Use Of Preimplantation Genetic Testing For Aneuploidy Research Articles

Preimplantation Genetic Testing for Aneuploidy: A Review.

Preimplantation genetic testing for aneuploidy (PGT-A) has undergone many technical developments over recent years, including changes in biopsy timings, methodology, and genetic analysis techniques. The evidence surrounding the efficaciousness of PGT-A is sporadic and inconsistent; as such, significant doubt and concern remain regarding its widespread implementation. This review seeks to describe the historical development of PGT-A and to analyze and summarize the current published literature. At times during its infancy, PGT-A failed to display conclusive improvements in results; with newer technologies, PGT-A appears to yield superior outcomes, including reductions in miscarriages and multiple gestations. Clinicians and patients should assess the use of PGT-A on a case-by-case basis, with laboratories encouraged to utilize blastocyst biopsy and next-generation sequencing when conducting PGT-A. Further studies providing cumulative live birth rates and time to live birth are required if PGT-A is to be proven as producing superior outcomes. PGT-A has the potential ability to impact in vitro fertilization success rates, and as it is increasingly adopted worldwide, it is crucial that clinicians are aware of the evidence for its continued use.

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

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. Randomized controlled trial. Not applicable. Women aged 25-40years undergoing IVF with at least two blastocysts that could be biopsied. Randomization for single frozen-thawed embryo transfer with embryo selection based on PGT-A euploid status versus morphology. Ongoing pregnancy rate (OPR) at 20weeks' gestation per embryo transfer. A total of 661 women (average age 33.7 ± 3.6years) 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 35-40years showed a significant increase in OPR per embryo transfer (51% [62/122] vs. 37% [54/145]) but not per ITT. 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 35-40years who had two or more embryos that could be biopsied, but this was not significant when analyzed by ITT. NCT02268786.

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

Preimplantation genetic testing for aneuploidy (PGT-A) is a suitable technique to identify euploid embryos, which have the highest potential to implant, thus increase the chance of a healthy live birth. The main indications of PGT-A are advanced maternal age, repeated implantation failure, repeated miscarriages and severe male infertility. Several studies have already proven that testing embryos for genetic abnormalities in the above cases results in higher implantation rate and reduced number of pregnancy loss. In spite of these – due to a legislative change in Hungary in 2015 – PGT-A was reclassified as an experimental procedure and its use became banned throughout the country. For this reason, after 4 years of successful practice, Hungarian patients were not able to participate in IVF procedure combined with PGT-A anymore.In this retrospective analysis, efficacy of PGT-A-based embryo selection was evaluated and was compared to the conventional morphology-based selection (MBS) in patients with advanced maternal age, between 2013 and 2017 at our private fertility clinic. PGT-A was performed with array comparative genomic hybridization.We found that implantation rate was significantly higher (43.62% vs. 27.88%; p = 0.0208) and miscarriage rate was significantly lower (17.07% vs. 37.93%; p = 0.0492) in the PGT-A group compared to the MBS group from 2013 to 2015. These outcomes were achieved with a significantly lower number of transferred embryos in the PGT-A group (1.25 vs. 1.58; p = 0.0003). In 2016–2017, the number of transferred embryos were significantly reduced in the MBS group as well (1.14 vs. 1.58; p < 0.0001). However, outcomes of the IVF treatments did not change significantly compared to the previous two years (2013–2015).Our results imply that PGT-A-based embryo selection is more efficient than morphology-based selection in patients with advanced maternal age. Therefore, prohibition of the use of PGT-A had significant consequences on the efficiency and safety of IVF treatment in the country.

The use of preimplantation genetic testing for aneuploidy and mitochondrial DNA scoring helps in improving assisted reproductive techniques outcome

Background: Aneuploidy is a leading cause of implantation failure and miscarriage. Preimplantation genetic testing for aneuploidy (PGT-A) with mitoscore enables screening of viable euploid embryos, thereby improving in vitro fertilization (IVF) outcome. Aim of the study: The aim of this study is to determine if the use of PGT-A in patients with valid indications can help improve assisted reproductive techniques outcome. Materials and Methodology: All patients undergoing IVF-PGT-A cycles between April 2016 and March 2018 were included (n = 42) in the study. Patients were compared with a control group consisting of fresh or frozen blastocyst transfers selected by morphology, during the same period (n = 226). Trophectoderm samples were subjected to chromosome analysis and mitoscore assessment using next-generation sequencing. Single-embryo transfer was done according to transfer priority determined by mitoscore. Statistical Analysis: The Chi-square test was used for comparisons between the study groups with respect to percentages. A value of P Results: The indications for PGT-A in our patients were advanced maternal age 33%, followed by recurrent pregnancy loss 25%, recurrent implantation failure 19%, previous history of aneuploidy 16%, and severe male factor 6%. An ongoing pregnancy rate (OPR) of 61% versus 48% (P = 0.0049) was achieved with PGT-A versus controls, respectively. Thirty-two percent of patients did not have any euploid embryos for transfer. Conclusion: Offering PGT-A with mitoscore for valid indications seems to be an impressive tool to increase implantation and OPRs and helps in counseling patients for further course of treatment.

Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage

To determine if preimplantation genetic testing for aneuploidy (PGT-A) is cost-effective for patients undergoing invitro fertilization (IVF). Decision analytic model comparing costs and clinical outcomes of two strategies: IVF with and without PGT-A. Genetics laboratory. Women ≤ 42years of age undergoing IVF. 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. 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. 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. 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.

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

Patients with cancer may overestimate FP success rates a. PGT-A aids in embryo selection and may provide a more accurate picture of future reproductive potential among banked embryos. We investigated the use of PGT-A among patients undergoing EB cycles for FP prior to cancer treatment. Retrospective cohort study of medical EB cycles between 1/2014 and 4/2018. Analysis of medical EB cycles performed in patients with cancer. PGT-A performed using trophectoderm biopsy with aCGH or NGS. Exclusive oocyte cryopreservation cycles were excluded. Data analyzed using student’s T-test, chi square, and Fishers Exact test (mean ± SD, p<0.05). 58 medical EB cycles were identified and compared; 34 cycles (59%) utilized PGT-A. 67% of patients banking embryos for breast cancer (18/27) utilized PGT-A; patients with lymphoma, endometrial ca, ovarian ca, and other cancers were evenly divided between PGT-A and no-PGT. PGT-A utilization increased over the study period. PGT-A and no-PGT groups were similar when comparing age (y) at FP cycle start (34.2±4 vs 35.5 ± 6), days of stimulation (11.8 ±2 vs. 11.1 ± 2), days from initial FP consultation to initiation of cancer treatment (36.9 ± 26 vs 36.4 ± 28), and timing of EB cycle start including day-2 or random-start protocol (p>0.05). Equal patients in each group cryopreserved both oocytes and embryos (n=5 PGT-A vs n=3 no-PGT). Groups were similar in no. oocytes retrieved (19 ±15 vs 17.5 ±14), 2PN zygotes (10.7 ± 9 vs 10 ± 9), and blastocysts (7.2 ± 7 vs 6.7 ± 5) excluding 6 patients in the no-PGT group who cryopreserved 2pn zygotes and 4 who froze an average of an additional 10.8 un-biopsied embryos (p>0.05). 5 PGT-A patients underwent a 2nd EB cycle (vs 2 among no-PGT); 2 for poor response, 3 for low or no euploidy. 6 in the no-PGT group cryopreserved 2PN zygotes; 3 were BRCA-positive and intended future PGT-M. Among PGT-A patients, 6.7 ± 5 blastocysts underwent PGT-A with 3.5 ± 3 (48.2%) euploid embryos available for future frozen embryo transfer (FET). Overall, PGT-A patients understood their final “usable” embryo number to be 3.5 ± 3 euploid embryos vs 7.2 ± 7 untested embryos in the non-PGT group. 2 breast cancer survivors in the PGT-A group have since undergone FET with 1 livebirth and 1 ongoing pregnancy; 2 others intend an upcoming FET. PGT-A in medical EB cycles provides critical information about future embryo potential and may be a helpful counseling tool. In some cases, poor PGT-A results informed patients to pursue a 2nd EB cycle without delaying cancer treatment. FP patients without PGT-A have a greater number of vitrified embryos but with unknown reproductive potential; patients may thus overestimate future success rates with devastating consequences. PGT-A results may require patients to prematurely address a terminal fertility diagnosis. The knowledge gained from PGT-A must thus be weighed against the financial cost and possible emotional toll; additional psychosocial support should be offered given the potential magnitude of information gained.

The effect of preimplantation genetic testing for aneuploidy (PGT-A) on in vitro fertilization (IVF) outcomes with donor oocytes and utilization of elective single embryo transfer (ESET)

Aneuploidy is a known detrimental factor limiting embryo implantation in patients undergoing IVF. As such, PGT-A has been shown to be a successful strategy to improve rates of embryo implantation and reduce the risk of miscarriage. ESET has also been shown to reduce the morbidity and mortality that is associated with multiple gestations. ESET with PGT-A has been well-studied among patients undergoing IVF with autologous oocytes, but few studies have examined the use of PGT-A with donor oocytes (DO).