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Early Autism Spectrum Disorders in Children Born to Fertile, Subfertile, and ART-Treated Women
Conclusion. Compared to children born to Fertile women, children born to ART, ICSI, or IVF, or Subfertile women are not at increased risk of receiving an ASD diagnosis.
Impact of male factor infertility on offspring health and development
Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. ..Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis: the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions.....
Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy
By applying an appropriate threshold for mosaicism, both the positive predictive value (PPV) and specificity for niPGT-A were much higher than TE-biopsy PGT-A. Furthermore, the concordance rates for both embryo ploidy and chromosome copy numbers were higher for niPGT-A than TE-biopsy PGT-A. These results suggest that niPGT-A is less prone to errors associated with embryo mosaicism and is more reliable than TE-biopsy PGT-A.
Worldwide live births following the transfer of chromosomally “Abnormal” embryos after PGT/A: results of a worldwide web-based survey
Conclusions: The transfers of “abnormal” embryos by PGT-A offered robust pregnancy and live birth chances with low miscarriage rates. These data further strengthen the argument that PGT-A cannot reliably determine which embryos should or should not be transferred and leads to disposal of many normal embryos with excellent pregnancy potential.
Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in
Conclusions. Among women undergoing first FET with high-quality embryo transfer, low BMI has limited impact on pregnancy and live birth rates. On the contrary, obesity was associated with worse IVF outcomes. Our findings further highlighted that endometrial receptivity played an important role in the poor reproductive outcomes of women with abnormal weight status.
The present crisis in male reproductive health: an urgent need for a political, social, and research roadmap
Summary. This paper has presented evidence that there is a present and growing global crisis in male reproductive health. Numerous scientific publications report that chronic illness, disease, and premature death in men are linked to their reproductive health. Further, emerging data demonstrate that the wellness of the female partner, their offspring, and grand‐::offspring all have connections to partner/father reproductive health. These mal
Can trophectoderm RNA analysis predict human blastocyst competency?
In this pilot study, we report that differential gene expression in human trophectoderm biopsies assayed by an ultra-sensitive next generation RNA sequencing strategy could predict blastocyst implantation competence....Following RNA sequencing, a total of 47 transcripts were found to be significantly differentially expressed between the trophectoderm cells from successfully implanted (competent) versus unsuccessful (incompetent) blastocysts.
Controlled ovarian hyperstimulation (COH) parameters associated with euploidy rates in donor oocytes
The study provides the first suggestion that patient stimulation parameters can affect the incidence of euploidy in embryos generated through the use of standard assisted reproductive techniques. The study is limited by its retrospective approach and because the aCGH analysis used is less sensitive than more recent NGS technology. Further, it provides a suggestion that the use of hMG is beneficial for obtaining euploid embryos.
Supraphysiological serum oestradiol negatively affects birthweight in cryopreserved embryo transfers: a retrospective cohort study
Conclusions: Peak serum oestradiol during COS is negatively associated with birthweight. This model proposes a novel concept as well as new evidence that the effect on birthweight is due to the primary influence of a high oestradiol concentration on oocytes during COS.
Can non-invasive testing of culture media provide an alternative to biopsy
Summary
New work suggests that niPGT-A testing may prove as good or better than PGT-A
Comment
niPGT-A or non-invasive PGT-A may be possible from a proof of concept publication by Mousa I. Shamonki et.al. from a USA clinic. Fifty seven embryos from 7 couples having PGT-A were transferred into individual culture drops and after 2 days were biopsied. The used culture media was then hybridised for 2 hours and amazingly, in 55 cases, DNA was detected. Six samples with the highest concentration of DNA underwent array comparative genomic hybridization (aCGH) and the results agreed with the PGT-A diagnosis.
Title
Can trophectoderm RNA analysis predict human blastocyst competency?
Summary
In this very small study on 8 embryos, it would appear RNA analysis be the new embryo test.
Comment
Based on a small collaborative project between the Genesis IVF clinic (Athens, Greece) and the University of Leeds (UK) the study sampled the RNA transcripts from biopsies of eight euploid blastocysts transferred to five clients. Three became pregnant [four embryos] and two were not pregnant [four embryos]. The team used a quite sophisticated RNA analysis process to explore which RNA transcripts differed in the material biopsied from the blastocysts of competent (CE- ie implanted) and non competent (NCE-failed to implant) embryos. Among the forty-seven transcripts reported in the analysis, five (HSD17B1, CYP11A1, DHCR7, BAK1 and KHDC1P1) were particularly interesting.|Most clinical embryologists would have limited knowledge on the technology on RNA analysis (including the commentator!) however, the key points of the report are that firstly, the new technology is able to process tiny amounts of RNA from trophectoderm biopsy material and assess which transcripts are up or down regulated and secondly the physiological functions linked to these transcripts imply a role for communication between the incoming blastocysts and the waiting endometrium.|The study reported that HSD17B1, CYP11A1 and DHCR7 transcripts associated with endocrine activity were up-regulated in CE embryos, while BAK1 and KHDC1P1, associated with apoptosis were up-regulated in NCE embryos.|Being linked to cell demise, the latter may have been anticipated. However, the activity of the up-regulated transcripts in the embryos that implanted and gave rise to viable pregnancies gave a fascinating insight the earliest stages of embryo-uterine interactions. For the first time, the dynamic sense of what an embryo needs to do to implant and how the endometrium may respond becomes more relevant to embryologists.|Reading this rather complicated paper (because of the technology) generates a range of ideas on how such information may be used in future. Embryo selection for uterine transfer is the most obvious, but other lines may include improvements that help minimise embryo death and maximise their chances of implantation and a greater, understanding linking early transcription to later fetal and child health. A better understanding of the oocyte and sperm biology leading to viable embryos, including their epigenetics is also possible.|Some of these ideas may seem a little futuristic. After all, the report is based on just eight embryos and further work is certainly needed to confirm the findings. By analysis of the culture media embryos were incubated in, avoiding biopsy altogether may also be possible with this type of technology. Regardless of the future, embryologists would do well to take more than a passing interest in this paper.|
Title
Does the Oestradiol concentration during the COH cycle effect the birthweight of children born after FET.?
Summary
A paper by Zhang, et.al. suggests that as the E2 concentration rises in the stimulation cycle, the birthweight of any children born from the cycle will decrease.
Comment
In this paper from a Chinese ART clinic, the authors looked at the birthweight of children born after FET transfers where all the embryos were frozen either due to a freeze-all or a failed transfer scenario. They only looked at single births with no other complications which were about 35% of all transfers in the study period. All embryos were vitrified and 80% were frozen and transferred as cleavage stage embryos. 70% were generated by IVF and 30% by ICSI. In all, 431 cycles were examined.|The authors initially identified female BMI, maximum E2 at hCG injection (E2max) and the gender of the babies having significant associations with the birthweight. Subsequent multivariate analysis confirmed E2max and gender were inversely linked to birthweight. They reported that the inverse link was primarily focused on the women with the lowest E2max. Gender failed to remain associated even though there remained suggestion the male embryos may have been disproportionately influenced by E2max of the mother at hCG.|In other words, the study implies that as the E2max increased with increased follicle recruitment, the birthweight of babies born in a separate FET cycle was reduced. The highest birthweight was recorded to women with the lowest E2max. This effect was not affected by an endometrium under the influence of high E2 during the stimulation cycle and transfer as has been the contention in many other studies.|In reality the birthweight only fell from 3487 gm in the first E2max quartile to 3373 gms in the 4th quartile. It was not clear whether the FET was conducted in a natural or managed cycle.|This paper needs to be seen in the context that in general, birthweights are higher in FET cycles that those reported for stimulation cycles and as such a lower birthweight may be seen as a balancing outcome. The lower E2max cycles may well have been derived from cases with transfer issues while the cycles with higher E2max may have been derived from freeze-all, high response cycles and may lead to an unspecified patient effect. Not-withstanding these comments, the authors point out that their data supports several publications reporting an association between COH cycle E2max and subsequent lower birthweights. Thus, some suggestions that it may be better to freeze all embryos and only transfer embryos in a more natural uterine environment still could fail to resolve the issues of birthweight if there remains a legacy impact on the oocytes and subsequent embryos of exposure to elevated E2 associated with COH.|IF there are residual effects of the ovarian environment on the developing fetus, then IVF clinics need to be aware of this and seek to minimise these by tying to keep ovarian stimulation to as low a level as appropriate. Clinics may also need to keep a link to the ovarian data in the cryostorage profile to ensure clients can be informed of any risks.|Indeed, if future studies confirm such legacies, then the issues of ART embryos being different to naturally conceived embryos will remain|
IVF Training - Questions relating to mailout links -
Open Challenge and complete Questions
Question
Type
Options
In this study, how many RNA Transcripts differed between competent embryos (produced a pregnancy) and non-competent embryos (did not produce a pregnancy).
1
5
In This Study, How Many RNA Transcripts were down-regulated in non-competent embryos (Did Not Produce A Pregnancy).
1
5
In this study, how many RNA transcripts were up-regulated in non-competent embryos (Did Not Produce A Pregnancy).
1
5
In this study, many of the transcripts that were down-regulated in non-competent have been linked to steroid activity
1
2
In this study, some of the transcripts that were up-regulated in non-competent have been linked to apoptosis.
1
2
Which of the following RNA transcripts were up-regulated in competent embryos and down-regulated in non-competent embryos
2
5
Which of the following RNA transcripts were up-regulated in non competent embryos and down-regulated in competent embryos
2
5
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