Testing For Aneuploidy Research Articles

Value of PGT-A when only one or two blastocysts are obtained: propensity-score matching and cost-effectiveness study.

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. 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). 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. 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.

Greater PGT-A utilization in IVF clinics does not improve live birth rates but relates to IVF center ownership: a preliminary report.

This study aims to assess whether increased utilization for preimplantation genetic testing for aneuploidy (PGT-A) relates to improved live birth rates in IVF and whether IVF clinic ownership relates to PGT-A utilization. In a retrospective cohort study involving > 90% of US IVF clinics reporting to the Center for Disease Control and Prevention (CDC), stratified for ages (< 35, 35-37, 38-40, 41-42, and ≥ 43 years), and with reference point cycle start, we investigated whether PGT-A utilization related to live birth rates and ownership format as either physician-, academic/hospital/military, or equity/venture capital (VC) owned clinics. The lowest PGT-A-utilizing clinics reported significantly better live birth rates than the highest-utilizing clinics. Youngest patients (under age 35) were most adversely affected by high PGT-A utilization. Clinic ownership, moreover, is significantly related to the utilization of PGT-A, with equity and/or venture capital (VC)-owned clinics being significantly overrepresented among high-utilizing clinics in comparison to clinics owned by private physicians or by academia, hospitals, and the military. PGT-A, overall, reduces live birth chances in IVF, with the risks of adverse outcome effects increasing with growing PGT-A utilization in primarily younger women under age 35. Equity/VC ownership favors increasing PGT-A utilization in comparison to private physician and academic/hospital/military clinic ownership. These findings suggest intervention strategies to reverse excessive PGT-A utilization.

The impact of Duostim protocol on pregnancy outcomes in infertile patients: A meta-analysis comparing single and double conventional stimulation cycles.

The DuoStim protocol has been proposed as an alternative to conventional single and double stimulation cycles in the treatment of infertility. However, its efficacy in improving pregnancy outcomes remains uncertain. To systematically evaluate the impact of the DuoStim protocol on pregnancy outcomes in infertile patients by comparing it with single and double conventional stimulation cycles. An online systematic search was conducted using PubMed, Cochrane Library, and EMBASE databases, covering the period from their inception to March 2024. Randomized controlled trials (RCTs) comparing the DuoStim protocol with single and double conventional stimulation cycles in infertile patients were identified. Data were extracted by two independent investigators who screened the literature and assessed the quality of the studies. Meta-analysis was performed using RevMan 5.4 software. A total of six RCTs involving 414 infertile patients were included. The DuoStim protocol significantly increased the total number of oocytes compared to single and double conventional stimulation (MD = - 1.47; 95% CI, - 2.12 to - 0.82; P < 0.00001). There were no statistically significant differences in the number of MII oocytes, total embryos, pregnancy rate, and live birth rate. Subgroup Analysis: compared to single stimulation, the DuoStim protocol significantly increased the number of MII oocytes (MD = 1.71; 95% CI, 0.77 to 2.66; P = 0.0004) and total embryos (MD = 1.34; 95% CI, 0.61 to 2.08; P = 0.0003). There were no significant differences in pregnancy rate and live birth rate. Secondary outcomes showed the effect of the DuoStim protocol in patients undergoing preimplantation genetic testing for aneuploidies (PGT-A). The time to obtain euploid blastocysts was significantly reduced in the DuoStim group compared to the control group (23.3 ± 2.8days vs. 44.1 ± 2.0days; P < 0.001). The DuoStim protocol shows a significant advantage in increasing the total number of oocytes, MII oocytes, and embryos compared to single stimulation. However, it does not significantly improve pregnancy and live birth rates. The protocol also shortens the time to obtain euploid blastocysts in patients undergoing PGT-A, indicating potential benefits for specific patient groups. Further research is needed to confirm these findings and evaluate long-term outcomes. Thus, the quality of evidence should be considered moderate, warranting cautious interpretation of the results.

From live birth to live birth: a strong correlation between the outcomes of first and second frozen-thawed euploid blastocyst transfers from sibling oocytes.

To investigate any correlation between the outcomes of the first euploid frozen-thawed blastocyst embryo transfer (FBT) and the subsequent euploid FBT derived from sibling oocytes. This retrospective study analyzed data from 1051 women who underwent preimplantation genetic testing for aneuploidy and had a euploid FBT. Of these patients, 159 underwent a second transfer. The primary outcome was the live birth rate. Overall, 159 women who underwent a second euploid FBT were categorized into two subgroups depending on the implantation success of the first FBT. Of these patients, 94 (59.1%) belonged to the nonclinical group, signifying a negative result or a biochemical pregnancy. The remaining 65 (40.9%) patients belonged to the clinical group, indicating either a miscarriage or a live birth. In the binary logistic regression analysis, the live birth outcome during the first euploid FBT was a statistically significant and independent predictor of live birth in the subsequent FBT [odds ratio 4.14, 95% confidence interval (1.184-14.531), p < 0.026). Miscarriages, including those that occurred before intracytoplasmic sperm injection and in the first euploid FBT, reduced the live birth rate by approximately 34% (p < 0.027). No significant difference in the miscarriage rate was found between the two subgroups (19.2% (10/52) vs. 25.4% (14/55), p = 0.38). The live birth outcome of the second euploid FBT is mainly determined by the live birth outcome of the first. Miscarriages that occurred before in vitro fertilization negatively affect the live birth outcome.

Assessing the clinical value of day 7 blastocysts: a predictive model for preimplantation genetic testing for aneuploidy (PGT-A) cycles.

To identify the benefit of extending embryo culture until day (D)7 based on patients and cycle characteristics. A retrospective cohort study was conducted including 25,120 blastocysts from 5278 PGT-A autologous cycles between 2017 and 2022. A theoretical cumulative live birth rate (CLBR) was calculated by binomial density function. An increase of ≥ 5% in theoretical CLBR was considered a tangible benefit when obtaining ≥ 1 euploid D7 blastocyst and ≤ 3 euploid blastocysts from D5/D6. A predictive model was built considering the number of embryos eligible for extended culture until D7, number of blastocysts already biopsied on D5/D6, and patient's age. Euploidy rates decreased for blastocysts biopsied on D5, D6, and D7 (55.6%, 39.7%, and 27.1%, P < 0.001, respectively). The probability of tangible benefit was increased with more embryos available for extended culture until D7, was decreased with higher D5/D6 blastocysts already biopsied and for older patients. The overall AUC of the final model in the validation sets was 0.75 (95% CI 0.72-0.78). Based on the predictive model, in poor cycles (< 1% tangible benefit), the benefit rate from extended culture was 0.3% and for moderate, good, and best cycles (1-10%, 10-20%, and ≥ 20% tangible benefit) were 4.4%, 14.0%, and 29.3%, respectively. An application of the predictive model is available online for external testing: https://artfertilityclinics.shinyapps.io/WET-D7/ . The predictive model provides a decision-making tool to objectively identify cycles that would benefit from extending embryo culture until D7.

Oocyte maturity rate is an age-independent predictor of blastocyst development and euploidy rates: a multicenter retrospective study

Research Question Can oocyte maturity rate predict blastocyst development and euploidy rates independently of patient age? Design A multicenter retrospective study including 1547 consecutive women undergoing first in-vitro fertilization cycle of oocyte retrieval-intracytoplasmic sperm injection with preimplantation genetic testing for aneuploidy (IVF/ICSI/PGT-A). Both centers used the same PGT lab for PGT-A testing. Oocyte maturity rate as a predictor for cycle outcomes of blastocyst development and euploidy rates was analyzed by Poisson regression model, after controlling for other known confounders. Results Oocyte maturity rate is positively correlated with blastocyst development rate and euploidy rate after controlling for patient age at cycle start, BMI, AMH levels, total FSH dosage, number of days of ovarian stimulation, and peak estradiol level (p&lt;0.01). Conclusion This study demonstrated that oocyte maturity rate can predict blastocyst development and euploidy rates independently of other confounding factors including patient age. This finding suggests that oocyte maturity rate may serve as an important biomarker for oocyte quality. This can be used by physicians to evaluate and improve the efficacy of ovarian stimulation regimens for IVF. This may further enhance artificial intelligence (AI) capabilities in optimizing ovarian stimulation protocols and outcomes of Assisted Reproductive Technologies (ART).

Comparative study on pregnancy complications: PGT-A vs. IVF-ET with gender-specific outcomes.

The safety and clinical effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) in improving pregnancy outcomes for sub-fertile patients remains controversial. Potential sex-based differences in the relationship between PGT-A and pregnancy complications have not been investigated, which could guide the appropriate clinical application of PGT-A. In this secondary analysis of data from a multicenter, randomized, controlled, non-inferiority trial (NCT03118141), 940 women who achieved singleton live birth during the trial were included to estimate the between-group differences in pregnancy complications following PGT-A versus conventional in vitro fertilization (IVF) vary with fetal sex. Logistic regression analysis was used to adjust for possible confounders, and subgroup analysis was also performed. Among male fetuses, the risk of maternal preeclampsia was significantly lower after PGT-A compared to conventional IVF treatment (3.37% vs. 7.88%; adjusted OR, 0.40; 95% CI, 0.17-0.92; P = 0.032). However, this protective effect was not observed in pregnancies with female fetuses (3.63% vs. 3.38%; adjusted OR, 1.04; 95% CI, 0.36-3.00; P = 0.937). In addition, no significant sex-dependent differences in the risks of other pregnancy complications or neonatal outcomes were detected between PGT-A and conventional IVF groups (P > 0.05). In summary, PGT-A was associated with a decreased risk of maternal preeclampsia in singleton pregnancies with male fetuses, highlighting its potential utility in preeclampsia prevention in addition to spontaneous abortion rate reduction.

Parental Balanced Translocation Carriers do not have Decreased Usable Blastulation Rates or Live Birth Rates Compared to Infertile Controls

ObjectiveTo determine if translocation carriers have a reduced number of usable blastocysts compared to infertile controls. DesignRetrospective cohort study. SubjectsAll cycles of balanced translocation carriers undergoing IVF with preimplantation genetic testing (PGT-SR) for structural rearrangements at a single infertility center compared to an age-matched control cycles of infertile patients undergoing preimplantation genetic testing for aneuploidy (PGT-A) from January 2012-August 2022. ExposureBalanced translocation carriers. Main Outcome MeasuresPrimary outcome measures were blastulation rate, usable blastulation rates and live birth rate. Secondary outcome measures were sustained implantation rate, fertilization rate, number of oocytes retrieved, number of metaphase II oocytes, total blastulation failure, number of 2 pronuclear embryos, and number of euploid embryos. Outcome measures were compared between male translocation carriers and controls, female translocation carriers and controls, and Robertsonian versus reciprocal translocation carriers. ResultsA total of 1,291 retrieval cycles from 993 patients were included, of which 255 patients were translocation carriers, while 738 were controls. Of those with translocations, 30 (11.5%) were Robertsonian and 231 (88.5%) were reciprocal carriers. There was a statistically significant difference in the blastulation rate between carriers and controls (59.5% versus 62.1%; p-value = 0.01). However, usable blastulation rates (47.2% versus 50.0%) were equivalent between groups. There were no differences in number of oocytes retrieved (18.5 versus 18.3), number of 2 pronuclear embryos (13.4 versus 12.5), sustained implantation rate (71.4% versus 75.1%) or live birth rate (63.0% versus 66.1%) between translocation carriers and controls. In both male and female translocation carriers versus controls, there were no differences in usable blastulation rates or live birth rates. When comparing Robertsonian with reciprocal translocation carriers, rates of blastulation, usable blastulation, sustained implantation, and live birth rate were equivalent. ConclusionDespite fewer euploid embryos, there were no differences in rates of usable blastulation or live birth rates in balanced translocation carriers, regardless of sex of affected partner or type of rearrangement, compared to controls. Routine karyotyping for blastulation failure may not be necessary based on these findings.

The presence of antinuclear antibodies does not affect the euploidy rate in patients undergoing PGT-A: a retrospective single-center study

Research QuestionThe effects of antinuclear antibodies (ANAs) on oocytes and embryos during IVF/ICSI procedures remain controversial. Do ANAs affect blastocyst aneuploidy rates during preimplantation genetic testing for aneuploidy (PGT-A) cycles? DesignWe conducted a retrospective cohort study of 259 patients who underwent PGT-A and immunological screening at our center between May 2018 and May 2023. Patients were divided into an ANAs-negative (ANAs-) group (213 cycles) and an ANAs-positive (ANAs+) group (46 cycles) based on the presence of ANAs, and embryo outcomes were compared. ResultsThere were significant differences between the ANAs- and ANAs+ groups in terms of male age (34 vs. 37 years, P=0.032), maternal age (33 vs. 35 years, P=0.046) and infertility duration (2 vs. 3 years, P=0.009), but there were no significant differences in the number of retrieved oocytes, metaphase II (MII) stage oocytes, available embryos, high-quality embryos, blastocysts biopsied, euploid blastocysts, MII stage oocyte rate, fertilization rate and high-quality embryo rate and euploidy rate. Multiple linear regression revealed that in infertile couples who underwent PGT-A treatment, only the maternal age was an independent factor influencing euploidy rates (regression coefficient of -0.009), whereas the presence of ANAs was not an independent factor influencing euploidy rates. ConclusionIn couples who underwent PGT-A treatment, the presence of ANAs did not affect the euploid rate, and this study did not observe any negative effects of ANAs on oocytes or embryos outcomes.

Comparative Analysis of Pregnancy Outcomes in Preimplantation Genetic Testing for Aneuploidy and Conventional In Vitro Fertilization and Embryo Transfer: A Stratified Examination on the Basis of the Quantity of Oocytes and Blastocysts From a Multicenter Randomized Controlled Trial

Comparative Analysis of Pregnancy Outcomes in Preimplantation Genetic Testing for Aneuploidy and Conventional In Vitro Fertilization and Embryo Transfer: A Stratified Examination on the Basis of the Quantity of Oocytes and Blastocysts From a Multicenter Randomized Controlled Trial

Aneuploidy rates and clinical pregnancy outcomes after preimplantation genetic testing for aneuploidy using the progestin-primed ovarian stimulation protocol or the gonadotropin-releasing hormone antagonist protocol.

To investigate the chromosome abnormality rates and clinical pregnancy outcomes after preimplantation genetic testing for aneuploidy (PGT-A) using either the progestin-primed ovarian stimulation (PPOS) protocol or the gonadotropin-releasing hormone (GnRH) antagonist protocol. The study included 431 PGT-A cycles in which controlled ovarian stimulation was performed using the PPOS protocol (n = 320 cycles) or GnRH antagonist protocol (n = 111 cycles) between January 2018 and December 2021. Frozen embryo transplantation was subsequently performed in 309 cycles with transplantable blastocysts. The number of retrieved oocytes, embryo development, next-generation sequencing results, and clinical pregnancy outcomes were compared between the two protocols. The primary outcome measure was the aneuploidy rate. Secondary outcome measures were clinical pregnancy per first frozen-thawed embryo transfer cycle and cumulative live birth rates per PGT-A cycle. There were no statistically significant between-group differences in the number of retrieved oocytes, available blastocysts, and high-quality blastocyst rate. The aneuploidy rates were similar between the two groups. There was no significant difference in clinical pregnancy outcomes, including the clinical pregnancy, implantation, miscarriage, live birth, or cumulative live birth rates, after frozen-thawed embryo transfer cycles (P>0.05). The study found no significant difference in the aneuploidy rate, clinical pregnancy rate and cumulative live birth rate after PGT-A cycles between those using the PPOS protocol and those using the GnRH antagonist protocol.

Impact of Microfluidic Sperm Sorting on Embryonic Euploidy in Infertile Patients with Sperm DNA Damage: A Retrospective Study.

Sperm DNA fragmentation is an important factor that affects male fertility. This study intends to evaluate the impact of sperm DNA damage [single-strand breaks (SSB) and double-strand breaks (DSB)] on fertilisation and embryonic euploidy after intracytoplasmic sperm injection (ICSI). Of the different sperm selection techniques, the novel microfluidic sperm sorting (MSS) ZyMōt™ ICSI device reduces both SSB and DSB in semen samples. The second objective is to study the impact of this MSS device on fertilisation and embryonic euploidy. This retrospective study included data from 167 ICSI treatments. The alkaline and neutral Comet assays were used to analyse SSB and DSB, respectively. Analysis of fertilisation and embryo euploidy rates was performed in four groups of patients with normal/altered SSB or DSB values. Density gradient centrifugation (DGC) and the ZyMōt™ ICSI MSS device were used for semen preparation. Fertilisation rates in 167 ICSI cycles were higher when using sperm from patients with normal SSB values (70.84%) and patients with abnormal SSB whose samples were processed using the MSS device (69.71%) compared to patients with abnormal SSB values using DGC (58.49%). Preimplantation genetic testing for aneuploidies (PGTA) revealed a higher embryo euploidy rate in patients with normal DSB values (60.00%) and patients with abnormal DSB whose samples were processed using the MSS device (44.59%) compared to patients with abnormal DSB values using DGC (36.84%). When female age was considered, there were fewer euploid embryos in women ≥35 years of age compared to younger women, independently of SSB and DSB. The number of euploid embryos increased when the MSS device was used. High SSB and DSB values in semen samples decreased fertilisation rates and embryonic euploidy, respectively. The ZyMōt™ ICSI device for semen preparation increased both rates, especially in couples that included women <35 years old.

Outcomes for Female Physicians Compared With Nonphysicians After Assisted Reproductive Technology.

To evaluate outcomes of female physicians after assisted reproductive technology (ART). We conducted a retrospective cohort study using data from 248 physician patients and 3,470 nonphysician patients who underwent a total of 10,095 fresh or frozen ART cycles at a single academic center in an insurance-mandated state between January 2015 and March 2022. The primary outcome was live-birth rate. The secondary outcomes were implantation rate, early pregnancy loss rate, and time to pregnancy. Models were adjusted for confounders where appropriate. Both groups were similar in age (mean physician age 36.29 years; mean nonphysician age 35.96 years, P=.35). Physicians had lower body mass index (BMI) (mean physician BMI 23.51, mean nonphysician BMI 26.37, P<.01), and a higher proportion were diagnosed with unexplained infertility (physician 33.9%, nonphysician 25.9%, P<.01) and used preimplantation genetic testing for aneuploidy (physician 21.5%, nonphysician 12.7%). Physicians and nonphysicians had similar live-birth rates (physician 39.3%, nonphysician 38.2%; adjusted relative risk [aRR] 1.01 95% CI, 0.91-1.13), implantation rates (physician 34.7%, nonphysician 33.7%; relative risk 1.03 95% CI, 0.94-1.14), and early pregnancy loss rates (physician 21.9%, nonphysician 19.8%; aRR 1.18 95% CI, 0.99-1.41) per transfer. Physicians had a shorter time from initial ART cycle to pregnancy (physician 21.82 weeks, nonphysician 25.16 weeks; aRR 0.86, 95% CI, 0.83-0.89). There was no difference between female physicians and nonphysicians in assisted reproduction cycle outcomes. Physicians become pregnant slightly faster than nonphysicians.

Non-invasive prediction of human embryonic ploidy using artificial intelligence: a systematic review and meta-analysis

Embryonic ploidy is critical for the success of embryo transfer. Currently, preimplantation genetic testing for aneuploidy (PGT-A) is the gold standard for detecting ploidy abnormalities. However, PGT-A has several inherent limitations, including invasive biopsy, high economic burden, and ethical constraints. This paper provides the first comprehensive systematic review and meta-analysis of the performance of artificial intelligence (AI) algorithms using embryonic images for non-invasive prediction of embryonic ploidy. Comprehensive searches of studies that developed or utilized AI algorithms to predict embryonic ploidy from embryonic imaging, published up until August 10, 2024, across PubMed, MEDLINE, Embase, IEEE, SCOPUS, Web of Science, and the Cochrane Central Register of Controlled Trials were performed. Studies with prospective or retrospective designs were included without language restrictions. The summary receiver operating characteristic curve, along with pooled sensitivity and specificity, was estimated using a bivariate random-effects model. The risk of bias and study quality were evaluated using the QUADAS-AI tool. Heterogeneity was quantified using the inconsistency index (I 2 ), derived from Cochran's Q test. Predefined subgroup analyses and bivariate meta-regression were conducted to explore potential sources of heterogeneity. This study was registered with PROSPERO (CRD42024500409). Twenty eligible studies were identified, with twelve studies included in the meta-analysis. The pooled sensitivity, specificity, and area under the curve of AI for predicting embryonic euploidy were 0.71 (95% CI: 0.59-0.81), 0.75 (95% CI: 0.69-0.80), and 0.80 (95% CI: 0.76-0.83), respectively, based on a total of 6879 embryos (3110 euploid and 3769 aneuploid). Meta-regression and subgroup analyses identified the type of AI-driven decision support system, external validation, risk of bias, and year of publication as the primary contributors to the observed heterogeneity. There was no evidence of publication bias. Our findings indicate that AI algorithms exhibit promising performance in predicting embryonic euploidy based on embryonic imaging. Although the current AI models developed cannot entirely replace invasive methods for determining embryo ploidy, AI demonstrates promise as an auxiliary decision-making tool for embryo selection, particularly for individuals who are unable to undergo PGT-A. To enhance the quality of future research, it is essential to overcome the specific challenges and limitations associated with AI studies in reproductive medicine. This work was supported by the National Key R&D Program of China (2022YFC2702905), the Shengjing Freelance Researcher Plan of Shengjing Hospital and the 345 talent project of Shengjing Hospital.

Two-year cumulative live-birth rates and maximum number of transfer cycles in women aged ≥ 40 years

This retrospective study aimed to clarify the cumulative live-birth rates (CLBRs) and cost per live-birth (LB) to evaluate the validity of frozen–thawed embryo transfer without preimplantation genetic testing for aneuploidy (PGT-A) in women aged ≥ 40 years. The study included 1,011 patients aged ≥ 40 years who underwent their first oocyte retrieval at our hospital between January 2010 and September 2017. They were followed up for up to two years or until either treatment discontinuation or a pregnancy that resulted in a live birth. The 2-year CLBRs were 55.6%, 39.0%, 31.3%, 19.1%, 10.6%, 4.4%, and 0% for patients aged 40, 41, 42, 43, 44, 45, and > 46 years, respectively. In approximately 80% of LB cases, patients aged 40–42 years and 43–44 years became pregnant by the fourth and second transfers, respectively. Costs per LB were $30,207, $49,034, $66,345, $102,759, and $195,862 for patients aged 40, 41, 42, 43, and 44, respectively. Cost per LB for each number of transfers reached $300,000 and $ 450,000 for the third transfer at 42 and 43 years of age, respectively. For cost-effectiveness, up to two ET cycles are recommended for patients aged 42–43, and none for patients aged ≥ 44 years.

Non Invasive Preimplantation Testing for Aneuploidies in Assisted Reproduction: A SWOT Analysis.

The implementation of non-invasive PGT-A offers a new strategy to genetically assess the preimplantation embryo and to enhance IVF results. The extraction of DNA from the embryo culture medium has been sufficiently demonstrated, and the ability to obtain chromosomal information as a result is particularly interesting. As morphological criteria have proven to have a weak correlation with embryo ploidy status, this technique emerges as a promising alternative for embryo selection. It also appears reasonable that avoiding biopsy may enhance further embryo development. However, there are growing concerns regarding several aspects of this technique, such as the origin of this cell free DNA, the degree of representativeness of the whole embryo, the need for extended culture or the absence of standardized protocols. Despite the published data on good prognosis couples are promising, niPGT-A is yet to be considered a substitute for trophectoderm biopsy. The current SWOT analysis aims to summarize both resolved and unresolved issues, as well as limiting aspects of niPGT-A.

Comparative Analysis of Fluorescence In Situ Hybridization and Next-Generation Sequencing in Sperm Evaluation: Implications for Preimplantation Genetic Testing and Male Infertility.

Pre-implantation genetic testing (PGT) is a crucial process for selecting embryos created through assisted reproductive technology (ART). Couples with chromosomal rearrangements, infertility, recurrent miscarriages, advanced maternal age, known single-gene disorders, a family history of genetic conditions, previously affected pregnancies, poor embryo quality, or congenital anomalies may be candidates for PGT. Preimplantation genetic testing for aneuploidies (PGT-A) enables the selection and transfer of euploid embryos, significantly enhancing implantation rates in assisted reproduction. Fluorescence in situ hybridization (FISH) is the preferred method for analyzing biopsied cells to identify these abnormalities. While FISH is a well-established method for identifying sperm aneuploidy, NGS offers a more comprehensive assessment of genetic material, potentially enhancing our understanding of male infertility. Chromosomal abnormalities, arising during meiosis, can lead to aneuploid sperm, which may hinder embryo implantation and increase miscarriage rates. This review provides a comparative analysis of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) in sperm evaluations, focusing on their implications for preimplantation genetic testing. This analysis explores the strengths and limitations of FISH and NGS, aiming to elucidate their roles in improving ART outcomes and reducing the risk of genetic disorders in offspring. Ultimately, the findings will inform best practices in sperm evaluations and preimplantation genetic testing strategies.

Preimplantation Genetic Testing for Aneuploidy (PGT-A) in In-Vitro Fertilisation (IVF) Treatment: Study Protocol for Pilot Phase of a Randomised Controlled Trial.

Introduction: Poor outcomes following IVF treatments are speculated to be due to the transfer of aneuploid embryos that cannot be identified based on morphological evaluation alone. This leads to patients requiring numerous embryo transfers and, consequently, a prolonged time interval before live birth. Embryo selection following preimplantation genetic testing for aneuploidy (PGT-A) with next-generation sequencing (NGS) has been suggested as an intervention to shorten time to pregnancy in women undergoing in vitro fertilisation (IVF). Past studies assessing the clinical efficacy of PGT-A in improving clinical outcomes have been conflicting and the associated clinical pregnancy rates and live birth rates following the transfer of a mosaic embryos have yet to be determined. None of the existing studies solely included women of advanced reproductive age (ARA). The pilot study and proposed RCT will determine if, compared to morphological evaluation alone, the use of PGT-A through NGS is a more clinically effective, safer, and more cost-effective way to provide IVF treatment in women of advanced reproductive age. Method and Analysis: The proposed pilot study will aim to randomise 100 patients within a single-centre study to evaluate recruitment, randomisation, and adherence to study protocol and allocated trail arms by participating patients. The results of the pilot study will enable us to determine the sample size for a larger study to establish the effectiveness of PGT-A in ARA women. Ethics and Dissemination: The study (Integrated Research Application System Number 236067) received approval from the Health Research Authority and Health and Care Research Wales (HCRW) and the East Midlands-Leicester South Research Ethics Committee (20/EM/0290). The results will be made available to patients, the funders, the Reproductive Medicine societies, and other researchers. Trial registration: ClinicalTrials.gov Identifier: NCT05009745, n.

Multi-omics PGT: re-evaluation of euploid blastocysts for implantation potential based on RNA sequencing.

In addition to chromosomal euploidy, can the transcriptome of blastocysts be used as a novel predictor of embryo implantation potential? This retrospective analysis showed that based on differentially expressed genes (DEGs) between euploid blastocysts which resulted and did not result in a clinical pregnancy, machine learning models could help improve implantation rates by blastocyst optimization. Embryo implantation is a multifaceted process, with implantation loss and pregnancy failure related not only to blastocyst euploidy but also to the intricate dialog between blastocyst and endometrium. Although in vitro studies have revealed the characteristics of trophectoderm (TE) differentiation in implanted blastocysts and the function of TE placentation at the implantation site, the precise molecular mechanisms of embryo implantation and their clinical application remain to be fully elucidated. This study involved 102 patients who underwent 111 cycles for preimplantation genetic testing for aneuploidies (PGT-A) between March 2022 and July 2023. The study included 412 blastocysts biopsied at Day 5 [D5] or Day 6 [D6] for patients who underwent PGT-A. The biopsy lysates were split and subjected to DNA and RNA sequencing (DNA- and RNA-seq). One part was used for PGT-A to detect DNA copy number variations, whereas the other part was assessed simultaneously by RNA-seq to determine the transcriptome characteristics. To validate the reliability and accuracy of RNA-seq obtained from this strategy, we initially analyzed the transcriptome of blastocysts with chromosomal aneuploidies. Subsequently, we compared the transcriptomic features of blastocysts with different rates of formation (D5 vs D6) and investigated the network of interactions between key blastulation genes and the receptive endometrium. Then to evaluate the implantation potential of euploid blastocysts, we identified DEGs between euploid blastocysts that resulted in clinical pregnancy (defined as the presence of a gestational sac detected by ultrasound after 5 weeks) and those that did not. These DEGs were then employed to construct a predictive model for optimizing blastocyst selection. The successful detection rate of PGT-A was remarkably high at 99.8%. The RNA data may infer aneuploidy for both trisomy and monosomy. Between the euploid blastocysts that formed on D5 and D6, 187 DEGs were predominantly involved in cell differentiation for embryonic placenta development, the PPAR signaling pathway, and the Notch signaling pathway. These D5/D6 DEGs also exhibited a functional dialog with the receptive phase endometrium-specific genes through protein-protein interaction networks, indicating that the embryo undergoes further differentiation for post-implantation development. Furthermore, a modeling strategy using 280 DEGs between blastocysts leading to successful clinical pregnancies or failing to produce clinical pregnancies was implemented to refine the euploid embryo optimization, achieving areas under the curves of 0.88, 0.71, and 0.84 for the random forest (RF), support vector machine, and linear discriminant analysis models, respectively. Finally, a retrospective analysis of 83 transferred euploid blastocysts using the RF model identified three types of euploid embryos with a decreasing trend in implantation potential. Notably, the implantation rate of the good group was significantly higher than that of the moderate group (88.6% vs 50.0% P = 0.001) and that of the moderate group was higher than that of the poor group (50.0% vs 20.8%, P = 0.035). The sample size was insufficient; thus, a prospective study is needed to verify the clinical effectiveness of the above model. Because we did not analyze blastocysts that led only to biochemical pregnancies but failed clinical pregnancies separately, our classification system still must be modified to screen these embryos. Transcriptomic analysis of blastocysts offers a novel approach for predicting embryo implantation potential, which can be utilized to optimize clinical embryo selection. The ranking system may be effective in reducing the times and costs involved in achieving a clinical pregnancy. This study was funded by the "Pioneer" and "Leading Goose" R&D Program of Zhejiang (No. 2023C03034), the National Natural Science Foundation of China (82101709), and the National Key Research and Development Program for Young Scientists of China (No. 2022YFC2702300). The authors state no competing interests. N/A.

Impact of autologous mitochondrial transfer on obstetric and neonatal health of offspring: A small single-center case series

IntroductionA pilot study was carried out to test the efficacy of the autologous mitochondrial transfer therapy (AUGMENT) technique. No improvements in pregnancy rate, development, or embryo quality were observed in the AUGMENT-treated group versus the Control group in this study. The main objective of this research is to analyze whether AUGMENT technology did have any impact on the obstetric and perinatal outcomes of pregnancies and children resulting from treated oocytes. MethodsFollow up study of women with a livebirth who participated in a pilot randomized controlled trial in which sibling MII oocytes were randomly allocated to AUGMENT + intracytoplasmic sperm injection (ICSI) (AUGMENT group) or ICSI alone (control group). Preimplantation genetic testing for aneuploidy was performed in both groups. Pregnancy and neonatal outcomes of 14 women (15 pregnancies) and their 18 children were analyzed. The information was retrieved by reviewing the medical records or through questionnaires sent to the patients. ResultsNo differences were found in this small case series between the AUGMENT and control groups regarding the rate of gestational complications, birth defects, gestational age at delivery (271.4 ± 12.56 vs 278 ± 10.4 days), birthweight (3.1 ± 0.6 kg vs. 3.1 ± 0.4 kg) and neonatal outcome. DiscussionThe few pregnancies achieved using AUGMENT oocyte therapy had similar outcomes than controls in this very small series. Our very preliminary data need to be confirmed in larger samples. The long term follow up of these children also needs to be analyzed.