Disentangling ovarian reserve and embryo quality in vaginal progesterone effectiveness studies

Dear Editors, We congratulate Dhillon-Smith et al. for the retrospective study including >42 000 ART cycles comparing vaginal oil capsules with progesterone pessaries for luteal phase support. They report higher live birth rates and lower miscarriage rates with capsules (Dhillon-Smith et al., 2026). However, we think that residual confounding due to differences in age, ovarian reserve, and embryo competence between the two groups substantially limits inference of superiority of one formulation over the other. Women in the pessary group were significantly older (median 36 vs 35 years), had lower anti-Müllerian hormone (AMH) (14.5 vs 15.2 pmol/l), and a lower antral follicle count (AFC) (13 vs 16) compared with women receiving capsules. They also had a higher prevalence of recurrent miscarriage (4.0% vs 3.5%). Despite some controversy, several studies, including our own recent study (Lawrenz et al., 2025), suggest that diminished ovarian reserve is not only a quantitative issue but also qualitatively associated with lower euploidy rates independent of chronological age. In a pre-implantation genetic testing for aneuploidy (PGT-A) cohort, Li et al. observed that women with lower AMH had a significantly lower proportion of euploid blastocysts across age strata (Li et al., 2023), indicating that AMH carries age-independent information about oocyte/embryo competence.