Search Results (125)

Background: Despite significant advances in assisted reproductive technology (ART), disparities in clinical outcomes persist. While patient-related factors are well-studied, the role of partner ethnicity remains understudied. We hypothesized that partner ethnicity affects ART outcomes. This study examined the association between partner ethnicity and ART outcomes. Methods: We conducted a retrospective cohort study among patients and their partners undergoing IVF treatment in the United Kingdom between 2017 and 2018. The exposure was partner ethnicity. Outcomes included biochemical pregnancy, clinical pregnancy, pregnancy loss, and live birth. We calculated risk ratios (RR) and 95% confidence intervals (CI) using multivariable regression models to estimate the association between partner ethnicity and IVF outcomes, adjusting for female patient age, partner age, patient ethnicity, gravidity, infertility diagnosis, treatment type, preimplantation genetic testing for aneuploidy, and number of prior in vitro fertilization (IVF) cycles. Results: Among 158,813 IVF cycles, live birth rates per cycle were 26.3% for couples with White partners and 23.1% for those with non-White partners. Non-White partners were associated with a 5% lower clinical pregnancy rate (RR 0.95, 95% CI 0.92–0.97) and a 6% lower live birth rate (RR 0.94, 95% CI 0.92–0.97). Specifically, Black (RR 0.82, 95% CI 0.77–0.87) and Asian (RR 0.67, 95% CI 0.59–0.76) partners had significantly reduced live birth rates, though these associations were attenuated after adjusting for patient ethnicity. Couples in which both the partner and patient were Black or Asian had 24–42% lower live birth rates compared with White couples (Black: RR 0.76, 95% CI 0.70–0.82; Asian: RR 0.58, 95% CI 0.49–0.68). Conclusions: Partner ethnicity is independently associated with IVF outcomes, with non-White partners showing lower rates of these outcomes. These findings suggest the clinical relevance of partner ethnicity in reproductive outcomes. Further research is warranted to elucidate the mechanisms underlying these associations. Full article

A predominant etiological factor in implantation failure and early pregnancy loss is embryonic chromosomal abnormalities. The current clinical standard for determining embryonic ploidy is invasive preimplantation genetic testing. This procedure imposes mechanical stress on embryonic cells during trophectoderm biopsy and fails to significantly improve live birth rates per transfer, likely due to its inability to evaluate the embryo’s implantation potential. Consequently, there is a clear need to develop a non-invasive method, suitable for routine clinical practice, that can simultaneously assess both the ploidy and implantation competence of a blastocyst prior to uterine transfer. Our research group was the first to achieve this by quantifying specific piwiRNAs (piR_016677, piR_017716, piR_020497, piR_015462) in spent culture medium. These data served as the foundation for logistic regression models tailored for day 5 blastocysts, day 6 blastocysts, and blastocysts irrespective of their developmental rate. These models demonstrated high diagnostic accuracy, with specificity ranging from 68% to 100% and sensitivity from 71% to 100%. The rationale for employing these molecules as biomarkers lies in their potential biological roles, which encompass maintaining genomic stability through LINE-1 regulation, as well as direct involvement in critical processes such as cell cycle control, spindle assembly, and cellular adhesion—all of which are imperative for successful implantation. Full article

Objectives: This study aimed to determine whether chromosomal mosaicism in blastocysts is associated with a distinct morphokinetic signature. Methods: Preimplantation genetic testing for aneuploidy (PGT-A) was performed on 182 human embryos via trophectoderm biopsy on day 5 and analyzed by next-generation sequencing. Embryos were classified as euploid (n = 55), mosaic (n = 39: 21 low-grade, 18 high-grade), or aneuploid (n = 88), of which 18 with concurrent mosaicism. Prior to biopsy, embryos were cultured in a time-lapse system (EmbryoScope), and 12 morphokinetic parameters were assessed, including pronuclei fading (tPNf), cleavage times (t2–t9), morula formation (tM), blastulation start (tSB), and full blastocyst formation (tB). These parameters were compared according to ploidy status. Results: Patients with euploid and mosaic embryos were comparable in terms of maternal age, ART indication and embryo quality (p > 0.05). In contrast, aneuploid embryos were obtained from older patients and had lower morphological grades. Mosaic embryos showed delayed tPNf (24.8 ± 6.5 vs. 22.8 ± 2.3 h, p = 0.03) and t2 (27.6 ± 6.6 vs. 25.4 ± 2.5 h, p = 0.02) compared to euploid embryos, mainly attributable to low-grade mosaic embryos. Whole-chromosome mosaicism, but not segmental mosaicism, was associated with delayed embryo development at several intermediate cleavage time points (t3, t4, t6, t7 and t9). Aneuploid embryos showed significant delays at later stages versus euploid embryos, particularly aneuploid embryos with mosaicism at t7 (56.6 ± 8.3 vs. 52 ± 5.6 h, p = 0.02), t8 (59.1 ± 9.6 vs. 54.8 ± 6.7 h, p = 0.04), tM (90.3 ± 7.7 vs. 83.6 ± 8.2 h, p = 0.006) and tB (113.0 ± 11.6 vs. 106.6 ± 8.9 h, p = 0.03). Conclusions: Mosaic embryos exhibit delays in early development (tPNf, t2) but reach later morphokinetic milestones at rates similar to euploid embryos. In contrast, aneuploid embryos, especially those with mosaicism, exhibit marked developmental delays at later stages (t7, t8, tM, tB). Full article

Background: PRKAG2-related disease is an autosomal dominant disorder caused by pathogenic variants in the PRKAG2 gene, leading to glycogen accumulation in cardiomyocytes. It is characterized by left ventricular hypertrophy (LVH), ventricular pre-excitation, and conduction disease. Due to the rarity of the condition and the frequent occurrence of private variants, functional or pathological testing is required for definitive pathogenicity classification. Case Presentation: We describe a 22-year-old male referred for evaluation after experiencing exertional dyspnea and a syncopal episode. Family history revealed sudden cardiac deaths and conduction disease requiring pacemaker implantation. The patient exhibited mild LVH on imaging, conduction abnormalities on electrophysiological study, and a heterozygous PRKAG2 variant (c.1643C>T; p.Ser548Leu), classified as likely pathogenic according to ACMG guidelines. Cascade screening identified the variant in three family members, one of whom exhibited a positive phenotype. Endomyocardial biopsy revealed glycogen accumulation, providing histopathological confirmation of PRKAG2-related disease. Conclusions: This case underscores the importance of integrating genetic, clinical, and histopathological data in variant interpretation. Endomyocardial biopsy can provide definitive evidence to reclassify a PRKAG2 variant as pathogenic, thereby guiding management and family screening. Full article

Preimplantation genetic testing for monogenic disorders (PGT-M) is a powerful tool for identifying genetic disorders prior to gestation. For hemoglobinopathies like thalassemias and sickle cell disease, PGT-M offers a preventative strategy to ensure that only embryos deemed genetically healthy are transferred. A comprehensive review of 22 original articles explores and summarizes the existing evidence on PGT-M techniques in hemoglobinopathies. The review focuses on key aspects such as accuracy, benefits, and drawbacks related to various hemoglobinopathies. Given the limited quantity of DNA obtained from an embryo biopsy, whole genome amplification (WGA) is a critical step for amplifying the sample. One of the available methods of WGA, multiple displacement amplification (MDA) is one of the most widely adopted method with acceptable allele drop-out (ADO) rates for hemoglobinopathies compared with traditional methods. Dealing with ADO constitutes a primary technical obstacle in PGT-M. The failure to amplify one allele in single-cell analysis is a major factor limiting the overall diagnostic accuracy of the procedure. To mitigate this issue, PCR-based and next-generation sequencing (NGS)-based approaches are employed. These methods incorporate linkage analysis with genetic markers such as short tandem repeats (STRs) or single-nucleotide polymorphisms (SNPs) to reduce the risk of incorrect interpretations from ADO and enhance the proportion of conclusive results. A future direction for PGT-M that involves the development of non-invasive methods (niPGT) will be included and discussed. Full article

Background: Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are significant challenges in reproductive medicine. For both, embryonic aneuploidy is the leading etiological factor. Preimplantation genetic testing for aneuploidy (PGT-A) via trophectoderm biopsy is the current standard for embryo selection. However, it is limited by its invasiveness, potential for embryo damage, and diagnostic errors due to mosaicism. Rationale/Objectives: This review critically evaluates the emerging role of noninvasive PGT (niPGT). NiPGT analyzes cell-free DNA from spent blastocyst culture media, thus, it is a potential alternative for managing RPL and RIF. Hence, the primary objective is to determine whether current evidence supports niPGT as a reliable replacement for conventional biopsy-based PGT-A in these high-risk populations. Outcomes: The analysis reveals that niPGT offers significant theoretical advantages. These include complete non-invasiveness, enhanced embryo preservation, and high patient acceptability. However, its clinical application is hampered by substantial limitations. Key amongst them is the inconsistent and often suboptimal diagnostic accuracy (sensitivity 70–85%, specificity 88–92%) compared to biopsy. Other significant factors include the high rates of amplification failure (10–50%), vulnerability to maternal DNA contamination, as well as low DNA yield. Crucially, there is a definitive lack of robust, prospective randomized controlled trial (RCT) data demonstrating improved live birth rates or reduced miscarriage rates specifically in RPL and RIF cohorts. As such, niPGT is not yet ready to be a standalone clinical adoption in RPL and RIF cases. However, it may serve as a valuable adjunct for rescue scenarios following biopsy failure or for ethical reasons. Wider Implications: The integration of niPGT with artificial intelligence, time-lapse imaging, and multi-omics profiling underlies a promising future. However, its transition from a predominantly research tool to a clinical standard necessitates various critical undertakings. These include rigorous multicenter RCTs, standardizing international protocol, and tailoring validation for the RPL and RIF subgroups. This review highlights the need for cautious optimism, positing that evidence-based integration, rather than premature adoption, is essential to realizing niPGT’s full potential without compromising patient care in these complex fertility scenarios. Full article

Time-lapse imaging (TLI) has emerged as a transformative technology in in vitro fertilization (IVF). This is because it offers continuous, non-invasive embryo assessment through morphokinetic profiling. It demonstrates key advantages such as reduced embryologist subjectivity, detection of dynamic anomalies, and improved implantation rates in niche populations. However, its clinical utility remains debated. Large trials and meta-analyses reveal no universal improvement in live birth rates compared to conventional methods. Key challenges underlying the outcome include algorithm generalizability, lab-specific protocol variability, and high costs. Nevertheless, TLI shows promise in specific contexts. For instance, Preimplantation Genetic Testing for Aneuploidies (PGT-A) cycles where it reduces unnecessary biopsies by predicting euploidy. However, even in this, its benefits are marginal in unselected populations. This review synthesizes evidence to highlight that TLI’s value is context-dependent, not universal. As such, adoption must be cautious to avoid resource misallocation without significant IVF outcome improvements. In future, personalized protocols, integration with non-invasive biomarkers, and multicenter collaboration are crucial to optimize TLI’s potential in assisted reproduction. Full article

Background/Objectives: Mosaicism in preimplantation embryos has important implications for embryo selection and reproductive outcomes. This study investigates the age-related frequency of mosaicism, analyzes its subtypes, and evaluates its clinical significance. Methods: A total of 36,506 blastocysts were analyzed using next-generation sequencing-based preimplantation genetic testing for aneuploidy between January 2021 and December 2023. The overall frequencies of euploid, aneuploid, mosaic, and no-call embryos were 20%, 56%, 23%, and 1%, respectively. In this study, we propose a new classification. Embryos were classified into two categories: Mosaic-A, referring to embryos identified as mosaic in standard genetic testing reports, and Mosaic-B, which includes both Mosaic-A and aneuploid embryos containing mosaicism. Results: The proportion of Mosaic-A embryos significantly decreased with maternal age (31% in women <35 years, 30% at 35–37 years, 23% at 38–40 years, 16% at 41–42 years, and 10% in women >42 years). By contrast, Mosaic-B embryos, which include Mosaic-A and aneuploid embryos with mosaicism, increased with age (46%, 49%, 53%, 56%, and 62% across the same age groups). Notably, as maternal age advanced, low-level complex mosaicism decreased, whereas high-level complex mosaicism significantly increased (p < 0.001, chi-square test for trend). Other mosaicism subtypes followed similar trends. These findings suggest that the increase in high-level complex mosaicism resulted from a higher incidence of post-zygotic mitotic errors occurring earlier in development and affecting a larger proportion of cells in older women. Conclusions: This study underscores the significance of incorporating a broader classification of mosaicism, including Mosaic-A and B, to enhance understanding of the biological behavior of mosaic embryos according to age and highlights the clinical importance of cryopreserving high-level or complex mosaic embryos for transfer in women of advanced age. Full article

The selection of the most suitable embryo, based on the morphology and shape, for embryo transfer is a critical aspect of the in vitro fertilization (IVF) process, as its precision can significantly enhance the overall effectiveness of IVF and contribute to a healthy birth. This study aimed to compare the chromosomal status and implantation potential of oval-shaped blastocysts versus normal-shaped blastocysts on day 5 post-ICSI (intracytoplasmic sperm injection). Initially, the frequency of oval blastocysts was assessed by analyzing 1328 embryos from 610 ICSI cycles. Subsequently, 80 patients undergoing ICSI and PGT-A (preimplantation genetic testing for aneuploidy), who had both normal and oval blastocysts in the same cycle, were selected to evaluate the euploid rate relative to blastocyst morphology. Finally, the implantation outcomes of fresh embryo transfers involving oval and normal-shaped blastocysts, neither of which had undergone PGT-A, were analyzed. Half of the blastocysts from each group were transferred after assisted hatching (AH), and the other half were transferred without AH. Blastocyst shape does not appear to correlate with an increased risk of aneuploidy but does influence hatching ability. Following AH, the implantation potential of elongated blastocysts is equivalent to that of normally shaped blastocysts, suggesting AH is beneficial for oval embryos. Consequently, the transfer of oval blastocysts is considered as safe and effective as the transfer of normally shaped embryos. Full article

Preimplantation genetic testing (PGT) reports play a decisive role in determining the fate of IVF-generated embryos. The identification of a chromosomal or genetic abnormality that could impact the health of the resulting newborn often leads to embryo disposal or indefinite storage in cryogenic containers. As a growing proportion of IVF cycles include PGT assessment, greater scrutiny is being placed on its clinical validity. Initially developed to detect monogenic disorders (PGT-M) and later expanded to identify full chromosomal aneuploidies, PGT is primarily used to identify embryos unlikely to implant (aneuploid), those that would lead to miscarriage, or those causing chromosomal syndromes or monogenic conditions. Advancements in genetic analysis now allow for the assessment of more complex traits and chromosomal features from a trophectoderm biopsy, including segmental aneuploidies, chromosomal mosaicism, and polygenic conditions. However, as technology pushes the limits of biological resolution, questions arise regarding the accuracy, clinical utility, and representativeness of these findings for the entire embryo. This article reviews the gold standards for validating clinical findings and reporting strategies, aiming to maximize diagnostic utility while minimizing false positives towards appropriately defined reproductive outcomes and phenotypes. Full article

Retinoblastoma is a rare but malignant pediatric retinal tumor, affecting 1 in 15,000–20,000 live births annually. It arises from biallelic mutations in the RB1 tumor suppressor gene (chromosome 13q14.2), leading to uncontrolled cell cycle progression. Clinically, it presents as unilateral (60%) or bilateral (40%) disease, with leukocoria and strabismus as hallmark signs. Untreated, retinoblastoma is fatal due to metastatic spread. The disease follows Knudson’s two-hit model: heritable forms (30–40% of cases) involve a germline RB1 mutation (M1) and a somatic second hit (M2), predisposing to bilateral/multifocal tumors and secondary cancers. Non-heritable cases (60–70%) result from somatic RB1 mutations or, rarely, MYCN amplification (2%). Genetic testing is critical to classify risk (H0, H1, and HX categories), guide surveillance, and inform family counseling. Bilateral cases almost always harbor germline mutations, while 15% of unilateral cases may carry germline/mosaic RB1 defects. Advanced techniques (Sanger/NGS sequencing for mutation detection, NGS for copy number alterations, and methylation assays) detect RB1 mutations, CNVs, and epigenetic silencing. Tumor DNA analysis resolves ambiguous cases. H1 patients require intensive ocular and brain MRI surveillance, while H0 cases need no follow-up. Prenatal/preimplantation genetic diagnosis (PGD) can prevent transmission in high-risk families. Emerging research explores additional genes (BCOR, CREBBP) and MYCN-amplified subtypes. Genetic counseling addresses recurrence risks, reproductive options, and long-term cancer monitoring. Integrating genetic insights into clinical practice enhances precision medicine, reducing morbidity and healthcare costs. Future directions include whole-genome sequencing and functional studies to refine therapeutic strategies. Full article

In this study, we aimed to correlate embryonic ploidy status studied with non-invasive preimplantation genetic testing for aneuploidy with the basic patient characteristics of the infertile couple to gain insight into the effects of parental physical health on embryo ploidy. We recruited 131 couples, who were stratified into 4 groups based on female age. We gathered general patient characteristics of the couple and determined the female’s hormonal status. We included 316 embryos in our study. Embryos were either transferred in the uterus in a fresh cycle or vitrified for later use. We collected spent embryo culture medium on either day 5 or 6 and performed whole genome amplification before using Next Generation Sequencing. Pregnancy outcomes were noted and cross-referenced with patient characteristics and the embryo’s ploidy status in a retrospective manner. While we have indirectly observed a level of maternal contamination, we nevertheless found a significant correlation between embryo ploidy status and cell free deoxyribonucleic acid concentration in spent embryo culture, as well a correlation between female age and embryo ploidy status. We observed a significant correlation between male body mass index and cell free deoxyribonucleic acid concentration in spent embryo culture medium and between male body mass index and pregnancy outcome. We illustrated a connection between male body mass index and cell free deoxyribonucleic acid, independent of female markers. This is the first study to observe not only female but male parameters in correlation to cell free deoxyribonucleic acid. Full article

Background: Embryo selection in in vitro fertilization (IVF) aims to prioritize embryos with the highest reproductive potential. While preimplantation genetic testing for aneuploidy (PGT-A) remains the gold standard for identifying euploid embryos, it is invasive and not universally applicable. Deep learning (DL)-based models, such as the intelligent data analysis (iDA) score, have emerged as non-invasive alternatives for embryo assessment. This review critically evaluates the relationship between iDAScore (versions 1.0 and 2.0), embryo euploidy, and clinical outcomes, including live birth and miscarriage rates. Methods: A narrative review was performed using PubMed and Google Scholar, covering studies published from January 2020 to May 2025. The search included terms such as “iDAScore,” “deep learning,” “euploidy,” and “live birth.” Only English-language full-text studies assessing the predictive performance of iDAScore relative to chromosomal status or reproductive outcomes were included. Results: Six retrospective studies met the inclusion criteria. All reported a statistically significant association between higher iDAScore values and embryo euploidy. AUC values for euploidy prediction ranged from 0.60 to 0.68. In several studies, iDAScore was also positively associated with live birth rates and negatively with miscarriage rates. However, the predictive accuracy was moderate when restricted to euploid embryo cohorts, indicating that iDAScore may be more effective in broader populations where chromosomal status is unknown. Conclusions: iDAScore represents a promising adjunct to traditional embryo assessment. Although it cannot replace PGT-A, it may aid in embryo prioritization when genetic testing is not feasible. Larger prospective studies are warranted to further validate its clinical utility. Full article

Background: Preimplantation genetic testing for aneuploidy (PGT-A) is a popular approach in assisted reproductive technology that improves embryo selection and implantation rates. Traditional approaches rely on trophectoderm (TE) biopsy, which is an invasive procedure that might jeopardize embryo integrity and create technical constraints such as mosaicism-related misclassification. Non-invasive preimplantation genetic testing (niPGT) has emerged as a possible alternative, using embryonic cell-free DNA (cfDNA) extracted from wasted culture media or blastocoel fluid to assess chromosomal status without requiring direct embryo manipulation. Methods: This systematic study investigates the molecular mechanisms behind cfDNA release, its biological properties, and the technological concerns that influence its utilization in niPGT. We look at recent advances in next-generation sequencing (NGS), whole-genome amplification (WGA), and bioinformatic techniques that improve cfDNA-based aneuploidy detection. In addition, we compare the sensitivity, specificity, and concordance rates of niPGT to conventional TE biopsy, highlighting the major aspects impacting its diagnostic performance. Results: The release of cfDNA from embryos is influenced by apoptotic and necrotic processes, active DNA shedding, and extracellular vesicle secretion, which results in fragmented chromosomal material of different qualities and quantities. While niPGT has shown promise as a noninvasive screening approach, significant variability in cfDNA yield, maternal DNA contamination, and sequencing biases all have an impact on test accuracy. Studies show that niPGT and TE biopsies have moderate-to-high concordance, although there are still issues in detecting mosaicism, segmental aneuploidies, and DNA degradation artifacts. Conclusions: NiPGT is a safer and less intrusive alternative to TE biopsy, with potential clinical benefits. However, technical advancements are required to improve cfDNA collecting procedures, reduce contamination, and improve sequencing accuracy. Additional large-scale validation studies are needed to create standardized methodologies and ensure that niPGT achieves the diagnostic reliability requirements required for widespread clinical deployment in IVF programs. Full article

Chromosomal structural rearrangements (SR) can impair gametogenesis, increasing the risk of embryos carrying unbalanced chromosomal content (i.e., with a gain or loss of chromosomal material). In such cases, assisted reproduction technologies (ARTs) with preimplantation genetic testing for structural rearrangements (PGT-SR) is recommended to identify embryos with a normal or balanced karyotype. However, data on IVF laboratory outcomes in this context remain limited. This retrospective cohort study analyzed 548 ART cycles, comprising 129 with PGT-SR and 419 with PGT-A, conducted at a single university-affiliated center. Following propensity score matching, laboratory outcomes were compared using logistic regression. The fertilization rate was comparable between groups, but the PGT-SR group had significantly lower blastocyst development (36.7% vs. 47.1%) and top-quality blastocyst development rates (9.6% vs. 21.1%). No significant differences were found either in the blastocyst development rate on days 5, 6, 7, or in euploidy rates. In the PGT-SR cohort, the generalized linear mixed-effects model indicated no significant effect of carrier gender on the normal/balanced blastocyst rate, while the type of SR was strongly associated with it: non-reciprocal SRs yielded a higher rate of normal/balanced blastocysts (89.9%) compared to reciprocal translocations (45.7%). These findings indicate that patients undergoing PGT-SR generate fewer blastocysts available for biopsy, and that in cases involving reciprocal translocations, the proportion of normal/balanced blastocysts suitable for transfer is significantly reduced. These results underscore the importance of personalized counseling in managing expectations and supporting informed clinical decision-making. Full article