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First PGT-A using human in vivo blastocysts recovered by uterine lavage: comparison with matched IVF embryo controls
Uterine lavage offers a nonsurgical, minimally invasive strategy for recovery of embryos from fertile women who do not want or need IVF and who desire PGT, fertility preservation of embryos or reciprocal IVF for lesbian couples. From a research and potential clinical perspective, this technique provides a novel platform for the use of in vivo conceived human embryos as the ultimate benchmark standard for future and current ART methods.
Preimplantation Genetic Testing for Aneuploidy. A Review
Relevance- PGT-A has the potential ability to impact in vitro fertilization success rates, and as it is increasingly adopted worldwide, it is crucial that clinicians are aware of the evidence for its continued use.
MicroRNA signature in spermatozoa and seminal plasma of proven fertile men and in testicular tissue of men with obstructive azoospermia
Our results suggest that there is a certain similarity between spermatozoa and seminal plasma for the relative miRNA expression changes with respect to testicular tissue and provide an overview of the miRNAs present in each sample type.
The role of miRNAs in male human reproduction: a systematic review
Our systematic review of descriptive and observational studies shows a consistent relationship between aberrant miRNA expression and infertility. Therefore, it seems reasonable that measuring the expression of particular miRNAs might be useful not only as infertility biomarkers, but also for developing therapeutic strategies.
Efficacy of intrauterine administration of autologous peripheral blood mononuclear cells on the pregnancy outcomes in patients with recurrent implanta
Findings demonstrated that implantation, pregnancy and live birth rate were statistically increased and the miscarriage rate was significantly decreased in the PBMC-treated group than that non-treated group. In conclusion, based on the evidence, PBMCs can be an effective therapeutic approach in women with at least three IVF/ET failure and lacking initial inflammation that is essential for implantation.
Can We Prepare IVF Culture Media Two Days Before Ovum Pick up Without Affecting Embryological Parameters? A Retrospective Case-Matched Study
Conclusion: Our data support the vision that culture media can be prepared 24 hr in advance compared to routine protocols without affecting embryological outcomes.
How common is real repeated implantation failure? An indirect estimate of the prevalence
Our analyses show that estimated prevalence of RIF is 15%. The frequently used definition of RIF based on three failed attempts (but not two) in good-prognosis couples seems justified. Physicians, however, should bear in mind that couples may be inappropriately labelled with this condition in one out of four cases.
The intriguing study published in this issue of HR by Munné and colleagues “First PGT-A using in vivo blastocysts recovered by uterine lavage: comparison with matched IVF embryo controls” (Munné et al., 2019) proposes an innovative minimally invasive procedure to recover in vivo conceived embryos for preimplantation genetic testing for aneuploidy (PGT-A).
The authors of this contribution report a proof-of-concept study on genetic screening of embryos obtained after uterine flushing. The embryos were collected from the uterus of women that were treated with ovarian hyperstimulation and intrauterine insemination. Since uterine flushing does not require oocyte collection, in vitro fertilization and embryo culture, this technique could theoretically be less invasive and more cost-effective....
Are in vivo human embryos better than in vitro embryos?
Summary
It would appear that by and large they are similar in quality and genetics with in vivo having better morphology.
Comment
There have been a few previous attempts to collect human embryos by uterine lavage but the open access article by a US and Mexican groups is the first large scale examination of this most important of topics. |
There are two parts to this paper. The first is the demonstration of the efficiency of the uterine lavage process and its suitability as a future clinical procedure. The second was the comparison in embryo quality and genetic quality between the in vivo process to embryos fertilized and cultured in vitro. Just how good is the in vitro environment? |
Firstly, the lavage technique. The process still utilized COS (controlled ovarian stimulation) to generate sufficient oocytes to raise the odds of embryo recovery. All cases involved IUI insemination with either healthy partners sperm or donor sperm followed by uterine lavage between 96 and 144 hours post IUI insemination. |
It appears that the better recovery was after 115 hours post IUI and that in a subgroup that had both lavage and a subsequent IVF cycles, significantly more embryos were recovered after IVF than by the lavage technique. One of the risks of using COS and in vivo culture, like GIFT in the past, is the possibility of uncontrolled implantations. This can occur if not all the embryos are recovered, some may have already implanted, some may not have arrived in the uterus or some may have been flushed back into the fallopian tubes. |
Except for one short session when a number of pregnancies occurred, in the other sessions, the authors reported very few pregnancies following the lavage process. None were ectopic and most resolved naturally while a few required interventions. It appears that the technique has some role to play in the risk of post lavage pregnancies and that in good hands is quite low. Still any pregnancy termination or loss is a difficult situation for many couples. There may be some additional risk in the hands of inexperienced operators and clients would need to be aware of this. There was no OHSS since all received GnRH agonists post hCG. So, in summary, blastocysts and slower embryos were recovered in 46% of cycles or about half of cycles. |
The real value of the technique is that it means some clients may be able to have their embryos tested for a genetic familiar risk without having to have the egg recovery with its associated high costs. The authors specifically mention its suitability for same sex couples who are by and large fertile. It is not outside the realms of possibility that in some countries, gender selection may also be a reason for using this technique? |
The real question this paper asked and answers is whether the in vitro culture system is similar to the natural system? IVF has largely developed in the absence of a natural benchmark. In many animal models, the in vivo embryos have been by and large better that any cultured in vitro. So, it was refreshing and very pleasing that the authors reported that the in vitro generated embryos were close to their in vivo cousins. They had similar rates of euploidy and aneuploidy, complex abnormal rates and high-mosaicism rates. In a funny way, it is quite remarkable that that for the first time it can be shown that the IVF in vitro culture systems have performed so well. Long considered the Achilles heel of IVF, it shows how far the industry has come in the last 40 or so years. |
Since both cohorts are derived from a COS forced follicle development, maybe the similarity in the results reflect the stimulation than anything else. In vivo blastocysts were on average of better quality so there maybe some more work to do in taking culture systems to a new level. Will the stability of time-lapse culture systems generate better grades of blastocysts? Now there is a benchmark to aim for, it will be interesting to see how the culture systems moves forward. |
IVF Training - Questions relating to mailout links -
Open Challenge and complete Questions
Question
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Options
What was the recovery rate where embryos were recovered after lavarge
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At the time of cryopreservation, what proportion of embryos were blastocysts
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In relation to a control IVF group, the quality of the blastocyts recovered was.....
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In relation to a control IVF group, the euplidy rate of the blastocyts recovered after lavarge was....
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In what percentage of cycles were pregnancy recorded from embryos that had not been recovered by the lavarge process.
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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.
Source
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