Frozen embryo transfer is now the dominant first-line procedure in ART. The talk compares HRT, modified natural and true natural cycles, examines E2 duration, day of progesterone before transfer, day-of-transfer progesterone monitoring, and the NPP protocol — a natural-cycle scheduling tool that uses vaginal progesterone instead of an HCG trigger.
HRT cycles are associated with significantly more preeclampsia, hypertensive disorders, postpartum haemorrhage and preterm birth than natural cycles. E2 preparation should not exceed 28 days; under 8-10 days is associated with worse outcomes. Day 5, 6 and 7 of progesterone before blastocyst transfer all give comparable pregnancy rates, with day 6 now adopted as standard. Day-of-transfer serum progesterone below 8.8-9.2 ng/mL is associated with significantly lower live birth, and adding a second route (subcutaneous progesterone or oral dydrogesterone) normalises outcomes.
Shift to natural or modified natural cycles where feasible, especially in patients with cardiovascular or obstetric risk. Measure serum progesterone on transfer day and rescue with a second route below the cut-off. The NPP protocol — starting vaginal progesterone when an adequate follicle and endometrium are seen, without HCG trigger — is a way to avoid weekend retrievals while keeping a corpus-luteum-supported luteal phase.
Dydrogesterone serum levels are not routinely measurable, so it is positioned as a second-line add-on. The 7 mm endometrial-thickness threshold is now disputed (Atta review): it was arbitrary, retrospective, and inter-observer variability exceeds 2 mm. The first-line role of progesterone monitoring in natural cycles is still debated, with conflicting data on whether routine luteal-phase support is needed.
HRT, modified natural or true natural cycle — which preparation actually delivers the best obstetric outcomes? A practical synthesis of recent data on E2 duration, progesterone route and timing, day-of-transfer monitoring, and the new NPP protocol that may reshape weekend scheduling.
Reproductive endocrinologist and gynecologist, and Medical Director of Brussels IVF — the Centre for Reproductive Medicine at University Hospital Brussels (UZ Brussel). Professor at the Vrije Universiteit Brussel and visiting professor at the University of Zagreb, with more than 20 years in reproductive medicine. His work focuses on ovarian stimulation, embryo transfer and assisted reproductive technologies, with more than 300 scientific publications.
Author of the lecture "Endometrial preparation for frozen embryo transfer"