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The cost-effectiveness of preimplantation genetic testing for aneuploidy in the United States: An analysis of cost and birth outcomes from 158,665 in vitro fertilization cycles
Abstract
Background
A controversial and unresolved question in reproductive medicine is the utility of preimplantation genetic testing for aneuploidy (PGT-A) as an adjunct to in vitro fertilization (IVF). Infertility is prevalent, but its treatment is notoriously expensive and typically not covered by insurance. Therefore, cost-effectiveness is critical to consider in this context.
Objective
To analyze the cost-effectiveness of PGT-A for the treatment of infertility in the United States
Study design
IVF cycles occurring between 2014 and 2016 in the United States, as reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System, a national data registry, were analyzed. A probabilistic decision tree was developed using empiric outputs to simulate the events and outcomes associated with IVF with and without PGT-A. The treatment strategies were (1) IVF with intended PGT-A, and (2) IVF with transfer(s) of untested embryo(s). Patients progressed through the treatment model until they achieved a live birth or twelve months after ovarian stimulation. Clinical costs related to both treatment strategies were extracted from the literature and considered from both the patient and payer perspectives. Outcome metrics included incremental cost (measured in 2018 US dollars), live birth outcomes, incremental cost-effectiveness ratio (ICER) and incremental cost per live birth between treatment strategies.
Results
The study population included 114,157 first fresh IVF stimulations and 44,508 linked frozen embryo transfer cycles. 16.2% intended PGT-A and 83.8% did not. In patients younger than 35, PGT-A was associated with worse clinical outcomes and higher costs. At age 35 and older, PGT-A led to more cumulative births, but was associated with higher costs from both perspectives. From a patient perspective, the incremental cost per live birth favored the no PGT-A strategy from <35 until age 38, and beginning at age 39 favored PGT-A. From a payer perspective, the incremental cost per live birth favored PGT-A regardless of patient age.
Conclusions
The cost-effectiveness of PGT-A is dependent on patient age and perspective. From an economic perspective, routine PGT-A should not be universally adopted, but may be cost-effective in certain scenarios.
... One hundred and two related articles were obtained in the initial examination, and 12 articles [13][14][15][16][17][18][19][20][21][22][23][24] were finally included after a layer-by-layer screening. The literature screening process and results are depicted in Fig. 2. ...
... Five studies [13,[19][20][21]23] were conducted in the United States (US), which is the country with the highest number of studies, followed by two studies each on Germany [14,17] and the Netherlands [15,22]. The remaining three studies were conducted in China [16], France [18], and Spain [24] ( Table 2). ...
... Six studies [16-19, 21, 23] restricted the age of patients. Further, six studies [13,15,16,20,21,24] limited the duration of treatment (the first IVF cycle) and treatment options (fresh/frozen embryo transfer). The patients in one study [18] had additional complications (endometriosis). ...
Background
With the increasing demand for fertility services, it is urgent to select the most cost-effective assisted reproductive technology (ART) treatment plan and include it in medical insurance. Economic evaluation reports are an important reference for medical insurance negotiation. The aim of this study is to systematically evaluate the economic evaluation research of ART, analyze the existing shortcomings, and provide a reference for the economic evaluation of ART.
Methods
PubMed, EMbase, Web of Science, Cochrane Library and ScienceDirect databases were searched for relevant articles on the economic evaluation of ART. These articles were screened, and their quality was evaluated based on the Comprehensive Health Economics Evaluation Report Standard (CHEERS 2022), and the data on the basic characteristics, model characteristics and other aspects of the included studies were summarized.
Results
One hundred and two related articles were obtained in the preliminary search, but based on the inclusion criteria, 12 studies were used for the analysis, of which nine used the decision tree model. The model parameters were mainly derived from published literature and included retrospective clinical data of patients. Only two studies included direct non-medical and indirect costs in the cost measurement. Live birth rate was used as an outcome indicator in half of the studies.
Conclusion
Suggesting the setting of the threshold range in the field of fertility should be actively discussed, and the monetary value of each live birth is assumed to be in a certain range when the WTP threshold for fertility is uncertain. The range of the parameter sources should be expanded. Direct non-medical and indirect costs should be included in the calculation of costs, and the analysis should be carried out from the perspective of the whole society. In the evaluation of clinical effect, the effectiveness and safety indexes should be selected for a comprehensive evaluation, thereby making the evaluation more comprehensive and reliable. At least subgroup analysis based on age stratification should be considered in the relevant economic evaluation.
... Seven papers included in this review assessed the economics of using PGT-A as an adjunct to IVF, with the outcome measure of live birth (Table 2). In five studies, the funder perspective was chosen, but three of these also calculated costs from the patient perspective (Lee et al., 2019(Lee et al., , 2021. ...
... In two studies, PGT-A lessened the live birth rate and increased costs (Somigliana et al., 2019;Lee et al., 2021). In the three studies using a health funder perspective and reporting higher live birth rates with PGT-A, the ICER to achieve an additional live birth ranged from an additional $20 507 to $607 833 (Lee et al., 2019;. ...
... (Ozgur et al., 2019;Theobald et al., 2020;Yan et al., 2021). The apparent lack of improvement in clinical efficacy is the driver for the high ICERs noted in this review (Collins et al., 2017;Neal et al., 2018;Lee et al., 2019Lee et al., , 2021Somigliana et al., 2019;. ICSI for non-male infertility does not increase live birth rates (Boulet et al., 2015; American Society for Reproductive Medicine, 2020; Dang et al., 2021) and is therefore not a cost-effective intervention. ...
STUDY QUESTION
Which assited reproductive technology (ART) interventions in high-income countries are cost-effective and which are not?
SUMMARY ANSWER
Among all ART interventions assessed in economic evaluations, most high-cost interventions, including preimplantation genetic testing for aneuploidy (PGT-A) for a general population and ICSI for unexplained infertility, are unlikely to be cost-effective owing to minimal or no increase in effectiveness.
WHAT IS KNOWN ALREADY
Approaches to reduce costs in order to increase access have been identified as a research priority for future infertility research. There has been an increasing number of ART interventions implemented in routine clinical practice globally, before robust assessments of evidence on economic evaluations. The extent of clinical effectiveness of some studied comparisons has been evaluated in high-quality research, allowing more informative decision making around cost-effectiveness.
STUDY DESIGN, SIZE, DURATION
We performed a systematic review and searched seven databases (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS, and CINAHL) for studies examining ART interventions for infertility together with an economic evaluation component (cost-effectiveness, cost-benefit, cost-utility, or cost-minimization assessment), in high-income countries, published since January 2011. The last search was 22 June 2022.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Two independent reviewers assessed publications and included those fulfilling the eligibility criteria. Studies were examined to assess the cost-effectiveness of the studied intervention, as well as the reporting quality of the study. The chosen outcome measure and payer perspective were also noted. Completeness of reporting was assessed against the Consolidated Health Economic Evaluation Reporting Standard. Results are presented and summarized based on the intervention studied.
MAIN RESULTS AND THE ROLE OF CHANCE
The review included 40 studies which were conducted in 11 high-income countries. Most studies (n = 34) included a cost-effectiveness analysis. ART interventions included medication or strategies for controlled ovarian stimulation (n = 15), IVF (n = 9), PGT-A (n = 7), single embryo transfer (n = 5), ICSI (n = 3), and freeze-all embryo transfer (n = 1). Live birth was the mostly commonly reported primary outcome (n = 27), and quality-adjusted life years was reported in three studies. The health funder perspective was used in 85% (n = 34) of studies. None of the included studies measured patient preference for treatment. It remains uncertain whether PGT-A improves pregnancy rates compared to IVF cycles managed without PGT-A, and therefore cost-effectiveness could not be demonstrated for this intervention. Similarly, ICSI in non-male factor infertility appears not to be clinically effective compared to standard fertilization in an IVF cycle and is therefore not cost-effective. Interventions such as use of biosimilars or HMG for ovarian stimulation are cheaper but compromise clinical effectiveness.
LIMITATIONS, REASONS FOR CAUTION
Lack of both preference-based and standardized outcomes limits the comparability of results across studies. The selection of efficacy evidence offered for some interventions for economic evaluations is not always based on high-quality randomized trials and systematic reviews. In addition, there is insufficient knowledge of the willingness to pay thresholds of individuals and state funders for treatment of infertility. There is variable quality of reporting scores, which might increase uncertainty around the cost-effectiveness results.
WIDER IMPLICATIONS OF THE FINDINGS
Investment in strategies to help infertile people who utilize ART is justifiable at both personal and population levels. This systematic review may assist ART funders decide how to best invest to maximize the likelihood of delivery of a healthy child.
STUDY FUNDING/COMPETING INTEREST(S)
There was no funding for this study. E.C. and R.W. receive salary support from the National Health and Medical Research Council (NHMRC) through their fellowship scheme (EC GNT1159536, RW 2021/GNT2009767). M.D.-T. reports consulting fees from King Fahad Medical School. All other authors have no competing interests to declare.
REGISTRATION NUMBER
Prospero CRD42021261537.
... Essentially, we would expect that half of patients would not have a successful live birth with the embryo exhibiting the lowest risk score, such that the previously reported RRRs and ARRs would be much lower than reported in Table 2. Consequently the NNTs would be higher and patients would invariably face transferring embryos that were not their lowest scoring ones. Lastly, PGT-A in patients younger than 35 years old is associated with decreased cumulative live birth rates (41). It is likely that PGT-P would have a similar effect if additional euploid embryos are de-selected or not transferred. ...
... These studies focused only on the live birth rate and cumulative birth rate and ignored other critical characteristics. In recent years, PGT has been widely applied in ART, and many studies have proven that PGT can improve clinical outcomes in ART [39][40][41]. However, none of the studies above explored the correction of the number of oocytes retrieved and the clinical outcomes of the PGT cycle. ...
Background
PGT is widely used in IVF center to improve the clinical outcomes. The number of oocytes retrieved is a critical indicator in IVF-PGT cycle.Therefor, We aim to determine whether the number of retrieved oocytes can affect the clinical outcomes of patients who undergoPGT.
Methods
The participating patients were divided into 6 groups according to the number of oocytes retrieved. The clinical outcomes of patients who underwent PGT and euploid blastocyst transfer at our IVF centre between January 2017 and December 2022 were retrospectively analysed.
Results
A total of 1084 cycles were includedin our study. Patient age and AMH levels were positively correlated with the number of oocytes retrieved and were significantly different among the 6 groups (P<0.001). Basal E2, basal FSH and basal LH levels were also significantlydifferent among the 6 groups (P<0.001). BMI and endometrial thickness did not significantly differ among the 6 groups (P=0.200 and P=0.065, respectively). The MII oocyte rate, 2PN embryo rate, and blastocystrate were significantly different among the 6 groups (P<0.001). However, the proportion of biopsied blastocysts did not significantly differ among the6 groups (P=0.257). The genetic testing revealedthat the euploid blastocyst rate and mosaic blastocyst rate were significantly different among the 6 groups (P=0.014 and P=0.038, respectively). The number of OHSS patients did not significantly differ among the 6 groups (P=0.110). After FET, the implantation rate (P=0.057), ectopicpregnancy rate (P=0.496), miscarriage rate (P=0.986), pretermbirth rate (P=0.051), birth defectrate (P=0.544), neonatal weight (P=0.913) and livebirth rate (P=0.339) did not significantly differ among the6 groups. Both the clinicalpregnancy rate and cumulative live birth rate were significantly different among the 6 groups(P=0.046 and P<0.001, respectively).
Conclusion
Our results suggest that the clinical pregnancy rate and cumulativelive birth rate of 21-25 oocytes increase, after which they plateau and donot increase therisk of OHSS. Thus, 21-25 is theoptimal number of oocytes retrieved in PGT cycles.
... A systematic review scrutinizing the cost-effectiveness analyses of PGT underscores the importance of evaluating these studies based on specific criteria to gauge their overall quality. This comprehensive review likely offers valuable insights into the economic implications of PGT within the context of IVF treatments [53]. Evidence suggests that PGT for aneuploidy proves cost-effective, reduces treatment duration, and diminishes the likelihood of failed embryo transfer. ...
Preimplantation genetic testing (PGT) has become an integral component of assisted reproductive technology (ART), offering couples the opportunity to screen embryos for genetic abnormalities before implantation during in vitro fertilization (IVF). This comprehensive review explores the advancements and applications of PGT in IVF, covering its various types, technological developments, clinical applications, efficacy, challenges, regulatory aspects, and future directions. The evolution of PGT techniques, including next-generation sequencing (NGS) and comparative genomic hybridization (CGH), has significantly enhanced the accuracy and reliability of genetic testing in embryos. PGT holds profound implications for the future of ART by improving IVF success rates, reducing the incidence of genetic disorders, and mitigating the emotional and financial burdens associated with failed pregnancies and genetic diseases. Recommendations for clinicians, researchers, and policymakers include staying updated on the latest PGT techniques and guidelines, exploring innovative technologies, establishing clear regulatory frameworks, and fostering collaboration to maximize the potential benefits of PGT in assisted reproduction. Overall, this review provides valuable insights into the current state of PGT and its implications for the field of reproductive medicine.
... This study provided an evidence for using noninvasive tools for PGT-A and avoiding false positive and negative results [110]. It has been observed that 5% reduction in live births in PGT-A occurs because of damage to embryo caused by biopsy related procedures, and false positive results occurring due to various technical errors [111,112]. ...
Background
Preimplantation genetic testing (PGT), also referred to as preimplantation genetic diagnosis (PGD), is an advanced reproductive technology used during in vitro fertilization (IVF) cycles to identify genetic abnormalities in embryos prior to their implantation. PGT is used to screen embryos for chromosomal abnormalities, monogenic disorders, and structural rearrangements.
Development of PGT
Over the past few decades, PGT has undergone tremendous development, resulting in three primary forms: PGT-A, PGT-M, and PGT-SR. PGT-A is utilized for screening embryos for aneuploidies, PGT-M is used to detect disorders caused by a single gene, and PGT-SR is used to detect chromosomal abnormalities caused by structural rearrangements in the genome.
Purpose of Review
In this review, we thoroughly summarized and reviewed PGT and discussed its pros and cons down to the minutest aspects. Additionally, recent studies that highlight the advancements of PGT in the current era, including their future perspectives, were reviewed.
Conclusions
This comprehensive review aims to provide new insights into the understanding of techniques used in PGT, thereby contributing to the field of reproductive genetics.
... Patients below the age of 35 do not benefit from use of PGT-A to improve LBR [22], so when left with only non-euploid embryos, these patients would likely proceed with a non-PGT IVF cycle, and should be counseled as such. For patients between 35 and 40, PGT-A may be beneficial in improving their outcomes, but the available data is inconclusive [22,23] and non-PGT tested IVF cycles are cost-effective compared to PGT-A cycles [20,24]; thus, patients in this age group should be counseled individually whether to transfer an untested embryo or biopsy it with PGT-A. MET is still a reasonable option for patients in this age group, particularly if treatment cost is a limiting factor. ...
To evaluate the relative live birth rate and net cost difference between mosaic embryo transfer and an additional cycle of IVF with PGT-A for patients whose only remaining embryos are non-euploid.
A decision analytic model was designed with model parameters varying based on discrete age cutoffs (<35, 35–37, 38–39, 40–42, 43–44, >44). Model inputs included probabilities of successful IVF, clinical pregnancy, and live birth as well as costs of IVF with PGT-A, embryo transfer, live birth, amniocentesis, and dilation and curettage. All costs were modeled from the healthcare system perspective and adjusted for inflation to 2023 16,633. For patients older than 42, mosaic embryo transfer resulted in a higher live birth rate (43–44, +5%; >44, +3%; average, +4%) while on average costing $9572 less than an additional cycle of IVF with PGT-A.
Mosaic embryo transfers are a superior alternative to an additional cycle of IVF with PGT-A for patients older than 42 whose only remaining embryos are non-euploid. Mosaic embryo transfers also should be considered for patients younger than 42 who are unable to pursue additional autologous IVF cycles. Counseling and care should be personalized to individual patients and embryos.
... Although it is difficult to quantify, as cycle costs vary considerably, the cost-effectiveness of PGT-A is an increasingly critical issue [16]. Some previous studies argued that it could be cost-effective in specific clinical settings and population groups [17][18][19][20]. Conversely, other studies revealed that PGT-A could not be recommended from a cost-effectiveness perspective [21][22][23]. ...
Background
There are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated.
Objective
To investigate the cost-effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) versus conventional technology in in vitro fertilization (IVF) from the perspective of the healthcare system in China.
Methods
Following the exact steps in the IVF protocol, a decision tree model was developed, based on the data from the CESE-PGS trial and using cost scenarios for IVF in China. The scenarios were compared for costs per patient and cost-effectiveness. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings.
Main outcome measures
Costs per live birth, Costs per patient, Incremental cost-effectiveness for miscarriage prevention.
Results
The average costs per live birth of PGT-A were estimated as ¥39230.71, which is about 16.8% higher than that of the conventional treatment. Threshold analysis revealed that PGT-A would need to increase the pregnancy rate of 26.24–98.24% or a cost reduction of ¥4649.29 to ¥1350.71 to achieve the same cost-effectiveness. The incremental costs per prevented miscarriage was approximately ¥45600.23. The incremental cost-effectiveness for miscarriage prevention showed that the willingness to pay would be ¥43422.60 for PGT-A to be cost-effective.
Conclusion
The present cost-effectiveness analysis demonstrates that embryo selection with PGT‑A is not suitable for routine applications from the perspective of healthcare providers in China, given the cumulative live birth rate and the high costs of PGT‑A.
... Embryo aneuploidy is an objective qualitative factor that is directly affected by intrinsic oocyte quality with definitive implications for ultimate IVF outcome, and now increasingly assessed via the use of preimplantation genetic testing for aneuploidy (PGT-A). Although its use and clinical utility remain controversial [28][29][30], the differentiation between PGT and non-PGT cycles in the SART-CORS data base beginning in 2014 provides an opportunity to correlate AMH and risk of aneuploidy as assessed by PGT. ...
Background:
While anti-Müllerian hormone (AMH) predicts quantitative IVF outcomes such as oocyte yield, it is not certain whether AMH predicts markers of oocyte quality such as aneuploidy.
Methods:
Retrospective case-control analysis of the SART-CORS database, 2014-2016, to determine whether anti-Müllerian hormone (AMH) predicts aneuploidy and live birth in IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A).
Results:
Of 51,273 cycles utilizing PGT-A for all embryos, 10,878 cycles were included in the final analysis; of these, 2,100 cycles resulted in canceled transfer due to lack of normal embryos and 8,778 cycles resulted in primary FET. AMH levels of cycles with ≥ 1 euploid embryo were greater than those of cycles with no normal embryos, stratifying by number of embryos biopsied (1-2, 3-4, 5-6, and ≥ 7), P < 0.017 for each stratum. Adjusting for age and number of embryos biopsied, AMH was a significant independent predictor of ≥ 1 euploid embryo for all age groups: < 35 yrs (aOR 1.074; 95%CI 1.005-1.163), 35-37 years (aOR 1.085; 95%CI 1.018-1.165) and ≥ 38 years (aOR 1.055; 95%CI 1.020-1.093). In comparative model analysis, AMH was superior to age as a predictor of ≥ 1 euploid embryo for age groups < 35 years and 35-37 years, but not ≥ 38 years. Across all cycles, age (aOR 0.945, 95% CI 0.935-0.956) and number of embryos (aOR 1.144, 95%CI 1.127-1.162) were associated with live birth per transfer, but AMH was not (aOR 0.995, 95%CI 0.983-1.008). In the subset of cycles resulting in ≥ 1 euploid embryo for transfer, neither age nor AMH were associated with live birth.
Conclusions:
Adjusting for age and number of embryos biopsied, AMH independently predicted likelihood of obtaining ≥ 1 euploid embryo for transfer in IVF PGT-A cycles. However, neither age nor AMH were predictive of live birth once a euploid embryo was identified by PGT-A for transfer. This analysis suggests a predictive role of AMH for oocyte quality (aneuploidy risk), but not live birth per transfer once a euploid embryo is identified following PGT-A.
... A screening test is the testing of unaffected people to find those at increased risk of having a disease or disorder. From a cost-effectiveness perspective, routinely adding PGT-A should not be recommended [9][10][11]. As of late 2022, there is no established diagnostic test that can be applied during early embryological stages to confirm the PGT-A results. ...
Preimplantation genetic testing for aneuploidy (PGT-A) has been used widely during in vitro fertilization procedures in assisted reproductive centers throughout the world. Despite its wide use, concerns arise from the use of PGT-A technology in clinical decision-making. We address knowledge gaps in PGT-A, summarizing major challenges and current professional guidelines. First, PGT-A is a screening test and not a diagnostic test. Second, mosaicism is much higher in the blastocyst stage from PGT-A than had been recognized previously and a mosaic embryo may not accurately represent the genetic disease risk for future fetal disorders. Third, PGT-A was not validated clinically before use in patients; the best use of this technology for selected age-groups remains uncertain. Given these gaps, we believe that current professional policies relying on industry-self-regulation are insufficient. In the USA, the Food and Drug Administration may be the most appropriate agency to provide more definitive guidelines and regulations that are needed for better practice.
... However, a substantial proportion of the transferred euploid embryos fail to undergo successful implantation. According to the registry of the Society for Assisted Reproductive Technology, USA, females <35 years of age undergoing elective single embryo transfer after PGT-A have a cumulative live birth rate of approximately 55% [1] . This observation highlights the possibility of endometrial defects, at least in part, in cases of failed implantation, though functional defects of the transferred embryos other than aneuploidy cannot be excluded. ...
... In the United States, current cost estimates range from $12,000 to $26,000 per in vitro fertilization (IVF) cycle (or $30,000 to $60,000 for IVF-donor egg cycles) and $40,000 to $85,000 per live birth using IVF, as more than one cycle is often needed; $100,000 to $150,000 for gestational carrier; and $20,000 to $70,000 for adoption. [10][11][12][13] Total costs can be difficult to predict, however, given the uncertainty surrounding the ART procedures needed (e.g., number of IVF cycles to achieve pregnancy), extent of insurance coverage, and legal and logistical difficulties, particularly, with surrogacy and adoption (e.g., lawyer fees, travel). ...
Purpose: Adolescent and young adult (AYA) survivors are at-risk for cancer-related financial difficulties (i.e., financial toxicity [FT]). Family building after cancer often requires reproductive medicine or adoption with high costs; AYAs experience financial barriers to family building. This study evaluated the relationships among cancer FT, reproductive concerns, and decision-making processes about family building after cancer. Methods: AYA female (AYA-F) cancer survivors completed a cross-sectional survey including measures of FT, reproductive concerns, decisional conflict about family building, and decision-making self-efficacy. Differences across FT subgroups (i.e., no/mild, moderate, and severe FT) were tested. Linear regression evaluated the relationships between FT and reproductive concerns and decision-making processes. Results: Participants (N = 111) averaged 31.0 years (standard deviation [SD] = 5.49), 90% were nulliparous, and 84% were employed full/part-time. The overall FT levels were in the "moderate" range (M = 20.44, SD = 9.83); 48% worried quite a bit or very much about financial problems because of cancer. AYA-Fs reporting severe FT (24% of sample) experienced higher levels of reproductive concerns compared with those reporting no/mild and moderate FT. Those reporting moderate FT (46% of sample) reported greater decisional conflict about family-building options, compared with the no/mild FT subgroup. Both moderate and severe FT subgroups reported lower decision-making self-efficacy compared with the no/mild FT subgroup. In separate models controlling for covariates, greater FT related to higher levels of reproductive concerns (B = -0.39, p < 0.001), greater decisional conflict about family building (B = -0.56, p = 0.02), and lower decision-making self-efficacy (B = 0.60, p = 0.01). Conclusions: Given the high costs of reproductive medicine and adoption, fertility counseling pre- and post-treatment must address survivors' financial concerns and barriers.
... Despite the conflicting evidence of the effectiveness of preimplantation genetic testing (PGT) in improving ART success rates [63][64][65][66][67], it is widely used as an embryo selection tool in many IVF clinics [65]. This growing demand for PGT has led to the development of AI integrated platforms such as PGTai SM (CooperSurgical, Denmark), a predictor algorithm that increases the sensitivity, efficiency, and objectivity of PGT-aneuploidy (PGT-A) sequencing data analysis by reducing human involvement in the process. ...
In vitro fertilisation (IVF) is estimated to account for the birth of more than nine million babies worldwide, perhaps making it one of the most intriguing as well as commoditised and industrialised modern medical interventions. Nevertheless, most IVF procedures are currently limited by accessibility, affordability and most importantly multistep, labour-intensive, technically challenging processes undertaken by skilled professionals. Therefore, in order to sustain the exponential demand for IVF on one hand, and streamline existing processes on the other, innovation is essential. This may not only effectively manage clinical time but also reduce cost, thereby increasing accessibility, affordability and efficiency. Recent years have seen a diverse range of technologies, some integrated with artificial intelligence, throughout the IVF pathway, which promise personalisation and, at least, partial automation in the not-so-distant future. This review aims to summarise the rapidly evolving state of these innovations in automation, with or without the integration of artificial intelligence, encompassing the patient treatment pathway, gamete/embryo selection, endometrial evaluation and cryopreservation of gametes/embryos. Additionally, it shall highlight the resulting prospective change in the role of IVF professionals and challenges of implementation of some of these technologies, thereby aiming to motivate continued research in this field.
Graphical abstract
... Учитывая, что анеуплоидии чаще всего выступают основной причиной невынашивания беременности (НБ) на ранних сроках, в большинстве центров в подавляющем большинстве случаев проводится исследование ПГТ, направленное на выявление количественных хромосомных изменений в клетках эмбриона (ПГТ-А) [4]. Несмотря на повышение стоимости программы ВРТ с применением ПГТ-А, существуют исследования, в которых показано, что определение хромосомного статуса эмбриона в определенных клинических ситуациях является экономически более выгодным [5][6][7][8]. Результаты ряда исследований показали, что проведение ПГТ-А позволяет сэкономить до 45% средств, затраченных на проведение протокола экстракорпорального оплодотворения/интрацитоплазматической инъекции сперматозоида, для достижения дополнительного 1% живорождения [6]. Тем не менее результаты других научных работ продемонстрировали отсутствие убедительных доказательств в пользу эффективности ПГТ в отношении увеличения числа живорождений [9]. ...
Introduction. A clinical and economic study was carried out to assess the effectiveness of infertility treatment using assisted reproductive technology programs with preimplantation genetic testing (PGT) in patients with various reproductive disorders.
Materials and methods. Twenty models representing discrete-time Markov processes are developed. A total of 10 possible paired scenarios for couples undergoing infertility treatment using assisted reproductive technology, depending on reproductive disorders and the use of PGT, were considered in the study.
Results. The most cost-effective scenarios from the simulation results should be the use of PGT in the group of females aged 3742 years and in the group of females under 35 years with missed abortion. These scenarios are not only resource-efficient in terms of the willingness-to-pay threshold, but they also preserve compulsory health insurance funds still with meaningful clinical efficiency. The remaining scenarios are characterized by significant clinical efficacy and low cost per added live birth, except for the PGT use in the group of males with teratozoospermia, which is characterized by a minimum of added live births and a maximum cost per added live birth.
Conclusion. The study results indicate the most optimal and economically feasible scenarios of PGT in patients depending on the infertility factor for implementation in the practical healthcare system of the Russian Federation.
... For these reasons, the decision tree model has been applied in several medicine branches, such as gastroenterology [36,37], breast oncological surgery [38], cardiology [39], orthopedic surgery [40], and even to diagnose SARS-CoV-2 infection [41]. Specifically in the ART setting, the decision tree model has been previously applied mainly in cost-effectiveness analyses, for instance to identify the most cost-effective ovarian stimulation drug for intra-uterine insemination (IUI) [42]; to evaluate the clinical utility for preimplantation genetic assessment for aneuploidy after IVF in the USA [43], and in Germany [44]; to highlight anti-Müllerian hormone (AMH) serum levels as informative for stimulation dose management for optimizing blastocyst development [45]; and to identify the most cost-effective policy in terms of ART success in case of female age below 38 years comparing expectant management, IUI with ovarian stimulation and IVF [46]. Moreover, a decision tree was applied to develop a model combining AMH, antral follicle counts, FSH basal levels and female age to obtain the true ovarian reserve [47], and to compare GnRH-agonist long protocol to GnRH-antagonist protocol in IVF, highlighting that GnRH-antagonist introduces an economic advantage in case of fresh embryos, while the GnRH-agonist long protocol is preferable considering the cumulative pregnancy rate using both fresh and frozen embryos [48]. ...
Purpose
Several mathematical models have been developed to estimate individualized chances of assisted reproduction techniques (ART) success, although with limited clinical application. Our study aimed to develop a decisional algorithm able to predict pregnancy and live birth rates after controlled ovarian stimulation (COS) phase, helping the physician to decide whether to perform oocytes pick-up continuing the ongoing ART path.
Methods
A single-center retrospective analysis of real-world data was carried out including all fresh ART cycles performed in 1998–2020. Baseline characteristics, ART parameters and biochemical/clinical pregnancies and live birth rates were collected. A seven-steps systematic approach for model development, combining linear regression analyses and decision trees (DT), was applied for biochemical, clinical pregnancy, and live birth rates.
Results
Of fresh ART cycles, 12,275 were included. Linear regression analyses highlighted a relationship between number of ovarian follicles > 17 mm detected at ultrasound before pick-up (OF17), embryos number and fertilization rate, and biochemical and clinical pregnancy rates (p < 0.001), but not live birth rate. DT were created for biochemical pregnancy (statistical power–SP:80.8%), clinical pregnancy (SP:85.4%), and live birth (SP:87.2%). Thresholds for OF17 entered in all DT, while sperm motility entered the biochemical pregnancy’s model, and female age entered the clinical pregnancy and live birth DT. In case of OF17 < 3, the chance of conceiving was < 6% for all DT.
Conclusion
A systematic approach allows to identify OF17, female age, and sperm motility as pre-retrieval predictors of ART outcome, possibly reducing the socio-economic burden of ART failure, allowing the clinician to perform or not the oocytes pick-up.
... Of note, only starting at the age 39, was the incremental cost per live birth favoring PGT-A from a patient perspective. 45 We agree with recommendations in favor of expectant management in most cases of RPL explained by ASRM or ESHRE guidelines. But we believe there might be a role for PGT-A in RPL, especially in cases with recurrent POC aneuploidy as identified by one of our proposed algorithms, 7 as well as in cases unexplained by ASRM or ESHRE workups having one episode of aneuploidy diagnosed as identified by the latest proposed criteria by our group. ...
Recurrent pregnancy loss (RPL) is an obstetrical complication that affects about 3% of reproductive age couples. Genetic and non-genetic causes of RPL are multiple; however, aneuploidy is the most common obstetrical complication that can explain single and recurrent pregnancy loss (present in about 60% of recognized clinical pregnancies which result in a miscarriage). Parental karyotyping will only be of potential benefit for 2 to 5 percentage of RPL couples who are translocation carriers. Products of conception (POC) karyotype analysis has been used to direct management in RPL and has been shown to be cost-effective, but the technique has many limitations including high culture failure rate and maternal cell contamination. These limitations can be significantly reduced using POC chromosomal microarray (CMA) technology. We believe that POC genetic testing should be performed after the second and subsequent pregnancy loss using CMA. Although the results will not generally alter the course of treatment, the knowledge of the reason for the loss is of great emotional comfort to many patients. In addition, POC CMA performed in conjunction with a regular complete maternal RPL work-up will identify the group of truly unexplained RPL. Thus, only 10% of patients with RPL will complete an evaluation having a euploid loss and an otherwise normal work-up. This group of “truly unexplained RPL” would be ideal for new research trials and therapies. Pre-implantation genetic testing (PGT) technology has improved recently with day 5 trophectoderm biopsy as compared to biopsy on day 3 as well as with the addition of CMA and next-generation sequencing technologies. The most recent studies on PGT-SR (PGT-Structural rearrangement) show improved clinical and live birth rates per pregnancy, as well as decreased miscarriage rate for translocation carriers. PGT-A (PGT-aneuploidy) may have a limited role in RPL in cases with documented recurrent POC aneuploidy.
Objective
To compare the effectiveness and cost of in‐vitro fertilization (IVF) with or without preimplantation genetic testing for aneuploidy (PGT‐A) when only one or two blastocysts are obtained.
Methods
A dataset was gathered from 1829 patients including 368 non‐PGT‐A and 1461 PGT‐A cycles with one or two blastocysts obtained, between April 2013 and July 2022. Patients were matched 1:1 by propensity‐score matching for maternal age, number of metaphase‐II oocytes inseminated and number of blastocysts obtained, achieving a database of 242 patients per group. The non‐PGT‐A and PGT‐A groups were compared for differences in live birth rate (LBR) per embryo transfer (ET), cumulative LBR per patient, miscarriage rate (MR) per clinical pregnancy, number of days between oocyte retrieval and conclusion of the IVF cycle (primary outcome), mean expenses incurred at the clinic and incremental cost‐effectiveness ratio (ICER).
Results
More than twice as many ETs were conducted in the non‐PGT‐A group compared with the PGT‐A group, yet the cumulative LBR per patient was similar between groups (23.6% (95% CI, 18.5–29.5%) vs 27.3% (95% CI, 21.9–33.4%)). This outcome was achieved with a higher LBR per ET (16.2% (95% CI, 12.6–20.5%) vs 41.5% (95% CI, 33.9–49.4%)) and lower MR per clinical pregnancy (30.1% (95% CI, 21.8–42.6%) vs 13.9% (95% CI, 7.5–24.0%)) in the PGT‐A group. The MR per patient was also lower in the PGT‐A group (9.5% (95% CI, 6.2–14.1%) vs 4.5% (95% CI, 2.4–8.2%)). The mean duration between oocyte retrieval and IVF cycle conclusion was 131 (95% CI, 113–150) days in the non‐PGT‐A group vs 74 (95% CI, 61–87) days in the PGT‐A group ( P < 0.001; power = 99.8%). The ICER of PGT‐A for the months saved between oocyte retrieval and conclusion of the IVF cycle was €499 overall, ranging between €170 and €2065 according to the number of blastocysts obtained and/or maternal age. The ICER of PGT‐A for prevented miscarriages was €18 968, decreasing to €3525 when calculated among patients aged ≥ 35 years with two blastocysts obtained.
Conclusions
When conducted in expert IVF clinics for patients indicated for the procedure, PGT‐A is clinically valuable even when only one or two blastocysts are obtained. PGT‐A reduces the number of ETs and miscarriages while the cumulative LBR per patient remains unaffected, and allows these outcomes to be achieved in a shorter timeframe. The ICER of PGT‐A vs non PGT‐A decreased as maternal age increased. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.
The use of novel technologies in the selection of embryos during in vitro fertilisation (IVF) has the potential to improve the chances of pregnancy and birth of a healthy child. However, it is important to be aware of the potential risks and unintended consequences that may arise from the premature implementation of these technologies. This article discusses the ethical considerations surrounding the use of novel embryo selection technologies in IVF, including the growing uptake of genetic testing and others, and argues that prioritising embryos for transfer using these technologies is acceptable, but discarding embryos based on unproven advances is not. Several historical examples are provided, which demonstrate possible harms, where the overall chance of pregnancy may have been reduced, and some patients may have missed out on biological parenthood altogether. We emphasise the need for caution and a balanced approach to ensure that the benefits of these technologies outweigh any potential harm. We also highlight the primacy of patients' autonomy in reproductive decision-making, especially when information gained by utilising novel technologies is imprecise.
Objectives
This research aims to assess the effectiveness and cost-effectiveness of pre-pregnancy deafness screening policies.
Methods
Married couples from Shanghai, Beijing, and Suzhou in China were enrolled. We conducted high-throughput, pre-pregnancy genetic screenings for deafness in women and their partners. We compared the cost-effectiveness of deafness genetic screening with the status quo. The two-step screening (wife then partner) and following treatments and interventions were included in the decision tree model. We conducted a cost-effectiveness analysis based on the decrease in deaf newborns, healthy newborn births, and cost-utility analysis of pre-pregnancy deafness genetic screening separately. Cost, utility, and probability data used in the three models were collected from a survey combined with literature and expert consultants. A 5% discount rate and a series of one-way sensitivity analyses along with a Monte Carlo simulation were used to test the reliability of this research.
Results
Between Jan 1, 2019, and Dec 31, 2021, we recruited 6,200 females and 540 male spouses from community health service centers in Shanghai, Beijing, and Suzhou. The incremental cost-effectiveness ratio (ICER) for reducing deaf newborn births was USD 32,656 per case and USD 1,203,926 per case for increasing one healthy newborn birth. This gap exists because of the overall decrease of newborn births. From the perspective of the whole society, deafness genetic screening is not cost-effective for reducing the overall quality-adjusted life years (QALY) in the population.
Discussion
Pre-pregnancy genetic testing is effective in decreasing the occurrence of congenital deafness. It is a cost-saving measure when compared with the costs of future medical expenditure and income loss for the affected families. However, such screening and preventive avoidance of pregnancy will decrease the population size and QALY. Only post-screening ART with PGT was shown to increase the birth of healthy newborns. Focusing on key groups such as premature births or consanguineous couples may improve the societal effects of screening.
Tremendous advances in genetics have transformed the field of reproductive endocrinology and infertility (REI) over the last few decades. One of the most prominent advances is preimplantation genetic testing (PGT), which allows for screening of embryos obtained during in vitro fertilization prior to transfer. PGT can be performed for aneuploidy screening (PGT-A), detection of monogenic disorders (PGT-M), or exclusion of structural rearrangements (PGT-SR). Refinement of biopsy techniques, such as obtaining samples at the blastocyst rather than cleavage stage, has helped optimize results from PGT, and technological advances including next generation sequencing have made PGT more efficient and accurate. Continued evolution of the approach to PGT has the potential to further enhance the accuracy of results, expand the application to other conditions, and increase access by reducing cost and improving efficiency.
Importance
Multiple gestation is one of the biggest risks after in vitro fertilization (IVF), largely due to multiple embryo transfer (MET). Single embryo transfer (SET) uptake has increased over time and has been attributed to various factors, such as mandated insurance coverage for IVF and preimplantation genetic testing for aneuploidy (PGT-A).
Objective
To investigate whether mandates for IVF insurance coverage are associated with decreased use of MET after PGT-A.
Design, Setting, and Participants
This cohort study was conducted using data on embryo transfers reported to the Society for Assisted Reproductive Technology between 2014 and 2016. Data were analyzed from January to October 2021.
Exposures
State-mandated coverage for fertility treatment and type of cycle transfer performed (PGT-A, untested fresh, and untested frozen).
Main Outcomes and Measures
Use of MET compared with SET, live birth, and live birth of multiples.
Results
There were 110 843 embryo transfers (mean [SD] patient age, 34.0 [4.5] years; 5520 individuals identified as African American [5.0%], 10 035 as Asian [9.0%], 5425 as Hispanic [4.9%], 45 561 as White [41.1%], and 44 302 as other or unknown race or ethnicity [40.0%]); 17 650 transfers used embryos that underwent PGT-A. Overall, among transferred embryos that had PGT-A, there were 9712 live births (55.0%). The odds of live birth were 70% higher with MET vs SET after frozen embryo transfer with PGT-A (OR, 1.70; 95% CI, 1.61-1.78), but the risk of multiples was 5 times higher (OR, 5.33; 95% CI, 5.22-5.44). The odds of MET in cycles with PGT-A in states with insurance mandates were 24% lower than in states without mandates (OR, 0.76; 95% CI, 0.68-0.85).
Conclusions and Relevance
This study found that despite the promise of using SET with PGT-A, MET after PGT-A was not uncommon. This practice was more common in states without insurance mandates and was associated with a high risk of multiples.
Study question:
Has the number of preimplantation genetic testing (PGT) cycles in the UK and USA changed between 2014 and 2016?
Summary answer:
From 2014 to 2016, the number of PGT cycles in the UK has remained the same at just under 2% but in the USA has increased from 13% to 27%.
What is known already:
PGT was introduced as a treatment option for couples at risk of transmitting a known genetic or chromosomal abnormality to their child. This technology has also been applied as an embryo selection tool in the hope of increasing live birth rates per transfer. ART cycles are monitored in the UK by the Human Fertilisation and Embryology Authority (HFEA) and in the USA by the Society for Assisted Reproductive Technology (SART). Globally, data are monitored via the ESHRE PGT Consortium.
Study design, size, duration:
This cross-sectional study used the HFEA and SART databases to analyse PGT cycle data and make comparisons with IVF data to examine the success of and changes in patient treatment pathways. Both data sets were analysed from 2014 to 2016. The UK data included 3385 PGT cycles and the USA data included 94 935 PGT cycles.
Participants/materials, setting, methods:
Following an extensive review of both databases, filters were applied to analyse the data. An assessment of limitations of each database was also undertaken, taking into account data collection by the ESHRE PGT Consortium. In the UK and USA, the publicly available information from these datasets cannot be separated into different indications.
Main results and the role of chance:
The proportion of PGT cycles as a total of ART procedures has remained the same in the UK but increased annually in the USA from 13% to 27%. Between 2014 and 2016 inclusive, 3385 PGT cycles have been performed in the UK, resulting in 1074 PGT babies being born. In the USA 94 935 PGT cycles have been performed, resulting in 26 822 babies being born. This gave a success rate per egg collection for PGT of 32% for the UK and 28% for the USA. Analysis of the data by maternal age shows very different patient populations between the UK and USA. These differences may be related to the way PGT is funded in the UK and USA and the lack of HFEA support for PGT for aneuploidy.
Limitations, reasons for caution:
Data reported by the HFEA and SART have different limitations. As undertaken by the ESHRE PGT Consortium, both data sets should separate PGT data by indication. Although the HFEA collects data from all IVF clinics in the UK, SART data only represent 83% of clinics in the USA.
Wider implications of the findings:
Worldwide, a consistent reporting scheme is required in which success rates can convey the effectiveness of PGT approaches for all indications.
Study funding/competing interest(s):
No specific funding was obtained and there are no competing interests to declare that are directly related to this project. Joyce Harper is the director of the Embryology and PGD Academy, which offers education in these fields.
Objective:
To evaluate the benefit of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) for embryo selection in frozen-thawed embryo transfer.
Design:
Randomized controlled trial.
Setting:
Not applicable.
Patient(s):
Women aged 25-40 years undergoing IVF with at least two blastocysts that could be biopsied.
Intervention(s):
Randomization for single frozen-thawed embryo transfer with embryo selection based on PGT-A euploid status versus morphology.
Main outcome measure(s):
Ongoing pregnancy rate (OPR) at 20 weeks' gestation per embryo transfer.
Result(s):
A total of 661 women (average age 33.7 ± 3.6 years) were randomized to PGT-A (n = 330) or morphology alone (n = 331). The OPR was equivalent between the two arms, with no significant difference per embryo transfer (50% [137/274] vs. 46% [143/313]) or per intention to treat (ITT) at randomization (41.8% [138/330] vs. 43.5% [144/331]). Post hoc analysis of women aged 35-40 years showed a significant increase in OPR per embryo transfer (51% [62/122] vs. 37% [54/145]) but not per ITT.
Conclusion(s):
PGT-A did not improve overall pregnancy outcomes in all women, as analyzed per embryo transfer or per ITT. There was a significant increase in OPR per embryo transfer with the use of PGT-A in the subgroup of women aged 35-40 years who had two or more embryos that could be biopsied, but this was not significant when analyzed by ITT.
Clinical trial registration number:
NCT02268786.
Purpose:
To determine the expected out-of-pocket costs of IVF with preimplantation genetic testing for aneuploidy (PGT-A) to attain a 50%, 75%, or 90% likelihood of a euploid blastocyst based on individual age and AMH, and develop a personalized counseling tool.
Methods:
A cost analysis was performed and a counseling tool was developed using retrospective data from IVF cycles intended for PGT or blastocyst freeze-all between January 1, 2014 and August 31, 2017 (n = 330) and aggregate statistics on euploidy rates of > 149,000 embryos from CooperGenomics. Poisson regression was used to determine the number of biopsiable blastocysts obtained per cycle, based on age and AMH. The expected costs of attaining a 50%, 75%, and 90% likelihood of a euploid blastocyst were determined via 10,000 Monte Carlo simulations for each age and AMH combination, incorporating age-based euploidy rates and IVF/PGT-A cost assumptions.
Results:
The cost to attain a 50% likelihood of a euploid blastocyst ranges from approximately 150,000 for the oldest women (44 years) with the lowest AMH values (< 0.1 ng/mL) in this cohort. The cost to attain a 75% versus 90% likelihood of a euploid blastocyst is similar (~ 280,000 and > 30,000 for a 90% likelihood of attaining a euploid embryo.
Conclusions:
This tool can serve as a counseling adjunct by providing individualized cost information for patients regarding PGT-A.
Purpose:
Adding preimplantation genetic screening to in vitro fertilization has been shown to increase live birth rate in women older than 37. However, preimplantation genetic screening is an expensive procedure. Information on the cost-effectiveness of preimplantation genetic screening can help inform clinical decision making.
Methods:
We constructed a decision analytic model for a hypothetical fresh, autologous in vitro fertilization cycle (with versus without preimplantation genetic screening) for women older than age 37 who had a successful oocyte retrieval and development of at least one blastocyst. The model incorporated probability and cost estimates of relevant clinical events based on data from published literature. Sensitivity analyses were performed to examine the impact of changes in model input parameters.
Results:
In base-case analysis, IVF-PGS offered a 4.2 percentage point increase in live birth rate for an additional cost of 105,489 per additional live birth. This ICER was below the expected cost of 19,415 per cycle for this patient population). Sensitivity analysis suggested that ICER improved substantially with decreases in PGS cost and increases in PGS effectiveness. Monte Carlo simulation showed PGS to be cost-effective in 93.9% of iterations at an acceptability cutoff of $145,063.
Conclusions:
Considering the expected cost of achieving one live birth with IVF, PGS is a cost-effective strategy for women older than 37 undergoing IVF. Additional research on patients' willingness-to-pay per live birth would further inform our understanding regarding the cost-effectiveness of PGS.
The Society for Assisted Reproductive Technology (SART) was established within a few years of assisted reproductive technology (ART) in the United States, and has not only reported on the evolution of infertility care, but also guided it toward improved success and safety. Moving beyond its initial role as a registry, SART has expanded its role to include quality assurance, data validation, practice and advertising guidelines, research, patient education and advocacy, and membership support. The success of ART in this country has greatly benefited from SART's role, as highlighted by a series of graphs. SART continues to set the standard and lead the way.
The purpose of this study was to document cost that is associated with multiple births vs singleton births in the United States.
This was a retrospective cohort study that used a claims database. Women 19-45 years old with live-born infants from 2005-2010 were identified. Infant deliveries were identified by International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes. The cost entailed all payment made by insurers and patients. For mothers, the cost included expenses from 27 weeks before delivery to 1 month after delivery. For infants, the cost contained all expenses until their first birthday. Adjusted cost was estimated by generalized linear models after adjustment for the potential confounding variables with a gamma distribution and a log link.
The analysis included 437,924 eligible deliveries. Of them, 97.02% were singletons; 2.85% were twins, and 0.13% was triplets or more. Women with multiple pregnancies had higher systemic and localized comorbidities compared with women with singleton pregnancies (P < .0001). Twins and triplets or more were more likely to have stayed in a neonatal intensive care unit than were singletons (P < .0001). On average, adjusted total all-cause health care cost was 21,302-21,614) per delivery with singletons, 103,402-106,280) with twins, and 384,984-430,695) with triplets or more.
Pregnancies with the delivery of twins cost approximately 5 times as much when compared with singleton pregnancies; pregnancies with delivery of triplets or more cost nearly 20 times as much.
To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility.
Adaptive decision model.
Academic infertility clinic.
A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF.
Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes.
Live birth rate, incremental cost-effectiveness ratio (ICER).
In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI (29,666.
In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI.
Objective:
To determine whether performing comprehensive chromosome screening (CCS) and transferring a single euploid blastocyst can result in an ongoing pregnancy rate that is equivalent to transferring two untested blastocysts while reducing the risk of multiple gestation.
Design:
Randomized, noninferiority trial.
Setting:
Academic center for reproductive medicine.
Patient(s):
Infertile couples (n = 205) with a female partner less than 43 years old having a serum anti-Müllerian hormone level ≥ 1.2 ng/mL and day 3 FSH <12 IU/L.
Intervention(s):
Randomization occurred when at least two blastocysts were suitable for trophectoderm biopsy. The study group (n = 89) had all viable blastocysts biopsied for real-time, polymerase chain reaction-based CCS and single euploid blastocyst transfer. The control group (n = 86) had their two best-quality, untested blastocysts transferred.
Main outcome measure(s):
The ongoing pregnancy rate to ≥ 24 weeks (primary outcome) and the multiple gestation rate.
Result(s):
The ongoing pregnancy rate per randomized patient after the first ET was similar between groups (60.7% after single euploid blastocyst transfer vs. 65.1% after untested two-blastocyst transfer; relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2). A difference of greater than 20% in favor of two-blastocyst transfer was excluded. The risk of multiple gestation was reduced after single euploid blastocyst transfer (53.4% to 0%), and patients were nearly twice as likely to have an ongoing singleton pregnancy (60.7% vs. 33.7%; RR, 1.8; 95% CI, 1.3-2.5).
Conclusion(s):
In women ≤ 42 years old, transferring a single euploid blastocyst results in ongoing pregnancy rates that are the same as transferring two untested blastocysts while dramatically reducing the risk of twins.
Single embryo transfer (SET) remains underutilized as a strategy to reduce multiple gestation risk in IVF, and its overall lower pregnancy rate underscores the need for improved techniques to select one embryo for fresh transfer. This study explored use of comprehensive chromosomal screening by array CGH (aCGH) to provide this advantage and improve pregnancy rate from SET.
First-time IVF patients with a good prognosis (age <35, no prior miscarriage) and normal karyotype seeking elective SET were prospectively randomized into two groups: In Group A, embryos were selected on the basis of morphology and comprehensive chromosomal screening via aCGH (from d5 trophectoderm biopsy) while Group B embryos were assessed by morphology only. All patients had a single fresh blastocyst transferred on d6. Laboratory parameters and clinical pregnancy rates were compared between the two groups.
For patients in Group A (n = 55), 425 blastocysts were biopsied and analyzed via aCGH (7.7 blastocysts/patient). Aneuploidy was detected in 191/425 (44.9%) of blastocysts in this group. For patients in Group B (n = 48), 389 blastocysts were microscopically examined (8.1 blastocysts/patient). Clinical pregnancy rate was significantly higher in the morphology + aCGH group compared to the morphology-only group (70.9 and 45.8%, respectively; p = 0.017); ongoing pregnancy rate for Groups A and B were 69.1 vs. 41.7%, respectively (p = 0.009). There were no twin pregnancies.
Although aCGH followed by frozen embryo transfer has been used to screen at risk embryos (e.g., known parental chromosomal translocation or history of recurrent pregnancy loss), this is the first description of aCGH fully integrated with a clinical IVF program to select single blastocysts for fresh SET in good prognosis patients. The observed aneuploidy rate (44.9%) among biopsied blastocysts highlights the inherent imprecision of SET when conventional morphology is used alone. Embryos randomized to the aCGH group implanted with greater efficiency, resulted in clinical pregnancy more often, and yielded a lower miscarriage rate than those selected without aCGH. Additional studies are needed to verify our pilot data and confirm a role for on-site, rapid aCGH for IVF patients contemplating fresh SET.
Objective:
To evaluate the economical benefit of preimplantation genetic testing of aneuploidies (PGT-A) when applied in an extended culture and stringent elective single ET framework.
Design:
Theoretical cost-effectiveness study.
Setting:
Not applicable.
Patients/animal(s):
None.
Intervention(s):
Comparison of the cost-effectiveness between two IVF treatment strategies: serial transfer of all available blastocysts without genetic testing (first fresh transfer and subsequent frozen-thawed transfer); and systematic use of genetic testing (trophectoderm biopsy, freeze-all, and frozen-thawed transfers of euploid blastocysts). The costs considered for this analysis are based on regional public health system provider.
Main outcome measure(s):
Costs per live birth.
Result(s):
Cost-effectiveness profile of PGT-A improves with female age and number of available blastocysts. Sensitivity analyses varying the costs of ET, the costs of genetic analyses, the magnitude of the detrimental impact of PGT-A on live birth rate, and the crude live birth rates change to some extent the thresholds for effectiveness but generally confirm the notion that PGT-A can be economically advantageous in some specific subgroups.
Conclusion(s):
PGT-A can be cost-effective in specific clinical settings and population groups. Economic considerations deserve attention in the debate regarding the clinical utility of PGT-A.
Objective:
To determine if preimplantation genetic testing for aneuploidy (PGT-A) is cost-effective for patients undergoing in vitro fertilization (IVF).
Design:
Decision analytic model comparing costs and clinical outcomes of two strategies: IVF with and without PGT-A.
Setting:
Genetics laboratory.
Patients:
Women ≤ 42 years of age undergoing IVF.
Intervention(s):
Decision analytic model applied to the above patient population utilizing a combination of actual clinical data and assumptions from the literature regarding the outcomes of IVF with and without PGT-A.
Main outcome measure(s):
The primary outcome was cumulative IVF-related costs to achieve a live birth or exhaust the embryo cohort from a single oocyte retrieval. The secondary outcomes were time from retrieval to the embryo transfer resulting in live birth or completion of treatment, cumulative live birth rate, failed embryo transfers, and clinical losses.
Results:
8,998 patients from 74 IVF centers were included. For patients with greater than one embryo, the cost differential favored the use of PGT-A, ranging from $931-2411 and depending upon number of embryos screened. As expected, the cumulative live birth rate was equivalent for both groups once all embryos were exhausted. However, PGT-A reduced time in treatment by up to four months. In addition, patients undergoing PGT-A experienced fewer failed embryo transfers and clinical miscarriages.
Conclusion:
For patients with > 1 embryo, IVF with PGT-A reduces healthcare costs, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage when compared to IVF alone.
The value of preimplantation genetic testing for aneuploidy (PGT-A) as a screening test for in vitro fertilization (IVF) patients has yet to be determined. Several studies demonstrate higher birth rates after aneuploidy testing and elective single-embryo transfer (eSET), suggesting the potential for this testing to decrease the risk of multiple gestations, though these studies have important limitations.
Study question:
What is the live-birth rate (LBR) and cost-effectiveness of fertility preservation with oocyte cryopreservation (FP-OC) compared to expectant management in cancer patients age 25-40 based on estimated gonadotoxicity of treatments 5 years after cancer diagnosis?
Summary answer:
Oocyte cryopreservation prior to cancer treatment is more costly, yet more effective (producing more live births), than not undergoing oocyte cryopreservation but it is most beneficial for patients undergoing high-risk chemotherapy (HRC).
What is known already:
The decision to undergo FP prior to treatment is multifactorial and can be costly and delay treatment. Not all treatments carry the same gonadotoxicity and patients may choose to undergo FP-OC based on the probability of premature ovarian insufficiency, predicted outcomes and cost. A comprehensive model that incorporates age at diagnosis and toxicity of treatment to help guide patients in the decision to undergo FP-OC does not yet exist.
Study design, size duration:
This study used a Decision Analysis Model to estimate effectiveness and cost of FP for cancer patients.
Participants/materials, setting, methods:
Age-based estimates of LBR and cost per live birth were calculated for ages 25-40 years based on gonadotoxicity of treatment. A decision analysis model was constructed using Treeage Pro 2015 with case base probabilities derived from national registries, practice guidelines and medical records from a national network of infertility practices (IntegraMed).
Main results and the role of chance:
Compared to no FP-OC, FP-OC improved LBRs for women of all ages undergoing either low-risk chemotherapy (LRC) or HRC; however, it was most cost effective for women undergoing LRC at older ages or HRC at younger ages. Although FP-OC results in higher LBRs, it was always more costly. Using donor oocyte IVF can be a successful alternative to autologous FP-OC.
Limitations reasons for caution:
Decision tree results reflect probabilities of certain events and are compiled from multiple reputable sources but are not directly derived from a recruited cohort of patients. Outcomes are based on United States estimates and should be interpreted in the broader context of individual patient diagnoses, treatment care plans and country of origin.
Wider implications of the findings:
The development of this analytic model will help guide practitioners in their counseling of women from age 25 to 40 years, who are considering FP-OC at the time of cancer diagnosis. It provides a realistic pathway from diagnosis to LB and accounts for the majority of costs and outcome possibilities.
Study funding/competing interest(s):
This study was partially funded by a grant from National Institute of Health (NIH)/National Institute of Child Health and Human Development (NICHD) (R01 HD67683) to A.Z.S. There are no conflicts of interest to declare.
Trial registration number:
N/A.
Objective:
To assess effectiveness of preimplantation genetic screening (PGS) in fresh IVF cycles.
Design:
Reanalysis of retrospective US national data.
Setting:
Not applicable.
Patient(s):
A total of 5,471 fresh autologous IVF cycles with PGS and 97,069 cycles without PGS, reported in 2011-2012 to the Centers for Disease Control and Prevention.
Intervention(s):
Not applicable.
Main outcome measure(s):
Cycles that reached ET, miscarriage rates, live birth rates per cycle and per transfer.
Result(s):
More PGS than non-PGS cycles reached ET (64.2% vs. 62.3%), suggesting favorable patient selection bias for patients using PGS. Nevertheless, live births rates per cycle start (25.2% vs. 28.8%) and per ET (39.3% vs. 46.2%) were significantly better in non-PGS cycles, whereas miscarriage rates were similar (13.7% vs. 13.9%). With a maternal age >37 years significantly more cycles in the PGS group reached ET (53.1% vs. 41.9%), suggesting a significant selection bias for more favorable patients in the PGS population. This bias rather than the PGS procedure may partially explain the observed improved live birth rate per cycle (17.7% vs. 12.7%) and lower miscarriage rate (16.8% vs. 26.0%) in the older PGS group.
Conclusion(s):
Overall, PGS decreased chances of live birth in association with IVF. National improvements in live birth and miscarriage rates reported with PGS in older women are likely the consequence of favorable patient selection biases.
Objective
To study whether preimplantation genetic screening with comprehensive chromosome screening (PGS-CCS) improves clinical implantation rates (IR) and sustained IR (beyond 20 weeks) compared with routine care for embryo selection in IVF cycles.
Design
Meta-analysis of randomized controlled trials (RCTs) and observational studies (OSs).
Setting
University-affiliated teaching hospital.
Patient(s)
Infertile couples undergoing IVF.
Intervention(s)
PGS-CCS with the use of different genetic platforms performed on polar body (PB), cleavage embryo, or blastocyst following embryo biopsy.
Main Outcomes Measure(s)
Clinical IR and sustained IR in RCTs as well as OSs comparing PGS-CCS and routine care were determined after a complete review of the literature. Pooled estimates of risk ratios (RRs) with their 95% confidence intervals (CIs) according to a fixed-effects model with the use of the Mantel-Haenszel method were calculated after the meta-analysis. Forest plots are provided for comparative purposes.
Result(s)
Out of 763 citations identified, 29 articles met initial eligibility criteria and were further analyzed. Of these, only three RCTs and eight OSs met full inclusion criteria, allowing direct comparison of PGS-CCS and routine IVF care based on embryo morphology selection. In the RCTs, all embryo biopsies were performed on day 5–6 of embryo development. In the OSs, biopsies were performed on different stages of embryo development, including PB, day 3, or day 5–6. Meta-analysis of the RCTs (3 studies; n = 659) showed that PGS-CCS was associated with a significantly higher clinical IR, with a pooled RR of 1.29 (95% CI 1.15–1.45), as well as a significantly higher sustained IR, with a pooled RR of 1.39 (95% CI 1.21–1.60). Similar findings were shown in the OSs, where the pooled RR for clinical IR was 1.78 (95% CI 1.60–1.99; 7 studies; n = 2,993) and for sustained IR was 1.75 (95% CI 1.48–2.07; 4 studies; n = 1,124). Statistical heterogeneity (I2) was minimal for RCTs and substantial among OSs.
Conclusion(s)
PGS with the use of CCS technology increases clinical and sustained IRs, thus improving embryo selection, particularly in patients with normal ovarian reserve. Results from ongoing RCTs conducted on different patient populations (e.g., decreased ovarian reserve) and different embryo stage biopsy (e.g., PB, day 3) may further clarify the role of this technology
To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL).
Decision analytic model comparing costs and clinical outcomes.
Academic recurrent pregnancy loss programs.
Women with unexplained RPL.
IVF/PGS with 24-chromosome screening and expectant management.
Cost per live birth.
The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing 418 per live birth with expectant management.
In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.
Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Objective:
To determine if cleavage- or blastocyst-stage embryo biopsy affects reproductive competence.
Design:
Paired randomized clinical trial.
Setting:
Academic-assisted reproduction program.
Patient(s):
Attempting conception through IVF.
Intervention(s):
After selecting two embryos for transfer, one was randomized to biopsy and the other to control. Both were transferred within shortly thereafter. The biopsy was submitted for microarray analysis and single-nucleotide polymorphism (SNP) profiling. Buccal DNA obtained from the neonate after delivery had microarray analysis and SNP profile compared with that of the embryonic DNA. A match confirmed that the biopsied embryo implanted and developed to term, whereas a nonmatch indicated that the control embryo had led to the delivery.
Main outcome measure(s):
Paired analysis of the delivery rates of the transferred embryos. Either twin delivery or failure to deliver represents equivalent outcomes for the biopsied and control embryos. In contrast, singletons were determined to be from the biopsied or the control embryo.
Result(s):
Blastomere biopsy on day 3 of development resulted in a significant reduction in sustained implantation. Only 30% of biopsied embryos had sustained implantation and ultimately developed into live-born infants versus 50% of unbiopsied controls, a relative reduction of 39%. In contrast, sustained implantation rates were equivalent (51% vs. 54%) for biopsied and control blastocysts.
Conclusion(s):
Cleavage-stage biopsy markedly reduced embryonic reproductive potential. In contrast, trophectoderm biopsy had no measurable impact and may be used safely when embryo biopsy is indicated.
Clinical trial registration number:
NCT01219504.
Objective:
To determine whether blastocyst biopsy and rapid quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening (CCS) improves in vitro fertilization (IVF) implantation and delivery rates.
Design:
Randomized controlled trial.
Setting:
Academic reproductive medicine center.
Patient(s):
Infertile couples in whom the female partner (or oocyte donor) is between the ages of 21 and 42 years who are attempting conception through IVF.
Intervention(s):
Embryonic aneuploidy screening.
Main outcome measure(s):
Sustained implantation and delivery rates.
Result(s):
We transferred 134 blastocysts to 72 patients in the study (CCS) group and 163 blastocysts to 83 patients in the routine care (control) group. Sustained implantation rates (probability that an embryo will implant and progress to delivery) were statistically significantly higher in the CCS group (89 of 134; 66.4%) compared with those from the control group (78 of 163; 47.9%). Delivery rates per cycle were also statistically significantly higher in the CCS group. Sixty one of 72 treatment cycles using CCS led to delivery (84.7%), and 56 of 83 (67.5%) control cycles ultimately delivered. Outcomes were excellent in both groups, but use of CCS clearly improved patient outcomes.
Conclusion(s):
Blastocyst biopsy with rapid qPCR-based comprehensive chromosomal screening results in statistically significantly improved IVF outcomes, as evidenced by meaningful increases in sustained implantation and delivery rates.
Clinical trial registration number:
NCT01219283.