Dr Anupa Nandi
Does the duration of embryo freezing affect your chances of getting pregnant?
A recent study tried to answer this question and found that embryos frozen by vitrification method gives lower chances of getting pregnant if stored for longer duration.
What does it mean to you and your treatment? How do you interpret the study?
This blog aims to look into the details of this study and help you understand its significance.
Why freeze embryos?
The first clinical pregnancy with frozen embryo was reported in 1983. Since then freezing embryos has been widely used in IVF treatment.
It gives patient the opportunity to have multiple attempts of embryo transfer from a single ovarian stimulation and increases the cumulative chances of getting pregnant.
In selected cases, it reduces the risk of ovarian hysperstimulation syndrome, by delaying the transfer.
It allows patients to undergo pre-implantation genetic testing of the embryos.
Egg/Embryo freezing is also considered for patients undergoing cancer treatment and for those who would like to delay pregnancy for various social reasons.
How do you freeze embryos?
One of the challenge of embryo freezing is the water within the cells of the embryo. This water forms ice crystals as the temperature of the embryo is lowered, which can damage the cells. To overcome this problem, labs use various cryoprotectants.
Slow freeze: The traditional way of freezing embryos is slow freezing technique. In this process, the temperature of the embryo is decreased slowly in a controlled rate. However, it is more time consuming. It uses relatively low levels of cryoprotectants, which may be insufficient to completely avoid ice crystal formation.
Vitrification: In this method, embryos are cooled very fast with higher levels of cryoprotectant, where the cells are turned into glass like state, without forming ice crystals. This way it avoids damage to the cells. It is not as time consuming as slow freezing. Embryos have a better survival rate with this technique. Hence it is becoming more popular.
However, there is a concern about the potential risk of toxic damage to the embryos due to higher level of cryoprotectant used in this technique.
What is this study all about?
This study aims to evaluate whether prolonged storage period after embryo freezing by vitrification affects embryo survival and pregnancy and neonatal outcomes.
What kind of study is this?
This is a retrospective study. That means, looking back at the outcomes for those who already had their treatment. Duration of study was January 2011 till December 2017.
This is a single centre study, which means all patients had their treatment in the same hospital. It was conducted in the Shanghai Ninth People’s Hospital (Shanghai, China)
Who were included in the study?
Women, who had their first frozen embryo transfer treatment after ‘freeze all’ strategy for their IVF cycle, were included in the study.
Embryos were frozen on day 3 if they were of top quality (Grade I and II as per Cummin’s criteria) and the remaining embryos of poorer quality were cultured till day 5 and frozen if better than 3CC (as per Gardner criteria).
How was the study conducted?
Women with regular menstrual cycle underwent natural cycle frozen embryo transfer treatment and those with irregular menstrual cycle had hormone therapy frozen embryo transfer treatment.
Patients were divided into four groups according to the storage times of the embryo and the outcome of their treatment were compared.
Group 1: 0-3 months
Group 2: 3-6 months
Group3: 6-12 months
Group 4: 12 – 24 months
What are the findings?
A total of 24698 patients were analysed. They found:
Lower implantation rate in the longer storage group (25.8% for group 4 compared to 39.8% for group 1)
Lower clinical pregnancy rate in the longer storage group (25.8% in group 4 compared to 55.6% in group 1)
Lower live birth rate in the longer storage group (25.8% in the group 4 compared to 47% in group 1)
The rate of miscarriage, ectopic pregnancy also increased with longer periods of storage, but did not reach statistical significance (meaning that the difference could be by chance and the authors cannot be certain that there is a difference)
There were no differences in the neonatal outcomes between the groups.
What are the strong points of this study?
This is an important study as it includes large number of patients (almost 25000 patients).
It tried to look at an important aspect of the most commonly used freezing method. It offers insight into the safety of using frozen embryos.
What are the drawbacks of this study?
This is a retrospective study, which is not considered high quality evidence.
The study period is 7 seven years during which much progress has been made in the virtification techniques.
In this study, the good embryos were frozen on day 3 and 90% of the patients had day 3 transfer. The practice widely used now is freezing and transferring blastocysts (day 5/6 embryos) rather than day 3. Hence this study finding cannot be applied for blastocysts, which most IVF units use.
Only 566 patients were in the Group 4, whereas the number of patients in Group 1 was >11000. If group 4 had more patients, the outcome could have been different.
More women in the group 4 had endometriosis and uterine factors compared to Group 1, which could have lowered their success.
This is a single centre study – results can be affected by the practice of that particular hospital. Multi-centre trials are considered as better quality of evidence.
What does this study mean to my treatment and me?
The most important finding of this study is that there was no adverse effect on the neonatal outcome. So you can be reassured that vitrification is safe.
If you have surplus embryos, which have been frozen, there is a good chance of having a baby.
Once embryos are frozen, they retain the quality as per the age of the woman when the eggs were collected. So you get the benefit of having embryos created with younger eggs when you do frozen embryo transfer at a later stage. This outweighs any possible reduction in success from prolonged storage.
Written by: Dr Anupa Nandi