Conference Coverage
A similar shift to fewer embryos transferred at a time appeared in the exclusively European registry with data derived from 33 countries that reported complete or partial data to the European IVF Monitoring Program, a project organized by ESHRE. The prevalence of triplet or greater deliveries from in vitro pregnancies fell in Europe from about 4% in 1999 to less than 1% in 2011. By 2011, roughly 28% of IVF or sperm-injected pregnancies involved placement of two embryos, and about 57% involved a single embryo, reported Dr. Markus S. Kupka, an ob.gyn. and reproductive medicine specialist who practices in Hamburg, Germany. Frozen embryos involved 31% of transfers in 2011 in Europe. European data for 2010 were included in the worldwide tallies reported by Dr. Adamson.
Vitrification’s safety
Despite growing use, some questions remain about vitrification’s impact on children, although the concern has not been strong enough to dim enthusiasm.
The most striking safety signal is a consistent, 50% increased rate of babies born following vitrification who are large for gestational age. Dr. Pinborg also cited a possibly increased rate of maternal preeclampsia.
"It’s only a 50% increased risk for large for gestational age with frozen embryo transfer. We should not pay too much attention to this, but it reminds us that when we freeze, it may have an effect on the children" Dr. Pinborg said in an interview.
"We can’t say that vitrified embryos do better than after fresh embryo transfer, but they have an altered risk profile." Frozen embryos have a reduced risk for preterm birth and small for gestational age, compared with fresh embryo transfers, but an increased risk of large for gestational age (LGA). "And the risk is small," stressed Dr. Pinborg. "When you stimulate ovulation, you harvest 10-fold as many oocytes than occur with a normal cycle, and the woman’s estrogen and progesterone levels are very high. So, you could ask: Why should we ever place an embryo during an oocyte harvesting cycle? We did that because we had poor freezing methods, but with vitrification we have a way to use preserved embryos and there is better cycle synchronization."
In addition, seeing increased rates of LGA babies following frozen embryo transfer may result from unadjusted confounding by, for example, the embryo’s age when cryopreservation occurred that could influence epigenetic changes that happen early after fertilization or maternal disorders such as polycystic ovary syndrome, Dr. Paulson said.
Safety aside, vitrification is very effective for assisted reproduction because any decrement in viability is counterbalanced by the advantage of placing embryos squarely during a natural cycle, these experts said.
Vitrification and oocytes
Vitrification does not stop with embryos. The impact it has had on oocyte banking has arguably been even greater.
Creating multiple embryos at one time is problematic, especially in the United States, Dr. Paulson said. "The obvious thing we should do is freeze oocytes. This approach would create another significant advantage. Routine vitrification at the oocyte stage rather than after embryos are made "would make donor oocytes a reality. You would be able to buy frozen oocytes the same way as sperm. Results from good randomized, controlled trials show that outcomes with cryopreserved oocytes are as good as with fresh oocytes, which was never possible with slow freezing."
"Vitrification created the ability to have oocyte banking. It has been a breakthrough in assisted reproductive technology," said Ana Cobo, Ph.D., director of the cryopreservation laboratory at the IVI Foundation in Valencia, Spain. Cryopreserving oocytes was essentially impossible before vitrification became available, she said in an interview. Studies run by her group showed that the vitrification process has no detectable effect on oocyte viability, embryo viability, or the health of the child. It also made oocyte donation much more feasible by eliminating the need for cycle synchrony between the donor and recipient.
The success rate of in vitro fertilization using a donated oocyte is generally much higher than for an autologous oocyte because "we use a highly selected population of young, healthy women with the best quality oocytes. In assisted reproductive technology, oocyte quality means a lot," Dr. Cobo said.
Dr. Pinborg said that she has received research grants from MSD and Ferring. Dr. Paulson said that he has been a speaker on behalf of Ferring and served on advisory boards for Origio and Cooper Surgical. Dr. Adamson said that he had received honoraria from or consulted for Bayer, Glycotype, and Ziva Medical, that he owns stock in Advanced Reproductive Care, and has received research support from Auxogyn and LabCorp. Dr. Kupka said he had no disclosures. Dr. Cobo had no disclosures.