From innovation to practice: evaluating the evidence for preimplantation genetic testing for aneuploidy.

Success Rates with Preimplantation Genetic Testing for Aneuploidy (PGT-A) in Good Prognosis Patients is Dependent on Age.

Prognostic data in fertility preservation: the role of preimplantation genetic testing for aneuploidy (PGT-A) among cancer patients undergoing embryo banking (EB)

Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation.

Preimplantation genetic testing for aneuploidy in patients under 37: easy come, easy go

Two’s company, three’s a crowd: involvement of a gestational carrier necessitates use of best and safe practices

Study question Do donor oocyte recipients benefit from preimplantation genetic testing for aneuploidy (PGT-A)? Summary answer The PGT-A does not improve the likelihood of live birth and time to pregnancy for recipients of vitrified donor oocytes. What is known already Oocyte vitrification has led to increased live birth from cryopreserved oocytes and has led to widespread use of this technology in donor egg IVF programs. However, oocyte cryopreservation has the potential to disrupt the meiotic spindle leading to abnormal segregation of chromosomes during meiosis II and may increase aneuploidy in the blastocyst. Therefore, PGT-A might have benefits in vitrified donor egg cycles. However, blastocysts derived from young donor oocytes are expected to be predominantly euploid, and trophectoderm biopsy may harm blastocysts compared to embryo transfer without PGT-A. Study design, size, duration Retrospective single-center study encompassing 2233 vitrified-warmed donor oocyte cycles conducted between March 2021 and August 2024 at a private Italian IVF clinic. The study included 299 donor cycles with and 1934 without PGT-A. Vitrified donor oocyte cycles were analyzed for live birth as the main outcome measure. Secondary outcomes were time to achieve pregnancy defined as the days from the egg thawing until a live birth achieved, clinical pregnancy, ongoing pregnancy miscarriage rates. Participants/materials, setting, methods The study included women aged 30-49 who underwent blastocyst single embryo transfer (SET). Trophectoderm biopsy was performed on day 5 or 6 based on embryo development. Both natural and artificial cycle SETs were considered. Exclusions were women with fibroids >3 cm, severe adenomyosis, or male partners with sperm concentration <1 million/ml. Statistical analyses included chi-square and Student’s t-tests for group comparisons. Logistic regression adjusted for confounders was used to analyze live birth rates (LBR). Main results and the role of chance The fertilization and blastulation rates were similar in both groups with PGT and no-PGT-A, respectively p = 0.24 and p = 0.49.The mean euploidy rate per recipient was 75.3% in the PGT-A group.No statistical differences were reported for age of the donor type of endometrial preparation (natural/artificial), endometrial thickness, and days of endometrial preparation.Regarding the sperm parameter in the PGT-A, the sperm concentration (mil/mL) and sperm motility was lower than no-PGT-A (p < 0.001).The live birth rate was not different in the PGT-A group 39.9% (CI95%35.31-44.74) vs no-PGT-A 42.9% (40.95-44.87), p = 0.27.The days to reach a live birth was higher in the group with PGT-A 65.5 (CI 95% 44.31-86.77) than no PGT-A 49.7 (CI95%42.52-56.95), p = 0.48.The pregnancy rate was lower in the PGT-A group 53.3% than in no-PGT-A 62.3% (p < 0.01), while no statistical differences were reported for the clinical pregnancy rate 52.33% (CI95% 47.72-56.92) vs 56.6% (CI95%54.79-58.50), p = 0.08.The miscarriage rate calculated on the pregnancy rate was 21.37%(CI95%16.44-27.00) in the PGT-A group vs 22.44%(CI95% 20.46-24.53) in the no-PGT-A group, p = 0.76.The multivariate analysis adjusted for several confounders (patients and oocyte age, BMI, male age, sperm characteristics, day of embryo transfer, endometrial thickness, PGT-A) confirmed that these factors do not influence the live birth rate. Limitations, reasons for caution The nature of the retrospective study and two different laboratories used for the PGT-A represent the principal limitation of the study. Wider implications of the findings PGT-A testing in donor oocyte-recipient cycles does not improve the chance for live birth nor decrease the risk of miscarriage. The use of PGT-A in the donor cycle does not reduce the time to reach a live birth. Further large studies are required to confirm these results. Trial registration number No

The efficacy of preimplantation genetic testing for aneuploidy (PGT-A) in couples with unexplained recurrent pregnancy loss (uRPL) may vary according to the number of good-quality blastocysts available. This study is to determine whether PGT-A could improve the cumulative live birth rate (CLBR) among couples experiencing uRPL as the number of high-quality blastocysts increases. A retrospective study involving 1073 couples with uRPL was conducted at a university-affiliated reproductive center. Patients were divided into two groups: 813 participants who underwent PGT-A and 260 participants who underwent conventional in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). A stratified analysis was conducted, which categorized the female participants into three subgroups based on the number of high-quality blastocysts: 1-3, 4-6, and ≥ 7. A binary logistic regression model was used to evaluate the associations between the number of high-quality blastocysts and the cumulative pregnancy outcomes. Among uRPL patients undergoing PGT-A or IVF/ICSI, there were respectively 421 vs. 129 with 1-3 blastocysts, 252 vs. 69 with 4-6 blastocysts, and 140 vs. 62 with ≥ 7 blastocysts. In 1-3 blastocysts subgroup, CLBR was 23.52% after PGT-A vs. 33.33% after IVF/ICSI (adjusted OR 1.005, 95% CI 0.604-1.674, p = 0.984). In 4-6 blastocysts subgroup, CLBR was 53.17% after PGT-A vs. 75.36% after IVF/ICSI (adjusted OR 0.398, 95% CI 0.197-0.802, p = 0.010). In ≥ 7 blastocysts subgroup, CLBR was 73.57% after PGT-A vs. 66.13% after IVF/ICSI (adjusted OR 1.660, 95% CI 0.729-3.799, p = 0.227). In these three subgroups, clinical pregnancy loss rates were all similar between the two treatment methods. In women with uRPL, PGT-A did not improve CLBR, irrespective of the number of high-quality blastocysts available. Routine use of PGT-A in this population is therefore not recommended. Future high-quality randomized controlled trials may better define its appropriate indications.

Study question How many eggs will be required to optimize the chances of a live birth with or without PGT-A? Summary answer The number of zygotes required for live birth is higher in women with an advanced age, and the use of PGT-A does not provide improvement. What is known already Women who are undergoing PGT-A often wish to know how many eggs will be required to optimize the chances of a live birth. This important information could be provided as part of prior genetic counseling, but there are no precise data on this at present. If the number of eggs required to give the best chance of a successful live birth was known, treatment plans with or without PGT-A could be better determined. Study design, size, duration We estimated the optimal number of eggs required for IVF treatment with PGT-A to produce at least a single live birth, stratified by maternal age, on the basis of information from prior studies and in current databases. Participants/materials, setting, methods We derived our calculation parameters from three prior large-scale clinical investigations associated with PGT-A. We estimated a live birth rate using the following factors: rate of zygotes that develop a useful blastocyst, euploid rate in PGT-A, and the live birth rate after euploid embryo transfer. All of these factors were assumed to be statistically independent in this study for the purposes of our calculations and the live birth rate per single zygote was calculated. Main results and the role of chance The estimations in our present analyses however indicate a probability of less than 10% that woman over 40 years of age will have a live birth from a single zygote, regardless of whether PGT-A is performed or not. We used a negative binomial distribution approach to calculate how many zygotes are needed to obtain at least one live birth. The plot of these results is provided in Figure 2. To achieve a 50% chance of getting at least one live birth, patients required 8 zygotes at age of 40 and 21 zygotes at the age of 43. Furthermore, to achieve an 80% chance of obtaining a live birth, our calculations estimate that 18 and 47 zygotes would be required at these two ages, respectively, which would be challenging to achieve. On the other hand, by avoiding unnecessary transplants using PGT-A, women may have to wait a shorter period to accomplish a live birth or may be able to avoid wasting their limited remaining reproductive period, particularly if they are older than 42. Limitations, reasons for caution The reference data from PGT-A studies that have estimated of the live birth rate include chromosomal quantitative PCR, microarray analysis, and next generation sequencing (NGS). There is a high possibility that the embryos designated as “euploid” in those studies include mosaic embryos, which represents a limitation of our present meta-analysis. Wider implications of the findings More details on the clinical outcomes of PGT-A will be revealed as clinical studies progress in the future. It is our hope that the results of this present study will assist with future genetic counseling strategies for PGT-A in the meantime. Trial registration number not applicable

Noninvasive preimplantation genetic testing for aneuploidy in spent culture medium as a substitute for trophectoderm biopsy

The impact of preimplantation genetic testing for aneuploidy on time to live birth in in vitro fertilization.

Natural fecundity of women decreases gradually and more rapidly after age 37 years. This decrease is accompanied by rising aneuploidy rates of pregnancies and can also be observed in products of conception of spontaneous abortions [1]. These observations lead to the hypothesis that transferring only euploid embryos in association with in vitro fertilization (IVF) might decrease miscarriages and increase live birth rates (LBRs), attesting-procedure now called preimplantation genetic testing (of embryos) for aneuploidy (PGT-A), until recently generally referred to as preimplantation genetic screening (PGS). Verlinsky and Kuliev further proposed that the removal of all aneuploid embryos prior to transfer would improve implantation rates and live birth rates and suggested that the diagnosis be made via biopsy of both polar bodies [2]. Polar body biopsy, however, proved technically too difficult for general IVF practice and would have revealed only meiotic aneuploidies. The procedure was, therefore, initially performed biopsying 1–2 blastomeres of day-3 cleavage-stage embryos, often given the acronym PGS 1.0. This form of embryo testing has, since, been replaced by PGS 2.0, with the embryo biopsy being moved from day-3 cleavage stage to trophectoderm biopsy of blastocyst-stage embryos on days 5–6 after fertilization. In July 2016, another major change in PGT-A was announced, for the first time introducing the concept pf “mosaic” embryos (also called PGS 3.) (Preimplantation Genetic Diagnosis Society (PGDIS) position statement on chromosome mosaicism and preimplantation aneuploidy testing at the blastocyst stage, Chicago, IL; July 19, 2016 http://pgdis.org/docs/newsletter_071816.html). After almost two decades of PGS 1.0 through PGS 3.0, the procedure has, however, still been unable to demonstrate the promised improvements in live births and anticipated declines in miscarriage rates [3–5]. Several studies, even summarized in a meta-analysis [6], have claimed improved clinical IVF outcomes following PGT-A. They, however, reported IVF outcomes with reference point embryo transfer rather than cycle start (intent-to-treat) and, therefore, by excluding poorer prognosis patients, were severely biased [7]. The STAR study This is why the recently published STAR study [8] attracted special attention: It avoided at least some patient selection biases of earlier fresh-cycle studies by being prospectively randomized and reporting on IVF outcomes from transfers of only single frozen-thawed embryos at blastocyst stage. That qualifying patients required having at least two frozen embryos from a prior fresh cycle, however, still demonstrates a favorable patient selection bias. Importantly, however, the study at least analyzed outcomes for study and control groups with reference point initial first cycle start [7]. In doing so, the study convincingly revealed no improvements in live birth rates and no reduction in miscarriage rates when cycle outcomes were compared in singe-embryo transfers at blastocyst stage between women, randomized to either PGT-A or only morphological assessments of a single embryo prior to transfers [8]. For no declared reason, the authors then, however, performed a post hoc sub-group analysis based on age and reported, between ages 35 and 40 years, that PGT-A, still, offered significant increases in ongoing pregnancy rate (OPR). In the discussion of their manuscript, they emphasized this finding as “continuous evidence” for the clinical utility of PGT-A in at least that age group. Again, in contrast to the overall study that had been performed with reference point cycle start (intent-to-treat), their post hoc analysis was performed with reference embryo transfer and, therefore, statistically suspect. Because results of the STAR study are already impacting IVF practice worldwide, we here offer a statistically corrected analysis of the STAR study, reaffirming the study’s overall findings by refuting the results of the post hoc analysis and its interpretation by the authors, claimed benefits for PGT-A utilization for all age groups.

Effects of preimplantation genetic testing for aneuploidy on embryo transfer outcomes in women of advanced reproductive age with no more than three retrieved oocytes.

The demise of preimplantation genetic testing for aneuploidy (PGT-A) in Hungary and its effect on patient care

Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial

Preimplantation genetic testing for aneuploidy is associated with reduced live birth rates in fresh but not frozen donor oocyte in vitro fertilization cycles: an analysis of 18,562 donor cycles reported to Society for Assisted Reproductive Technology Clinic Outcome Reporting System