Two studies in the same center, on the same patient population and topic, but with different results. Is the experimental design to blame?

Endometrial Receptivity Analysis (ERA) with its surrogate treatment—personalized embryo transfer (pET)—was designed to improve the clinical care of our most difficult patients, those with recurrent implantation failure of endometrial origin ( 1 Ruiz-Alonso M. Blesa D. Díaz-Gimeno P. Gómez E. Fernández-Sánchez M. Carranza F. et al. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013; 100: 818-824 Abstract Full Text Full Text PDF PubMed Scopus (323) Google Scholar ). Nine years later, an independent meta-analysis concluded that pET significantly increased the pregnancy rates for non-receptive patients with recurrent implantation failure ( 2 Liu Z. Liu X. Wang M. Zhao H. He S. Lai S. et al. The clinical efficacy of personalized embryo transfer guided by the Endometrial Receptivity Array/analysis on IVF/ICSI outcomes: a systematic review and meta-analysis. Front Physiol. 2022; 13841437 Google Scholar ). Recently, we evaluated ERA’s usefulness in good-prognosis patients in a randomized controlled trial (RCT), resulting in comparable outcomes by intention-to-treat analysis due to an expected high dropout rate; however, per-protocol analysis demonstrated significant improvements in the pregnancy, implantation, and cumulative pregnancy/live birth rates for pET compared with those in frozen/fresh embryo transfer (ET) ( 3 Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. et al. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod Biomed Online. 2020; 41: 402-415 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ). We now note that a retrospective study by Cozzolino et al. ( 4 Cozzolino M. Diáz-Gimeno P. Pellicer A. Garrido N. Use of the endometrial receptivity array to guide personalized embryo transfer after a failed transfer attempt was associated with a lower cumulative and per transfer live birth rate during donor and autologous cycles. Fertil Steril. 2022; 118: 724-736 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar )—developed in the same center on the same patient population and topic—reports different results (Table 1). We delineate potential explanations to clarify this situation. Table 1Comparative results from autologous without preimplantation genetic testing for aneuploidy Instituto Valenciano de Infertilidad (IVI) patients extracted from the Endometrial Receptivity Analysis randomized controlled trial ( 3 Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. et al. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod Biomed Online. 2020; 41: 402-415 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ) vs. the study by Cozzolino et al. ( 4 Cozzolino M. Diáz-Gimeno P. Pellicer A. Garrido N. Use of the endometrial receptivity array to guide personalized embryo transfer after a failed transfer attempt was associated with a lower cumulative and per transfer live birth rate during donor and autologous cycles. Fertil Steril. 2022; 118: 724-736 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ) in the same patient. population, topic, and center group. Clinical outcome IVI patients from the study by Simon et al. ( 3 Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. et al. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod Biomed Online. 2020; 41: 402-415 Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar ) IVI patients from the study by Cozzolino et al. ( 4 Cozzolino M. Diáz-Gimeno P. Pellicer A. Garrido N. Use of the endometrial receptivity array to guide personalized embryo transfer after a failed transfer attempt was associated with a lower cumulative and per transfer live birth rate during donor and autologous cycles. Fertil Steril. 2022; 118: 724-736 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ) pET (HRT) FET (HRT) Fresh ET (COS) pET (HRT) FET (Nat + HRT) Fresh ET (COS) Pregnancy rate 75.0% (33/44) 56.9% (29/51) 57.1% (28/49) 40.91% (36/88) 57.39% (602/1,049) 52.36% (543/1,037) Implantation rate 61.7% (37/60) 44.2% (34/77) 37.7% (29/77) 30.68–45.13 39.7–45.02 32.79–41.1 Live birth 54.5% (24/44) 41.2% (21/51) 46.9% (23/49) 18.18% (16/88) 35.18% (369/1,049) 34.43% (357/1,037) Cumulative pregnancy rate 100% (44/44) 84.3% (43/51) 65.3% (32/49) 42.98% (52/121) 54.27% (852/1,570) 51.43% (612/1,190) Cumulative live birth rate 77.3% (34/44) 62.7% (32/51) 51% (25/49) 18.18% (22/121) 33.76% (530/1,570) 33.61% (400/1,190) COS = controlled ovarian stimulation; ET = embryo transfer; FET = frozen embryo transfer; HRT = hormone replacement therapy cycle; Nat = natural cycle; pET = personalized embryo transfer. Open table in a new tab COS = controlled ovarian stimulation; ET = embryo transfer; FET = frozen embryo transfer; HRT = hormone replacement therapy cycle; Nat = natural cycle; pET = personalized embryo transfer. Reply of the Authors: Not in the same patient population but on the same topic. The endometrial receptivity array test has not proven clinically useful to improve implantation yet, and our data support this factFertility and SterilityVol. 119Issue 3PreviewResponse to: Two studies in the same center, on the same patient population and topic, but with different results. Is the experimental design to blame? Full-Text PDF