Patients
This observational, retrospective, multicenter study evaluated ART results from couples with RIF between 2013 and 2018 using data from 17 IVIRMA clinics in Europe. Infertile patients between 18 to 45 years old at the first transfer who experienced RIF after repeated ART with their own or donated oocytes had a minimum of three embryos transferred in different single embryo transfers. Patients with lacked any evidence of prior implantation events, including previous births, voluntary interruptions of pregnancy, or clinical miscarriages were included in the study. Patients with an abnormal karyotype such as translocation or an inversion carrier and with thrombophilia, either congenital or acquired, were excluded. Patients presenting severe metabolic or endocrine disorders and patients with atrophic endometrium were not included in the study. Submucous myomas or polyps, previous ET with high difficulty, and/or bleeding without previous hysteroscopy correction were excluded23.
Only embryos of good quality were transferred and day-5 embryos (blastocysts) were graded according to expansion and quality of the inner cell mass and trophoectoderm32. Patients who failed to achieve a pregnancy after transfer of three to five good quality embryos transferred in single embryo transfers were considered RIF. We have previously observed that 94.9% of patients with three embryos transferred achieve clinical pregnancy33, so we compared patients who had at least three embryos transferred with patients who had a least five embryos transferred.
A moderate RIF (M-RIF) group consisted of patients who first received at least three transferred in single embryo transfer (SET) without achieving implantation and without having received PGT-A or ERA. Subsequent ETs were categorized depending on the treatment received (Figure 1). Severe RIF (S-RIF) patients undergone five transferred embryos summed across consecutive cycles without ERA or PGT-A testing. All subsequent ET were categorized after ERA, PGT-A, or both. Patients who underwent frozen ET had either natural or hormonal cycles.