Fresh transfer or frozen
It depends on who you are, and the trade-off is in the pregnancy rather than the pregnancy test.
"Freeze everything and transfer later" is often presented as the modern, better approach. Three large randomized trials say it depends entirely on the patient.
| Trial | Population | Live birth, frozen | Live birth, fresh |
|---|---|---|---|
| 1,508 women | Polycystic ovary syndrome | 49.3% | 42.0% (frozen better, P = 0.004) |
| 2,157 women | Ovulatory, no PCOS | 48.7% | 50.2% (no difference) |
| 782 women | No polycystic ovaries | 33.8% | 31.5% (no difference) |
Pooled across eight randomized trials in 4,712 women, cumulative live birth was the same: odds ratio 1.08 (95% CI 0.95 to 1.22).
What freezing does change is the pregnancy that follows:
- Hypertensive disorders of pregnancy roughly double, odds ratio 2.15 (95% CI 1.42 to 3.25)
- Large-for-gestational-age babies roughly double, odds ratio 1.96 (95% CI 1.51 to 2.55)
- Babies weigh about 127 g more on average (95% CI 77 to 178 g)
The detail that turns this into a choiceThat harm is concentrated in programmed frozen cycles, where hormone tablets and patches replace your own cycle and there is no corpus luteum, the structure that produces the hormones supporting early pregnancy.
In a prospective cohort, preeclampsia occurred in 12.8% of programmed frozen transfers with no corpus luteum against 3.9% of modified natural frozen transfers with one. Preeclampsia with severe features, 9.6% against 0.8%.
In a Swedish national registry of 9,726 frozen transfer births, programmed cycles carried higher hypertensive disorders than natural cycles (adjusted odds ratio 1.78) and more postpartum haemorrhage over 1,000 mL (2.63). Stimulated cycles looked like natural ones. The gradient follows the corpus luteum, not the freezing.
In a prospective cohort, preeclampsia occurred in 12.8% of programmed frozen transfers with no corpus luteum against 3.9% of modified natural frozen transfers with one. Preeclampsia with severe features, 9.6% against 0.8%.
In a Swedish national registry of 9,726 frozen transfer births, programmed cycles carried higher hypertensive disorders than natural cycles (adjusted odds ratio 1.78) and more postpartum haemorrhage over 1,000 mL (2.63). Stimulated cycles looked like natural ones. The gradient follows the corpus luteum, not the freezing.
The question"If we do a frozen transfer, can it be a natural or modified natural cycle rather than a programmed one?"
Programmed cycles are easier to schedule, which is a real advantage for a busy laboratory and for a patient who travels. It is a scheduling decision with a health consequence, and it should be made as one.
Programmed cycles are easier to schedule, which is a real advantage for a busy laboratory and for a patient who travels. It is a scheduling decision with a health consequence, and it should be made as one.
Where this comes from:
56. Chen Z, Shi Y, Sun Y, Zhang B, Liang X, Cao Y, et al. Fresh versus frozen embryos for infertility in the polycystic ovary syndrome. N Engl J Med. 2016;375(6):523-533.
57. Shi Y, Sun Y, Hao C, Zhang H, Wei D, Zhang Y, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med. 2018;378(2):126-136.
58. Vuong LN, Dang VQ, Ho TM, Huynh BG, Ha DT, Pham TD, et al. IVF transfer of fresh or frozen embryos in women without polycystic ovaries. N Engl J Med. 2018;378(2):137-147.
49. Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021;2(2):CD011184.
59. Ginström Ernstad E, Wennerholm UB, Khatibi A, Petzold M, Bergh C. Neonatal and maternal outcome after frozen embryo transfer: increased risks in programmed cycles. Am J Obstet Gynecol. 2019;221(2):126.e1-126.e18.
60. von Versen-Höynck F, Schaub AM, Chi YY, Chiu KH, Liu J, Lingis M, et al. Increased preeclampsia risk and reduced aortic compliance with in vitro fertilization cycles in the absence of a corpus luteum. Hypertension. 2019;73(3):640-649.
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