Can Comprehensive Chromosome Screening Technology Improve IVF/ICSI Outcomes? A Meta-Analysis

Chen, Minghao; Wei, Shiyou; Hu, Junyan; Song, Qisheng

doi:10.1371/journal.pone.0140779

Cited by 112 publications

(96 citation statements)

References 77 publications

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“…Chromosome screening on all 24 chromosomes has been mostly used on patients with advanced maternal age, recurrent pregnancy loss, repeated implantation failure, as well as on patients with abnormal karyotype such as balanced translocation and Robertsonian translocation (32)(33)(34)(35)(36)(37). Extensive use of PGS on all IVF/ICSI cycles has been hotly debated in the past few years (38)(39)(40)(41) due to the invasiveness of the biopsy procedure itself, particularly regarding the potential harm on the trophectoderm and possible compromise of implantation potential, as well as potential concerns on long-term effects on the offspring, which are very difficult to assess. In addition, the procedure of performing blastocyst-stage biopsy requires considerable training and expertise to perform the sophisticated embryo manipulation, increasing the costs of performing PGS.…”

Section: Discussion Blastocyst Biopsy and The Controversy Of Extensivmentioning

confidence: 99%

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

Fang

Chen

et al. 2016

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

207

218

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Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.

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Section: Discussion Blastocyst Biopsy and The Controversy Of Extensivmentioning

confidence: 99%

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

Fang

Chen

et al. 2016

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

207

218

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“…Furthermore, this study was conducted prior to the routine use of advanced preimplantation genomic screening techniques, which have been shown to improve IVF outcomes [34]. Prospective studies in a greater number of patients, including those who undergo embryo biopsy and genetic screening, are needed to better characterize the impact of OCP pretreatment in GnRH antagonist cycles.…”

Section: Discussionmentioning

confidence: 99%

Profound Pituitary Suppression Following Oral Contraceptive Pretreatment in Gonadotropin-releasing Hormone Antagonist Cycles Does Not Impact Outcome: A Retrospective Cohort Study

Vela¹,

Ruman²,

Luna³

et al. 2017

J Fertil In Vitro IVF Worldw Reprod Med Genet Stem Cell Biol

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Background: This retrospective study evaluated the effect of profound pituitary suppression with oral contraceptive pill (OCP) pretreatment in gonadotropin-releasing hormone (GnRH) antagonist cycles stimulated with recombinant follicle stimulating hormone plus highly purified human menopausal gonadotropin. Results:In the LH ≤1.5 and >1.5 mIU/mL groups, respectively, the mean number of stimulation days was 10.9 and 9.5 days (P<0.0001); mean total gonadotropin use was 4,328 and 3,543 IU (P<0.0001). Oocyte retrieval was greater in the LH ≤1.5 versus >1.5 mIU/mL group (17.7 vs. 14.9 oocytes; P=0.02). Pregnancy outcomes were similar between groups. Longer OCP duration correlated with lower day 1 LH levels (r=-0.161, P=0.007). Greater LH suppression correlated with increased total gonadotropin dose (r=-0.227, P<0.001) and days of stimulation (r=-0.445, P<0.001). Conclusion:Women with profound LH suppression following OCP pretreatment demonstrated comparable prognosis compared with women without profound LH suppression, despite requiring longer stimulations and a higher total gonadotropin dose.

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“…These trial characteristics lead to a distortion of the real a priori benefit for patients, as they do not represent those patients that for instance do not obtain blastocysts for analysis, or only have abnormal embryos and therefore do not even reach embryo transfer. Although these three RCTs were on specific patient categories, they are often cited as demonstrating PGS efficacy for all IVF patients [62,66,71,72].…”

Section: Pgs and Its Troubled Relationship With Evidence-based Medicinementioning

confidence: 99%

Preimplantation Genetic Screening

Sermon¹

2017

obm genet

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The main aim of PGS has always been to improve IVF outcome, especially in patient groups assumed to have higher rates of chromosomally abnormal embryos, such as patients of advanced maternal age. In that sense, PGS is quite different from other types of screening as discussed in other papers in this issue. Today it bears no doubt that blastocysts found to be uniformly aneuploid in a biopsy will fail to implant, or worse, will implant and lead to a pregnancy and birth carrying a major chromosomal abnormality, such as trisomy 21. However, it has been argued that a cohort of embryos cannot be improved, and that PGS is only a selection method for which efficiency has not been proven. PGS would never increase the live birth rate for that given cohort, even with a 100% efficiency rate of embryo cryopreservation. The current debate on whether PGS should be applied and to which patients it should be offered has shifted from the effect on live birth rates towards other outcomes such as the reduction of transfers and of miscarriages. Taking the undeniable higher cost of IVF into account when PGS is included, what is the benefit to the patient? The views on this question differ on whether PGS is an additional source of income for the IVF clinic and may or may not balance the extra cost for cryopreservation and embryo transfer for the patients, or whether society pays for IVF treatments and may decide not to want to invest in a medical act that does not improve the primary goal of IVF, i.e. having a healthy child. PGS is also often presented as diminishing patient anxiety and stress through decreasing unnecessary embryos transfers and miscarriages, although no data on this

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Can Comprehensive Chromosome Screening Technology Improve IVF/ICSI Outcomes? A Meta-Analysis

Cited by 112 publications

References 77 publications

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

Profound Pituitary Suppression Following Oral Contraceptive Pretreatment in Gonadotropin-releasing Hormone Antagonist Cycles Does Not Impact Outcome: A Retrospective Cohort Study

Preimplantation Genetic Screening

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