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Prevalence and risk factors of zygotic splitting after 937 848 single embryo transfer cycles
Clinicians should consider whether to counsel couples about the small increase in the risk of zygotic splitting associated with some embryo manipulations.
Performance of Day 5 KIDScore™ morphokinetic prediction models of implantation and live birth after single blastocyst transfer
KIDScore™ Day 5 predictive models are significantly associated with implantation rates after day 5 single blastocyst transfer. However, their predictive performance remains perfectible. The use of these predictive models holds promises as decision-making tools to help the embryologist select the best embryo, ultimately facilitating the implementation of SET policy. However, embryologists’ expertise remains absolutely necessary to make the final d
The KidscoreTM D5 algorithm as an additional tool to morphological assessment and PGT-A in embryo selection: a time-lapse study. [PDF Download]
CONCLUSION.Embryo selection based on the KS5 algorithm score improved the implantation rates of single euploid blastocyst transfers. Furthermore, embryos with the highest KS5 score had a higher probability of being euploid and implanting.
Conventional freezing vs. cryoprotectant-free vitrification of epididymal (MESA) and testicular (TESE) spermatozoa: Three live births
This is the first report of full-term pregnancies and babies born after ICSI with epididymal and testicular spermatozoa vitrified without cryoprotectants. In conclusion, cryoprotectant-free vitrification can be successfully applied for the cryopreservation of motile TESE- and MESA-spermatozoa.
Aseptic Technology for Cryoprotectant-Free Vitrification of
Human Spermatozoa by Direct Dropping into Clean Liquid Air:
Apoptosis, Necrosis, Motilit
It is concluded that cryoprotectant-free vitrification by the direct dropping of human spermatozoa in a clean cooling agent (liquid air) is a good alternative to the use of nonsterile liquid nitrogen and can be used to cool cells while minimising the risk of microbial contamination.
“Naturalization” of Routine Assisted Reproductive Technologies by In Vitro Culture of Embryos with Microvibration: Sex Ratio, Body Length, and Weight
The proportion of males at birth was significantly associated with mode of in vitro culture of embryos only among women aged 40 years and older...It was concluded that birth weight of infants was positively associated with mode of in vitro culture of embryos under microvibration among women of all age groups.
The BlastGen study: A randomised controlled trial of GM-CSF supplemented blastocyst media.
This study demonstrated a significant reduction in Day 5 embryo outcome parameters using Embryogen®/BlastGen™ compared to standard medium, and insufficient evidence of a difference in pregnancy outcomes. Taking into consideration the small samples size, study limitations, and strict inclusion criteria of this single-centred study, further research is necessary to determine the efficacy of Embryogen®/BlastGen™ medium in couples undergoing IVF/ICSI
Prospective randomized multicentre comparison on sibling oocytes comparing G-Series media system with antioxidants versus standard G-Series media syst
Conclusions. The presence of antioxidants during IVF and embryo culture for patients 35 to 40 years resulted in a significant increase in implantation and pregnancy rate. Supplementation of antioxidants to IVF and culture media may therefore improve the viability of human embryos in ART, plausibly through the reduction of oxidative stress.
Shooting STAR: re-interpreting the data from the “Single Embryo Transfer of Euploid Embryo” randomized clinical trial
According to our model, the STAR trial has demonstrated that transferring only blastocysts classified as “euploid” after PGT-A test leads to a reduction from 82.2 % to 50.0 % of the live birth rate for competent embryos, thus supporting the idea that PGT-A is associated with some embryo wastage.
Mechanical stimulation of embryos in surrounding culture fluid induces and amplifies the cell to cell communication and leads to positive effects on embryo development and quality. An additional effect of micro-vibrations can be found in the continuous refreshment of the medium surrounding the embryo.
Business Products / [Posted:11/2/2020] / [Source:www.invitro360.com] Viewed: 859
Comments Linked to this Mailout
Title
Can additional antioxidants restore embryo ROS Resistance in older women
Summary
A paper by Gardiner, et,al, suggests that embryos from older women can restore their ROS Resistance
Comment
In a paper in RBMO by Gardiner, et.al, the results from two Japanese clinics of supplementing standard G-series embryo culture with three additional antioxidants does appear to restore the implantation potential of embryos for women between 35 and 40 to those observed for women less than 35 years of age. |
The three antioxidants acetyl-l-carnitine (ALC), N-acetyl-l-cysteine (NAC) and alpha-lipoic acid (ALA) were added as a group (called A3) to standard Vitrolife G-series in 5% O2. The authors reported that while no difference in the appearance in the day 5 embryos using standard scoring criteria, previous studies in the mouse suggests the A3 increased the blastocyst cell count. The authors did notice that day 3 embryos in the presence of A3 were slightly more advanced. |
Even though the number of clients was limited, they reported the implantation rate and the ongoing pregnancy rate was unaffected by A3 in women under 35 years of age but the rates were significantly higher in women between 35 and 40 years of age. The data suggested the rates in the older women were restored to those of the younger clients. There was no data for women older than 40 year of age. |
The authors suggested that from their earlier work in mice and from this paper that embryos from older women are less able to protect themselves from reactive oxygen species (ROS) produced both from their own active metabolism and from the environment. ROS damage has been linked to rates of aneuploidy. A3 restore this protection up to the level seen for younger embryos. |
Most embryo culture media already contain a number of antioxidants including ascorbate, vitamins D and E and glutathione (GSH). These mainly act to remove ROS by scavenging them directly while the A3 antioxidants may act more as a metabolic stimulant to raise GSH levels. The paper also implies that the current media formulations contain insufficient antioxidative potential to totally support embryos of diminished capacity. It would be great to see in future publications the impact on embryos from women over 40 years of age. |
Their studies reported the ROS levels are reduced by 25% by adding A3. The degree of reduction is important because ROS also acts as a signaling agent. Thus, the management of ROS concentrations by external antioxidants may be critical for implantation. It seems that the management of ROS requires some finesse since removing ROS completely (if possible) may be counterproductive. It also raises the question whether one media formulation is appropriate for all embryos. |
A key observation was that A3 supplementation did not improve the implantation rate of embryos from younger women (OPR 50% x 44% +A3, NS) and bigger studies may be needed to confirm there is no other risk from exposing healthy embryos to A3 supplementation. |
Another interesting observation both in this paper and the supporting mouse research was that adding A3 to culture medium did not influence the rate and quality of blastocyst development. Yet the mouse research found that both ICM and trophectoderm cell numbers were higher in the presence of A3 antioxidants and at low oxygen concentrations. One is drawn to a conclusion that the visual assessment of blastocysts may fail to delineate embryo cell numbers and presumably implantation potential. |
However, the observation that different media formulations may affect embryos differently asks the question whether one media for all embryos remain the best option. As time-lapse and PGT-A progress, it may well allow media manufacturers to fine tune their formulations to better provide embryos of varying ages or quality with media specifically designed to their needs. Environmental variations such as the oxygen concentration (in different clinics) during culture may also require differing levels of antioxidants. Single one-time use, small volume, disposable media bottles will allow clinics in the future to customize embryo culture to their client’s conditions. |
Title
Background information on the role of antioxidants
Summary
Comment
T Truong, D K Gardner, Antioxidants improve IVF outcome and subsequent embryo development in the mouse, Human Reproduction, Volume 32, Issue 12, December 2017, Pages 2404–2413, https://doi.org/10.1093/humrep/dex330 |
Thi T. Truong, Yu May Soh, David K. Gardner, Antioxidants improve mouse preimplantation embryo development and viability, Human Reproduction, Volume 31, Issue 7, July 2016, Pages 1445–1454, https://doi.org/10.1093/humrep/dew098 |
The key features of these open access papers include - |
In vivo epididymal and fallopian environments have natural antioxidants to protect gametes and embryos at low O2 levels while removal of these fluids at atmosphere concentrations expose them to increase risk of oxidative damage. |
Oxidative damage is higher at atmospheric oxygen concentrations and less at 5% O2 culture conditions. Thus any processing of gametes and embryos at 20% O2 significantly increases the risk of oxidative damage. |
L-Carnitine (LC) reduces sperm apoptosis, support motility and DNA integrity, and protects sperm membranes. The mechanism of LC may be through the regulation and transport of long chain fatty acids into mitochondria for beta-oxidation and ATP production and through its antioxidant actions by reducing the levels of ROS. |
a-Lipoic Acid (ALA) regulates mitochondrial function and assists in the production of ATP for energy production and has been shown to stimulate expression of antioxidant genes involved in defending against oxidative stress. ALA is an antioxidant which can act as a potent free radical scavenger and metal chelator, is a co-enzyme for mitochondrial multi-enzyme complex reactions, and is responsible for recycling other cellular antioxidants including GSH and vitamins C and E Addition of ALA to mouse embryo culture medium improves embryo development at high oxygen tension by conferring protection against oxidative stress. |
Cysteine analogues, including N-Acetyl-L-Cysteine (NAC), increased fertilization rates of mouse oocytes. Cysteine may function through the up regulation of GSH synthesis. Thus, the improved embryo quality may be a result of cysteine affecting GSH levels, therefore protecting the cell from oxidative stress through an increased antioxidant capacity. GSH synthesis is dependent on the availability of cysteine and, intracellular levels of cysteine determine the upper concentration of cellular GSH. Cysteine, as a rate-limiting factor, may therefore impact on subsequent embryo development. Studies have shown that cysteine supplementation to bovine in vitro maturation (IVM) medium increased GSH levels and cleavage and blastocyst rates. Therefore, an increase in GSH may protect the cell from oxidative stress due to a greater antioxidant capacity thus facilitating improved embryo quality. [see papers for specific reference links]. |
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Which of the followwing are antioxidants
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The supplementation of culture with additional antioxidants significantly improved day 3 embryo quality
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The Supplementation Of Culture With Additional Antioxidants Significantly Improved Day 5/6 Embryo Quality
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The Supplementation Of Culture With Additional Antioxidants Significantly Improved the implantation rate
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