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Objective: The purpose of this study was to evaluate the influence of abnormal semen parameters on embryo aneuploidy based on single nucleotide polymorphism microarray (SNP array)., Methods: A total of 464 blastocysts from 103 PGT-A cycles were analyzed. The embryo quality and embryo aneuploidy rates were compared between different groups which divided by male semen parameters (sperm concentration, motility, morphology, and DFI) according the WHO criteria (2021)., Results: The total blastocysts chromosome aneuploidy rate was 42.3% (191/452). In the teratozoospermia group, the good-quality embryo and blastocyst formation rate were lower than the normal group(44.4% vs 60.7%, P <0.01; 33.3% vs 43.5%, P <0.05), The good-quality embryo rate in normal DFI group was significantly higher than high-DFI group (59.0% vs 48.4%, P < 0.05). The blastocyst aneuploidy rate in low sperm concentration group, and high DFI group was no differences between with that in normal sperm concentration and DFI group (47.7% vs 37.8% and 44.7% vs 37.8%, P>0.05). The aneuploid rate of blastocyst in teratozoospermic and asthenozoospermia group was significantly higher than that of normal morphology and motility group (50.0% vs 34.0% and 46.7% vs 33.7%, P<0.05)., Conclusion: Our study revealed that sperm DFI were positively correlated with blastocyst aneuploidy rate, while sperm motility and sperm morphology rate were negatively correlated with blastocyst aneuploidy rate. Abnormal semen parameters may affect embryo quality and increase the aneuploidy rate of blastocyst chromosomes, suggesting that in clinical practice of assisted reproduction patients with abnormal semen parameters can be treated in advance to improve sperm quality, so as to reduce the impact on embryo quality and achieve a better pregnancy outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Liu, Niu, Yang, Wang, Jin and Li.)

Infertile women with diminished ovarian reserve (DOR) confront an increased miscarriage rate in assisted reproductive technology (ART). Genetic abnormality is the most important factor. However, the effects of DOR and female age on the molecular karyotype of products of conception (POCs) remain unknown. We analyzed POCs using a single nucleotide polymorphism (SNP) microarray from women with DOR who experienced first-trimester miscarriage in IVF/ICSI cycles. The SNP microarray revealed chromosomal abnormalities in 74.6% (47/63) of POCs, including trisomy in 83.0% (39/47). Chromosomal aberrations were more frequent in women older than 32 years old with DOR than in young women aged 20-32 years old (86.7% vs. 44.4%, P = 0.001). Univariate and multivariable analyses identified advanced age as a risk factor for chromosomal aberration-related miscarriage in women with DOR, with odds ratios of 8.125 (95% CI: 2.291-28.820, P = 0.001) and 5.867 (95% CI: 1.395-24.673, P = 0.016), respectively. The results showed that older women (older than 32 years old) with DOR had a high risk of miscarrying a chromosomally aberrant embryo/fetus, regardless of basal follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC) and previous reproductive history. This finding indicates a novel cut-off value of age for women with DOR related to chromosomal aberration-related miscarriage.

Missed abortion is one of the common complications of assisted reproductive technology (ART). Genetic abnormality is the most important factor. However, the effect of ART on the molecular karyotype of products of conception (POC) remains unknown. We explored the effect of ART on the molecular karyotype of POC in miscarriage. POC were obtained from women undergoing ART. Single nucleotide polymorphism (SNP) microarray was used to analyze the molecular karyotype. A total of 1493 POC were collected for SNP array analysis. The total rate of karyotypic abnormalities was 63.1% (943/1493). The proportion of karyotypic abnormalities was 70.4% (193/416) in >35-year-old group, which was significantly higher than that (60.6%) (343/566) in <30-year-old group and that (60%) (307/511) in the 30-35-year-old group. In natural conception (NC) group, the proportion of karyotypic abnormalities was 64.6% (201/311), whereas in ART group it was 62.7% (742/1182) and, there was no significant difference. The ratio between male and female fetuses was 1:1.13 (698/795). The rate of karyotypic abnormalities in male was 62.9% (439/698) and that in female was 63.4% (504/795), and these values did not differ significantly ( P =0.84). Molecular karyotypic abnormality is the most important reason in miscarriage, and female age is a significant factor influencing the karyotypic abnormalities. Comparison with NC, ART, and gender of aborted embryos may not increase the rate of molecular karyotypic abnormality in miscarriage., (© 2018 The Author(s).)

Reciprocal translocations (RecT) and Robertsonian translocations (RobT) are among the most common chromosomal abnormalities that cause infertility and birth defects. Preimplantation genetic testing for aneuploidy using comprehensive chromosome screening for in vitro fertilization enables embryo selection with balanced chromosomal ploidy; however, it is normally unable to determine whether an embryo is a translocation carrier. Here we report a method named "Mapping Allele with Resolved Carrier Status" (MaReCs), which enables chromosomal ploidy screening and resolution of the translocation carrier status of the same embryo. We performed MaReCs on 108 embryos, of which 96 were from 13 RecT carriers and 12 were from three RobT carriers. Thirteen of the sixteen patients had at least one diploid embryo. We have confirmed the accuracy of our carrier status determination in amniotic fluid karyotyping of seven cases as well as in the live birth we have thus far. Therefore, MaReCs accurately enables the selection of translocation-free embryos from patients carrying chromosomal translocations. We expect MaReCs will help reduce the propagation of RecT/RobT in the human population., Competing Interests: Conflict of interest statement: S.L. and X.S.X. are cofounders and shareholders of Yikon Genomics Company, Ltd. Z.Z., Y. Gao, W.L., S.B., M.H., and J.R. receive research funding from Yikon Genomics Company, Ltd.

Purpose: Providing feasible preimplantation genetic testing strategies for monogenic disorders (PGT-M) for prevention and control of genetic cancers. Methods: Inclusion of families with a specific pathogenic mutation or a clear family history of genetic cancers. Identification of the distribution of hereditary cancer-related mutations in families through genetic testing. After a series of assisted reproductive measures such as down-regulation, stimulation, egg retrieval, and in vitro fertilization, a biopsy of trophectoderm cells from a blastocyst was performed for single-cell level whole-genome amplification (WGA). Then, the detection of chromosomal aneuploidies was performed by karyomapping. Construction of a haplotype-based linkage analysis to determine whether the embryo carries the mutation. Meanwhile, we performed CNV testing. Finally, embryos can be selected for transfer, and the results will be verified in 18–22 weeks after pregnancy. Results: Six couples with a total of 7 cycles were included in our study. Except for cycle 1 of case 5 which did not result in a transferable embryo, the remaining 6 cycles produced transferable embryos and had a successful pregnancy. Four couples have had amniotic fluid tests to confirm that the fetus does not carry the mutation, while 1 couple was not tested due to insufficient pregnancy weeks. And the remaining couples had to induce labor due to fetal megacystis during pregnancy. Conclusion: Our strategy has been proven to be feasible. It can effectively prevent transmission of hereditary cancer-related mutations to offspring during the prenatal stage. [ABSTRACT FROM AUTHOR]

Study Question: Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)?Summary Answer: Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC.What Is Known Already: Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge.Study Design, Size, Duration: This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed.Participants/materials, Setting, Methods: This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA.Main Results and the Role Of Chance: The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040-0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338-0.879), P = 0.013; and aOR: 0.357 (0.175-0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05).Limitations, Reasons For Caution: This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy.Wider Implications Of the Findings: To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients.Study Funding/competing Interest(s): This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Studies have shown that early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol (EFLL), a popular controlled ovarian hyperstimulation protocol widely used in China, leads to higher rates of implantation and clinical pregnancy, as well as lower rates of spontaneous abortion and ectopic pregnancy in patients undergoing in vitro fertilization treatment. However, the impact of EFLL on euploid embryos and its underlying mechanisms remain unclear. To address these gaps of knowledge, we conducted a retrospective comparative study of 310 preimplantation genetic testing (PGT) cycles with a total of 1,541 embryos using the EFLL protocol or midluteal short-acting GnRH agonist long protocol (MLSL). Patients were matched by PGT subtype [aneuploidies (PGT-A) vs. PGT for chromosomal structural rearrangements (PGT-SR)], age (±2 years), and body mass index (±1 kg/m2). For PGT-A, there was no significant difference in the number of euploid embryos (1.80 ± 1.47 for EFLL vs. 1.84 ± 2.03 for MLSL, p > 0.05) or the rate of euploidy (44.6 vs. 36.9%, p > 0.05). For PGT-SR, the number of euploid embryos in the EFLL group was significantly higher than that in the MLSL group (1.76 ± 1.54 vs. 1.21 ± 1.24, p < 0.05). A higher euploidy rate was also observed with the EFLL protocol compared with that obtained in MLSL (31.9 vs. 25.7%), although the difference was not statistically significant (p > 0.05). Compared with the MLSL protocol, more euploid embryos were achieved when using the EFLL protocol in PGT-SR, demonstrating the value in PGT-SR. To the best of our knowledge, this study is the first one to compare embryonic outcomes between EFLL and MLSL, providing key insights into the clinical application of EFLL in PGT cycles. In the light of the limited sample size of our study, we recommend that these questions be explored using a larger prospective study. [ABSTRACT FROM AUTHOR]

Uniparental disomy (UPD) has been shown to be rare in human normal blastocysts, but its frequency in discarded morphologically abnormal embryos and its relevance to embryonic self-correction of aneuploid remains unknown. The aim of this study was to detect UPD in discarded morphologically abnormal embryos. Both discarded morphologically abnormal embryos, including zero-pronuclear zygotes (0PN), one-pronuclear zygotes (1PN), three-pronuclear zygotes (3PN) and 2PN embryos scored as low development potential were cultured into blastocysts then underwent trophectoderm biopsy. Genome-wide UPD screening of the trophectoderm of 241 discarded morphologically abnormal embryo sourced blastocysts showed that UPD occurred in nine embryos. Five embryos exhibited UPDs with euploid chromosomes, and four displayed UPDs with chromosomal aneuploid. The percentage of UPDs among the morphologically abnormal sourced blastocysts was 3.73%, which is significant higher than the percentage observed in normal blastocysts. The frequency of UPD in 3PN-sourced blastocysts was 7.69%, which is significantly higher than that in normal blastocysts. This study provides the first systematic genome-wide profile of UPD in discarded morphologically abnormal embryos. Our results indicated that UPD may be a common phenomenon in discarded morphologically abnormal embryos and may be relevant to human embryonic self-correction. [ABSTRACT FROM AUTHOR]