MUNICH – Vitrification, quick freezing oocytes or embryos with concentrated cyroprotectant and no ice crystal formation to better preserve viability, has been around clinically some 15 years, but now is gathering steam and may have already helped downshift the rate of triplets or higher pregnancies for women undergoing assisted reproduction.
While vitrification of all embryos fertilized in vitro has not proven superior to fresh embryo transfers and may even be inferior for older women whose eggs may not be as forgiving of cryopreservation, its use has grown. It offers the unique advantage over fresh embryos of easier coordination between the in vitro fertilization process and subsequent transfer to the woman who will carry the pregnancy. Vitrification has also made possible true oocyte banking, be it autologous for fertility preservation, or for oocyte donation.
"It is now possible to freeze embryos with a 90% survival rate; with slow freezing there was 50%-60% survival. Now we have a technique that is really good, and it may cause a paradigm shift toward elective freezing," said Dr. Anja Pinborg, a professor of ob.gyn. at Hvidovre (Denmark) Hospital.
Most clinicians still use the approach of placing an embryo during the same cycle when the oocyte was harvested, "the way it’s always been done, but at many clinics now they see that with vitrification they can get pregnancy rates that are similar to or even better than fresh embryo transfer. I think they will go more and more to frozen embryos," Dr. Pinborg said in an interview during the annual meeting of the European Society of Human Reproduction and Embryology.
For now the trend is specific for women younger than 35 years. Safety and efficacy of vitrification for embryos made from oocytes taken from older women has not yet been studied, cautioned Dr. Pinborg and others.
"All we know about cryopreservation is from young women with young oocytes. We don’t know what will happen with oocytes from women who are 41 or 42, who are the types of patients I see," said Dr. Richard J. Paulson, professor of ob.gyn. and chief of the division of reproductive endocrinology and infertility at the University of Southern California and director of USC Fertility in Los Angeles. "Vitrification is so good and embryos come out of it so well that the benefit from improved endometrial receptivity outweighs any change in embryo quality. The timing coordinates so much better."
The biggest impact of vitrification for embryo freezing may be its ability to successfully cryopreserve blastocysts. "We will see many more programs going to 5-day embryos" for implantation, and this will allow preimplantation genetic diagnosis (PGD), predicted Dr. Paulson during an interview at the meeting. "It looks like you can do pretty good trophectoderm biopsy on a vitrified blastocyst, so you can place only chromosomally normal embryos. That will reduce miscarriages." So far, only a handful of groups have presented case reports using this approach, with "very good numbers," he said.
Vitrification’s impact on embryo transfer number
Despite lingering questions about vitrification safety and limited knowledge of its efficacy for embryos begun from oocytes from older women, the most recent worldwide and European data on patterns of assisted reproductive technology show increases in frozen embryo use and decreases in triplets or greater multiples.
Worldwide, frozen embryo transfers grew from 10% of all in vitro fertilization or sperm injection procedures in 1991 to 28% in 2010, the most recent year with worldwide data available. Transfers of one or two embryos grew from 20% of all in vitro procedures done in North America in 1998 to 68% in 2010. In Australia in 2010, the rate of one- or two-embryo transfers stood at 98%.
"The trend is for more frozen transfers, and for reducing multiple rates. I think that is a very positive development," said Dr. David Adamson, a reproductive endocrinologist who practices in Palo Alto, Calif., and presented at the meeting worldwide data collected by the International Committee Monitoring Assisted Reproductive Technologies (ICMART). "The pregnancy rate is continuing to go up, but the multiple rate is dropping. We hope that will continue," he said in an interview.
"There is no question that because vitrification works so much better than slow freezing, clinics have more confidence to put in fewer embryos and still have viability," he said. "We’ll see more frozen embryo transfers in the next few years. When you decrease the number of embryos transferred, you increase the likelihood that you’ll need to follow with a frozen embryo transfer, but now you have higher-quality embryos."