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An evidence-based scoring system for prioritizing mosaic aneuploid embryos following preimplantation genetic screening
A composite score was obtained for each individual mosaic aneuploidy after assignment of an individual risk score based on the incidence/likelihood of each adverse outcome. A final additional score was assigned to viable full or mosaic aneuploidies with a well-defined phenotype. The higher the composite score the lower the priority for embryo transfer. In conclusion, due to the paucity of prospective studies on the actual transfer of mosaic aneu
ICSI Versus Conventional IVF in Women Aged 40 Years or More and Unexplained Infertility- A Retrospective Evaluation of 685 Cycles with Propensity Scor
No differences were observed in morphological embryo quality, in the number of cleavage stage embryos, in the number of transferred embryos, and in the number of vitrified embryos. As for the clinical outcome, no differences were observed in pregnancy rate, cumulative pregnancy rate, live birth rate, cumulative live birth rate, and abortion rate. The present results suggest that ICSI is not associated with increased likelihood of a live birth for
The Concept of Growth Hormone Deficiency Affecting Clinical Prognosis in IVF
The idea that the age-related reduction in fertility prognosis is a feature of growth hormone deficiency is supported by our studies showing an elevated binding protein IGFBP-3/IGF-1 ratio and this can be reduced to a normal range (matching younger, good prognosis women) by the administration of GH as an adjuvant.
Repeated GnRH agonist doses for luteal support: a proof of concept
Conclusions- Repeated doses of GnRH agonist every other day as a method of luteal support provided safe and effective luteal support for women who underwent GnRH agonist triggering in a GnRH antagonist IVF cycle.
Metabolomics shows no impairment of the microenvironment of the cumulus–oocyte complex in women with isolated endometriosis
Conclusions: No specific metabolomic signature of endometriosis was found in the follicular fluid of women undergoing IVF. These results suggest that there is no microenvironmental impairment of the COC in cases of isolated endometriosis among women with infertility.
When to do intracytoplasmic sperm injection: a prospective comparison
Conclusions: In conclusion, in couples with normal strict sperm morphology :≤: :4%, there is an advantage of ICSI over IVF in terms of fertilization rate, quantity and quality of cleavage stage embryos and blastocysts. Based on the results, ICSI seems reasonable as a first-line treatment in patients with normal strict sperm morphology :≤: :4%, as well as in patients with unexplained infertility.
What is the prognosis for a live birth after unexplained recurrent implantation failure following IVF/ICSI?
This study reports a favorable overall prognosis for achieving live birth in women who have previously experienced RIF, especially in those who continue with further IVF/ICSI treatments. However since 51% did not achieve a live birth during the follow-up period, there is a need to distinguish those most likely to benefit from further treatment. In this study, no clinical factors were found to be predictive of those achieving a subsequent live bir
A Neofunctionalized X-Linked Ampliconic Gene Family Is Essential for Male Fertility and Equal Sex Ratio in Mice
Males carrying Slxl1 deletions sire more male offspring, whereas males carrying Slx and Slxl1 duplications sire more female offspring, which directly correlates with Slxl1 gene dosage and gene expression levels. SLX and SLXL1 proteins interact with spindlin protein family members (SPIN1 and SSTY1/2) and males carrying Slxl1 deletions downregulate a sex chromatin modifier, Scml2, leading us to speculate that Slx and Slxl1 function in chromatin reg
Genes linked to sex ratio and male fertility in mice
One of the more recent trends among parents-to-be is the so-called gender reveal, a party complete with pink or blue cake to answer the burning question, "Is it a boy or girl?" After all, it's presumed that there's a 50-50 chance you'd have one or the other. In a new article published in Current Biology, Michigan Medicine researchers studying the sex chromosomes have discovered genes that, at least in mice, skew that assumed ratio to favor one se
Can the size of an ampliconic gene influence sex ratio (in mice)?
Summary
The higher the number of multiple copies of two genes on the X chromosome may bias the sex ratio towards female offspring and vice versa for males.
Comment
In a complex study from a US university, researchers have identified 2 genes on the X-chromosome that may exist in multiple copies. Called ampliconic genes, these genes called Six and Sixl1, are copies of an autosomal gene (Sycp3) that is found in the nucleus that is associated with the meiotic complex. Six and Sixl1 are however not nuclear but cytoplasmic and are only expressed in the post meiotic testicular germ cell (round cell and later). If you remove these genes using CRIPSR, there are fewer sperm cells and these are abnormal with elongated heads. The males are infertile. So, it appears that these two genes on the X chromosome that are modified copies of a different meiotic gene and only expressed in the testis before meiosis but can influence the sperm cell (that may or may not have an X-chromosome) and control male fertility by controlling down-stream sperm development. If the gene is absent or nonfunctional, the male is infertile. Interestingly, if the round cell is injected into mouse oocytes, the gender bias is not apparent and the cells are viable proving that the effect of these gene products is after the meiotic division.| OK but here is the twist. These genes can have multiple copies. Depending on how many copies of the gene exist, the sex ratio of the embryos can vary. When there are fewer copies, the sex ratio is skewed towards more male embryos and when there are many copies, the sex ratio is skewed towards female. The range is between 40% to 60% so it is not an absolute control on the sex ratio but can influence it to some degree. It is argued by the authors that it is a dynamic evolutionary process that continues to evolve but implies that over time there are pressures to generate more copies of such gene allowing for more females to be born and that there are counter measures that bring the sex ratio back to 50:50. How does operate? |The authors argue that there is another reciprocal ampliconic gene on the Y-chromosome called Sly. They suggest that both genes are expressed prior to meiosis and the mRNA is translated as the germ cell divides and the protein products actively compete to regulate other genes that may influence the health of the sperm cell. The target gene is thought to be one that effects sex chromosome silencing via chromatin modifications. They suggest SPIN1 may be one target since it is a chromatin reader and a controller of mRNA stability. So, as the sperm cell develops, depending on whether it contains a X or a Y chromosome, the degree of competition between Sixl1 and Sly will influence the health of the cell. An abundance of Sixl1 over SLY will bias towards healthier sperm cells with an X-chromosome and vice versa, an abundance of Sly products over Sixl1 will bias towards healthier cells with a Y-chromosome. Cells containing the alternative sex chromosome will be malformed (elongated) to fail to develop. Overall, if the amount of duplication of Sixl1 and SLY are similar, the sex ratio will be even. |Does this matter to IVF clinics and their clients. Well no, not really. Sixl1 does not exist in humans in the same form as in the mouse but it may well exist in some other form. The process of ampliconic gene formation currently is not understood. There are couples who present with a family history of children of one gender and may desire to complete their family with the last child of the opposite gender. Where permitted by law, this can be achieved by PGT-A testing of the embryos. Clinics may use this theory to explain to the couple why there may be gender bias (maybe by a genetic counsellor). In time, it may have some impact on understanding the origins of oligospermia or teratospermia. Possibly, using ICSI to achieve a pregnancy from samples with severe oligospermia/teratospermia where the few sperm are abnormal, may propagate genetic conditions such as something similar to what has been described here. Until such conditions can be diagnosed, it is only a possible explanation. Clinics though need to be aware of the genetic foundations of male infertility and this study allows one to visualise how it may work. | [This is a draft commentary pending the authors review]. |
Title
The Concept of Growth Hormone Deficiency Affecting Clinical Prognosis in IVF
Summary
The idea that the age-related reduction in fertility prognosis is a feature of growth hormone deficiency is supported by our studies showing an elevated binding protein IGFBP-3/IGF-1 ratio...
Comment
THIS IS A COPY OF THE CONCLUSION FROM AN OPEN ACCESS ARTICLE BY J YOVICH eet. al. ON GROWTH HORMONE AND AGE RELATED DECLINE IN FERTILITY.|
From a clinical perspective, this review article makes the case to consider that women requiring assisted reproduction and are classified as poor prognosis, may potentially be considered to have a subclinical degree of AGHD. |In association with the rapidly increasing trend for delaying reproduction beyond age 35 years, GH is being widely researched now as a potential adjuvant for infertility treatment in this group who, studies consistently show, have a poorer prognosis than younger females when relying on autologous oocytes.| The idea that the age-related reduction in fertility prognosis is a feature of GHD is supported by our, yet unpublished, studies showing an elevated binding protein IGFBP-3/IGF-1 ratio and this can be reduced to a normal range (matching younger, good prognosis women) by the administration of GH as an adjuvant.| In studies from different directions arising from its use as an adjuvant for IVF, it is likely that GH will be shown to have major enhancement effects on oocyte competence.| Such studies should reveal major influences in the physiology of folliculogenesis and oocyte maturation. This will not only benefit older women but also younger women who currently have unexplained poor prognosis.| We believe there is sufficient evidence to promote studies in two directions. Firstly, to precisely define the subclinical AGHD condition among women attending fertility clinics and secondly, to explore a more rationalized approach to the clinical use of GH.| We would propose that studies should urgently be undertaken to assess whether IGF-I levels or IGFBP/IGF-I ratio can be a predictor of poor-prognosis. If so, then an RCT is required on naïve IVF cases to determine if GH adjuvant can provide a better chance for pregnancy and live birth in those predicted to have poor-prognosis.| Further studies are also required to determine appropriate and optimal dosage regimens.| Currently most GH adjuvant use is applied concomitantly with the FSH-stimulation phase. However, should the GH exposure begin much earlier, at the initiation of follicle recruitment and early oocyte activation. There is also a pressing need for studies to determine if GH can favorably influence the age-related effects on aneuploidy which is a reflection of diminished oocyte competency.|
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S-Cryolock is the slimmer version of the original. It is a versatile, simple and efficient vitrification device that is intended for the holding, cryopreservation and storage of oocytes or embryos in liquid nitrogen.
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