In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial

Forman, Eric J.; Hong, K.H.; Ferry, K.M.; Tao, Xin; Taylor, Deanne; Levy, Brynn; Treff, Nathan R.; Scott, Richard T.

doi:10.1016/j.fertnstert.2013.02.056

Cited by 438 publications

(376 citation statements)

References 36 publications

Supporting

Mentioning

362

Contrasting

Unclassified

Order By: Relevance

“…There are various PGS methods for comprehensive chromosome screening currently in clinical use, including comparative genomic hybridization (array-CGH) (4,5), single-nucleotide polymorphism (SNP) arrays (6-9), multiplex quantitative PCR (10), and next-generation sequencing (NGS) (11,12). Multiple clinical trials have confirmed the clinical efficacy of PGS, including increasing implantation and clinical pregnancy rates, as well as decreasing miscarriage rates (13)(14)(15)(16). However, the applicability of PGS has been limited for a number of reasons:…”

mentioning

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.

199

218

View full text Add to dashboard Cite

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.

show abstract

mentioning

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.

199

218

View full text Add to dashboard Cite

show abstract

“…In our database, 31.8 % (139/437) of patients who sent samples to Reprogenetics for CCS met this criteria. Furthermore, in the randomized controlled trial of SET following CCS versus DET of unbiopsied embryos by Forman et al [32] the average number of surplus euploid embryos following a SET was 3.2. Thus, a significant number of patients meet this criteria.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it stands to reason that achieving a larger cohort of confirmed euploid blastocysts would be similarly associated with higher pregnancy rates. In Forman et al [32] for example, the average number of confirmed euploid blastocysts remaining following SET was 3.2. This suggests a surplus of euploid embryos may have been a marker for the excellent outcomes seen following SET in this study.…”

Section: Introductionmentioning

confidence: 95%

“…Improved pregnancy rates and decreased miscarriage rates have been reported in SET cycles following CCS compared with SET using standard morphologic criteria [31,28]. Recent data from a randomized controlled trial even demonstrated that a SET of a chromosomally normal embryo has similar pregnancy rates to a DET of untested embryos [32]. However, studies examining CCS have not reported specifically on the characteristics of the biopsied cohort.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A greater number of euploid blastocysts in a given cohort predicts excellent outcomes in single embryo transfer cycles

Morin

Melzer-Ross²,

McCulloh

et al. 2014

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose This multicentered retrospective study analyzed whether the quantity of euploid blastocysts in a given cohort after comprehensive chromosomal screening can be used to identify candidates for single embryo transfer. Methods Blastocysts from 437 patients underwent trophectoderm biopsy followed by array comparative genomic hybridization. Embryos were then selected for single or double embryo transfer. The number of euploid blastocysts produced and transferred for each patient was recorded, as was clinical pregnancy rate and multiple gestation rate. Results In patients with e3 euploid blastocysts, clinical pregnancy rate was higher in double, compared to single embryo transfers. However, in patients with Q4 euploid blastocysts, clinical pregnancy rate was not reduced with single embryo transfer was performed, whereas the multiple gestation rate was greatly reduced. Conclusions Size of the euploid embryo cohort is a marker for success in single embryo transfer cycles. Patients who produce at least four euploid blastocysts are outstanding candidates for single embryo transer.

show abstract

“…The three earliest RCTs which are often cited as sound evidence in favour of PGS [68][69][70] have however been heavily criticized [12]. The main criticisms are the small size of the study [68], the fact that transfer of cryopreserved embryos which could have been higher in the control group was not taken into account and could have led to additional pregnancies [68,70], the inclusion of good prognosis patients only with at least a number of analysable embryos, the difference in number of embryos transferred between the two study groups and finally the use of implantation rate as outcome measure [69,70]. 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.…”

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

confidence: 99%

Preimplantation Genetic Screening

Sermon¹

2017

obm genet

View full text Add to dashboard Cite

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

show abstract

In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial

Abstract: In women ≤ 42 years old, transferring a single euploid blastocyst results in ongoing pregnancy rates that are the same as transferring two untested blastocysts while dramatically reducing the risk of twins.

Cited by 438 publications

References 36 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

A greater number of euploid blastocysts in a given cohort predicts excellent outcomes in single embryo transfer cycles

Preimplantation Genetic Screening

Contact Info

Product

Resources

About