The Historic Development and Incorporation of Four Assisted Reproductive Technologies Shaping Today′s IVF Industry

Abstract

The concept of assisted reproductive technologies was most notably derived from the late 19th Century experiments of Sir Walter Heape who successfully transplanted rabbit embryos. Interestingly, it was not until the late 1940's and 1950's that renewed interests in rabbit embryo transfer and cryobiology occurred. The history behind developing effective procedures can be fascinating, though few could be more accidental than Dr. Chris Polge's discovery of glycerol (1948), from a mislabeled bottle of sugar solutions, being an effective cryoprotective agent for sperm freezing. The purpose of this review paper is to discuss four key scientific breakthrough technologies occurring between 1985 and 1995, which ultimately shaped the future of today's human in vitro fertilization (IVF) industry. More importantly, this paper highlights the foundation of underlying related discoveries and some unique stories involving their development and publication. In the end, this paper emphasizes the value of understanding scientific discovery timetables and the eventual re-discovery in the hands and minds of creative, determined and dedicated scientists, as history tends to repeat itself before its useful application is realized.

Vitrification: Fundamental Principles and Its Application for Cryopreservation of Human Reproductive Cells

“…While a device system may be perfected, or not, within a laboratory, when samples are transferred for warming to another laboratory, reduced outcomes may occur. This interlaboratory variation poses potential liability issues to both programs [45,46]. Even when both programs are competent in their procedures, the relationships between cooling and warming thermodynamics as discussed above can have applied consequences.…”

“…Little to no progress has been made over the past 5 years to correct or understand why overall blastocyst development may be reduced between cryopreserved batches. The inefficiencies of oocyte cryopreservation go beyond the device system used or technical variation and undoubtedly rest on improving our understanding of the membrane integrity and cytoplasmic sensitivity of this large single cell [45,70,71]. There remains a need to understand more about cytosolic factors at the level of gene regulation and energetics of vitrified-warmed oocytes that could be responsible for decreasing their developmental potential [72][73][74].…”

Quality Control Factors Influencing the Successful and Reliable Implementation of Oocyte and Embryo Vitrification

“…In addition, it has been developed without commercial influence and marketing pressure, thus providing the added benefit of substantial cost-savings. In today's IVF industry, which is increasingly reliant of biopsying and vitrifying every fair to excellent quality blastocyst to optimize pregnancy success [58], costs are an increasingly important factor to consider. This is especially true when one realizes that 50-75% of the genetically tested blastocysts will be aneuploidy and destine to be discarded after shortterm storage.…”

Vitrification: the pioneering past to current trends and perspectives of cryopreserving human embryos, gametes and reproductive tissue

“…Under cold room experimental conditions, they successfully vitrified mouse embryos in 1985, 11 as previously reviewed. 12 In Rall's 13 efforts to develop an effective procedure working under room temperature conditions, it was determined that propylene glycol was highly toxic at higher concentrations. However, a third-generation vitrification solution (VS3a, a 6.5 M glycerol solution) produced high survival levels and positive pregnancy outcomes in closed one-step 0.25 mL straws, being comparable to conventional slow freezing of mouse embryos 14 and sheep blastocysts.…”

“…This is particularly true in conjunction with blastocyst biopsy/preimplantation genetic screening (PGS)-single ET applications, 60,61 where over 99% survival can be typically achieved, 62 along with efficient pregnancy success across all age groups following single euploid ET. With embryo and oocyte vitrification being the most significant procedure applied to the assisted reproductive technology (ART) industry since the development of intracytoplasmic sperm injection (ICSI), 12 it is inconceivable why any IVF program would still be applying conventional slow-freeze (SF) procedures. 63 In this era of ART where many different vitrification devices and commercial solutions exist, as well as programs transitioning their cryoinventories from slow frozen to vitrified oocytes and embryos, it is important to realize that 1.0 M sucrose is an effective "universal" warming solution.…”