket, this timeline needs to be accelerated, particularly if >1 child is the ultimate goal. Options for oocyte freezing and/or banking should be offered and discussed as a potential way to safeguard oocyte quality. In light of the unfavorable benefit–risk profile from the chance of success balanced against the maternal health risks ( 8 ), women > 44 years should be counselled to consider oocyte donor cycles to achieve their desired family size ( 43 ). Across all age groups, appropriate evidence-based counselling regarding age-related fertility decline and the importance of timely, informed intervention, the benefits and risks of oocyte banking, the likelihood of success associated with these methods, and the financial and ethical implications should be integrated into the treatment pathway. These discussions should also address the emotional challenges associated with infertility and MAR in ARA women ( 44 ), as well as the potential for age-related comorbidities and increased awareness of the risk factors that may affect fertility or pregnancy outcomes. Time to pregnancy is inherently age dependent and should be prioritized according to desired family size and patient age. For example, a woman aged between 35 and 39 years who desires only one child to complete their family should still receive expedited access to assessment and treatment, but there would be a greater urgency to access the treatment pathway for a woman of the same age who desires >1 child or a woman who is older (40–43 years) who desires either 1 or >1 child. Real-world data show a correlation between the number of oocytes retrieved in a stimulated cycle and improved outcomes ( 45 ), with a strong association between the number of oocytes and live births per fresh cycle ( 29 , 46 – 54 ). Reported cumulative live birth rate data, which is defined as the first live birth following the use of all fresh and frozen embryos obtained from a single OS cycle, confirms that a higher oocyte count is associated with better overall success, potentially minimizing the need for further OS cycles ( 49 , 51 , 53 , 55 – 58 ). However, to increase the probability of completing their family in the available timescale, the target number of oocytes should be based on the potential of each woman and aim to obtain as many oocytes as possible so as to give an ARA women the best chance of achieving their family goals, which may be lower than the recommended optimum of 15 oocytes in ARA women ( 29 ), and may require more than one OS cycle. Notwithstanding the need to maximize each MAR cycle, we acknowledge that high oocyte numbers do not automatically translate into increased live births for ARA women and the relations between oocyte number and euploid blastocysts, miscarriages, treatments, costs and dropouts need to be considered. As part of the 3F framework, we have estimated the number of oocytes required to obtain a pre-specified number of euploid blastocysts (e.g., ≥1 or ≥3) for each of the proposed age groups ( Table 1 ). These estimates should be interpreted advisedly, as they are based on population-level counselling strata derived from published prediction models using retrospective cohort data ( 31 – 33 ) and on recognized changes in reproductive potential and pregnancy-related risk. We also acknowledge that oocyte yield and modelled euploid-blastocyst yield are intermediate outcomes and are no guarantee of live birth or completion of the patient’s family-building goal. As an example based on these modelling estimates, women aged 35–39 and 40–44 years who desire >1 child may need to bank oocytes through sequential cycles to accumulate sufficient euploid blastocysts to achieve this goal over the shortest possible timeframe ( Table 1 ). Women in these age groups who only want one child to complete their family should also receive prioritized access to assessment and treatment, to mitigate any further decline in oocyte quality. Although the efficacy of Duostim remains unproven in ARA women, it may be considered to accelerate the oocyte retrieval process and potentially reduce the number of full cycles required in cases of very low ovarian reserve or an urgent need to bank embryos, if an acceptable number of euploid embryos are obtained in the initial stimulation ( 59 ). Pre-implantation genetic testing for aneuploidy (PGT-A) is not routinely recommended as part of the 3F framework unless specifically indicated (e.g., high rates of miscarriage or recurring unsuccessful MAR cycles) ( Table 1 ). This is due to the absence of evidence-based clinical data to support its effectiveness in routine clinical practice ( 60 , 61 ) and the potential for otherwise viable embryos displaying mosaicism to be deprioritized and transferred when only no fully euploid embryos are available ( 62 – 66 ). Furthermore, the substantial additional financial burden incurred by PGT-A ( 67 ) may present a substantial opportunity cost for ARA women, reducing the total number of cycles that can be achieved ( 68 ). Overall, any decision to go ahead with PGT-A should be individualized through shared decision-making, taking account of age, ovarian reserve, embryo availability, previous reproductive history, potential benefits and limitations, cost and patient preferences. While the intention to pursue more than one cycle may seem counterintuitive, timing is one factor that all clinicians can control. By banking oocytes or viable embryos, when appropriate, and accepting from the outset that more than one round of OS will be needed, adopting the 3F approach may still enable a high number of good-quality oocytes to be obtained safely in ARA women ( 53 , 58 ), which, in turn, may increase their chances of having the desired number of children. Furthermore, through careful embryo selection and single embryo transfer, the 3F approach should also aim to minimize the risks associated with multiple pregnancies. OS regimens should aim to optimize oocyte yield and quality, while always following best practices; however, achieving the optimal or maximum number of oocytes/euploid blastocysts presents unique challenges for ARA women. Various strategies have been suggested for personalizing gonadotropin regimens ( Table 1 ). Ultimately, gonadotrophin choice should be guided by availability, convenience, cost and predictability of response. Accordingly, the weight we place on the below treatment recommendations reflect the opinion and clinical experience of the authors, corroborated by relevant published evidence, rather than a comparison of all available formulations and, as is the case with every opinion article, should be considered in the context of the funding source disclosed. When selecting gonadotropins for use in ARA women, several key attributes must be considered to optimize OS and treatment outcomes. Potency and biological activity determine the efficacy, effectiveness and dosing of gonadotropins for OS. For example, recombinant human FSH (r-hFSH) has a high potency due to its purity, glycosylation composition and standardized formulation, and prospective randomized trials on its use in OS suggest a higher number of oocytes at lower r-hFSH doses compared with non-recombinant FSH preparations ( 69 – 74 ). However, a recent Cochrane Systematic Review reports that clinical pregnancy and live birth after fresh transfer are probably modestly lower with r-hFSH compared with HMG/HP-HMG, although there is probably little or no difference in cumulative ongoing pregnancy/live birth between the two preparations ( 75 ). Quality attributes such as consistency and purity also play a significant role in effectiveness, with recombinant gonadotropins offering superior consistency and reduced variability compared with urinary-derived options, enhancing the predictability in treatment responses ( 76 ). However, all r-hFSH products may not be considered equally effective. Recently published evidence from a meta-analysis, which was independently conducted, PROSPERO-registered, unfunded and graded as of moderate-quality evidence, has reported differences in live birth rates for biosimilars of the originator r-hFSH compared with the originator product ( 77 – 80 ). A similar higher live birth rate with r-hFSH compared with biosimilars has also been reported in a recent Cochrane systematic review, which included the findings of Kiose et al. ( 75 ). Finally, there is emerging evidence from a retrospective cohort database analysis ( 81 ) and a systematic review and meta-analysis ( 82 ) that co-treatment with r-hFSH and r-hLH may be beneficial for ARA women by supporting follicular development at the granulosa cell level, improving oocyte quality and reproductive outcomes. Although r-hFSH and recombinant human luteinizing hormone (r-hLH) co-treatment has been included as a conditional recommendation in the latest ESHRE Guidelines on OS ( 34 ), additional studies are needed to confirm whether this translates into increased live birth rates. Optimizing the starting dose of gonadotropins is crucial, particularly for low responders, which includes most ARA women ( 83 ). Evidence from randomized controlled trials, summarized in recent Cochrane reviews, shows that higher doses—such as 225–300 IU per day—can lead to a greater number of oocytes retrieved compared with the standard 150 IU per day dose ( 84 , 85 ). However, to avoid cycle cancellation due to ovarian hyperstimulation syndrome, the choice of starting dose should be considered according to an individual’s predicted response. Furthermore, an increase in oocyte yield may or may not correlate with improved cumulative outcomes, and further research is needed to support the use of tailored dosing strategies for this population ( 84 – 86 ). Modelling studies, biomarker analyses, literature reviews and retrospective analyses suggest that gonadotropin dose can be adjusted during OS based on response ( 84 , 87 – 92 ). A retrospective analysis reported that within-cycle dose adjustment were reported to occur in approximately 40–45% of OS cycles ( 91 , 92 ). However, the effects of within-cycle dose adjustments on live-birth outcomes still need further investigation. As this strategy is probably not recommended according to current guidelines, the starting dose should be rigorously selected based on patient characteristics and desired outcome ( 34 ). While the 3F protocol is designed to provide sufficient embryos to meet the desired family size for each ARA woman, there remains the potential for the creation of supernumerary embryos in the process of meeting this goal. We recommend that dispositional discussions are included as part of the pre-treatment counselling process, according to local regulations and legislation, to determine the parent’s attitudes and beliefs regarding discarding the embryos (if permitted) or retaining them in case individual family expectations change ( 93 ). Furthermore, as these embryos were obtained from ARA women, there will be practical and ethical issues surrounding the donation of supernumerary embryos to childless couples or for research purposes, if permitted.