Recurrent implantation failure: a registry-corroborated, age-stratified definition and pragmatic five-tiered management algorithm.
4 affiliations
- 1Reproductive Services Unit, City Fertility and The Royal Women's Hospital, Melbourne, VIC, Australia.
- 2Shady Grove Fertility Center, Solana Beach, CA, United States.
- 3UniKiD - Department of Reproductive Endocrinology and Reproductive Medicine, University Medical Centre, Heinrich Heine University, Düsseldorf, Germany.
- 4School of Clinical Medicine, University of New South Wales and Monash IVF Sydney, Sydney, NSW, Australia.
Abstract
Recurrent implantation failure (RIF) remains a significant challenge in reproductive medicine, imposing substantial emotional, clinical, and financial burden on affected couples. RIF is generally defined as failure to achieve pregnancy after multiple transfers of good-quality embryos, yet progress in the field has been constrained by the absence of a universally accepted definition and by the inherent complexity of investigating the embryo-endometrial interface. Recent evidence has prompted a reappraisal of the factors contributing to RIF, distinguishing it from the mechanistically distinct entity of embryo-intrinsic failure (recurrent embryo arrest and poor embryo development). This narrative review synthesises epidemiological data, evaluates the evidence base for available diagnostic modalities, and appraises current management strategies, including the controversies surrounding adjunctive treatments. We propose a registry-corroborated, age-stratified definition of RIF - the ABCDE framework - and a five-tiered, clinically applicable management algorithm that integrates the available evidence with expert recommendation to guide clinicians within a shared decision-making framework. Future directions include prospective multicentre validation, incorporation of artificial intelligence for risk prediction, and development of novel therapeutic approaches targeting the embryo-endometrial interface.
Related
- Beyond the Embryo: Rethinking the Genetics of Recurrent Implantation Failure in the PGT-A Era
- Autophagy as a potential link between progesterone responsiveness and endometrial immune function in recurrent implantation failure
- Altered IRE1α-Dependent Decidual Programming Links Impaired Inflammation and Angiogenesis in Recurrent Implantation Failure.
- Liquid Biopsy as a Screening Tool in Recurrent Implantation Failure During IVF: A Narrative Review.
- Live Birth Outcomes Following subendometrial platelet rich plasma versus Intrauterine platelet rich plasma infusion in Women with Recurrent Implantation Failure: A Cohort Study
BibTeX
@article{elzeiny2026recurrent,
title = {{Recurrent implantation failure: a registry-corroborated, age-stratified definition and pragmatic five-tiered management algorithm.}},
author = {Hossam Elzeiny and Alexander M Quaas and Alexandra P Bielfeld and Michael F Costello},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1930159},
url = {https://europepmc.org/article/MED/42898951},
note = {CC BY},
}
RIS
TY - JOUR
TI - Recurrent implantation failure: a registry-corroborated, age-stratified definition and pragmatic five-tiered management algorithm.
AU - Hossam Elzeiny
AU - Alexander M Quaas
AU - Alexandra P Bielfeld
AU - Michael F Costello
PY - 2026
DA - 2026/10/05
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1930159
UR - https://europepmc.org/article/MED/42898951
AB - Recurrent implantation failure (RIF) remains a significant challenge in reproductive medicine, imposing substantial emotional, clinical, and financial burden on affected couples. RIF is generally defined as failure to achieve pregnancy after multiple transfers of good-quality embryos, yet progress in the field has been constrained by the absence of a universally accepted definition and by the inherent complexity of investigating the embryo-endometrial interface. Recent evidence has prompted a reappraisal of the factors contributing to RIF, distinguishing it from the mechanistically distinct entity of embryo-intrinsic failure (recurrent embryo arrest and poor embryo development). This narrative review synthesises epidemiological data, evaluates the evidence base for available diagnostic modalities, and appraises current management strategies, including the controversies surrounding adjunctive treatments. We propose a registry-corroborated, age-stratified definition of RIF - the ABCDE framework - and a five-tiered, clinically applicable management algorithm that integrates the available evidence with expert recommendation to guide clinicians within a shared decision-making framework. Future directions include prospective multicentre validation, incorporation of artificial intelligence for risk prediction, and development of novel therapeutic approaches targeting the embryo-endometrial interface.
SN - 1664-2392
ER -