Embryos derived from small follicles (<8 mm) exhibit delayed blastulation: a retrospective time-lapse analysis

Oocytes from small follicles are frequently discarded, although they may represent an additional resource in patients with few available oocytes. This study aimed to evaluate whether blastocysts derived from follicles <8 mm exhibit altered morphokinetic patterns compared with those from larger follicles.

This retrospective study analyzed 62 blastocysts from 18 women undergoing ICSI: 20 from follicles <8 mm and 42 from follicles ≥11 mm. Morphokinetic parameters (tPNa-tB) were recorded by time-lapse monitoring. As several women contributed to both groups, linear mixed models with a random intercept for patient accounted for clustering. Oocyte- and embryo-level rates were compared using generalized estimating equations with patient as the clustering variable.

No between-group differences were observed for tPNa, tPNf or t2-t8. tSB occurred later in the <8 mm group (median 101.2 vs 95.3 h; p = 0.001), as did tB (108.1 vs 104.3 h; p=0.004). Differences persisted after accounting for within-patient clustering (tSB β = 7.91 h; tB β=8.29 h; both p<0.001). Day-5 blastocyst formation per fertilized oocyte was lower in the <8 mm group (28.8% vs 49.3%; p = 0.040), whereas overall blastocyst formation (38.5% vs 56.5%; p = 0.105) and day-6 rates (9.6% vs 7.2%; p = 0.683) did not differ significantly after accounting for within-patient clustering. Euploidy rates did not differ significantly between blastocysts derived from follicles <8 mm (5/10, 50.0%) and ≥11 mm (7/23, 30.4%; p = 0.433), although the number of biopsied embryos was small. Frozen-thawed single embryo transfer of two euploid blastocysts derived from follicles <8 mm resulted in two live births.

Follicle size is associated with the timing of blastocyst development, with embryos from smaller follicles showing an approximately 8-hour delay in blastulation. Day-6 blastocyst rates and euploidy rates did not differ significantly between groups. These exploratory findings suggest that delayed blastulation alone should not be taken as evidence of impaired developmental potential in embryos derived from small follicles.