Comparative study on risk for birth defects among infants after in vitro fertilization and intracytoplasmic sperm injection
Jing Zhu, Qianqian Zhu, Yun Wang, Bian Wang, Qifeng Lyu, and Yanping Kuang
Syst Biol Reprod Med 2019; 65(1):54–60.
Highight
Research focusing on the birth defects among children after ART has been growing. Results from previous studies comparing the risk of birth defects between infants with in vitro fertilization (IVF) and those with intracytoplasmic sperm injection (ICSI) have been inconsistent. A large retrospective study titled ‘Comparative study on risk for birth defects among infants after in vitro fertilization and intracytoplasmic sperm injection’ by Jing Zhu, Qianqian Zhu, Yun Wang, Bian Wang, Qifeng Lyu, and Yanping Kuang was carried out to assess the risk of birth defects among infants conceived by IVF compared to those with ICSI to begin to resolve this issue. The effect of frozen embryo transfer (FET) on the risk of birth defects among infants born by IVF and ICSI was also assessed in this cohort of 18,221 infants born by IVF and those born by ICSI. In the study, no significant difference between IVF and ICSI was found among all infants, singleton births or twin births. Additionally, in assessing ART infants born after FET, the authors did not detect a difference in the risk for birth defects between infants born by IVF and those born by ICSI. These results indicate that among the entire cohort of children conceived from ART and among the children conceived from FET, the risk for birth defects after ICSI is similar to that after IVF. However, more studies evaluating long-term outcomes of children conceived by ICSI and IVF are needed.
Preliminary functional inquiry of lncRNA ENST00000433673 in embryo implantation using bioinformatics analysis
Dong Li, Weihua Jiang, Yiqun Jiang, Shanshan Wang, Junshun Fang, Lihua Zhu, Yinchun Zhu, Guijun Yan, Haixiang Sun, Linjun Chen, and Ningyuan Zhang
Syst Biol Reprod Med 2019; 65(2):164–173.
Highlight
This study was undertaken to assess the abnormal expression of lncRNA in granulosa cells of PCOS patients. In ‘Preliminary functional inquiry of lncRNA ENST00000433673 in embryo implantation using bioinformatics analysis’ Dong Li, Weihua Jiang, Yiqun Jiang, Shanshan Wang, Junshun Fang, Lihua Zhu, Yinchun Zhu, Guijun Yan, Haixiang Sun, Linjun Chen, and Ningyuan Zhang hypothesized that these lncRNAs are also abnormally expressed in the endometrium of infertile patients with different clinical diseases. Combined with relevant bioinformatics analysis, they initially explored its function in embryo implantation, which lays a theoretical foundation for the transcriptional level of candidate lncRNAs. This also provides a basis for establishing an effective embryo implantation system. The next step will be a detailed study of its functions and mechanisms.
Clinical application of NGS-based SNP haplotyping for the preimplantation genetic diagnosis of primary open angle glaucoma
Xingzhe Ji, Zhou Zhang, Juanzi Shi, and Bin He
Syst Biol Reprod Med 2019; 65(3):258–263.
Highlight
This paper titled ‘Clinical application of NGS-based SNP haplotyping for the preimplantation genetic diagnosis of primary open angle glaucoma’ by Xingzhe Ji, Zhou Zhang, Juanzi Shi, and Bin He describes a successful case of preimplantation genetic diagnosis (PGD) of primary open angle glaucoma (POAG) that has a poor prognosis. In this study, they applied next-generation sequencing (NGS) technique as part of PGD to effectively detect POAG prior to blastocyst implantation. Each biopsy was subject to whole genome amplification (WGA) and copy number variation (CNV) and the results indicated that chromosomes of the successfully amplified samples were balanced (46, XN). Sanger sequencing and NGS-based single nucleotide polymorphism (SNP) haplotyping identified the unaffected blastocyst that was transferred into the uterus of the patient. A healthy baby without the POGA disease causing MYOC c.1109C>T mutation was born 39 weeks after transplantation. The study suggests that NGS-based SNP haplotyping is an effective technique for the PGD of POAG that could also be applied to other genetic diseases.
Ultrastructural identification of CD9 positive extracellular vesicles released from human embryos and transported through the zona pellucida
Parshvi Vyas, Hanna Balakier, and Clifford L. Librach
Syst Biol Reprod Med 2019; 65(4):273–280.
Highlight
There is growing evidence for the critical role of extracellular vesicles (EVs), particularly exosomes, in key reproductive processes including follicular growth, oocyte and sperm maturation, fertilization, embryo development and implantation. Although EVs have been shown to be released from many different cell and tissue types in the body and have been found to be present in embryo conditioned culture media in animal models and in human, their content and secretion by human embryos remains to be well characterized. The study titled ‘Ultrastructural identification of CD9 positive extracellular vesicles released from human embryos and transported through the zona pellucida’ by Parshvi Vyas, Hanna Balakier, and Clifford L. Librach provides visual evidence that human embryos produce and release EVs during preimplantation development, which can traverse through the ZP and be released into the surrounding culture medium. This is the first study to assess ultrastructure morphology of EVs released from human embryos at all developmental stages during the preimplantation period. Further advanced studies are needed on the fundamental mechanisms of intracellular communication, signaling and regulation of EVs during gametogenesis, early embryo development and implantation. The knowledge gained through these studies will have a significant impact on clinical applications, specifically identifying biomarkers of embryo competence by non-invasive diagnostic methods for embryo assessment and selection during IVF. Moreover, the investigations of the potential role of EVs in the modulation of the maternal immune system through embryo-endometrial cross-talk will be crucial for potential therapeutic use to promote the establishment of a successful pregnancy.
Can trophectoderm RNA analysis predict human blastocyst competency?
Panagiotis Ntostis, Georgia Kokkali, David Iles, John Huntriss, Maria Tzetis, Helen Picton, Konstantinos Pantos, and David Miller
Syst Biol Reprod Med 2019; 65(4):312–325.
Highlight
Worldwide, approximately 15% of couples experience difficulty having a child. Of those seeking assisted reproduction treatments (ART) ~25% can expect a live birth. There is, therefore, room for improvement in ART success rates that have remained relatively static in recent years. Given that implantation of the embryo is crucial for establishing pregnancy and embryo (trophectoderm) biopsy seems not to compromise implantation rates, several studies have reported trophectoderm gene expression profiles in relation to implantation competency. The aim of the work presented in ‘Can trophectoderm RNA analysis predict human blastocyst competency?’ by Panagiotis Ntostis, Georgia Kokkali, David Iles, John Huntriss, Maria Tzetis, Helen Picton, Konstantinos Pantos, and David Miller was to provide a summary of these studies and with a more sensitive molecular/bioinformatics approach, to report the results of their complementary pilot study looking at potentially informative gene candidates. Considering the challenges recruiting patients for embryo biopsy, sample size was noted as the main limitation of this study. Chromosomal anomalies were also considered as a potential confounding factor. The pilot study showed that their biopsies were chromosomally normal and that the trophectoderm transcriptome could assist with the selection of healthy embryos for embryo transfer. The authors believe this work could contribute to the development of a molecular test that better selects the most implantation competent blastocysts for uterine transfer. Ultimately, this work could help couples successfully conceive and deliver a healthy child while avoiding multiple embryo transfers with its attendant hazards.
Incidence of high sperm DNA fragmentation in a targeted population of subfertile men
Chitra Vinnakota, Lynsey Cree, John Peek, and Dean E. Morbeck
Syst Biol Reprod Med 2019; 65(6):451–457.
Highlight
The cost of fertility treatment is a significant burden for patients. While most of the cost is incurred during IVF/ICSI treatment, medical testing to determine cause of infertility is an overlooked cost that can quickly add up. Since time and money are finite resources for patients, the authors decided to assess their guidelines for testing for sperm DNA fragmentation. Determining if there is a male factor of infertility is challenging when the semen analysis is normal. We know that some men have enough sperm but the conditions for the sperm in the reproductive tract result in high DNA fragmentation. Though studied extensively, we really do not have good evidence for when to order this test, which costs $300–500. This study, ‘Incidence of high sperm DNA fragmentation in a targeted population of subfertile men’ by Chitra Vinnakota, Lynsey Cree, John Peek, and Dean E. Morbeck, was performed to determine the incidence of high DNA fragmentation in the population targeted in their clinic policy in order to determine if their inclusion criteria are effective. They found that the incidence of high DNA fragmentation increases with age and when sperm motility is poor, and importantly, that the incidence is very low in men without indications. These findings allowed the authors to refine their testing policy further, giving doctors and patients evidence for when this extra test is needed – and when it is not likely to be helpful.