Expert / 3 November, 2020 / Dr Larisa Corda
IVF since its inception 40 years ago, is not without its controversies, and they don’t come much bigger than the perennial debate of whether fresh or frozen is better, in terms of success and pregnancy outcomes. Depending on who you ask, everyone seems to have a different opinion and what to do. The amount of information out there is seriously confusing, yet it doesn’t seem any closer to being able to explain this reproductive enigma.
Let’s first of all look at what happens in an IVF cycle. No matter whether you’re having a long, short, antagonist, agonist or natural cycle, the same principles apply. You are given drugs to stimulate the growth and production of several eggs until one or more are collected and then fertilised with sperm.
Fertilisation happens through in vitro fertilisation (IVF), or intracytoplasmic sperm injection (ICSI). The latter involves the individual injection of sperm into an egg, which is usually reserved for those with sperm abnormalities.
In a completely natural cycle, no stimulation is given and instead, growth of a single dominant follicle is closely monitored.
What happens next is where the jury is out and where experts share many different points of view. Do you go ahead with the fresh transfer of an embryo that has developed over several days, or do you wait and freeze the embryo after culturing and defer transfer until a subsequent menstrual cycle?
Sometimes, there are strong factors which will heavily influence this decision. For example, practically all experts will agree that if you were to develop signs of ovarian hyperstimulation, associated with a profound response to the drugs used to encourage follicular growth, deferral of transfer until symptoms resolve is a necessity.
There may also be practical reasons in play. For example, if a patient is travelling or has an important commitment which means they are unable to continue with a fresh embryo transfer.
Or if a patient is having pregenetic tests done, the results of which can require some time to return, a frozen transfer is done only after the results.
Then there are those circumstances where the decision is not so clear cut. For example, if you have endometriosis, or a polyp in the womb, or a fibroid that may need resecting, do you collect and pool all the embryos together first and then perform any necessary surgery before proceeding with transfer, or do you perform the surgery first and then carry out stimulation and fresh transfer straight afterwards?
The answer to this will in large part depend on your individual circumstances, the extent of the pathology, its location as well as when it’s discovered. Sometimes polyps are only picked up during the scans a patient has whilst undergoing ovarian stimulation, in which case any surgery that may be needed can only be done after freezing the embryos created.
But what about those where there is no strong indication to do either fresh or frozen transfer? What is the best thing to do and what are some of the pros and cons of each method? And why are some clinics now routinely offering elective freezing of all embryos?
In short, IVF experts disagree about whether transferring a fresh or frozen embryo to a patient’s womb offers the best opportunity for healthy babies. According to a study of almost 83,000 IVF patients published in the journal Fertility and Sterility, there is no one-size-fits-all solution. There is a commonly held belief that the process of stimulation prior to transfer creates a more unfavourable environment for the embryo. Holding off and waiting for this environment to normalise is thought to be advantageous and potentially more natural.
It is also believed that using frozen embryos may reduce the risk of underweight babies and preterm labour. On the other hand, fresh transfers are more convenient to do, less taxing on a woman who would normally struggle to get the time off work to have IVF. They could be less costly and not so emotionally draining due to the waiting involved.
The data in the study came from first-time IVF patients included in a registry of the Society for Assisted Reproductive Technology in the US between 2014 and 2015. The study concluded that the benefit of frozen transfer may only apply to those patients who are deemed to be high responders and produce more than 15 eggs in a cycle. One of the main shortcomings of the study was that they were unable to ascertain the reasons behind why a patient opted for a frozen transfer compared to a fresh one.
In a study in the Lancet published earlier this year, results were taken from the largest randomised controlled trial on elective frozen-thawed versus fresh single blastocyst (day 5 or 6 embryo) transfer in healthy young women undergoing IVF. The investigators reported a substantially higher live birth rate in women in the elective frozen transfer group than in those in the fresh transfer group. However, elective frozen transfer increased the risk of pre-eclampsia and the birth of babies large for their gestational age.
These same risks did not seem to apply to cycles where a frozen transfer was done in a natural cycle without artificial endometrial preparation. The reasons behind this are not fully understood or explained, but could be to do with the fact that a corpus luteum, or follicle which releases an egg, is absent from a medicated frozen transfer yet could confer some benefit in helping to protect the patient’s circulatory system.
Over the last decade, the use of frozen embryo transfer (FET) cycles has dramatically risen. According to a report conducted by the Society for Assisted Reproductive Technology (SART), the number of FET cycles has increased by 82.5% between 2006 and 2012, outpacing the increasing rate of fresh embryo transfer cycles.
According to the latest Human Fertilisation and Embryology Authority (HFEA) Trends and Figures report published in May 2019, FET cycles have increased by 11% between 2016 and 2017 alone, whilst the number of fresh embryo transfers has dropped by 2%. For the first time, FET cycles are now more successful than fresh (23 vs 22%) based on the HFEA’s national figures.
In the latest European survey, FET cycles accounted for 32.4% of all IVF and ICSI cycles, which was a significant increase compared with a previous report.
The main reasons underlying the increasing trend for FET cycles are threefold:
First, a newer vitrification technology has become the dominant method used for embryo cryopreservation, increasing the chance of embryo survival dramatically compared to the slow freeze technology of the past.
The embryos are frozen and preserved at the time of their creation and do not deteriorate in quality over time. The latest time-lapse technology in the laboratory helps embryologists to decide the best time for embryo transfer individualised for you specifically.
A rapid rise in single embryo transfer combined with the development of pre-implantation testing has increased the number of embryos available for freezing.
Finally, a large number of studies have demonstrated that FET may lead to better outcomes overall for mother and baby . For example, in a large Nordic cohort study, singletons born after FET had a lower risk of preterm birth and being small for their gestational age.
There is a very small chance the embryos will not survive the freezing and thaw process. In these instances, either another embryo will be thawed (if available) or the embryo transfer will be cancelled, but the risk of this is incredibly small, normally less than 5%.
Quite possibly, but this will depend on more research in this field to help us uncover the best answer and what particular patients may benefit most. At the moment, there is no clear consensus and the debate continues.
From a patient perspective, what does appear reassuring is that having a frozen transfer does not appear to be less successful compared to fresh, it may in fact be slightly better in some circumstances, and is safe to perform.
Article by fertility expert, Dr Larisa Corda