Journal of Assisted Reproduction and Genetics最新文献

Purpose: Recent evidence showed that the phase between pronuclear fading and the first cleavage is a perilous bridge connecting the zygote and the embryo. Indeed, delay in the short interval between pronuclear breakdown (PNBD) and the first cytokinesis may result in chromosome segregation errors. We tested the hypothesis that delays in this final phase of fertilization are associated with a detrimental impact on embryo development.

Methods: This is a retrospective study of 1315 zygotes cultured using time lapse technologies generated in 205 first ICSI-cycles.

Results: We observed an association between increasing times of the pronuclear fading-first cleavage interval (t2-tPNf) and the rates of trichotomous/direct unequal cleavage at the first (DUC-1) and second (DUC-2) mitotic cycle. Moreover, we observed a reduced blastulation rate. No significant associations were observed between rates of direct unequal cleavage at the third mitotic cycle (DUC-3) and top-quality blastocysts, euploidy, and live births. To evaluate whether the interval t2-tPNf could have a predictive value for the onset of DUC-1 and DUC-2, ROC curve analyses were performed. The area under the curve values obtained for DUC-1 showed a significant prediction accuracy. The best cut-offs to identify zygotes with a high risk of DUC-1 and DUC-2 occurrence were t2-tPNf > 2.78 (hours) and t2-tPNf > 2.50 (hours), respectively.

Conclusion: Delay in the short interval between PNBD and the first cytokinesis result in trichotomous cleavage and early developmental arrest. However, if the embryos reach the blastocyst stage, rates of euploidy and live birth do not appear to be compromised.

Objective: To evaluate whether the ZyMōt™ Multi 850 μl sperm separation device (SSD) effectively recovers motile spermatozoa from cryopreserved ejaculates and compare its effect on key embryology outcomes including fertilization, cleavage stage, and total and top-quality blastocyst formation rates to the traditional Density Gradient Centrifugation (DGC) method.

Methods: In this prospective, single-center, controlled study, we used fresh sibling donor oocytes and non-donor cryopreserved ejaculates. In total, 150 couples participated in this study. At least eight MII donor oocytes were allocated to each couple split into two arms. One arm underwent ICSI with the control DGC-processed sample, and the other arm processed with SSD.

Results: No significant difference on fertilization and cleavage stage embryo rates was observed between the two techniques. We observed a significant increase in the percentage of total (SSD: 74.03 ± 23.47% vs. DGC: 67.86 ± 23.92%; p = 0.016) and top-quality (SSD: 66.38 ± 24.94% vs. DGC: 60.98 ± 24.40%; p = 0.035) blastocysts formed post-SSD processing. Sub-analysis showed that this increase remained significant for the WHO-normal group (n = 118), but not for the WHO-abnormal group (n = 32).

Conclusion: The SSD was successfully applied in all 150 cases, providing adequate numbers of spermatozoa to undergo ICSI. Additionally, SSD significantly improved blastocyst development rates; however, this was of limited clinical impact considering the minor improvement on the average number of top-quality blastocysts. It can be hypothesized that this positive contribution may be stronger and clinically significant when a larger number of oocytes is used or in homologous oocyte ICSI cycles, where the repair mechanisms of the oocytes may insufficient for promoting healthy embryo development.

The field of reproductive medicine has witnessed rapid advancements in artificial intelligence (AI) methods, which have significantly enhanced the efficiency of diagnosing and treating reproductive disorders. The integration of AI algorithms into the in vitro fertilization (IVF) has the potential to represent the next frontier in advancing personalized reproductive medicine and enhancing fertility outcomes for patients. The potential of AI lies in its ability to bring about a new era characterized by standardization, automation, and an improved success rate in IVF. At present, the utilization of AI in clinical practice is still in its early stages and faces numerous ethical, regulatory, and technical challenges that require attention. In this review, we present an overview of the latest advancements in various applications of AI in IVF, including follicular monitoring, oocyte assessment, embryo selection, and pregnancy outcome prediction. The aim is to reveal the current state of AI applications in the field of IVF, their limitations, and prospects for future development. Further studies, which involve the development of comprehensive models encompassing multiple functions and the conduct of large-scale randomized controlled trials, could potentially indicate the future direction of AI advancements in the field of IVF.

Purpose: Oocyte aging is a significant factor in the negative reproductive outcomes of older women. However, the pathogenesis of oocyte aging remains unclear. This study aimed to identify the hub genes involved in oocyte aging via bioinformatics methods.

Methods: The oocyte aging datasets GSE155179 and GSE158802 were obtained from the GEO database and analyzed as the training set. The GSE164371 dataset was then defined as the validation set. Differentially expressed genes were analyzed via the limma package and weighted gene coexpression network analysis, and intersected with cellular senescence-associated genes from the Cell Senescence database. The hub genes were identified via three machine learning algorithms, namely, support vector machine recursive feature elimination, random forest, and least absolute shrinkage and selection operator logistic, which were also confirmed via the validation set. Finally, a microRNA-mRNA‒transcription factor regulatory network and single-gene gene set enrichment analysis were performed to clarify the pathogenesis of oocyte aging.

Results: A competing endogenous RNA network of GSE155179 and GSE158802 with 124 mRNAs, 31 long noncoding RNAs, and 31 miRNAs was constructed. Two modules with 814 genes were considered the key modules of oocyte aging. PDIK1L, SIRT1, and MCU were subsequently identified as hub genes; on the basis of these hub genes, a regulatory network of oocyte aging with 8 miRNAs, 3 mRNAs, and 227 TFs was ultimately constructed.

Conclusions: This study contributes to a deeper understanding of oocyte aging and may aid in the development of therapeutic approaches to improve reproductive outcomes in older women.

Purpose: Uniparental disomy (UPD) is a genetic condition which both copies of a chromosome are inherited from a single parent, potentially leading to imprinting disorders. This study aimed to assess the integration of Short Tandem Repeat (STR) analysis into Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) to assess UPD risk and its impact on selecting euploid embryos for embryo transfer in couples with chromosomal translocations involving imprinted chromosomes.

Methods: This study evaluated three couples carrying balanced chromosomal translocations: 45,XX,der(13;14)(q10;q10), 46,XX,t(10;11)(q22;q13), and 45,XY,der(14;15)(q10;q10). STR analysis was performed on trophectoderm (TE) biopsies after Whole Genome Amplification (WGA) after PGT-SR analysis using parental blood samples to assess UPD risk in euploid embryos. Haplotyping was conducted with five to six STR markers specific to each rearranged chromosome to detect UPD in euploid embryos.

Results: Of the four embryos analyzed across the three families, two couples had euploid embryos that tested negative for UPD. These embryos were successfully transferred, resulting in the birth of two healthy children. In the third family, the euploid embryo also tested negative for UPD but failed to implant after transfer, resulting in no pregnancy.

Discussion: Despite its rarity, UPD involving imprinted chromosomes poses significant clinical risks, as seen in disorders such as Prader-Willi syndrome and Angelman syndrome. This study highlights the importance of integrating UPD screening into PGT-SR protocols, to detect both heterodisomic and isodisomic UPD events minimizing the risk of severe genetic disorders.

Conclusion: Integrating STR-based UPD screening within PGT-SR workflows is a reliable and cost-effective strategy that enhances embryo selection and mitigates the risk of imprinting disorders. This approach improves reproductive outcomes for families with chromosomal rearrangements, offering a practical advancement in assisted reproduction.

Purpose: This study aimed to analyze the current status of women's perception of social support levels, psychological resilience, anxiety, and depression levels during IVF-ET, as well as investigate the influence of perceived social support and psychological resilience on the anxiety and depression levels of women undergoing IVF-ET and the mediating role of psychological resilience in this process.

Methods: In this study, a convenience sampling method was used to administer a questionnaire survey among 433 women undergoing IVF-ET. Then, multivariate linear regression models were applied to identify factors influencing anxiety and depression. Lastly, mediation effect analysis was conducted to explore the mediating role of psychological resilience.

Results: The incidence of anxiety and depression was 42% and 46.4%, respectively. The mean score of the Perceived Social Support Scale (PSSS) indicated a high to moderate level of support, while the mean score of the Conner-Davidson Resilience Scale (CD-RISC) suggested moderate psychological resilience. Perceived social support was positively correlated with psychological resilience, and both were negatively correlated with anxiety and depression. Perceived social support and psychological resilience were identified as influencing factors of anxiety and depression (P < 0.001). Moreover, there was a partial mediating effect of psychological resilience between perceived social support and both anxiety and depression (P < 0.01).

Conclusions: These results highlight the need for healthcare providers to assess patients' levels of psychological resilience and perceived social support when developing mental health interventions in order to mitigate the risk of anxiety and depression and concomitantly enhance fertility outcomes.

Background: Luteinizing hormone (LH) plays a crucial role in the postnatal development and maturation of gonads. Inactivating mutations of the luteinizing hormone beta subunit (LHB)gene are extremely rare and can result in congenital hypogonadotropic hypogonadism (CHH).

Methods: We conducted DNA sequencing on an 18-year-old female patient with undetectable LH and clinical symptoms of CHH. Pulsatile GnRH was administered to promote puberty development. In vitro construction of mutant genes, confocal microscopy, and protein functional assays were used to investigate the effects of genetic variants on hormone function and secretion. Experiments were conducted in HEK293T cells to examine the colocalization and dimerization of LH subunits, as well as to measure intracellular and extracellular LH concentrations.

Results: Compound heterozygous mutations of c.252C>G (p.F84L) and c.364G>A (p.G122S) were found in the patient's genome. Pulsatile GnRH therapy was effective in promoting puberty development and ovulation. The LH alpha subunit was found to co-localize with both mutant beta subunits after immunofluorescence staining, and immunoprecipitation detected the dimerization of the LH alpha subunit with both mutant beta subunits. Higher intracellular LH concentrations and lower extracellular LH concentrations compared to the wild type indicate secretion dysfunction for LH.

Conclusion: Compound heterozygous mutations of c.252C>G (p.F84L) and c.364G>A (p.G122S) in the LHB gene may lead to CHH for female patient. These mutations do not impair the expression and dimerization of the alpha and beta subunits, but they do prevent the secretion of LH. The study expands our understanding of the clinical manifestation of LHB gene mutations in females and provides a treatment for these patients.

After over 20 years of progressively increasing clinical utilization of PGT-A (and its precursors), the American Society for Reproductive Medicine (ASRM) and its daughter society, the Society for Assisted Reproduction (SART), for the first time published a committee opinion clearly acknowledging that "the value of PGT-A as a routine screening test for patients undergoing in vitro fertilization (IVF) has not been demonstrated." This statement is timely and welcome but requires some additions and raises some new questions, among those why, if PGT-A in a general population does not improve IVF cycle outcomes, the routine clinical utilization of PGT-A should continue.

Purpose: To explore whether a 25 mg subcutaneous progesterone daily rescue daily improves the reproductive outcomes in patients with low serum progesterone (P₄) levels (7-10 ng/mL), measured one day before true natural cycle (t-NC) frozen embryo transfer (FET).

Methods: A cohort study of 192 women undergoing t-NC warmed blastocyst transfer. Patients were stratified into three different groups based on serum P₄ levels on the FET-1 day: patients who had serum P₄ levels of 7-10 ng/mL and underwent rescue progesterone administration (rescue group), patients with serum P₄ levels of 7-10 ng/mL without progesterone administration (non-rescue group), and patients with serum P₄ > 10 ng/mL on FET-1 day (control group). The primary outcome was possible differences in live birth rate (LBR) between groups.

Results: The LBRs for the serum P₄ 7-10 ng/mL without rescue, 7-10 ng/mL with rescue, and > 10 ng/mL (control) groups were 41%, 46%, and 52%, respectively (p = 0.61). The estimated adjusted probability of live birth for serum P₄ 7-10 ng/mL without rescue, 7-10 ng/mL with rescue, and > 10 ng/mL (control) groups were also comparable: 43.5% (95% CI, 20.0-70.4%), 49.8% (95% CI, 28.1-71.6%), and 57.4% (95% CI, 44.0-69.8%), respectively.

Conclusion: Serum P₄ levels higher than 7 ng/mL seem to secure LBRs in patients undergoing t-NC FET. A rescue policy consisting of a daily subcutaneous 25 mg progesterone dose in patients with serum P₄ levels 7-10 ng/mL does not further enhance LBRs when compared to those patients with similar serum P₄ levels without rescue.