Preimplantation genetic diagnosis and screening: Current status and future challenges

Chen, Shee‐Uan; Ma, Gwo‐Chin; Hsieh, Sung‐Tsang; Tsai, Horng‐Der; Yang, Yu Shih; Chen, Ming

doi:10.1016/j.jfma.2017.08.006

Cited by 40 publications

(30 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even with timed intercourse the chances of conception are no more than 25% per cycle (41). Couples undergoing in vitro fertilization procedures may subvert certain fertility issues, such as embryonic trisomies and other nondisjunction syndromes, via genetic testing of embryos prior to implantation (42), but the rates of implantation even for perfectly healthy blastocysts are still dependent on the adequately robust decidualization of the uterus, allowing it to be receptive to the embryo, and the synchronized timing of these events (43). It has long been known that uterine decidualization is dependent on, and titrated by, the presence and levels of ovarian hormones (2).…”

Section: Discussionmentioning

confidence: 99%

Development and utilization of human decidualization reporter cell line uncovers new modulators of female fertility

Haller

Yin

2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Failure of embryo implantation accounts for a significant percentage of female infertility. Exquisitely coordinated molecular programs govern the interaction between the competent blastocyst and the receptive uterus. Decidualization, the rapid proliferation and differentiation of endometrial stromal cells into decidual cells, is required for implantation. Decidualization defects can cause poor placentation, intrauterine growth restriction, and early parturition leading to preterm birth. Decidualization has not yet been systematically studied at the genetic level due to the lack of a suitable high-throughput screening tool. Herein we describe the generation of an immortalized human endometrial stromal cell line that uses yellow fluorescent protein under the control of the prolactin promoter as a quantifiable visual readout of the decidualization response (hESC-PRLY cells). Using this cell line, we performed a genome-wide siRNA library screen, as well as a screen of 910 small molecules, to identify more than 4,000 previously unrecognized genetic and chemical modulators of decidualization. Ontology analysis revealed several groups of decidualization modulators, including many previously unappreciated transcription factors, sensory receptors, growth factors, and kinases. Expression studies of hits revealed that the majority of decidualization modulators are acutely sensitive to ovarian hormone exposure. Gradient treatment of exogenous factors was used to identify EC50 values of small-molecule hits, as well as verify several growth factor hits identified by the siRNA screen. The high-throughput decidualization reporter cell line and the findings described herein will aid in the development of patient-specific treatments for decidualization-based recurrent pregnancy loss, subfertility, and infertility.

show abstract

Section: Discussionmentioning

confidence: 99%

Development and utilization of human decidualization reporter cell line uncovers new modulators of female fertility

Haller

Yin

2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Theoretically, PGT-A should not only improve outcomes but also reduce the financial burdens of multiple embryo transfers, emotional stress of miscarriages and alleviate the complications associated with multiple gestations through single embryo transfers. In practice, however, the PGT field has been fraught with challenges (Chen et al 2018). Some of these challenges have been mitigated by changing the technology from FISH to array comparative genomic hybridization (aCGH), and more recently next generation sequencing.…”

Section: Preimplantation Genetic Testing For Aneuploidy (Pgt-a) In Pamentioning

confidence: 99%

Meiotic nondisjunction and sperm aneuploidy in humans

2018

View full text Add to dashboard Cite

Infertility is relatively common affecting approximately 1-in-6 couples. Although the genetic basis of infertility is increasingly being uncovered, the contribution of male infertility often remains unexplained. The leading cause of pregnancy loss and cognitive impairment in humans is chromosome aneuploidy. Sperm aneuploidy is routinely evaluated by fluorescence in situ hybridization. The majority of studies have reported similar findings, namely: (1) all men produce aneuploid sperm; (2) certain chromosomes are more prone to undergo chromosome nondisjunction; (3) infertile men typically have significantly higher levels of sperm aneuploidy compared to controls and (4) the level of aneuploidy is often correlated with the severity of the infertility. Despite this, sperm aneuploidy screening is rarely evaluated in the infertility clinic. Within recent years, there appears to be renewed interest in the clinical relevance of sperm aneuploidy. We shall examine the gender differences in meiosis between the sexes and explore why less emphasis is placed on the paternal contribution to aneuploidy. Increased sperm aneuploidy is often perceived to be modest and not clinically relevant, compared to the female contribution. However, even small increases in sperm aneuploidy may impact fertility and IVF cycle outcomes. Evidence demonstrating the clinical relevance of sperm aneuploidy will be discussed, as well as some of the challenges precluding widespread clinical implementation. Technological developments that may lead to widespread clinical implementation will be discussed. Recommendations will be suggested for specific patient groups that may benefit from sperm aneuploidy screening and whether preimplantation genetic testing for aneuploidy should be discussed with these patients.

show abstract

“…AMA is a known indication for PGS in women undergoing IVF [9]. However, universal utilization of PGS in these patients is still an area of controversy despite data that is suggestive of the time and cost effectiveness of PGS in women of AMA [10,11]. Our case illustrates a benefit of PGS when poor survival of frozen blastocysts is encountered in otherwise morphologically normal embryos resulting from a non-PGS IVF cycle.…”

Section: Introductionmentioning

confidence: 90%

Utility of Preimplantation Genetic Screening in Women of Advanced Maternal Age with Poor Embryo Survival: A Case Report

Stephens¹,

Kanter²,

Gavrilova-Jordan³

2018

Gynecol Reprod Health

View full text Add to dashboard Cite

A crucial component of In-Vitro Fertilization (IVF) success is selection of excellent quality embryos for uterine transfer. The ability to correlate excellent quality embryos with successful implantation is diminished in women of advanced maternal age (AMA). In recent years, controversy has surrounded the universal use of preimplantation genetic screening (PGS) in women undergoing IVF. A 39-year-old Caucasian nulligravida with age related infertility underwent an unsuccessful fresh IVF cycle that was followed by the unusually poor survival of morphologically good quality frozen blastocysts. Subsequently, she underwent a second IVF cycle with PGS of fresh blastocysts as well as blastocysts from the first IVF cycle. A successful transfer of euploid embryos resulted in a live birth. This case, although not conclusive, delineates the additional benefit of using PGS in women of advanced maternal age with poor survival of morphologically good quality embryos.

show abstract

Preimplantation genetic diagnosis and screening: Current status and future challenges

Cited by 40 publications

References 57 publications

Development and utilization of human decidualization reporter cell line uncovers new modulators of female fertility

Development and utilization of human decidualization reporter cell line uncovers new modulators of female fertility

Meiotic nondisjunction and sperm aneuploidy in humans

Utility of Preimplantation Genetic Screening in Women of Advanced Maternal Age with Poor Embryo Survival: A Case Report

Contact Info

Product

Resources

About