No adverse fetal outcomes with prolonged storage of frozen embryos

‘It’s very reassuring that this paper has not found any adverse outcomes from babies born from embryo transfers that have been frozen for longer.’
 
That is CREI fertility sub-specialist and gynaecologist Dr Raelia Lew from Melbourne IVF.
 
She is talking to newsGP about new research, published in Human Reproduction, which found length of storage of vitrified embryos does not influence neonatal outcomes.
 
The retrospective study was performed among 24,698 patients in China, with the first vitrified embryo transfer following a freeze-all strategy during the period of January 2011 to December 2017.
 
While there have been concerns that prolonged vitrification could lead to poorer outcomes for embryos, Dr Lew said the results fit with her belief that the process is safe, regardless of length of storage time.
 
‘This paper was very reassuring for women who have IVF babies that there was no evidence of any adverse fetal outcomes ­[and] no adverse obstetric or neonatal outcomes from babies born that have been frozen for longer,’ she said.
 
‘It confirmed what I thought.’
 
While the study found no adverse events associated with embryo freezing, it did find length of storage time of embryos might affect the chances of women becoming pregnant and having a live birth.
 
The researchers found a 40% implantation rate for women who had vitrified embryos stored for up to three months. That figure dropped to 26% for women whose embryos were stored for 12–24 months.
 
This means that 47 out every women who had embryos stored for less than three months would achieve a live birth. Only 34 out of every 100 women who had embryos stored for 12–24 months would achieve a live birth.
 
However, Dr Lew said those results do not reflect what she sees in her practice, nor what she believes is happening elsewhere in Australia.
 
‘It’s certainly not something that we’ve seen here, that there’s been reduced outcomes over time for how long embryos have been frozen,’ she said.
 
Dr John Stevens, Director of Assisted Reproductive Technology (ART) services at Melbourne IVF, told newsGP he agrees with Dr Lew’s views.
 
‘I’ve had a look at Melbourne IVF live birth rates from our vitrified frozen embryo transfers and it does not appear that we see the same decrease in success rates based on storage time,’ he said.


Fertility expert Dr Raelia Lew says this research confirms her belief that prolonged storage of frozen embryos is safe.

Dr Lew said there are a number of factors that may lead to such discrepancies between the study’s results and what she sees happening in Australia.
 
Firstly, she said, 90% of the embryos used in the study were cleavage stage and most involved transfers involved double embryos. In Australia, Dr Lew said embryo vitrification usually use blastocysts and single-embryo transfers instead.
 
According to Dr Lew, cleavage-stage embryos are those on day two or three of development that consist of somewhere between three and eight cells.
 
Blastocysts, on the other hand, are frozen on day five or six of development and consist of somewhere between 150–200 pluripotent stem cells.
 
‘So if a blastocyst loses some of those cells in the freeze and the warm, it’s got a much better potential to rally [than a cleavage-stage embryo], because it can replace those cells,’ she said.
 
‘It’s a very different stage of development.’
 
Dr Lew is also concerned differences in laboratory conditions may have affected outcomes.
 
‘The thing that raised a bit of alarm bells for me was that they said the changes in the lab had been minimal from 2011–17, which is weird because there’s so much that’s changed in IVF in that space,’ Dr Lew said.
 
‘The conditions in the lab studied was very different to the conditions in our lab in Australia.’
 
Also, the patients in the study froze their embryos and then did not have a transfer for around two years.
 
‘That’s not the norm,’ she said.
 
From a medical perspective, Dr Lew said she could not see how length of storage could affect ensuing chances of pregnancy and live birth.
 
‘I would think from first principles they shouldn’t deteriorate because the cells are metabolically arrested, and really the danger points of the embryo being damaged are on the way down to the freeze point, and on the way up, not necessarily the length of time they’re in liquid nitrogen,’ she said.
 
Dr Gill Lockwood, the Medical Director at Care Fertility Tamworth in England, shares Dr Lew’s view.
 
‘Couples who have embryos cryopreserved because they are happily expecting the birth of their first successful embryo transfer should be reassured that there is a good prospect of a “frozen sibling” arriving even if there is a delay of a year or more,’ she said.
 
‘The advantage for women over 35 of storing supernumerary embryos, which are literally “frozen in time” at the age the woman was when the eggs were collected, far outweighs any possible reduction in success rates from extended storage.’
 
Instead of length of storage being important in determining viability of future pregnancies, Dr Lew said the ages of the woman at egg collection and at the creation of the embryo are more significant factors.
 
While she disagreed with the finding that embryo storage length may affect chances of pregnancy, Dr Lew said the finding that vitrification is safe is a worthy takeaway message.
 
‘From a clinical perspective, it’s very reassuring that this paper has not found any adverse outcomes from babies born from embryo transfers remote from the egg collection by two years, and that there’s been no difference in the health of the children ,’ she said.
 
‘Because, at the end of the day, that’s really my biggest priority: to help people have healthy babies.’
 
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