Reproductive Medicine & Preimplantation Genetic Diagnosis (PGD)
Conditions for PGS: a good EGP, a good vitrification protocol, standards of embryo-classification
It is proclaimed that PGS has a positive impact on IVF success in cases such as advanced maternal age (AMA), recurrent implantation failure (RIF) or recurrent miscarriage (RM). However, solid data are still missing.
The problem of contradictions of different investigations lies not only in the heterogeneity of study populations but also reflect the short follow-up with often low statistical power and lack of control for important confounders, such as cause of subfertility and parity as well as neglecting patients’ life-style, personal anamnesis and hereditary risks.
To begin discussing the “New era” of PGD with all the new fancy technologies evolving, we should touch base and start addressing simple but crucial questions before giving false hope to patients.
Next to this: PGS on polar body, day 3 or day 5? Interestingly, there is a new trend of polar body biopsy observable. Is this do to the fact that many labs are not able or willing to opt for blastocyst culture? If so, why even start discussing PGS if labs are still working under suboptimal conditions? And for those labs, which are performing blastocyst culture, what is their Expected Gametes Performance (EGP) and do they perform IMSI? If a lab cannot specify its individual EGP based on its used stimulation protocol and culture system, it should not start discussing PGS.
And if a lab has its individual EGP also reflected in high success rates of establishing viable single pregnancies after single embryo transfer: how do they classify a viable embryo and how many of those are eligible for biopsy?
What does EGP mean? We believe that urgent action is needed as to the current grouping of the women in so-called responder-groups (Low / Poor, Normal, High). The reason: An accurate and uniform definition of these "responder"- groups and a holistic view of the different components that may influence a fertility treatment are still missing! Typically, the responder-groups reflect the expected number of oocytes for a specific age group after hormonal stimulation and egg retrieval. Sperm quality, fertilization rate and embryo developmental potential have not been taken into account here. For us it is therefore clear that it is not sufficient to determine the number of oocytes in order to provide the couples with meaningful predictions regarding the possible success of the treatment. What matters is to view together female and male factors and give a prognosis based on blastocyst outcome. The EGP standard defines blastocyst outcome as a common denominator. This is due to the interaction of parental factors during the first five days of embryonic development. The onset of the embryonic genome that only takes place between the 2nd and the 3rd day of embryonic development brings about the influence of paternal factors. It is quite common in fertility treatment that women being classified as "Low / Poor Responder" can, nonetheless, achieve a good blastocyst outcome. It is therefore not the number of oocytes retrieved that matters, but the blastocyst outcome that should be taken into consideration in order to predict individual success rates.
Additionally, is the lab able to freeze surplus embryos, also those which seem to be arrested in development or show slow growth? Because such embryos can give viable pregnancies if managed properly. However, such embryos might not be suitable for biopsy. In cases of AMA, most embryos are rather slow growing or not good for a biopsy. Is RIF maybe due to the fact, that inferior lab conditions are present (day 2/3 transfer), or other factors such as sperm-factor, suboptimal endometrium, allergy on culture media to name but a few. IS RM next to possible aneuploidy of embryos, due to e.g. suboptimal hormonal supplementation? How are embryos classified? According to time-lapse analysis? And if, why? Would someone choose let`s say a 2CC blastocyst (it could also be a early blastocyst) with good time-lapse classification over a 4 AA blastocyst which does not fulfil published criteria for embryo transfer (ET)? And who would biopsy a 2CC (or early blastocyst)? Would both be transferred with the 4AA being biopsied – well, then a cryo-ET would be needed. Is the lab willing and able to freeze the other 2 CC (or early blastocyst) which fulfils time-lapse criteria; would it discard it because being classified as non-viable or disregarded as a blastocyst at all; or would it keep the embryo in culture until day 6 and then see what happens?
What is the implantation rate of such embryos? Would a single ET be better instead of transferring both? Would the second embryo negatively influence implantation? And which one would negatively influence the others potential, if it exists?