Initial problems encountered with egg freezing, continued:
Use of cryoprotectants (such as ethylene glycol, glycerol, and dimethylsulfoxide) can prevent ice crystals from forming, but high concentrations are toxic. The balance between protection and toxicity is what led to the development of diverse egg freezing protocols using various types and concentrations of cryoprotectants. Unfortunately, the progression of oocyte freezing was significantly slowed due to inconsistent results and lack of reproducibility in the lab, as well as important concerns about post-thaw oocyte function and safety. By the end of the 1980s, clinical oocyte cryopreservation had been limited to confined to small groups of researchers with little success.
Luckily in 1997, clinical work resumed with a Bologna team reporting up to 80% survival rates for post-thawing oocytes using propanediol as the primary cryoprotectant, as well as viable pregnancies with the use of intracytoplasmic sperm injection (ICSI) for fertilization. Since the late 1990s, continued developments in freezing technologies have resulted in even greater success. Currently both slow freezing and vitrification methods are used to preserve oocytes.
Slow freezing requires declining the temperature of oocytes at a low rate while simultaneously increasing the concentration of cryoprotectants. As the metabolic activity of the oocyte decreases, the concentration of cryoprotectant can be increased in order to prevent ice crystals from forming. Once an oocyte is solidified, it can be exposed to freezing at colder temperatures. Results of a meta-analysis of 26 studies revealed that, compared with using fresh oocytes, eggs thawed after slow-freezing yielded significantly lower rates of fertilization (61.0% vs 76.7%), clinical pregnancy rate per transfer (27.1% vs 68.5%), and live birth per transfer (21.6% vs 32.4%).
Vitrification requires rapid cooling of cells to extremely low temperatures. During vitrification, oocytes are exposed to high concentrations of cryoprotectants as they are rapidly cooled. The rate of cooling reaches up to 20,000°C per minute—so fast that ice doesn’t even have time to form, and a glass-like state can be achieved. Studies suggest that the use of vitrification improves oocyte survival and function compared to the process of slow freezing. A randomized controlled trial comparing frozen/thawed with vitrified/warmed oocytes demonstrated greater oocyte function in the vitrification group, with higher oocyte survival (81% for vitrification/warming vs 67% for slow freezing/thawing); higher rates of fertilization, cleavage, and embryo morphology; as well as higher clinical pregnancy rates (38% for vitrified/warmed vs 13% for frozen/thawed).
In 2013, the Practice Committee of ASRM published a guideline for mature cryopreservation after reviewing the literature on its efficacy and safety. Although data are limited, studies comparing outcomes of IVF using cryopreserved versus fresh oocytes provide evidence that previously vitrified/thawed eggs result in similar fertilization and pregnancy rates as IVF/ICSI with fresh oocytes. Although, decreased success with oocyte vitrification is seen in women with advanced age, and delivery rates, not unexpectedly, are inversely correlated with maternal age.
This topic will be continue next month!