Response to: Comments on the methodology of an endometrial receptivity array trial

We read with interest the letter by Lensen et al., 2020Lensen S. Wilkinson J. van Wely M. Farquhar C. Comments on the methodology of an endometrial receptivity array trial.Reprod. Biomed. 2021; 42 (Online (in this issue)): 283Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar concerning our study (Simón et al., 2020Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. Boynukalin K. Findikli N. Bahceci M. Ortega I. Vidal C. Funabiki M. Izquierdo A. López L. Portela S. Frantz N. Kulmann M. Taguchi S. Labarta E. Colucci F. Mackens F. Santamaría X. Muñoz E. Barrera S. García-Velasco J. Fernández M. Ferrando M. Ruiz M. Mol B. Valbuena D. for the ERA-RCT Study Consortium GroupA 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.Reprod. Biomed. 2020; (Online 41, 567–415)Abstract Full Text Full Text PDF Scopus (68) Google Scholar). Here we respond to their criticisms.1The initial trial registration was amended due to recruitment difficulties; patients were unwilling to participate in blinded sub-randomization. We modified the design to an unblinded, 3-arm study in 458 women (IRB-approved 28 April, 2016; updated on clinicaltrials.gov 24 May, 2016). Initial registration included a primary outcome live birth rate, the most stringent and reliable metric of intervention performance in reproductive medicine.2Our analyses were limited by unexpected high patient drop-out, wherein early randomization resulted in patients deferring from protocol before treatment (see Figure 1 in Simón et al., 2020Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. Boynukalin K. Findikli N. Bahceci M. Ortega I. Vidal C. Funabiki M. Izquierdo A. López L. Portela S. Frantz N. Kulmann M. Taguchi S. Labarta E. Colucci F. Mackens F. Santamaría X. Muñoz E. Barrera S. García-Velasco J. Fernández M. Ferrando M. Ruiz M. Mol B. Valbuena D. for the ERA-RCT Study Consortium GroupA 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.Reprod. Biomed. 2020; (Online 41, 567–415)Abstract Full Text Full Text PDF Scopus (68) Google Scholar); further departures occurred because of patient safety/well-being risks, e.g., high levels of progesterone during ovarian stimulation, risk of ovarian hyperstimulation syndrome, etc. However, enrolled participants did not differ in epidemiological characteristics (see Table 1 in Simón et al., 2020Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. Boynukalin K. Findikli N. Bahceci M. Ortega I. Vidal C. Funabiki M. Izquierdo A. López L. Portela S. Frantz N. Kulmann M. Taguchi S. Labarta E. Colucci F. Mackens F. Santamaría X. Muñoz E. Barrera S. García-Velasco J. Fernández M. Ferrando M. Ruiz M. Mol B. Valbuena D. for the ERA-RCT Study Consortium GroupA 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.Reprod. Biomed. 2020; (Online 41, 567–415)Abstract Full Text Full Text PDF Scopus (68) Google Scholar) or embryological outcomes (see Table 2 in Simón et al., 2020Simón C. Gómez C. Cabanillas S. Vladimirov I. Castillón G. Giles J. Boynukalin K. Findikli N. Bahceci M. Ortega I. Vidal C. Funabiki M. Izquierdo A. López L. Portela S. Frantz N. Kulmann M. Taguchi S. Labarta E. Colucci F. Mackens F. Santamaría X. Muñoz E. Barrera S. García-Velasco J. Fernández M. Ferrando M. Ruiz M. Mol B. Valbuena D. for the ERA-RCT Study Consortium GroupA 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF.Reprod. Biomed. 2020; (Online 41, 567–415)Abstract Full Text Full Text PDF Scopus (68) Google Scholar), and drop-outs were homogeneously distributed among study arms. Sample size was balanced across arms within the per protocol analysis, which therefore does not negate the effects of randomization.3For cumulative outcomes, all embryo transfers following the same type of transfer arm into which the patient was randomized were considered. For a patient randomized to fresh embryo transfer, we considered the results of the next fresh embryo transfer. If the patient later underwent frozen embryo transfer or personalized embryo transfer, these results were excluded from the cumulative outcome. Further, the total number of embryo transfers per arm did not statistically differ. Probably our critics did not access Supplemental Table 2 in the published paper in which cumulative live birth rate is presented per number of embryo transfers performed, enabling our interpretations. We embrace transparency in reporting trial data to enable readers to interpret the results at different levels and to promote informed clinical decision-making regarding endometrial receptivity array and personalized embryo transfer.