Better IVF

Natural-cycle FET beats medicated, even over 40

Once you have a euploid embryo, a 42-year-old's transfer works about as well as a 32-year-old's. And a natural cycle is the stronger way to prepare for it, at every age.

Study Summary

3 minute read

Once 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 gave significantly higher ongoing pregnancy rates than a medicated one, and female age had no effect at all. The ongoing pregnancy rate sat at about 51% whether a woman was under 35 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: age does not lower the ongoing pregnancy rate of a euploid transfer, and a natural cycle clearly beats 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.

Interactive · modelled
Natural versus medicated FET, by your BMI
Set your BMI and whether you've given birth before. The two lines are the study's lining-prep methods; the gap between them is the lever you can influence.
Your BMI
24
Given birth before?
0% 30% 60% 90% Normal Overweight Obese Body mass index 55% 45%
Natural FET Medicated FET

The study

Published
2024, Reproductive BioMedicine Online (Lawrenz et al.), 49(2)
Study type
Retrospective, 1,923 single euploid frozen transfers in 1,464 women, 2017 to 2023, natural cycle versus medicated (HRT) lining prep
Outcome
Ongoing pregnancy rate, 51.48% overall (990 of 1,923)
Headline
Natural cycle odds ratio 1.50 (95% CI 1.23 to 1.83, p<0.001); female age no effect (about 51% across every band, including over 40)
What this study measured
Egg retrieval
Fertilisation
Blastocyst
Euploidy (PGT-A)
Implantation
Clinical pregnancy
Ongoing preg. / birth
measured here

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.

May help most

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.

Applies less

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% under 35, 49.1% at 36 to 37, 53.3% at 38 to 40 and 52.3% over 40, with no downward trend (p=0.68). In the adjusted model, no age group differed from the under-35 group, and the over-40 odds ratio was 1.12, which wasn't significant.

Ongoing pregnancy by age band
With a euploid embryo, the rate stays flat across every age. There was no significant downward trend (p=0.68).
Under 35
51.4%
36 to 37
49.1%
38 to 40
53.3%
Over 40
52.3%
Ongoing pregnancy rate, single euploid frozen transfers. Source: Lawrenz 2024.

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 actually moves the odds
Adjusted odds ratios. The dashed line is 1.0, where a factor makes no difference. Bars to the right raise the odds, bars short of it lower them.
1.0 · no change
Natural cycle (vs medicated)
1.50x
Good embryo (vs fair)
1.94x
Overweight (vs normal BMI)
0.74x
Obese (vs normal BMI)
0.71x
Adjusted odds ratios for ongoing pregnancy. Source: Lawrenz 2024.

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.

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).

Michelle Bourke

Written by

Michelle Bourke

Founder of Better IVF. I went through IVF over 38 myself, and I write these guides to be the clear, properly-sourced resource I wish I'd had, more honest than the forums and deeper than the clinic pages.

Because women after 38 deserve more.

You are not alone, and you have options. Wherever you are in this, there is usually a next step worth taking. Let's find yours.