In assisted reproductive technology, particularly in vitro fertilization (IVF), optimizing ovarian stimulation protocols using individualized recombinant follicle-stimulating hormone (FSH) preparations, such as follitropin delta, has gained attention for its potential to improve treatment outcomes and reduce the risk of ovarian hyperstimulation syndrome (OHSS). This study aimed to evaluate the efficacy of combining follitropin delta and clomiphene citrate (CC) in women with a suboptimal response to ovarian stimulation using follitropin alpha during IVF.

A retrospective study was conducted in women undergoing two consecutive IVF cycles at the Military Institute of Clinical Embryology and Histology, Vietnam. The first cycle utilized follitropin alpha, followed by a second cycle with follitropin delta plus CC. Embryological outcomes were assessed, including the number of stimulated follicles, the number of oocytes retrieved, and embryo quality at cleavage and blastocyst stages. A mixed-effects model with a negative binomial or Poisson distribution was applied to analyze repeated measurements within the same individual.

A total of 57 women were included in the final analysis. Following a suboptimal response to follitropin alpha, ovarian stimulation with follitropin delta plus CC resulted in a significant increase in the number of total day 3 embryos (p = 0.018), total day 5–6 embryos (p = 0.017), and good-quality blastocysts (p = 0.028). The number of stimulated follicles also showed a trend toward improvement (p = 0.043). No significant differences were observed in the number of oocytes retrieved or metaphase II (MII) oocytes.

In women who previously demonstrated a suboptimal ovarian response, follitropin delta combined with CC was associated with improved embryological outcomes compared to conventional follitropins. These findings suggest that combining follitropin delta and CC may optimise ovarian response and embryo quality in this patient population. Further studies are warranted to confirm these results and assess the impact of this combination treatment on clinical pregnancy and live birth rates.