Study Summary
3 minute readOnce a genetically tested (euploid) embryo is frozen, the lining has to be prepared before it goes back. That's done one of two ways: a medicated cycle, where oestrogen and progesterone are given as tablets or patches, or a natural cycle, timed to your own ovulation so your body makes its own hormones. This large study asked whether a woman's age changes the odds of a euploid transfer working, and it compared the two lining-prep methods.
A natural cycle was associated with significantly higher ongoing pregnancy rates than a medicated one, and the study found no significant effect of female age. The ongoing pregnancy rate sat at about 51% whether a woman was 35 or under, or over 40. So once you have a euploid embryo, the transfer works about as well at 42 as at 32, and a natural cycle is the stronger way to prepare for it, at every age.
- Hypothesis: that female age lowers the ongoing pregnancy rate in single euploid frozen embryo transfers, and, alongside that, that the way the lining is prepared has an impact.
- Study Type: a retrospective study of 1,923 single euploid frozen transfers in 1,464 women, with a multivariable analysis that adjusts for embryo quality, body mass index and lining-prep method at the same time.
- Conclusion: the study did not find that age lowered the ongoing pregnancy rate of a euploid transfer, and a natural cycle was associated with higher odds than a medicated one (odds ratio 1.50).
See it as a graph
A natural cycle is the single biggest thing you can influence here, and it holds over 40. The graph below models the study's numbers (its overall 51% rate and its adjusted odds ratios), not a personal prediction.
The study
This study followed already-tested euploid embryos through transfer, recording ongoing pregnancy.
Study population
These were women transferring a single genetically normal frozen embryo, with a mix of ages up to and past 40. It speaks directly to two decisions: whether to worry that your age lowers the odds of a euploid embryo transfer working, and whether to choose a natural or a medicated cycle.
Anyone with a normal, ovulatory cycle choosing between a natural and a medicated transfer, and especially older women told their age lowers the odds of the transfer itself.
If you don't have a regular ovulatory cycle, a natural cycle may not be an option yet, and if you're transferring untested (not euploid) embryos this doesn't apply. A higher body mass index and lower embryo quality still lower the odds whichever prep you use.
Methodology
- The 1,923 transfers were split by lining-prep method, natural cycle or medicated, and by age band. A multivariable regression then estimated the effect of each factor while holding the others constant, so the age effect is judged after allowing for embryo quality, body mass index and lining-prep method.
- The team also ran the analysis allowing age to interact with embryo quality and with prep method, and plotted the results, to check whether age mattered inside any subgroup. It did not.
What they found
A natural cycle beats a medicated one
Preparing the lining in a natural cycle gave an odds ratio of 1.50 (1.23 to 1.83, p<0.001) for an ongoing pregnancy compared with a medicated cycle. It's the single biggest lever in the study that a patient can influence, and it fits a growing body of randomised evidence that natural transfers lower miscarriage and raise live birth in women with normal cycles.
Age does not lower the odds with a euploid embryo
Ongoing pregnancy with euploid embryos was about 51% at every age: 51.4% at 35 or under, 49.1% at over 35 to 37, 53.3% at over 37 to 40 and 52.3% at over 40, with no downward trend (p=0.68). In the adjusted model, no age group differed from the 35-or-under group, and the over-40 odds ratio was 1.12, which wasn't significant.
The natural-cycle advantage holds over 40
When age was allowed to interact with prep method, the natural-cycle benefit didn't diminish with age. So the advantage of a natural transfer isn't something only younger women get. Women over 40 get it too.
Embryo quality and body mass index also change the odds
Good-quality embryos raised the odds (odds ratio 1.94 versus fair), while a higher body mass index lowered them (overweight 0.74, obese 0.71).
What it means for older women
Almost everything in IVF gets harder with age. The number of eggs falls, the fertilisation rate falls (from about 74% under 30 to 48% by 45 in one large series), fewer eggs make it to blastocyst, and the share that are euploid also drops.
What this study isolates, though, is the very last step: transferring a euploid embryo. And it shows that a 42-year-old with a euploid embryo has about the same ongoing pregnancy chance from it as a 32-year-old.
And there's one very easily modifiable choice that works to improve the outcome. If you have a normal cycle, a natural transfer beats a medicated one over 40 just as it does at 30.
Evidence strength
This is a large, patient-level study with fine-tuned adjustments, which makes its findings more trustworthy than a registry count. It's retrospective though, not randomised, so the natural-versus-medicated result is a strong association rather than causation (although randomised trials in women with normal cycles point the same way). It's strong enough to prefer a natural cycle where you have one, and to stop treating age as a barrier to the transfer itself.
The outcome is ongoing pregnancy, not live birth, so it stops short of the thing that matters most. The model does not adjust for the time between egg retrieval and transfer (which can dilute any age effect), for endometrial thickness, or for male-factor infertility. The embryo-grading and PGT-A methods are not described in detail, and because the data span six years (2017 to 2023), changes in laboratory practice over that period could have influenced the results. And because natural versus medicated preparation was chosen clinically rather than randomised, that comparison may be confounded by why each protocol was chosen.
Things you can discuss with your doctor
- If you have a normal, ovulatory cycle, ask your clinic about a natural-cycle transfer rather than a medicated one. On this data it's the stronger choice, and it stays stronger over 40.
- Don't accept that your age makes a euploid transfer less likely to work. The data shows it doesn't.
- Ask about the things that do move the odds: your body mass index, and getting a good-quality euploid embryo transferred.
- If your menstrual cycle isn't regular yet, that's worth raising first, because it's what makes a natural transfer possible.
Source: Lawrenz B, Kalafat E, Ata B, et al. Ongoing pregnancy rates in single euploid frozen embryo transfers remain unaffected by female age. Reprod Biomed Online, 2024;49(2).
Written by
Michelle Bourke
Founder of Better IVF and citizen researcher. Infertility diagnosis at 36, two children via IVF (first at 37 and second at 41). Leveraged research to shift euploidy rate at age 40 from average 43 year old to average 25-30 year old.