The Future of Cryopreservation in Assisted Reproductive Technologies

Abstract

Societal changes and the increasing desire and opportunity to preserve fertility have increased the demand for effective assisted reproductive technologies (ART) and have increased the range of scenarios in which ART is now used. In recent years, the "freeze-all" strategy of cryopreserving all oocytes or good quality embryos produced in an IVF cycle to transfer later-at a time that is more appropriate for reasons of medical need, efficacy, or desirability-has emerged as an accepted and valuable alternative to fresh embryo transfer. Indeed, improvements in cryopreservation techniques (vitrification) and the development of more efficient ovarian stimulation protocols have facilitated a dramatic increase in the practice of elective frozen embryo transfer (eFET). Alongside these advances, debate continues about whether eFET should be a standard treatment option available to the whole IVF population or if it is important to identify patient subgroups who are most likely to benefit from such an approach. Achieving successful outcomes in ART, whether by fresh or frozen embryo transfer, is influenced by a wide range of factors. As well as the efficiency of IVF and embryo transfer protocols and techniques, factors affecting implantation include maternal aging, sperm quality, the vaginal and endometrial microbiome, and peri-implantation levels of serum progesterone. The safety of eFET, both during ART cycles and on longer-term obstetric and neonatal outcomes, is also an important consideration. In this review, we explore the benefits and risks of freeze-all strategies in different scenarios. We review available evidence on the outcomes achieved with elective cryopreservation strategies and practices and how these compare with more traditional IVF cycles with fresh embryo transfers, both in the general IVF population and in subgroups of special interest. In addition, we consider how to optimize and individualize "freeze-all" procedures to achieve successful reproductive outcomes.

Individualized follitropin delta dosing reduces OHSS risk in Japanese IVF/ICSI patients: a randomized controlled trial

“…The freeze-all strategy, i.e. elective freezing of embryos/blastocysts and transfer in subsequent cycles, has been shown to reduce the risk of OHSS (Bosch et al, 2020;Roque et al, 2019). Although fresh cycles are still predominantly used in many countries, the number of freeze-all cycles has increased substantially in Japan since 2007 and is now used in about 45% of all COS for in vitro fertilisation (IVF) / intracytoplasmic sperm injection (ICSI) cycles (EIM et al, 2020;Ishihara et al, 2020b).…”

“…Although fresh cycles are still predominantly used in many countries, the number of freeze-all cycles has increased substantially in Japan since 2007 and is now used in about 45% of all COS for in vitro fertilisation (IVF) / intracytoplasmic sperm injection (ICSI) cycles (EIM et al, 2020;Ishihara et al, 2020b). While pregnancy rates are not compromised, the main objections to the freeze-all strategy are the extended time to pregnancy and the additional patient burden and/or costs (Bosch et al, 2020;Roque et al, 2019). When shorter time to pregnancy and therefore fresh cycle transfer is implemented, COS protocols based on dosing regimens with reduced OHSS risk may be of preference as long as the probability of pregnancy and live birth is not decreased.…”

Preimplantation Genetic Testing for Monogenic Disorders

“…Vitrification has been shown to be superior to slow-freezing in terms of survival rate for both cleavage-stage embryos and blastocysts [37]. The evidence overall indicates that clinical outcomes after elective frozen embryo transfer are equivalent with the outcome after fresh embryo transfer for the general population (normo-ovulatory patients) and prove even better for specific subgroups such as patients at high risk of ovarian hyperstimulation syndrome (OHSS) [38].…”

Impact of Maturation and Vitrification Time of Human GV Oocytes on the Metaphase Plate Configuration

“…In the recent years, many children were born after OV [ 30 , 31 , 32 , 33 ], IVM [ 34 , 35 , 36 , 37 , 38 , 39 ], or a combination of both [ 40 , 41 ]. However, this combination remains controversial [ 42 , 43 ].…”