Keywords
Modified natural cycle
Artificial cycle
Hormonal replacement therapy
How to Cite
Copyright © | All rights reserved.
The journal holds the exclusive copyright for the publication of this article under the terms of Brazilian law 9610/98.
Partial reproduction
The use of parts of the texts, figures and questionnaire of the article is free, being mandatory the citation of the authors and journal.
Total reproduction
It is expressly prohibited and must be authorized by the journal.
Abstract
Objective: To synthesize and compare scientific evidence on gestational and safety outcomes associated with different endometrial preparation protocols – natural, modified natural, stimulated, and artificial – for frozen embryo transfer (FET). Methods: An integrative literature review was conducted, following PRISMA assumptions, in the PubMed and Virtual Health Library databases. The search strategy was guided by the PCC framework (Population: women undergoing FET; Concept: endometrial preparation protocols; Context: cryopreserved embryos). Studies published between 2020-2025 were included, focusing on strong to moderate levels of evidence. Results: The analysis of nine studies showed equivalence in live birth rates among the protocols in ovulatory women. However, natural and modified natural cycles demonstrated a superior safety profile, with significant reductions in the risk of pre-eclampsia, postpartum hemorrhage, and preterm birth. In contrast, the artificial cycle showed greater predictability, with cancellation rates close to zero. For subpopulations, the letrozole-stimulated cycle emerged as an effective alternative with the potential for a lower miscarriage rate. Final considerations: This study reinforces the need for personalized protocol selection, balancing efficacy, safety, and logistical aspects. The main limitation lies in the methodological heterogeneity of the included studies, preventing a formal meta-analysis.
References
AN J, et al. A clinical and basic study of optimal endometrial preparation protocols for patients with infertility undergoing frozen-thawed embryo transfer. Experimental and Therapeutic Medicine, 2020; 20(3): 2191-2199.
ANDRADE VAB, et al. Possíveis repercussões da reprodução assistida na saúde materno-infantil. Revista Eletrônica Acervo Saúde, 2025; 25: 19603.
BELLVER J, et al. Risk of preeclampsia and other pregnancy complications in frozen single euploid embryo transfers after natural versus artificial endometrial preparation: A truncated randomized controlled trial. Placenta, 2025; 163: 1-7.
BELSEY J e SNELL T. What is evidence-based medicine? 2nd edition. Oxford, UK: Hayward Medical Communications, 2009.
EBRAHIMI R, et al. Comparison of tamoxifen and hormone replacement cycle (HRT) in frozen embryo transfer. A randomized controlled trial. JBRA Assisted Reproduction, 2023; 27(2): 241-246.
GLUJOVSKY D, et al. Endometrial preparation for women undergoing embryo transfer with frozen embryos or embryos derived from donor oocytes. Cochrane Database of Systematic Reviews, 2020; 10: 6359.
HO VNA, et al. Livebirth rate after one frozen embryo transfer in ovulatory women starting with natural, modified natural, or artificial endometrial preparation in Viet Nam: an open-label randomised controlled trial. Lancet, 2024; 404(10449): 266-275.
HUNTER H, et al. Influence of embryo transfer timing on clinical pregnancy rates: a retrospective analysis. Journal of Assisted Reproduction and Genetics, 2020; 37(2): 327-334.
LIU X, et al. Natural cycle versus hormone replacement therapy as endometrial preparation in ovulatory women undergoing frozen-thawed embryo transfer: The compete open-label randomized controlled trial. PLoS Medicine, 2025; 22(6): 1004630.
LUO L, et al. Pregnancy outcome and cost-effectiveness comparisons of artificial cycle-prepared frozen embryo transfer with or without GnRH agonist pretreatment for polycystic ovary syndrome: a randomised controlled trial. BJOG, 2021; 128(4): 667-674.
ROCHA KNS, et al. Atualizações sobre a fertilização in vitro para reprodução humana. Brazilian Journal of Health Review, 2022; 5(1): 3081-3100.
ROELENS C e BLOCKEEL C. Impact of different endometrial preparation protocols before frozen embryo transfer on pregnancy outcomes: a review. Fertility and sterility, 2022; 118(5): 820-827.
SILVA PXM, et al. Criopreservação: a importância da preservação da fertilidade em mulheres submetidas a tratamento oncológico. Brazilian Journal of Biological Sciences, 2024; 11(25): 63.
STEPTOE PC e EDWARDS RG. Birth after the reimplantation of a human embryo. Lancet, 1978; 2(8085): 366.
SUNDERAM S, et al. Assisted reproductive technology surveillance – United States, 2018. MMWR. Surveillance Summaries, 2022; 71(4): 1-19.
TRICCO AC, et al. PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Annals of Internal Medicine, 2018; 169(7): 467-473.
XU J, et al. Endometrial preparation for frozen-thawed embryo transfer with or without pretreatment with GnRH agonist: a randomized controlled trial at two centers. Frontiers in Endocrinology, 2021; 12: 722253.
ZAAT TR, et al. Obstetric and neonatal outcomes after natural versus artificial cycle frozen embryo transfer and the role of luteal phase support: a systematic review and meta-analysis. Human Reproduction Update, 2023; 29(5): 634-654.
ZENG MF, et al. Stimulated cycle versus artificial cycle for frozen embryo transfer in patients with polycystic ovary syndrome: a Meta-analysis. Gynecological Endocrinology, 2021; 37(4): 294-299.
ZHANG Y, et al. Preparation of the endometrium for frozen embryo transfer: an update on clinical practices. Reproductive Biology and Endocrinology, 2023; 21(1): 52.