Recurrent implantation failure (RIF) and ART adjuncts — definition, the ESHRE good practice recommendations, endometrial receptivity, and the PGT-A controversy

It is Wednesday afternoon, and a 36-year-old woman sits in front of you with a folder of four failed frozen embryo transfers and a printed list of add-ons she found online — embryo glue, endometrial scratch, PGT-A, intralipid, PRP. She has spent a great deal of money and has a great deal of grief. Your job is not to add another invoice; it is to reframe her care around the ESHRE good practice recommendations, calculate her real cumulative chance, treat the evidence-based causes, and refuse to sell her interventions that the evidence does not support. This topic is that reframe.^[1][2]

Overview and definition

RIF is the failure of apparently viable embryos to implant after enough transfers that further investigation is warranted. The defining question has always been "how many failed transfers counts as RIF?" — and the answer has moved.^[1]

The ESHRE 2023 good practice recommendation reframes RIF as a secondary phenomenon of ART, and adopts this description: "RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions." The working group recommends a cumulative predicted chance of implantation threshold of 60 per cent: when a couple has not achieved implantation by a certain number of transfers and the cumulative predicted chance associated with that number is greater than 60 per cent, further investigation is warranted.^[1]

This replaced older fixed-count definitions. Coughlan 2014 defined RIF as failure to achieve a clinical pregnancy after transfer of at least four good-quality embryos in a minimum of three fresh or frozen cycles in a woman under 40. Polanski 2014, after a systematic review, proposed absence of implantation after two consecutive cycles where the cumulative number of transferred embryos was no less than four cleavage-stage or no less than two blastocysts, all of good quality. Polanski also named RIF an iatrogenic condition — the result of repetitive unsuccessful IVF or ICSI cycles.^[3][4]

^{[1] [2]}

References20ShowHide

1. [1]Cimadomo D, de Los Santos MJ, Griesinger G, et al. ESHRE good practice recommendations on recurrent implantation failure Hum Reprod Open, 2023.PMID 37332387
2. [2]Lundin K, Bentzen JG, Bozdag G, et al. Good practice recommendations on add-ons in reproductive medicine Hum Reprod, 2023.PMID 37747409
3. [3]Coughlan C, Ledger W, Wang Q, et al. Recurrent implantation failure: definition and management Reprod Biomed Online, 2014.PMID 24269084
4. [4]Polanski LT, Baumgarten MN, Quenby S, et al. What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion Reprod Biomed Online, 2014.PMID 24581986
5. [5]Cimadomo D, Rienzi L, Conforti A, et al. Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis Hum Reprod Update, 2023.PMID 37192834
6. [6]Munné S, Kaplan B, Frattarelli JL, et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial Fertil Steril, 2019.PMID 31551155
7. [7]Verpoest W, Staessen C, Bossuyt PM, et al. Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: a randomized clinical trial Hum Reprod, 2018.PMID 30085138
8. [8]Pagliardini L, Viganò P, Alteri A, et al. Shooting STAR: reinterpreting the data from the 'Single Embryo TrAnsfeR of Euploid Embryo' randomized clinical trial Reprod Biomed Online, 2020.PMID 32273162
9. [9]Hyttel CB, Løssl K, Wang NF, et al. The effect of preimplantation genetic testing for aneuploidy (PGT-A) on obstetric and neonatal outcomes: a systematic review and meta-analysis Hum Reprod, 2026.PMID 41966094
10. [10]Cornelisse S, Zagers M, Kostova E, et al. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation Cochrane Database Syst Rev, 2020.PMID 32898291
11. [11]Lensen S, Cedars MI, Mastenbroek S From innovation to practice: evaluating the evidence for preimplantation genetic testing for aneuploidy Fertil Steril, 2025.PMID 41106955
12. [12]Gleicher N, Orvieto R Is the hypothesis of preimplantation genetic screening (PGS) still supportable? A review J Ovarian Res, 2017.PMID 28347334
13. [13]Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology The use of preimplantation genetic testing for aneuploidy: a committee opinion Fertil Steril, 2024.PMID 38762806
14. [14]Simón C, Gómez C, Cabanillas S, et al. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF Reprod Biomed Online, 2020.PMID 32723696
15. [15]Ruiz-Alonso M, Valbuena D, Gomez C, et al. Endometrial Receptivity Analysis (ERA): data versus opinions Hum Reprod Open, 2021.PMID 33880420
16. [16]Perera AK, Gan J, Afroz A, et al. Endometrial injury in women undergoing in vitro fertilisation (IVF) Cochrane Database Syst Rev, 2026.PMID 42138348
17. [17]Busnelli A, Somigliana E, Cirillo F, et al. Efficacy of therapies and interventions for repeated embryo implantation failure: a systematic review and meta-analysis Sci Rep, 2021.PMID 33462292
18. [18]He Y, Tang R, Yu H, et al. Comparative effectiveness and safety of 36 therapies or interventions for pregnancy outcomes with recurrent implantation failure: a systematic review and network meta-analysis J Assist Reprod Genet, 2023.PMID 37661207
19. [19]Singh N, Davis AA, Kumar S, et al. The effect of administration of intravenous intralipid on pregnancy outcomes in women with implantation failure after IVF/ICSI with non-donor oocytes: A randomised controlled trial Eur J Obstet Gynecol Reprod Biol, 2019.PMID 31228675
20. [20]Coughlan C, Clarke H, Cutting R, et al. Sperm DNA fragmentation, recurrent implantation failure and recurrent miscarriage Asian J Androl, 2015.PMID 25814156