Preimplantation Genetic Testing Research Articles

Dual trigger versus human chorionic gonadotropin trigger for blastocyst quality and cumulative live birth.

To evaluate the difference in the number of euploid blastocysts and cumulative live birth rate (LBR) between dual and human chorionic gonadotropin (hCG) triggers in poor and normal ovarian responders undergoing preimplantation genetic testing (PGT) cycles. This retrospective cohort study was enrolled from July 2018 to December 2021 and followed up until June 2024 at a single reproductive medical center. Overall, 1040 in vitro fertilization (IVF)-PGT and 784 frozen-thawed embryo transfer (FET) cycles were assessed. Dual (triptorelin acetate 0.2 mg and recombinant hCG [rhCG] 250 µg) or hCG (rhCG 250 µg) trigger was used for oocyte maturation in the gonadotropin-releasing hormone antagonist protocol and PGT cycles. We assessed the embryo outcomes and FET cumulative pregnancy outcomes. The number of oocytes retrieved (10.17 ± 5.22 vs 10.27 ± 5.14, P = 0.789), MII oocytes (8.24 ± 4.26 vs 8.28 ± 4.05, P = 0.888), blastocysts (2.16 ± 1.50 vs 2.12 ± 1.49, P = 0.729), euploid blastocysts (1.06 ± 1.14 vs 1.09 ± 1.23, P = 0.726), and the rate of cumulative LBR (24.9% vs 24.9%, P = 1.000) in the dual trigger group were comparable with those in the hCG group. The trigger method was not correlated with higher LBR based on logistic regression analysis (odds ratio[OR] = 1.040 [0.778-1.392], P = 0.790). For poor and normal ovarian responders, the dual trigger, compared with the hCG trigger, did not improve the PGT embryo outcomes and FET cumulative pregnancy outcomes.

A systematic review and meta-analysis of double trophectoderm biopsy and/or cryopreservation in PGT: balancing the need for a diagnosis against the risk of harm.

To prevent the transfer of embryos affected by monogenic conditions and/or chromosomal defects, preimplantation genetic testing (PGT) requires trophectoderm biopsy and cryopreservation. In 2-6% of biopsies, the diagnosis may be inconclusive due to DNA amplification failure or low-quality results. In these cases, a round of re-warming, re-biopsy, and re-cryopreservation is required to obtain a genetic diagnosis. In other cases, when the IVF centre starts providing PGT and/or when the patients develop an indication because of multiple failures, miscarriages or the birth of an affected child after IVF, cryopreserved untested embryos may be warmed, biopsied, and then re-vitrified. However, it is still unclear whether multiple manipulations may reduce reproductive outcomes after PGT. This study aimed at conducting a systematic review to investigate the available evidence on the safety of double biopsy and/or double cryopreservation-warming and provide recommendations in this regard. We performed meta-analyses of the differences in the reproductive outcomes (live birth per embryo transfer [LBR per ET], clinical pregnancy rate per ET [CPR per ET], and miscarriage rate per clinical pregnancy [MR per CP]) in double cryopreservation and single biopsy (CBC) or double biopsy and double cryopreservation (BCBC) flows vs the control single biopsy and single cryopreservation (BC) flow. Cryo-survival rates before ET and gestational and perinatal outcomes were also reported. PRISMA guidelines were followed to gather all available information from the literature (PubMed, Scopus, and Embase). We used Medical Subject Headings (MeSH) terms and a list of specific keywords relevant for the study question. We searched for original studies in humans, published in peer-reviewed journals in English up to April 2024. Four independent authors assessed the articles for inclusion. One included paper was retrieved from another source. A total of 4219 records were identified, and 10 studies were included in the meta-analysis. Certainty of evidence level ranged from low to moderate. Both the CBC and BCBC groups showed reduced reproductive outcomes compared to the control (BC). Specifically, live birth rates per embryo transfer were lower in the CBC group (OR: 0.56, 95% CI: 0.38-0.81, I2 = 58%; six studies) and the BCBC group (OR: 0.51, 95% CI: 0.34-0.77, I2 = 24%; six studies). CPR per ET were also lower in the CBC group (OR: 0.68, 95% CI: 0.51-0.92, I2 = 57%; seven studies) and the BCBC group (OR: 0.60, 95% CI: 0.46-0.78, I2 = 0%; seven studies). Additionally, MR per CPs were higher in both the CBC group (OR: 1.68, 95% CI: 1.02-2.77, I2 = 50%; seven studies) and the BCBC group (OR: 2.08, 95% CI: 1.13-3.83, I2 = 28%; seven studies). Cryo-survival as well as gestational and perinatal outcomes were within the expected norms in the studies reporting them. Improved genetic technologies, standardization of laboratory protocols, operators' proficiency with biopsy and cryopreservation, and continuous monitoring of the performance are essential to minimize inconclusive diagnoses and the putative impact of additional embryo manipulations. Although poorer reproductive outcomes might result from double biopsy and/or double cryopreservations, these practices may still be worthwhile to avoid transferring affected/aneuploid blastocysts. Therefore, the risks must be weighed against the potential benefits for each specific couple. PROSPERO (ID: CRD42024503678).

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).

Analysis of non-targeted variants by invasive prenatal diagnosis for pregnant women undergoing preimplantation genetic testing

To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism. Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022ZSLYEC-491). A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS). Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.

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 &amp;gt; 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.

Effect of Paternal Body Mass Index on Cumulative Live Birth Rates: Retrospective Analysis of 3048 Embryo Transfers in Couples Using Autologous Gametes

Obesity is a multifactorial disease present worldwide and correlated with hormonal alterations that may cause a decrease in reproductive outcomes and seminal quality. However, the specific mechanisms involved are unknown. This led us to examine the relationship between paternal body mass index (BMI) and clinical reproductive outcomes by evaluating the cumulative live birth rates (CLBRs) per number of embryo transfers (ETs), embryos replaced (EmbRs), and oocytes used (OUs) in consecutive treatments until achieving the first newborn. A retrospective study was performed, and Kaplan–Meier survival curves were created to observe CLBRs with regard to the paternal BMI, adjusted by relevant confounders through Cox regression models. The participants were couples undergoing intracytoplasmic sperm injection (ICSI) and ET in Spanish IVIRMA clinics using autologous gametes. The cohort was subdivided based on paternal BMI: normal (18.5–24.99 kg/m2) (N), overweight (25–29.99 kg/m2) (OV), or obese (≥30 kg/m2) (OB) patients. A total of 4750 ICSI cycles were included, encompassing 49,485 mature oocytes, 23,963 blastocysts, and 3048 ETs. When calculating CLBRs based on the number of ETs carried out until live birth was achieved, no statistically significant differences were found (p = 0.72). After adjusting for maternal age and BMI, female infertility diagnosis, the use of preimplantation genetic testing, and the number of ETs, Cox regression showed that there were no statistically significant differences between the BMI groups (HR: 0.94 [95% CI: 0.7–1.2]; p = 0.59). When calculating CLBRs considering EmbRs, there was a similarity between the BMI groups (p = 0.57). However, there were no statistically significant differences in the adjusted Cox regression (HR: 0.93 [95% CI: 0.7–1.2]; p = 0.51). Finally, when calculating CLBRs considering OUs, the results were comparable among BMI subgroups (p = 0.75), and there were no statistically significant differences with adjusted Cox regression (HR: 0.95 [95% CI: 0.8–1.2]; p = 0.66). In conclusion, paternal BMI was not associated with clinical reproductive outcomes when considering the ETs, EmbRs, or OUs needed to reach the first liveborn (LB).

Predictions of live birth in IVF programs of patients with recurrent implantation failure

BackgroundWhen a high-quality embryo is implanted into the uterus, but the pregnancy is not established as shown by the ultrasound visualization of an intrauterine gestational sac, this is known as “implantation failure.” Cases when more than two times implantation failure occurred was defined as recurrent implantation failure (RIF). Additional testing is done at this stage of infertility treatment to avoid a repeat of the same result with a future in vitro fertilization (IVF) effort. Aim of the studyThe study aimed to evaluate predictive value of using embryo transfer personalization because of the implantation window study in combination with preimplantation genetic testing in patients with recurrent implantation attempts. MethodsBriefly describe the main methods or treatments applied: Ninety-three infertile women make up the sample for this prospective cohort study. In regard to treatment results, the study intends to assess the predictive importance of patient characteristics, screening indicators, and several features of IVF cycles, such as the quantity, quality, and developmental stage of the transferred embryos. Statistical methods employed include the calculation of the median (Me) and interquartile range (IQR) for continuous variables. The Mann-Whitney U test was used to discern differences between unrelated samples, while categorical variables were presented as absolute and percentage values. The Pearson’s Chi-squared test assessed differences between groups. Logistic regression, utilizing both enter and backward Wald methods, was applied to establish associations with binary outcomes. ResultsThe integration of individualized embryo transfer and preimplantation genetic testing (PGT) significantly enhanced the likelihood of live births by 3.4 times in patients experiencing recurrent implantation failure (RIF), with a statistical significance of p = 0.026. In contrast, employing PGT alone increased the probability of live births by 1.5 times; however, this result was not statistically significant (p = 0.439). The predictive model for live birth in patients with RIF, based on our study findings, is defined as follows: the probability of live birth = 1.936 + [1.014 if PGT-A embryos are utilized for transfer] + [1.742 if endometrial preparation is tailored according to the Wellbeing Index (WI)] − [1.860 in cases of secondary infertility] − [1.891 when a male factor is involved]. ConclusionsThe determination of the implantation window (IW) and PGT of the embryo are efficient methods of live birth achievement for patients with RIF.

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

To determine if translocation carriers have a reduced number of usable blastocysts compared to infertile controls. Retrospective cohort study. All 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. Balanced translocation carriers. Primary 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. A 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. Despite 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.

A novel approach to detecting microduplication in split hand/foot malformation type 3 at the single-cell level: SHFM as a case study

BackgroundSplit hand/foot malformation (SHFM) is a congenital limb deficiency characterized by missing or shortened central digits. Several gene loci have been associated with SHFM. Identifying microduplications at the single-cell level is challenging in clinical practice, and traditional detection methods may lead to misdiagnoses in embryos and pregnant women.ResultsIn this research, we utilized a low cell count and whole-genome amplification products to employ single nucleotide polymorphism arrays, next-generation sequencing, and third-generation sequencing methods to detect copy number variants of microduplications in a SHFM3 case with limited DNA. Additionally, Karyomapping and combined linkage analysis were conducted to validate the results.ConclusionsThis study establishes a new strategy for identifying microduplications or microdeletions at the single-cell level in clinical preimplantation genetic testing, enhancing the efficiency and accuracy of diagnosing microduplication or microdeletion diseases during IVF-PGT and prenatal diagnosis.

Reproductive outcomes after preimplantation genetic testing in couples with sex chromosome abnormalities: a retrospective cohort study of 83 couples.

To explore the effects of parental sex chromosome abnormality on their preimplantation embryos. This is a retrospective cohort study including 83 couples with sex chromosome abnormalities undergoing preimplantation genetic testing (PGT) between 2013 to 2023. The preimplantation genetic testing results and pregnancy outcomes were compared to those of a control group consisting of 166 age-matched couples with normal karyotypes who underwent preimplantation genetic testing for monogenic disorders (PGT-M). Student's t-tests, chi-square or Fisher's exact tests were applied to compare clinical characteristics. The embryo euploidy rate was lower (58.94% vs 65.44%, P = 0.048, OR 0.76, 95%CI [0.58,0.99]) and the sex chromosomal aneuploidy rate was higher in the couples with sex chromosome abnormalities than control group (6.62% vs 2.63%, P = 0.004, OR 2.63, 95%CI [1.37,5.05]). The pregnancy outcomes including clinical pregnancy rates (48.57% vs 57.25%, P = 0.305) and live birth rates (47.14% vs 52.90%, P = 0.465) were similar between the two groups in their first embryo transfer cycles. To avoid high risk of embryo aneuploidy and sex chromosome abnormalities, preimplantation genetic testing should be recommended to couples with sex chromosome abnormalities.

Hereditary Neuromuscular Disorders in Reproductive Medicine

Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients’ quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot–Marie–Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb–Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.

The clinical application of affected-embryo-based SNP haplotype analysis for patients with de novo pathogenic mutations in PGT-M cycles.

In preimplantation genetic testing for monogenic/single gene disorders (PGT-M) cycles, direct detection of the pathogenic mutation combined with indirect haplotype analysis are recommended to achieve accurate diagnosis. However, it poses a challenge to conduct haplotype analysis for patients carried de novo pathogenetic mutations or without no identified haplotype in families. Herein, the strategy of affected-embryo-based haplotype analysis was implemented in clinical practice to provide a convenient, economical and effective way for such patients. Eight cases with de novo mutations were recruited. Six cases found the embryo-proband from biopsied blastocysts, and two case (case5 and 6) found them from developmental arrested embryos. A total of thirty-seven biopsied blastocysts from eight PGT-M cycles were performed direct detection and affected-embryo-based single nucleotide polymorphism (SNP) haplotype analyses. Till now, five cases (case 1, 2, 3, 7, 8) had delivered healthy babies and one case (case6) achieved successful ongoing pregnancy. We reported for the first time to find proband from developmental arrested embryos to complete haplotype analyses when no carriers were found in biopsied ones in clinical practice. Our study further proves and expands the application of the double-checking strategy based on affected-embryo proband and allows patients with de novo mutations or lack positive family members to benefit from the strategy.

Defining ethical criteria to guide the expanded use of Noninvasive Prenatal Screening (NIPS): Lessons about severity from preimplantation genetic testing.

We hypothesized that ethical criteria that guide the use of preimplantation genetic testing (PGT) could be used to inform policies about expanded use of non-invasive prenatal screening (NIPS). We used a systematic review of reasons approach to assess ethical criteria used to justify using (or not using) PGT for genetic conditions. Out of 1135 identified documents, we retained and analyzed 216 relevant documents. Results show a clear distinction in acceptability of PGT for medical vs. non-medical conditions. Criteria to decide on use of PGT for medical conditions are largely based on their severity, but there is no clear definition of "severity". Instead, characteristics of the condition that relate to severity are used as sub-criteria to assess severity. We found that characteristics that are used as sub-criteria for assessing severity include monogenic etiology, high penetrance, absence of treatment, early age of onset, shortened lifespan, and reduced quality of life. Consensus about the use of PGT is highest for conditions that meet most of these criteria. There is no consensus around the acceptability of using PGT to detect non-medical conditions. We propose that the same severity criteria could be used by policymakers to assess the acceptability of using other genetic tests in screening and practice, including for the use of NIPS for additional conditions as indications broaden.

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.

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.

A method for determining potential parental contamination: linkage disequilibrium-based log-likelihood ratio analysis for IVF-PGT

BackgroundAt present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.MethodsIn this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.ResultsWith IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.ConclusionsIn this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

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.