Linli Hu

Molecular karyotype single nucleotide polymorphism analysis of early fetal demise

We explored the application of single nucleotide polymorphism microarray (SNP array) in molecular karyotype analysis for early spontaneous abortion detection in assisted reproductive technology (ART). SNP array was performed in 81 cases. Of the 81 cases, 16 experienced natural conception (NC) and 65 were pregnant by ART. Of the 65 cases, 4 underwent artificial insemination (AI), 32 fresh in vitro fertilization-embryo transfer (IVF-ET), 9 fresh intracytoplasmic sperm injection (ICSI), and 20 thawed embryo transfer. In the 81 cases examined 69.1% displayed an abnormal molecular karyotype. In the subjects greater than 35 years of age, the abnormal molecular karyotype rate was 87.5% higher compared to 61.4% in younger individuals (P < 0.05). There was no significant difference in the abnormal molecular karyotype rate or type between ART (64.6%) and NC (87.5%). Compared with traditional cytogenetic diagnosis, the SNP array can identify a greater number of abnormal karyotypes.

Effect of paternal overweight or obesity on IVF treatment outcomes and the possible mechanisms involved

Leukocyte telomere lengths (LTLs) are shorter in obese compared with normal weight people. However, it is not known whether sperm telomere length (STL) is related to obesity. The aim of the study was to evaluate the impact of men’s body mass index (BMI) on STL, embryo quality, and clinical outcomes in couples undergoing IVF. In total, 651 couples were recruited, including 345 men with a normal BMI and 306 men with an overweight BMI (normal BMI group: 20–25 kg/m2; overweight BMI group: >28 kg/m2). We found that couples with male’s BMI over 28 kg/m2 exhibited a significantly lower fertilization rate, good-quality embryo rate and clinical pregnancy rate compared to their normal BMI counterparts. The mean STL in the overweight BMI group was also significantly shorter than that of the normal BMI group. The results also showed that individuals with higher BMI had higher ROS (Reactive oxygen species) content and sperm DNA fragmentation rate when compared with normal BMI individuals. Mitochondrial activity was also lower in the overweight BMI group than in the normal BMI group. This is the first report to find that STL is shorter in overweight/obese men, which may account for their poorer treatment outcomes in IVF cycles.

miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly targeting IGF2BP2

Pre-eclampsia is a pregnancy-related disease that may cause maternal, neonatal and fetal morbidity and mortality and exists in 3–5% of pregnancies worldwide. The discovery of dysregulated microRNAs and their roles in placental development has provided a new avenue for elucidating the mechanism involved in this pregnancy-specific disorder. Here, the roles of human miR-181a-5p, a microRNA that is increased in both the plasma and placenta of severe pre-eclamptic patients, in invasion and migration of trophoblasts were investigated. Ectopic-expression of miR-181a-5p impaired the invasion and migration of HTR-8/SVneo cells, whereas miR-181a-5p inhibition had the opposite effects. IGF2BP2, which harbors a highly conserved miR-181a-5p-binding site within its 3ʹ-UTR, was identified to be directly inhibited by miR-181a-5p. Moreover, siRNAs targeting IGF2BP2 imitated the effects of overexpressed miR-181a-5p on HTR-8/SVneo cell invasion and migration, whereas restoring IGF2BP2 expression by overexpressing a plasmid encoding IGF2BP2 partially reversed the studied inhibitory functions of miR-181a-5p. Thus, we demonstrated here that miR-181a-5p suppresses the invasion and migration of cytotrophoblasts, and its inhibitory effects were at least partially mediated by the suppression of IGF2BP2 expression, thus shedding new light on the roles of miR-181a-5p in the pathogenesis of severe pre-eclampsia.

Recombinant luteinizing hormone priming in early follicular phase for women undergoing in vitro fertilization: Systematic review and meta-analysis

Objectives To investigate the effect of recombinant human luteinizing hormone supplementation (rLH priming) during the early follicular phase on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. Methods In order to evaluate available evidence regarding the efficacy of rLH priming in IVF/ICSI procedures, a systematic review and meta-analysis was preformed. Searches were conducted on MEDLINE®, EMBASE and the Cochrane Database of Clinical Trials without language limitation, but were restricted to randomized controlled trials (RCTs). Results Three RCTs including 346 patients were included in this meta-analysis, which demonstrated that rLH priming did not increase ongoing pregnancy rate. Although less recombinant follicle-stimulating hormone (rFSH) was required and the oestradiol level was higher on the day of human chorionic gonadotropin administration in the rLH priming group, the numbers of oocytes retrieved and embryos produced were comparable between patients treated with rLH priming and those treated with rFSH alone. Conclusions This systematic review and meta-analysis has demonstrated that at present there is insufficient evidence that patients undergoing IVF/ICSI may benefit from rLH priming during the early follicular phase.

Mapping allele with resolved carrier status of Robertsonian and reciprocal translocation in human preimplantation embryos

Significance In in vitro fertilization, it is difficult, if not impossible, with current methods to determine whether an embryo carries a chromosomal translocation. We have established a method for diagnosing chromosome abnormality named “Mapping Allele with Resolved Carrier Status” (MaReCs), which enables simultaneous screening of chromosomal ploidy and translocation in an embryo by next-generation sequencing. We demonstrate and validate that MaReCs allows accurate selection of translocation-free embryos, preventing the transmission of chromosomal translocations to future generations. 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.

The influence of male age on treatment outcomes and neonatal birthweight following assisted reproduction technology involving intracytoplasmic sperm injection (ICSI) cycles

The aim of this study was to investigate the effect of male age on treatment outcomes and neonatal birthweight following intracytoplasmic sperm injection (ICSI). This study included 2,474 ICSI cycles. Male partners were stratified into 5‐year age categories (up to 25, 26–30, 31–35, 36–40 and 41 and up). Multilevel logistic regression was used to evaluate the relationship between male age and treatment outcomes. After adjusting for confounders, we found no difference in the clinical pregnancy rate. However, we observed that the 31‐ to 35‐year group had a higher odds of live birth than that of the >41‐year group (aOR 1.63, p = .03), and that the risk of abortion in the 31‐ to 35‐year group was lower than that of the reference group (aOR 0.41, p = .02). A total of 754 single‐foetus newborns and 556 twin newborns were analysed. Among the singletons, none of the variables differed among the five groups (p > .05). Among the twins, the infants in the 36‐ to 40‐year group had a lower neonatal birthweight and a higher low‐birthweight rate than those of the other groups (p < .05). Our study indicates that increased paternal age negatively affects the live birth and miscarriage rates. In addition, advanced paternal age may affect the birthweight of twins.