Perinatal Outcomes of Singleton Live Births Following Preimplantation Genetic Testing for Chromosomal Structural Rearrangements in Single Frozen-Thawed Blastocyst Transfer Cycles: a Retrospective Cohort Study.

This study investigated whether singleton pregnancies conceived after preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) are associated with a higher risk of adverse perinatal outcomes than singleton pregnancies conceived after intracytoplasmic sperm injection (ICSI). We collected data on singleton live births after PGT-SR (n = 107) and ICSI (n = 585) in our hospital from January 2017 to August 2020. Multivariable analyses were used to adjust for maternal age, body mass index, gravidity and parity, paternal age, ovulatory disorder, and recurrent spontaneous abortion. The unadjusted results showed a significantly higher risk of hypertensive disorders of pregnancy (HDP) (odds ratio (OR) = 2.47; 95% confidence interval (CI): 1.10-5.54; P = 0.029) associated with PGT-SR singleton pregnancies than with ICSI singleton pregnancies. However, after adjusting for potential confounders, there were no longer any significant differences in the risk of HDP (adjusted OR = 2.24; 95% CI: 0.92-5.48; P = 0.077) between PGT-SR and ICSI singleton pregnancies. There were no significant differences between PGT-SR and ICSI singleton pregnancies in terms of gestational diabetes, preterm premature rupture of membranes, placenta previa, cesarean delivery, gestational age (weeks), preterm delivery (< 37 weeks), very preterm delivery (≥ 28 weeks and < 32 weeks), birth weight (g), low birth weight (< 2500 g), very low birth weight (< 1500 g), birth height (cm), birth defects, and 1-min and 5-min Apgar scores. In conclusion, for single frozen-thawed blastocyst cycles, there were no significant differences in adverse perinatal outcomes between PGT-SR and ICSI singleton pregnancies. However, due to the limited sample size, these conclusions need to be confirmed by further studies.

Integrated Analysis of Hub Genes and MicroRNAs in Human Placental Tissues from In Vitro Fertilization-Embryo Transfer.

Objective: Supraphysiological hormone exposure, in vitro culture and embryo transfer throughout the in vitro fertilization-embryo transfer (IVF-ET) procedures may affect placental development. The present study aimed to identify differences in genomic expression profiles between IVF-ET and naturally conceived placentals and to use this as a basis for understanding the underlying effects of IVF-ET on placental function. Methods: Full-term human placental tissues were subjected to next-generation sequencing to determine differentially expressed miRNAs (DEmiRs) and genes (DEGs) between uncomplicated IVF-ET assisted and naturally conceived pregnancies. Gene ontology (GO) enrichment analysis and transcription factor enrichment analysis were used for DEmiRs. MiRNA-mRNA interaction and protein-protein interaction (PPI) networks were constructed. In addition, hub genes were obtained by using the STRING database and Cytoscape. DEGs were analyzed using GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed miRNAs were validated through qRT-PCR. Results: Compared against natural pregnancies, 12 DEmiRs and 258 DEGs were identified in IVF-ET placental tissues. In a validation cohort, it was confirmed that hsa-miR-204-5p, hsa-miR-1269a, and hsa-miR-941 were downregulation, while hsa-miR-4286, hsa-miR-31-5p and hsa-miR-125b-5p were upregulation in IVF-ET placentas. Functional analysis suggested that these differentially expressed genes were significantly enriched in angiogenesis, pregnancy, PI3K-Akt and Ras signaling pathways. The miRNA-mRNA regulatory network revealed the contribution of 10 miRNAs and 109 mRNAs while EGFR was the most highly connected gene among ten hub genes in the PPI network. Conclusion: Even in uncomplicated IVF-ET pregnancies, differences exist in the placental transcriptome relative to natural pregnancies. Many of the differentially expressed genes in IVF-ET are involved in essential placental functions, and moreover, they provide a ready resource of molecular markers to assess the association between placental function and safety in IVF-ET offspring.

Obstetric and neonatal outcomes of pregnancies resulting from preimplantation genetic testing: a systematic review and meta-analysis.

BACKGROUND: Preimplantation genetic testing (PGT) includes methods that allow embryos to be tested for severe inherited diseases or chromosomal abnormalities. In addition to IVF/ICSI and repeated freezing and thawing of the embryos, PGT requires a biopsy to obtain embryonic genetic material for analysis. However, the potential effects of PGT on obstetric and neonatal outcomes are currently uncertain. OBJECTIVE AND RATIONALE: This study aimed to investigate whether pregnancies conceived after PGT were associated with a higher risk of adverse obstetric and neonatal outcomes compared with spontaneously conceived (SC) pregnancies or pregnancies conceived after IVF/ICSI. SEARCH METHODS: PubMed, EMBASE, MEDLINE, Web of Science and The Cochrane Library entries from January 1990 to January 2021 were searched. The primary outcomes in this study were low birth weight (LBW) and congenital malformations (CMs), and the secondary outcomes included gestational age, preterm delivery (PTD), very preterm delivery (VPTD), birth weight (BW), very low birth weight (VLBW), neonatal intensive care unit (NICU) admission, hypertensive disorders of pregnancy (HDP), gestational diabetes, placenta previa and preterm premature rupture of membranes (PROM). We further pooled the results of PGT singleton pregnancies. Subgroup analyses included preimplantation genetic diagnosis (PGD), preimplantation genetic screening (PGS), cleavage-stage biopsy combined with fresh embryo transfer (CB-ET) and blastocyst biopsy combined with frozen-thawed embryo transfer (BB-FET). OUTCOMES: This meta-analysis included 15 studies involving 3682 babies born from PGT pregnancies, 127 719 babies born from IVF/ICSI pregnancies and 915 222 babies born from SC pregnancies. The relative risk (RR) of LBW was higher in PGT pregnancies compared with SC pregnancies (RR = 3.95, 95% confidence interval [CI]: 2.32-6.72), but the risk of CMs was not different between the two groups. The pooled results for the risks of LBW and CMs were similar in PGT and IVF/ICSI pregnancies. The risks of PTD (RR = 3.12, 95% CI: 2.67-3.64) and HDP (RR = 3.12, 95% CI: 2.18-4.47) were significantly higher in PGT pregnancies compared with SC pregnancies. Lower gestational age (mean difference [MD] = -0.76 weeks, 95% CI -1.17 to -0.34) and BW (MD = -163.80 g, 95% CI: -299.35 to -28.24) were also noted for PGT pregnancies compared with SC pregnancies. Nevertheless, compared with IVF/ICSI pregnancies, the risks of VPTD and VLBW in PGT pregnancies were significantly decreased by 41% and 30%, respectively, although the risk of HDP was still significantly increased by 50% in PGT pregnancies compared with IVF/ICSI pregnancies. The combined results of obstetric and neonatal outcomes of PGT and IVF/ICSI singleton pregnancies were consistent with the overall results. Further subgroup analyses indicated that both PGD and PGS pregnancies were associated with a higher risk of PTD and a lower gestational age compared with SC pregnancies. WIDER IMPLICATIONS: This meta-analysis showed that PGT pregnancies may be associated with increased risks of LBW, PTD and HDP compared with SC pregnancies. The overall obstetric and neonatal outcomes of PGT pregnancies are favourable compared with those of IVF/ICSI pregnancies, although PGT pregnancies were associated with a higher risk of HDP. However, because the number of studies that could be included was limited, more randomised controlled trials and prospective cohort studies are needed to confirm these conclusions.

Independent Variables for Determining the Cumulative Live Birth Rates of Aged Patients with Polycystic Ovary Syndrome or Tubal Factor Infertility: A Retrospective Cohort Study.

Objective: To assess whether women of advanced age (≥35 years) with polycystic ovary syndrome (PCOS) have the same cumulative live birth rate (CLBR) as their age-matched controls with tubal factor infertility and to determine the influencing factors on the CLBRs of aged women. Design: A retrospective cohort study. Setting and Population: A total of 160 women of advanced age (≥35 years) with PCOS and 1073 women with tubal factor infertility were included in our study. All patients underwent their first fresh cycles and subsequent frozen cycles within in one year in our centre from 2015 to 2020. Methods: To determine independent influencing factors on the CLBRs of these aged patients, a multivariable Cox regression model of CLBR according to the transfer cycle type was constructed. Main outcome measure(s): CLBRs. Result: The Cox regression model of the CLBRs indicated that there was no significant difference between the PCOS group and the tubal infertility group in terms of advanced age (HR, 0.95; 95% CI, 0.71-1.27, P=0.732). The CLBR significantly decreased for women of advanced reproductive age up to 37 years of age (HR, 0.46; 95% CI, 0.39-0.56, P<0.001). The CLBR increased by 63% when more than ten oocytes were retrieved (HR, 1.63; 95% CI, 1.34-1.98, P<0.001). Patients with an AMH level above 32.13pmol/l were likely to have a 72%(HR, 1.72; 95% CI, 1.08-2.73, = 0.023) and 34% (HR, 1.34; 95% CI, 1.07-1.68, P=0.010)improvement in CLBR compared to those with an AMH below 7.85pmol/l and 7.85-32.12pmol/l, respectively. Conclusion: Despite the higher number of oocytes retrieved in PCOS patients, the reproductive window is not extended for PCOS patients compared with tubal factor infertility patients. Age, AMH and the number of oocytes retrieved play crucial roles in the CLBRs of patients of advanced age (≥35 years).

Neonatal outcomes of singleton live births with vanishing twin syndrome following double embryos transfer in assisted reproductive technology: a retrospective cohort study.

BACKGROUND: Women with vanishing twin syndrome are associated with increased risks of adverse neonatal outcomes, such as preterm birth (PTB) and low birthweight (LBW), compared with those in singleton live births following single embryo transfer (SET) in assisted reproductive technology (ART). METHODS: Anonymized data on all cycles performed in China were obtained from the Reproductive Medicine Department at the Third Affiliated Hospital of Zhengzhou University, which had involved 127597 cycles following double embryos transfer (DET), including 54585 fresh embryos transfer (ET) cycles and 73012 frozen embryos transfer (FET) cycles. In addition, the obstetric outcomes, such as gestation age, PTB, small for gestation age (SGA), birthweight (BW), LBW, congenital malformation, pediatric admission and Neonatal Intensive Care Unit (NICU) admission in the fresh ET and FET cycles, were analyzed. Moreover, logistic regression analysis was performed to adjust the confounders, including age of women, body weight index (BMI), value of AMH, infertile years, current cycle, antral follicles, cause of infertility, number of oocytes retrieved, endometrial thickness at the date of transplantation, number of high-quality embryos, and embryo stage. RESULTS: In the fresh ET cycles, the BW and gestational age in study group were lower than those in control group, which were (2962.4 ± 563.1vs. 3104.9 ± 498. 5, p = 0.000) and (262.8 ± 8.4 vs. 268.9 ± 13.9, p = 0.000), respectively. Relative to control group, the study group was linked with increased risks of PTB (adjusted odds ratio (aOR) 2.45, 95% CI:1.98-3.03, adjusted p = 0.000), LBW (aOR2.11, 95% CI:1.67-2.65, adjusted p = 0.000), pediatric admission (aOR 2.55, 95% CI2.07-3.13, adjusted p = 0.000), and NICU admission (aOR 1.98, 95% CI1.32-2.96, adjusted p = 0.001), but there were no statistically significant differences in the risks of SGA (aOR 1.09, 95% CI0.82-1.45, adjusted p = 0.960) and congenital malformation (aOR 0.94, 95% CI0.53-1.68, adjusted p = 0.640) between the two groups. In the FET cycles, the gestational age and BW in study group were lower than those in control group, which were (263.0 ± 15.7vs. 273.0 ± 10.5, p = 0.000) and (3099 ± 662.1vs. 3352 ± 671.5), respectively. The study group was associated with increased risks of PTB (aOR2. 45, 95% CI: 2.23-3.43, adjusted p = 0.000), LBW (aOR 2.67, 95% CI: 2.13-3.34, adjusted p = 0.000), pediatric admission (aOR2.62, 95% CI2.14-3.21, adjusted p = 0.000), and NICU admission (aOR 2.22, 95% CI1.43, 3.46, adjusted p = 0.001) compared with those in control group, but differences in the risks of SGA (aOR 0.98, 95% CI0.71-1.36, adjusted p = 0.730) and congenital malformation (aOR 0.99, 95% CI 0.60,1.63, adjusted p = 0.940) between the two groups were not statistically significant. CONCLUSIONS: Our study finds that singleton live births with VTS have higher risks of LBW, PTB, pediatric admission and NICU admission than those without VTS in both the fresh and frozen cycles, even after adjusting for confounders. However, no increased risks of SGA or congenital malformation are observed in singleton live births in both the fresh and frozen ART cycles following DET.