Making IVF more effective through the evolution of prediction models: is prognosis the missing piece of the puzzle?

Simopoulou, Mara; Sfakianoudis, Konstantinos; Antoniou, N. G.; Maziotis, Evangelos; Rapani, Anna; Bakas, Panagiotis; Anifandis, George; Kalampokas, Theodoros; Bolaris, Stamatis; Pantou, Agni; Pantos, Konstantinos; Koutsilieris, Michael

doi:10.1080/19396368.2018.1504347

Cited by 20 publications

(7 citation statements)

References 84 publications

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“…It would be interesting, however, to combine several parameters to build an algorithm that could predict the outcome of IVF treatment, e.g. to combine caspase-3 levels in the secretome with detailed studies of embryo development (as in the study by Dominguez), in combination with age, BMI and possible biological markers studied in other investigations (reviewed in [47]).…”

Section: Discussionmentioning

confidence: 99%

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts

et al. 2019

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Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolomics, genomics and proteomics, to improve the evaluation of embryo quality even further. The aim of this study was to investigate if different levels of caspase-3 and histidine-rich glycoprotein (HRG), secreted by the embryo into the culture media, can be used as biomarkers of embryo quality. In this study, a total of 334 samples of culture media were collected from in vitro fertilization (IVF) treatments at three different clinics. Protein analysis of the culture media was performed using multiplex proximity extension protein analysis to detect levels of caspase-3 and HRG in the embryo secretome. Protein levels were compared in secretome samples from high- and low-quality blastocysts and embryos that became arrested during development. Correlation between protein levels and time to morula formation was also analyzed. Furthermore, protein levels in secretomes from day-2 cultured embryos were compared on the basis of whether or not pregnancy was achieved. The results showed that caspase-3 levels were lower in secretomes from high-quality vs. low-quality blastocysts and those that became arrested (p ≤ 0.05 for both). In addition, higher HRG levels correlated with a shorter time to morula formation (p ≤ 0.001). Caspase-3 levels were also lower in secretomes from day-2 cultured embryos resulting in a pregnancy vs. those that did not (p ≤ 0.05). Furthermore, it was shown that caspase-3 might be used as a marker for predicting potential success rate after transfer of day-2 cultured embryos, where a caspase-3 cutoff level of 0.02 gave a prediction probability of 68% (p = 0.038). In conclusion, in future prediction models, levels of caspase-3 and HRG might be used as potential markers of embryo quality, and secreted caspase-3 levels could to some extent predict the outcome after transfer of day-2 cultured embryos.

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Section: Discussionmentioning

confidence: 99%

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts

et al. 2019

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“…The levels of AMH in the blood of cows subjected to superovulatory treatment were used as a marker to predict ovarian responses and consequently the quality of recovered embryos [14,18,23,24]. The study herein showed that, the correlations between AMH concentrations and ovarian response were significant positive (P<0.05) for CL (r=0.36), total ovarian response (P<0.01; r=0.80), transferable embryos (r=0.32), and freezable embryos (r=0.35).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, antral follicle count and AMH level are contributed to these variability's [12,13]. Selection of candidate donor's cows for embryos production based on AMH level will reduce this variability [14]. AMH secreted by the granulosa cells of the ovary and characteristic for each animal on a long term period [15] and providing highly accurate information on the ovarian follicular pool and follicular responsiveness [16].…”

Section: Introductionmentioning

confidence: 99%

Impact of Type and Dose of Recombinant Human Follicle Stimulating Hormone on Embryos Production in Dairy Cows and Their Relationship with AMH Concentration

Mohammed¹,

Darwish²,

Dohreig³

et al. 2019

AVS

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The study was investigated to compare the effectiveness of Folltropin and two products (Fostimon and Menogon) of a recombinant human follicle stimulating hormone (rhFSH) on ovarian super-stimulation and embryo production in dairy Holstein cows. Two different doses for each super-ovulatory product were investigated. The relationship between the levels of Anti-Mullerian Hormone (AMH) in the blood serum before super-stimulation initiation and ovarian response and embryos production were also evaluated. At random stage of the estrus cycle, the donor cows were received intra-vaginal controlled internal drug release device (CIDR) and injected with 100µg of gonadotropin-releasing hormone (GnRH). On fourth day of CIDR insertion, cows were divided according to the product types of superovulatory hormones into three equal main groups. According to hormonal dose, each main group was re-divided into two equally subgroups ; low and high dose. Superovulatory hormones was injected IM as decreasing doses; 40%, 30%, 20% and 10% of the total dose twice daily for 4 days. On day 7, CIDRs were removed and each cow received 2 doses of PGF 2 α with 12hr interval. Based upon heat detection, donor's cows were inseminated with frozen semen three times 8-10hrs interval and concurrent with 100µg GnRH injection at first insemination. Non-surgical embryos recovery was performed on day's 7-8 post insemination and ovarian super-stimulation was checked using sonography to estimate ovarian response. Recovered embryos were morphologically evaluated as grades. Twelve embryos collected from Menogon donors group were transferred to six recipient's cows. The mean numbers of CL, recovered embryo/ova, fertilized ova and transferable embryos are significantly (P<0.01) higher in Folltropin and Menogon treated cows than Fostimon group. Donor cows treated with high doses of Folltropin and Menogon showed higher means for transferable and freezable embryos. Three recipients (50%) who received embryos appeared pregnant and one of them born calf. Significant positive correlations were reported between AMH on one side and CL, total ovarian response, transferable and freezable embryos on the other side, and cows having AMH≥230ng/L exhibited significant higher means. In conclusion: Menogon can be used as rhFSH for embryos production with transferable quality. AMH can be used as indicator to helpful select cow's candidates as donors. More studies are needed using Fostimon accompanied with different levels of LH.

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“…Decades after the first successful application of ART in humans, over 8 million infants have been born with ART assistance worldwide ( Wade et al, 2015 ; Rao et al, 2018 ; Fauser, 2019 ; Leaver and Wells, 2019 ). ART has become well-accepted and popular in recent years ( Liu et al, 2015 ; Simopoulou et al, 2018 ; Gleicher et al, 2019 ). Epidemiological and animal experiments show that the early stage of fetal development is particularly sensitive to changes in the environment and that the environmental abnormalities suffered during this period may lead to problems later in life ( Faulk and Dolinoy, 2011 ; Hanson and Gluckman, 2014 ; Grandjean et al, 2015 ; Heindel et al, 2017 ; Li T. et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates

et al. 2021

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The DNA methylation of human offspring can change due to the use of assisted reproductive technology (ART). In order to find the differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent DNA methylation background, which will add noise to the real difference, must be removed. We analyzed newborns’ heel blood from six families to identify the DMRs between ART and natural pregnancy newborns, and the genetic model of methylation was explored, meanwhile we analyzed 32 samples of umbilical cord blood of infants born with ART and those of normal pregnancy to confirm which differences are consistent with cord blood data. The DNA methylation level was lower in ART-assisted offspring at the whole genome-wide level. Differentially methylated sites, DMRs, and cord blood differentially expressed genes were enriched in the important pathways of the immune system and nervous system, the genetic patterns of DNA methylation could be changed in the ART group. A total of three imprinted genes and 28 housekeeping genes which were involved in the nervous and immune systems were significant different between the two groups, six of them were detected both in heel blood and cord blood. We concluded that there is an ART-specific DNA methylation pattern involved in neuro- and immune-system pathways of human ART neonates, providing an epigenetic basis for the potential long-term health risks in ART-conceived neonates.

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Making IVF more effective through the evolution of prediction models: is prognosis the missing piece of the puzzle?

Cited by 20 publications

References 84 publications

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts

Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts

Impact of Type and Dose of Recombinant Human Follicle Stimulating Hormone on Embryos Production in Dairy Cows and Their Relationship with AMH Concentration

Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates

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