Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review.

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.

Potential Costs and Benefits of Incorporating PGT-A Across Age Groups: A Canadian Clinic Perspective.

OBJECTIVE: To assess the potential costs and benefits of preimplantation genetic testing for aneuploidy (PGT-A) across age groups, considering financial costs, total euploidy rates and the potential for morphology grading to predict a euploid embryo. METHODS: This study is a blinded retrospective chart review of patients who incorporated PGT-A as part of their in vitro fertilization (IVF) treatment cycle at a university-affiliated fertility clinic. Patients between 25-44 years of age undergoing IVF with intracytoplasmic sperm injection and PGT-A with autologous oocytes (n = 220) were included in this study. Number of blastocysts achieved, euploidy rates and PGT-A costs were compared between 3 age groups: <35 years, 35-37, and ≥38. Additionally, agreement on the top-quality embryo based on morphology assessment alone versus PGT-A selection was analyzed and further compared based on the number of blastocysts achieved. RESULTS: A significant negative correlation between patient age and number of embryos produced, PGT-A costs, and euploidy rates (P < 0.001) was observed. Additionally, morphology alone ratings were able to predict the top-quality euploid embryo 78% of the time in the <35 age group, but only 32% of the time in the ≥38 age group (P < 0.05), with a trend toward even lower agreement when 3 or fewer blastocysts were produced. CONCLUSION: Based on our cost analysis, it may be advantageous to incorporate PGT-A when maternal age is ≥38, given the lower financial costs associated with each cycle and the low likelihood of transferring a euploid embryo on the first attempt for this age group. Nevertheless, we acknowledge that PGT-A remains a complex decision influenced by a multitude of factors.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis.

BACKGROUND: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. METHODS: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. RESULTS: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. CONCLUSIONS: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

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.

BACKGROUND: A controversial and unresolved question in reproductive medicine is the utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization. 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: This study aimed to analyze the cost-effectiveness of preimplantation genetic testing for aneuploidy for the treatment of infertility in the United States. STUDY DESIGN: As reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System, a national data registry, in vitro fertilization cycles occurring between 2014 and 2016 in the United States were analyzed. A probabilistic decision tree was developed using empirical outputs to simulate the events and outcomes associated with in vitro fertilization with and without preimplantation genetic testing for aneuploidy. The treatment strategies were (1) in vitro fertilization with intended preimplantation genetic testing for aneuploidy and (2) in vitro fertilization with transfers of untested embryos. Patients progressed through the treatment model until they achieved a live birth or 12 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, and incremental cost per live birth between treatment strategies. RESULTS: The study population included 114,157 first fresh in vitro fertilization stimulations and 44,508 linked frozen embryo transfer cycles. Of the fresh stimulations, 16.2% intended preimplantation genetic testing for aneuploidy and 83.8% did not. In patients younger than 35 years old, preimplantation genetic testing for aneuploidy was associated with worse clinical outcomes and higher costs. At age 35 years and older, preimplantation genetic testing for aneuploidy 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 preimplantation genetic testing for aneuploidy strategy from the <35 years age group to the 38 years age group and beginning at age 39 years favored preimplantation genetic testing for aneuploidy. From a payer perspective, the incremental cost per live birth favored preimplantation genetic testing for aneuploidy regardless of patient age. CONCLUSION: The cost-effectiveness of preimplantation genetic testing for aneuploidy is dependent on patient age and perspective. From an economic perspective, routine preimplantation genetic testing for aneuploidy should not be universally adopted; however, it may be cost-effective in certain scenarios.

The prevalence, promotion and pricing of three IVF add-ons on fertility clinic websites.

RESEARCH QUESTION: How are IVF clinic websites advertising three common IVF add-ons: assisted hatching, time-lapse embryo imaging and preimplantation genetic testing for aneuploidies (PGT-A)? DESIGN: The Human Fertilisation and Embryology Authority 'Choose a fertility clinic' website service was used to identify IVF clinics and their websites. Assisted hatching, time-lapse embryo imaging and PGT-A were examined to determine which websites advertised them, what price they charged and what claims they made in relation to the add-ons. RESULTS: Eighty-seven eligible clinics were identified, with 72 unique websites; 37 (43%) clinics were part of one of nine groups of IVF clinics, of sizes ranging from two to eight clinics in the UK. Time-lapse imaging (TLI) was the most frequently advertised of the three add-ons (67% of clinics), followed by PGT-A (47%) and assisted hatching (28%). Very few websites stated that the effectiveness of the add-on was in doubt or unclear (four, two and one websites for TLI, PGT-A and assisted hatching, respectively), and none raised the possibility that an add-on might have negative effects. Claims of efficacy were often based on upstream outcomes (e.g. implantation, pregnancy). Some claims that PGT-A and TLI improved live birth rates were found. There was substantial variation in pricing. CONCLUSIONS: IVF clinic websites provide valuable information for patients seeking fertility treatment so it is key that the information is accurate and complete. There is a need for transparent information on interventions, including uncertainties and risks, to be made available by IVF clinics to support well-informed treatment decisions. The selected add-ons are widely advertised, and there is wide variation in pricing.

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age.

OBJECTIVE: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36-40 years of age? DESIGN: Decision tree model. POPULATION: A randomised clinical trial on PGT-A (ESTEEM study). METHODS: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A. Costs and effects were analysed with this model for four different cost scenarios: high-, higher medium, lower medium and low-cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost-effectiveness implications of PGT-A. RESULTS: PGT-A increased the cost per live birth by approximately 15% in the high-cost scenario to approximately 285% in the low-cost scenario. Threshold analysis revealed that PGT-A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high-cost scenario) to US$4,888 (low-cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT-A using the base case assumptions was calculated to be US$34,427 (high-cost scenario) to US$51,146 (low-cost scenario). A probabilistic sensitivity analysis showed cost-effectiveness for PGT-A from 1.9% (high-cost scenario) to 0.0% (low-cost scenario) of calculated samples. CONCLUSIONS: While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high-cost implications of applying PGT-A using aCGH on polar bodies. TWEETABLE ABSTRACT: PGT-A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.

Assessment of pre-implantation genetic testing for embryo aneuploidies: A SWOT analysis.

The recently re-named pre-implantation genetic testing for determining embryo aneuploidies (PGT-A) is presently very popular although its acceptance by the scientific community is controversial. This approach still encounters drawbacks. This paper uses a SWOT (strengths, weaknesses, opportunities and threats) analysis to discuss salient points to be considered when examining the pre-implantation genetic testing (PGT-A) strategy to gather information from a range of perspectives. One of the strengths associated with the procedure is represented by an increase in implantation rate although data from the highest level of evidence do not support an increase in cumulative pregnancy rates. The current difficulty in the management of mosaicisms represents a weakness of PGT-A. The application of the strategy represents an opportunity to favor the single embryo transfer while other advantages, such as reduction of time to pregnancy and emotional distress are controversial. Potential important threats, at present still undefined, are represented by the biopsy-related damage to the blastocyst and the impact on neonatal and long-term outcomes.

Definition and validation of a custom protocol to detect miRNAs in the spent media after blastocyst culture: searching for biomarkers of implantation.

STUDY QUESTION: Can miRNAs be reliably detected in the spent blastocyst media (SBM) after IVF as putative biomarkers of the implantation potential of euploid embryos? SUMMARY ANSWER: Adjustment of the data for blastocyst quality and the day of full-expansion hinders the predictive power of a fast, inexpensive, reproducible and user-friendly protocol based on the detection of 10 selected miRNAs from SBM. WHAT IS KNOWN ALREADY: Euploidy represents so far the strongest predictor of blastocyst competence. Nevertheless, ~50% of the euploid blastocysts fail to implant. Several studies across the years have suggested that a dialogue exists between the embryo and the endometrium aimed at the establishment of a pregnancy. MicroRNAs have been proposed as mediators of such a dialogue and investigated in this respect. Several expensive, time-consuming and complex protocols have been adopted and promising results have been produced, but conclusive evidence from large clinical studies is missing. STUDY DESIGN, SIZE, DURATION: This study was conducted in two phases from September 2015 to December 2017. In Phase 1, the human blastocyst miRNome profile was defined from the inner cell mass (ICM) and the corresponding whole-trophectoderm (TE) of six donated blastocysts. Two different protocols were adopted to this end. In parallel, 6 pools of 10 SBM each were run (3 from only implanted euploid blastocysts, IEBs; and 3 from only not-implanted euploid blastocysts, not-IEBs). A fast, inexpensive and user-friendly custom protocol for miRNA SBM profiling was designed. In Phase 2, 239 SBM from IEB and not-IEB were collected at three IVF centres. After 18 SBM from poor-quality blastocysts were excluded from the analysis, data from 107 SBM from not-IEB and 114 from IEB were produced through the previously developed custom protocol and compared. The data were corrected through logistic regressions. PARTICIPANT/MATERIALS, SETTINGS, METHODS: Donated blastocysts underwent ICM and whole-TE isolation. SBM were collected during IVF cycles characterized by ICSI, blastocyst culture in a continuous media, TE biopsy without zona pellucida opening in Day 3, quantitative PCR (qPCR)-based aneuploidy testing and vitrified-warmed single euploid embryo transfer. Not-IEB and IEB were clustered following a negative pregnancy test and a live birth, respectively. The Taqman Low Density Array (TLDA) cards and the Exiqon microRNA human panel I+II qPCR analysis protocols were adopted to analyse the ICM and whole-TE. The latter was used also for SBM pools. A custom protocol and plate was then designed based on the Exiqon workflow, validated and finally adopted for SBM analysis in study Phase 2. This custom protocol allows the analysis of 10 miRNAs from 10 SBM in 3 hours from sample collection to data inspection. MAIN RESULTS AND ROLE OF THE CHANCE: The TLDA cards protocol involved a higher rate of false positive results (5.6% versus 2.8% with Exiqon). There were 44 miRNAs detected in the ICM and TE from both the protocols. One and 24 miRNAs were instead detected solely in the ICM and the TE, respectively. Overall, 29 miRNAs were detected in the pooled SBM: 8 only from not-IEB, 8 only from IEB and 13 from both. Most of them (N = 24/29, 82.7%) were also detected previously in both the ICM and TE with the Exiqon protocol; two miRNAs (N = 2/29, 6.9%) were previously detected only in the TE, and three (N = 3/29, 10.3%) were never detected previously. In study Phase 2, significant differences were shown between not-IEB and IEB in terms of both miRNA detection and relative quantitation. However, when the data were corrected for embryo morphology and day of full development (i.e. SBM collection), no significant association was confirmed. LIMITATIONS, REASONS FOR CAUTION: This study did not evaluate specifically exosomal miRNAs, thereby reducing the chance of identifying the functional miRNAs. Ex-vivo experiments are required to confirm the role of miRNAs in mediating the dialogue with endometrial cells, and higher throughput technologies need to be further evaluated for miRNA profiling from clinical SBM samples. WIDER IMPLICATIONS OF THE FINDINGS: Although no clinical predictive power was reported in this study, the absence of invasiveness related with SBM analysis and the evidence that embryonic genetic material can be reliably detected and analysed from SBM make this waste product of IVF an important source for further investigations aimed at improving embryo selection. STUDY FUNDING/COMPETING INTEREST(S): This project has been financially supported by Merck KgaA (Darmstadt, Germany) with a Grant for Fertility Innovation (GFI) 2015. The authors have no conflict of interest to declare related with this study. TRIAL REGISTRATION NUMBER: None.

Review of 10 years of preimplantation genetic diagnosis in South Africa: implications for a low-to-middle-income country.

PURPOSE: To evaluate the preimplantation genetic diagnosis (PGD) service, for the period of January 2006 to December 2016, through a South African academic and diagnostic Human Genetics Unit, and to assess the outcomes and cost of PGD. METHODS: A retrospective review of PGD files available at the Human Genetics Unit was performed. Data was collected from genetic counseling, fertility, and PGD-specific records. RESULTS: Amongst the 22 couples who had PGD, 42 in vitro fertilisation cycles were completed with 228 embryos biopsied and included in the analysis. Most (59%) of the conditions for which PGD was requested were autosomal recessive. Of the biopsied embryos, 71/228 (31.1%) were suitable for transfer and 41/71 (57.7%) were transferred. Of these, 14/41 (34.0%) successfully implanted and 11/14 (78.6%) resulted in a liveborn infant. The clinical pregnancy rate per embryo transfer was 29.3%. Overall, 10/22 (45.5%) couples had a successful cycle resulting in a liveborn infant. On average, one cycle of PGD costs USD 9525. CONCLUSIONS: This is the first study to assess the success rates and the cost of PGD in South Africa and provides evidence for the feasibility in a low-to-middle-income country. The success rates in this sample are comparable to those achieved globally. South Africa has the infrastructure and expertise to provide PGD; the limiting factor is the lack of funding initiatives for PGD. Although the sample size was small, the findings from this study will enable genetic counselors to offer couples in South Africa evidence-based and locally accurate information regarding outcomes, success rates, and costs.

The cost of a euploid embryo identified from preimplantation genetic testing for aneuploidy (PGT-A): a counseling tool.

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 $15,000 U.S. dollars (USD) for younger women with higher AMH values (≥ 2 ng/mL) to > $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 (~ $16,000) for younger women with higher AMH values, but varies for the oldest women with low AMH values (~ $280,000 and > $450,000, respectively). A typical patient (36-37 years, AMH 2.5 ng/mL) should expect to spend ~ $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.

Cost-effectiveness of preimplantation genetic screening for women older than 37 undergoing in vitro fertilization.

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 $4509, yielding an incremental cost-effectiveness ratio (ICER) of $105,489 per additional live birth. This ICER was below the expected cost of $145,063 for achieving one live birth with IVF (assuming an average LBR of 13.4% and $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.

Referral of patients for pre-implantation genetic diagnosis: A survey of obstetricians.

BACKGROUND: Pre-implantation genetic diagnosis (PGD) is a molecular diagnostic technique in which embryos are tested for specific genetic abnormalities to enable the selection of those unaffected by the condition. Previous Australian evidence suggested that women who are not informed about PGD by their obstetrician feel disempowered about not being given this option. AIMS: This study aimed to explore obstetrician knowledge regarding PGD and identify barriers to referral. MATERIALS AND METHODS: An invitation to the study with a link to an online questionnaire was e-mailed by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists to their members. RESULTS: In total, 372 practising obstetricians responded. Perceptions of their patients' financial status and ability to access PGD were identified as barriers to referral. There was variability in referral for PGD and/or genetic services according to the clinical scenario and in the perceived appropriateness of PGD for different indications. Obstetricians who had undergone professional development related to PGD were more likely to discuss PGD than those who had not (χ2 = 6.44; P < 0.01). CONCLUSIONS: The results highlight the need for additional training, development of educational resources and awareness of appropriate referral pathways to ensure that those couples who are eligible for PGD are informed.

The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review.

STUDY QUESTION: Is preimplantation genetic diagnosis for aneuploidy (PGD-A) with analysis of all chromosomes during assisted reproductive technology (ART) clinically and cost effective? SUMMARY ANSWER: The majority of published studies comparing a strategy of PGD-A with morphologically assessed embryos have reported a higher implantation rate per embryo using PGD-A, but insufficient data has been presented to evaluate the clinical and cost-effectiveness of PGD-A in the clinical setting. WHAT IS KNOWN ALREADY: Aneuploidy is a leading cause of implantation failure, miscarriage and congenital abnormalities in humans, and a significant cause of ART failure. Preclinical evidence of PGD-A indicates that the selection and transfer of euploid embryos during ART should improve clinical outcomes. STUDY DESIGN, SIZE AND DURATION: A systematic review of the literature was performed for full text English language articles using MEDLINE, EMBASE, SCOPUS, Cochrane Library databases, NHS Economic Evaluation Database and EconLit. The Downs and Black scoring checklist was used to assess the quality of studies. Clinical effectiveness was measured in terms of pregnancy, live birth and miscarriage rates. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Nineteen articles meeting the inclusion criteria, comprising three RCTs in young and good prognosis patients and 16 observation studies were identified. Five of the observational studies included a control group of patients where embryos were selected based on morphological criteria (matched cohort studies). MAIN RESULTS AND ROLE OF CHANCE: Of the five studies that included a control group and reported implantation rates, four studies (including two RCTs) demonstrated improved implantation rates in the PGD-A group. Of the eight studies that included a control group, six studies (including two RCTs) reported significantly higher pregnancy rates in the PGD-A group, and in the remaining two studies, equivalent pregnancies rates were reported despite fewer embryos being transferred in the PGD-A group. The three RCTs demonstrated benefit in young and good prognosis patients in terms of clinical pregnancy rates and the use of single embryo transfer. However, studies relating to patients of advanced maternal age, recurrent miscarriage and implantation failure were restricted to matched cohort studies, limiting the ability to draw meaningful conclusions. LIMITATIONS, REASONS FOR CAUTION: Relevant studies may have been missed and findings from RCTs currently being undertaken could not be included. WIDER IMPLICATIONS OF THE FINDINGS: Given the uncertain role of PGD-A techniques, high-quality experimental studies using intention-to-treat analysis and cumulative live birth rates including the comparative outcomes from remaining cryopreserved embryos are needed to evaluate the overall role of PGD-A in the clinical setting. It is only in this way that the true contribution of PGD-A to ART can be understood.

An economic assessment of embryo diagnostics (Dx) - the costs of introducing non-invasive embryo diagnostics into IVF standard treatment practices.

BACKGROUND: New techniques in assessing oocytes and embryo quality are currently explored to improve pregnancy and delivery rates per embryo transfer. While a better understanding of embryo quality could help optimize the existing "in vitro fertilization" (IVF) therapy schemes, it is essential to address the economic viability of such technologies in the healthcare setting. METHODS: An Embryo-Dx economic model was constructed to assess the cost-effectiveness of 3 different IVF strategies from a payer's perspective; it compares Embryo-Dx with single embryo transfer (SET) to elective single embryo transfer (eSET) and to double embryo transfer (DET) treatment practices. RESULTS: The introduction of a new non-invasive embryo technology (Embryo-Dx) associated with a cost up to €460 is cost-effective compared to eSET and DET based on the cost per live birth. The model assumed that Embryo-Dx will improve ongoing pregnancy rate/realize an absolute improvement in live births of 9% in this case. CONCLUSIONS: This study shows that improved embryo diagnosis combined with SET may have the potential to reduce the cost per live birth per couple treated in IVF treatment practices. The results of this study are likely more sensitive to changes in the ongoing pregnancy rate and consequently the live birth rate than the diagnosis costs. The introduction of a validated Embryo-Dx technology will further support a move towards increased eSET procedures in IVF clinical practice and vice versa.

A qualitative inquiry of the financial concerns of couples opting to use preimplantation genetic diagnosis to prevent the transmission of known genetic disorders.

Preimplantation genetic diagnosis (PGD) is an innovative prenatal testing option because the determination of whether a genetic disorder or chromosomal abnormality is evident occurs prior to pregnancy. However, PGD is not covered financially under the majority of private and public health insurance institutions in the United States, leaving couples to decide whether PGD is financially feasible. The aim of this qualitative study was to understand the role of finances in the decision-making process among couples who were actively considering PGD. In-depth, semi-structured interviews were completed with 18 genetic high-risk couples (36 individual partners). Grounded theory guided the analysis, whereby three themes emerged: 1) Cost is salient, 2) Emotions surrounding affordability, and 3) Financial burden and sacrifice. Ultimately, couples determined that the opportunity to avoid passing on a genetic disorder to a future child was paramount to the cost of PGD, but expressed financial concerns and recognized financial access as a major barrier to PGD utilization.

Preimplantation genetic diagnosis after 20 years.

Preimplantation genetic diagnosis (PGD) should not be an option only for the few couples at risk of serious genetic conditions who can afford it. We appear to have lost sight of the original driving force behind the development of PGD, which is that most couples who carry a serious genetic disorder find it more acceptable to choose to conceive with healthy embryos tested in-vitro at preimplantation stages of development within the first week following fertilization, even if that means discarding those diagnosed as affected. It has been shown using cystic fibrosis as an example, that the cost savings to the US healthcare system of providing free IVF-PGD to all carrier couples compared to the lifetime costs of medical treatment for patients affected by this disease, run to dozens of billions of dollars. With the increasing emphasis in medicine on early diagnosis and prevention of disease together with the availability of new molecular genetic diagnostic tools, a national IVF-PGD programme seems to be the next step in modern health care.

Improved detection of aneuploid blastocysts using a new 12-chromosome FISH test.

Fluorescence in-situ hybridization (FISH) has been the principal method used for the identification and preferential transfer of chromosomally normal embryos, in the context of both preimplantation genetic diagnosis (PGD) and screening (PGS). Generally, the probe combinations used during PGS have focused on chromosomes frequently identified as abnormal in prenatal samples or material derived from first-trimester spontaneous abortions. Recent data, however, obtained with the use of comparative genomic hybridization (CGH), have suggested that commonly used PGS strategies may fail to detect a large number of aneuploidies affecting preimplantation embryos. Some chromosomes, which have been relatively neglected in PGS protocols thus far, display a disproportionate contribution to embryo aneuploidy and should be prioritized for screening. Using CGH data, it is possible to design new probe combinations that examine between 10 and 12 chromosomes and are capable of accurately diagnosing 89-91% of anomalies seen in embryos. At present, 24-chromosome tests, such as CGH, array CGH or single nucleotide polymorphism arrays, remain relatively costly and, in some cases, are yet to be fully validated. For these reasons, a cost-effective method, capable of accurately detecting almost all aneuploid embryos, represents an attractive alternative to comprehensive chromosome screening approaches.