Embryo quality

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Embryo quality is the ability of an embryo to perform successfully either or both in terms of conferring a high pregnancy rate or/and resulting in a healthy person. Embryo profiling is the estimation of embryo quality by qualification and/or quantification of various parameters. Estimations of embryo quality guides the choice in embryo selection in in vitro fertilization.

Prediction of pregnancy rates[edit]

Microscopy[edit]

Embryo quality is mainly evaluated by microscopy at certain time points using a morphological scoring system. This has shown to significantly improve pregnancy rates.[1]

Time-lapse microscopy is an expansion of miscroscopy wherein the morphology of embryos is studies over time. A review in 2014 considered its evidence to be lacking, and that it should thereforeremain an experimental strategy subject to institutional review and approval.[2] Studies using the EmbryoScope(tm) time-lapse incubator have used several indicators for embryo quality, such as direct cleavage from 1 to 3 cells,[3] as well as the initiation of compaction and start of blastulation.[4][5][6] Also, two-pronuclear zygotes (2PN) transitioning through 1PN or 3PN states tend to develop into poorer-quality embryos than those that constantly remain 2PN.[7]

Molecular analysis[edit]

The presence of soluble HLA-G might be considered as another parameter if a choice has to be made between embryos of equal visible quality.[1]

Also, methods are emerging in making comprehensive analyses of up to entire genomes, transcriptomes, proteomes and metabolomes which may be used to score embryos by comparing the patterns with ones that have previously been found among embryos in successful versus unsuccessful pregnancies:[8]

  • In transcriptome evaluation, however, gene expression profiling studies of human embryos are limited due to legal and ethical issues.[8] An alternative or complement is gene expression profiling of cumulus cells surrounding the oocyte and early embryo, or on granulosa cells.[8] Profiling of cumulus cells can give valuable information regarding the efficiency of an ovarian hyperstimulation protocol, and may indirectly predict oocyte aneuploidy, embryo development and pregnancy outcomes, without having to perform any invasive procedure directly in the embryo.[8]
  • Proteome profiling of embryos can indirectly be evaluated by sampling of proteins found in the vicinity of embryos, thereby providing a non-invasive method of embryo profiling.[8] Examples of protein markers evaluated in such profiling include CXCL13 and granulocyte-macrophage colony-stimulating factor, where lower protein amounts are associated with higher implantation rates.[8]

Another level of opportunity can be achieved by having the evaluation of the embryo profile tailored to the maternal status in regard to, for example health or immune status, potentially further detailed by similar profiling of the maternal genome, transcriptome, proteome and metabolome. Two examples of proteins that may be included in maternal profiling are endometrium-derived stathmin 1 and annexin A2, whose down- and up-regulation, respectively, are associated with higher rates of successful implantation.[8]

Health prediction[edit]

The main method currently used to predict the health of a resultant person of an embryo is preimplantation genetic diagnosis (also called preimplantation genetic screening, preimplantation genetic profiling or PGP), in order to determine whether the resultant person will inherit a specific disease or not. On the other hand, a systematic review and meta-analysis of existing randomized controlled trials came to the result that there is no evidence of a beneficial effect of PGP as measured by live birth rate.[9] On the contrary, for women of advanced maternal age, PGP significantly lowers the live birth rate.[9] Technical drawbacks, such as the invasiveness of the biopsy, and chromosomal mosaicism are the major underlying factors for inefficacy of PGP.[9]

References[edit]

  1. ^ a b Rebmann, V.; Switala, M.; Eue, I.; Grosse-Wilde, H. (2010). "Soluble HLA-G is an independent factor for the prediction of pregnancy outcome after ART: A German multi-centre study". Human Reproduction 25 (7): 1691–1698. doi:10.1093/humrep/deq120. PMID 20488801. 
  2. ^ Kaser, D. J.; Racowsky, C. (2014). "Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review". Human Reproduction Update 20 (5): 617–631. doi:10.1093/humupd/dmu023. ISSN 1355-4786. 
  3. ^ Rubio, I.; Kuhlmann, R.; Agerholm, I.; Kirk, J.; Herrero, J.; Escribá, M. A. J.; Bellver, J.; Meseguer, M. (2012). "Limited implantation success of direct-cleaved human zygotes: A time-lapse study". Fertility and Sterility 98 (6): 1458–1463. doi:10.1016/j.fertnstert.2012.07.1135. PMID 22925687. 
  4. ^ Campbell, A.; Fishel, S.; Bowman, N.; Duffy, S.; Sedler, M.; Hickman, C. F. L. (2013). "Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics". Reproductive BioMedicine Online 26 (5): 477–485. doi:10.1016/j.rbmo.2013.02.006. PMID 23518033. 
  5. ^ Meseguer, M.; Herrero, J.; Tejera, A.; Hilligsøe, K. M.; Ramsing, N. B.; Remohí, J. (2011). "The use of morphokinetics as a predictor of embryo implantation". Human Reproduction 26 (10): 2658–2671. doi:10.1093/humrep/der256. PMID 21828117. 
  6. ^ Dal Canto, M.; Coticchio, G.; Mignini Renzini, M.; De Ponti, E.; Novara, P. V.; Brambillasca, F.; Comi, R.; Fadini, R. (2012). "Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation". Reproductive BioMedicine Online 25 (5): 474–480. doi:10.1016/j.rbmo.2012.07.016. PMID 22995750. 
  7. ^ Reichman, D. E.; Jackson, K. V.; Racowsky, C. (2010). "Incidence and development of zygotes exhibiting abnormal pronuclear disposition after identification of two pronuclei at the fertilization check". Fertility and Sterility 94 (3): 965–970. doi:10.1016/j.fertnstert.2009.04.018. PMID 19476942. 
  8. ^ a b c d e f g The Evian Annual Reproduction (EVAR) Workshop Group 2010; Fauser, B. C. J. M.; Diedrich, K.; Bouchard, P.; Domínguez, F.; Matzuk, M.; Franks, S.; Hamamah, S.; Simón, C.; Devroey, P.; Ezcurra, D.; Howles, C. M. (2011). "Contemporary genetic technologies and female reproduction". Human Reproduction Update 17 (6): 829–847. doi:10.1093/humupd/dmr033. PMC 3191938. PMID 21896560. 
  9. ^ a b c Mastenbroek, S.; Twisk, M.; Van Der Veen, F.; Repping, S. (2011). "Preimplantation genetic screening: A systematic review and meta-analysis of RCTs". Human Reproduction Update 17 (4): 454–466. doi:10.1093/humupd/dmr003. PMID 21531751.