The role of macrophage colony-stimulating factor (M-CSF) on folliculogenesis and ovulation and its clinical application

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We previously reported that macrophage colony-stimulating factor (M-CSF) and/or macrophages are involved in folliculogenesis and promote ovulation in eCG/hCG-primed immature rats and osteopetrotic (op/op) mutant mice. In this study, we clinically investigated M-CSF concentrations in serum and follicular fluid through IVF-ET cycles, and the effectiveness of M-CSF on poor ovarian responders to hMG. Serum M-CSF concentration was gradually increased throughout the cycle, and reached a peak around the day of oocyte retrieval, while no significant change of M-CSF concentration was observed in cases of poor ovarian response to hMG. The M-CSF (8 X 10^6 IU/day) was administered intravenously 3 or 7 times to 13 poor responders (16 cycles), who had shown no or poor follicular development at previous hMG cycles. They were categorized as "normal", "subnormal", and "negative" group according to the results of the clonidine test. In 4 of 5 cycles in "normal" group and 2 of 5 cycles in "subnormal" group, multiple dominant follicles were successfully achieved with adequate estradiol and progesterone levels. However, no multiple dominant follicles were observed in "negative" group. The results suggested that the ovarian production of M-CSF in response to gonadotropins may be impaired in poor responders, and demonstrated that the supplementary M-CSF administration can improve the follicular development on clonidine-positive ("normal" and "subnormal") poor ovarian responders.