Debate: Do we need PGT-A for drawing a diagnosis of RIF? - YES

Probably we should use PGT-a for drawing a diagnosis of RIF

It is reasonable to state that implantation failures, let alone RIF, can stem from either an embryo or endometrial cause.  Hence, for narrowing our research, we focused on studying implantations of euploid embryos transferred in a standardized E2 and IM progesterone – HRT – replacement cycle (1-3).  The former was meant to limit embryo factors of ART failure, such as notably, the age-related decrease in embryo euploidy rates.  The latter was chosen because HRT regimens using E2 and IM progesterone has been the long-lasting reference for reliably priming endometrial receptivity (1-3).  Therefore PGT-a should be used for determining RIF, in order to control for embryonic competence, even more so in a research setting. In our first study, we showed that, if it exists, RIF is a very rare occurrence, affecting only ≤5% of women whose uterus is normal, and the endometrium is ≥7 mm (1).  Subsequently, a workshop mustering international experts from both the US and Europe in 2022 – the ‘Lugano Workshop’ – to further study RIF (4).  The conclusions of this workshop were outlined in the “Lugano Paper”(4).  It confirmed that an extensive review of available data indicate that RIF may exist, but is extremely rare, only affecting ≤5% of ART patients whose uterus is morphologically normal (4).  Recent data presented confirmed that endometrial receptivity is amazingly resilient in women whose uterus is morphologically normal. This therefore obliges us to reconsider that other possible causes of repeated ART failures may exist, such as possibly, recurrent aneuploidy (RA).  If endometrial receptivity in women whose uterus is morphologically normal is so resilient that RIF only exist in ≤5% or less of cases following euploid FET in E2 and progesterone cycles, we must query about other possible causes of ART failure.  Specifically, we must ask ourselves whether some couples might never have euploid embryos.  This condition of possible maternal or paternal origin would consist in recurrent aneuploidy (RA).  RA would evidently cause repeated ART failures, but might be wrongly accounted as RIF, if embryos are not genetically screened.  Therefore, this is yet another reasonable indication for PGT-a in order to determine a diagnosis of RIF.

1.       Pirtea P, De Ziegler D, Tao X, Sun L, Zhan Y, Ayoubi JM, et al. Rate of true recurrent implantation failure is low: results of three successive frozen euploid single embryo transfers. Fertil Steril. 2021;115(1):45-53.

2.       Pirtea P, Scott RT, Jr., de Ziegler D, Ayoubi JM. Recurrent implantation failure: how common is it? Curr Opin Obstet Gynecol. 2021;33(3):207-12.

3.       Pirtea P, de Ziegler D, Ayoubi JM. Recurrent Implantation Failure-Is It the Egg or the Chicken? Life (Basel). 2021;12(1).

4.       Pirtea P, Cedars MI, Devine K, Ata B, Franasiak J, Racowsky C, et al. Recurrent implantation failure: reality or a statistical mirage?: Consensus statement from the July 1, 2022 Lugano Workshop on recurrent implantation failure. Fertil Steril. 2023;120(1):45-59.