Luteal phase stimulation in double ovarian stimulation cycles is not affected by the follicle-stimulating hormone (FSH) receptor genotype: double ovarian stimulation is beneficial independently of the genotype at position 680 of the follicle-stimulating hormone receptor.

Objectives: To determine whether follicle-stimulating hormone receptor (FSHR) genotype influences the outcome of ovarian stimulation treatment in luteal phase.

Methods: A total of 299 patients were included in a retrospective study between July 2017 and December 2021. These patients carried out a double stimulation protocol and the variant Asn680Ser (rs6166; c.2039A>G) of FSH receptor was genotyped either as part of the pre-treatment fertility tests or for the current study. Patients undergoing a double stimulation treatment who could not be genotyped were excluded from this analysis.

Results: The results obtained from ovarian stimulation in luteal phase were better than those obtained in conventional follicular phase. Statistically significant differences ( P  < 0.001) were found in the number of retrieved oocytes (5.47 vs. 4.18), retrieved MII (4.52 vs. 3.29) and fertilised oocytes (3.81 vs. 2.20). Furthermore, these differences remained regardless of the FSH receptor genotype for the 680 position in all groups ( P  < 0.05). In addition, stimulation in luteal phase lasts longer and requires more gonadotropins than in follicular phase. This is especially noteworthy in patients with Ser/Ser genotype, who required a slightly higher dose of gonadotropins compared to other genotypes in luteal phase, as previously observed in the follicular phase for this genotype. No significant differences in age, anti-Müllerian hormone levels, antral follicle count, BMI and type of trigger used in luteal phase were observed among groups of patients with different FSH receptor genotypes.

Conclusion: All patients undergoing IVF seem to benefit from luteal phase ovarian stimulation, regardless of their FSHR genotype.