New research finds that frozen embryo transfer is associated with higher live birth rates than transfer in a fresh cycle. But what is the explanation and should we be advising freeze-all for all?
SHANDONG, China — Researchers in China randomly assigned 1650 couples to either transfer of a single blastocyst in a fresh cycle or freezing all embryos and returning them in a frozen embryo replacement cycle. All women included in the study were 35 years old, or younger and had regular periods, meaning they all had a good chance of success.
Results published in The Lancet, showed women with a frozen embryo transfer were more likely to have a baby (50% vs 40%), but they were also more likely to go on to develop preeclampsia (3.1% vs 1%).
So why was this the case and what does it mean for patients?
The rationale for embryo transfer is to maximise pregnancy rates but reduce the risk from multiple pregnancies and ovarian hyper-stimulation syndrome (OHSS).
Many IVF clinics transfer one embryo at the blastocyst stage, in a fresh cycle five days after egg collection. This strategy of elective single embryo transfer compared with two cleavage stage embryos (day 3) has reduced the number of multiple pregnancies but maintained live birth rates.
Embryo replacement in a fresh cycle can drive late onset OHSS which is a significant risk from IVF treatment.
Embryo freezing through the fast process of vitrification is now commonplace in IVF laboratories. Over 95% of embryos survive thawing with no detrimental effect on implantation potential.
Ovarian stimulation leads to a negative effect on the womb environment. IVF results in massively elevated estrogen levels not seen in a natural cycle. Previous studies have shown negative effects on the lining of the womb where the endometrium exhibits abnormal gene expression. Given this significant effect, it is surprising our patients get pregnant at all. So transferring frozen embryos in a cycle unaffected by high estrogen levels is the reason for higher success rates.
Drawbacks of using a so called “freeze all” approach is that women with few embryos may not have anything suitable to freeze. The delay of at least 4 weeks between treatment can be associated with emotional and financial costs too. Further studies need to investigate why it is associated with more preeclampsia.
Interestingly, this study had high rates of live birth in both groups. Most clinics would consider a live birth rate of 40–50% per cycle excellent.
The authors described their study as “practice-changing”. But this is the first randomised trial showing real improvement using a freeze in a general fertility population. The evidence is still patchy. Two high-quality trials have only shown benefit in women with polycystic ovary syndrome (PCOS), not women who are ovulating.
So while this study is encouraging, freeze-all for all has yet to be proven.
Authors
Matt is an NHS Consultant in Newcastle with over ten years of experience. His PhD research into subfertility and miscarriage involved developing a clinical trial and patient engagement.
