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

我们之前报道了巨噬细胞集落刺激因子（M-CSF）和/或巨噬细胞在eCG/ hcg启动的未成熟大鼠和骨质疏松（op/op）突变小鼠中参与卵泡形成和促进排卵。在这项研究中，我们通过IVF-ET周期临床研究了血清和卵泡液中M-CSF的浓度，以及M-CSF对hMG反应不良的卵巢的有效性。血清M-CSF浓度在整个周期中逐渐升高，并在取卵当天达到峰值，而在卵巢对hMG反应较差的情况下，M-CSF浓度无明显变化。M-CSF （8 × 10^6 IU/天）被静脉注射3或7次给13个不良反应者（16个周期），他们在之前的hMG周期中没有显示卵泡发育或卵泡发育不良。根据可乐定试验结果将其分为“正常”、“亚正常”和“阴性”组。在“正常”组的5个周期中，有4个周期和“亚正常”组的5个周期中，有2个周期成功地实现了多个优势卵泡，雌二醇和黄体酮水平充足。阴性组未见多个显性卵泡。结果表明，促性腺激素反应不良的卵巢产生的M-CSF可能会受损，并证明补充M-CSF可以改善阳性（“正常”和“亚正常”）卵巢反应不良的卵泡发育。

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.