Day 3 embryo selection by metabolomic profiling of culture medium with near-infrared spectroscopy as an adjunct to morphology: a randomized controlled trial

Purpose The arrangement of the blastomeres within the 4-cell stage embryo reflects the orientation of the cleavage planes during the second division. To examine their relevance, the developmental capacity and the pregnancy rate were compared between tetrahedral-shaped and non-tetrahedralshaped 4-cell stage human embryos. Methods The study included 3,546 4-cell stage embryos. The arrangement of the blastomeres at the 4-cell stage was annotated as being tetrahedral or non-tetrahedral on day 2 of preimplantation development. Embryo quality was compared on day 3 and day 5. Pregnancy rates were calculated per single embryo transfer on day 3 or day 5. Results In total, 2,803 4-cell stage embryos (79 %) displayed a tetrahedral arrangement and 743 (21 %) displayed a non-tetrahedral arrangement. Tetrahedralshaped embryos developed more into high-quality embryos on day 3 (p<0.001) and day 5 (p=0.036) and had a higher blastulation rate (p=0.009). Though, the number of high-quality embryos selected for transfer did not differ between both groups on day 3 (p=0.167) and day 5 (p~1). Three hundred thirty single embryo transfers were analysed. No significant difference in clinical pregnancy was found between both groups after transfer on day 3 (p=0.209) and day 5 (p=0.653). Conclusions The arrangement of the blastomeres according to their previous cleavage planes was correlated to the developmental potential of the 4-cell stage embryo up to the blastocyst stage. If embryo transfers are performed on day 3 and day 5 of development using embryos of adequate quality, the blastomere arrangement at the 4-cell stage had no predictable value regarding pregnancy success.

Section: Introductionmentioning

confidence: 99%

Developmental capacity and pregnancy rate of tetrahedral- versus non-tetrahedral-shaped 4-cell stage human embryos

Cauffman

Verheyen

Tournaye

2014

“…Worldwide, years and years of research have been done on this subject, but it has not (yet) led to a novel tool, uniformly used in IVF laboratories, that (non-invasively) identifies the best embryo to transfer more accurately than standard morphology. For example, pre-implantation genetic screening (PGS) and metabolomic profiling of embryo culture media by Near Infrared Spectroscopy were (recently developed) tools that did not redeem the promise of better pregnancy outcomes [8,13,20]. In the current study we tried to objectify familiar parameters of embryo morphology to analyze whether this relatively simple novel method of measuring instead of estimating important embryo quality parameters could refine the way of selecting the most viable embryo within a cohort of good quality embryos and hence lead to a higher implantation rate.…”

Section: Discussionmentioning

confidence: 99%

The association of the blastomere volume index (BVI), the blastomere symmetry index (BSI) and the mean ovality (MO) with ongoing implantation after single embryo transfer

Vergouw

Nofal

Kostelijk

et al. 2013

Purpose To generate novel, objective variables that resemble embryo quality and relate them to ongoing implantation, using multilevel imaging of single-transferred embryos. Methods Retrospective analysis of multilevel images of 659 day 3 single-transferred embryos. Each embryo was photographed on seven different levels, in order to measure the largest diameter of every blastomere within an embryo. The volume of each blastomere was calculated using the equation 1=6p Ã diameter 3 . The blastomere volume index (BVI) represented the ratio between the total blastomeric volume of an embryo and the mean cytoplasmic volume of an oocyte on day 0. The blastomere symmetry index (BSI) represented the ratio between the greatest blastomere volume and the smallest blastomere volume within an embryo. The mean ovality (MO) represented the presence of non-spherical blastomeres. Analyses were performed to compare the BVI, BSI and MO between patients with and without an ongoing implantation. Results The mean BVI was significantly higher for embryos in the ongoing implantation group compared to the no ongoing implantation group. The mean BSI was associated with ongoing implantation for unevenly cleaved embryos. The MO of blastomeres within an embryo was similar for embryos in the ongoing implantation group compared to the no ongoing implantation group. The association of the BVI and BSI with ongoing implantation was confounded, because only female age and cleavage rate were significantly associated with ongoing implantation in multiple logistic regression analyses. Conclusions The BVI, BSI and MO are objective variables that resemble embryo quality, but they are not suitable to use as embryo selection tools.

“…Several attempts have been made to classify embryo viability by measuring products released by the embryo into the culture medium. Metabolic profiling of the culture medium, based on the measurement of simple metabolites such as lactose, was proposed commercially 2 years ago but interest appears to have dissipated [47] and this technology again revolved around expensive equipment. Other ideas were to measure the secretion of factors such as HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G (HLA-G).…”

Section: Clinical Concernsmentioning

confidence: 99%

Trends, Fads and ART!

Dale¹,

Ménézo²,

Coppola³

2015

Morphological selection techniques of gametes and embryos are of current interest to clinical practice in ART. Although intracytoplasmic morphologically selected sperm injection (IMSI), time lapse imaging morphometry (TLIM) or quantification of chromosome numbers (PGS) are potentially useful in research, they have not been shown to be of statistically predictive value and, thus, have only limited clinical usefulness. We make the point that morphological markers alone cannot predict the success of the early embryo, which depends on the correct orchestration of a myriad of physiological and biochemical activation events that progress independently of the maternal or zygotic genome. Since previous attempts to identify metabolic markers for embryo quality have failed and there is no evidence that the intrinsic nature of gametes and embryos can be improved in the laboratory, embryologists can only minimize environmental or operator induced damage while these cells are manipulated ex vivo.