脱氢表雄酮对卵巢储备功能减退患者IVF结局及卵泡液GDF-9、BMP-15的影响

目的 探讨脱氢表雄酮(dehydroepiandrosterone, DHEA)对卵巢储备功能减退(diminished ovarian reserve, DOR)患者的卵巢功能、卵泡液中生长分化因子-9(growth differentiation factor-9, GDF-9)、骨形态发生蛋白-15(bone morphogenetic protein-15, BMP-15)浓度及体外受精/卵胞质内单精子显微注射-胚胎移植(in vitro fertilization/intracytoplasmic sperm injection-embryo transfer, IVF/ICSI-ET)结局的影响。方法 采用历史性队列研究,共纳入163例行IVF/ICSI-ET助孕的DOR患者,根据预处理方案分为DHEA组和对照组。比较两组患者基础内分泌水平、抗苗勒管激素(anti-Müllerian hormone, AMH)、窦卵泡数(antral follicle counts, AFC)、促性腺激素(gonadotropin, Gn)总量、Gn使用天数、人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)日激素浓度和子宫内膜厚度、获卵数、成熟卵数、受精率、优胚率、胚胎种植率及临床妊娠率。比较两组患者卵泡液GDF-9、BMP-15浓度,并将其与卵巢储备功能指标进行相关性分析。结果 DHEA预处理前两组基础内分泌、AMH、AFC差异均无统计学意义(P>0.05),预处理后,DHEA组基础卵泡刺激素(basal follicle stimulating hormone, bFSH)降低、AFC增加,差异均有统计学意义(P<0.05)。Gn总量、Gn天数、hCG日激素浓度、hCG日子宫内膜厚度、获卵数、成熟卵数、受精率、优胚率、胚胎种植率、临床妊娠率差异均无统计学意义(P>0.05)。DHEA组卵泡液中BMP-15浓度高于对照组,差异有统计学意义(P<0.05),GDF-9差异无统计学意义(P>0.05)。双侧Pearson相关系数分析显示卵泡液BMP-15表达与基础雌二醇(estradiol,E₂)呈正相关。结论 DHEA可通过增加AFC和下调FSH改善DOR患者的卵巢储备功能并提高卵泡液BMP-15的浓度。

Effect of dehydroepiandrosterone on clinical outcome and GDF-9 and BMP-15 level in follicular fluid of the diminished ovarian reserve women who underwent IVF

Objective To investigate the effects of dehydroepiandrosterone (DHEA) on clinical outcome, the growth differentiation factor-9 (GDF-9), and bone morphogenetic protein-15 (BMP-15) level in follicular fluid of the diminished ovarian reserve (DOR) women who underwent in vitro fertilization embryo transfer/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).Methods A historical cohort study was performed and the clinical data of 163 DOR women undergoing IVF/ICSI-ET treatment were analyzed. According to pretreatment regiments, the patients were divided into DHEA group and control group. The indexes were compared between two groups, including serum basal hormone levels, anti-Müllerian hormone (AMH), antral follicle counts (AFC), the total doses and duration of gonadotropin (Gn), hormone levels and endometrium thickness on human chorionic gonadotropin (hCG) day, the number of retrieved oocytes, the number of fertilized oocytes, high quality embryo rate, implantation rate, and clinical pregnancy rate. The levels of GDF-9 and BMP-15 in follicular fluid were compared between the two groups, and their correlations with ovarian reserve were analyzed. Results Before pretreatment, there was no significant difference among the two groups in the basal hormone levels, AMH and AFC (P>0.05). Compared with the control group, the AFC of the DHEA group was significantly increased and the basal follicle stimulating hormone (bFSH) was slightly decreased(P<0.05). There was no significant difference between the two groups in the indexes such as the total doses and duration of Gn, hormone levels and endometrium thickness on hCG day, the number of retrieved oocytes, the number of fertilized oocytes , high quality embryo rate, implantation rate, and clinical pregnancy rate (P>0.05). Compared with the control group, the level of BMP-15 in follicular fluid of DHEA group was significantly increased (P<0.05), with no significant difference in GDF-9 (P>0.05). Bilateral Pearson correlation coefficient analysis showed that the expression of BMP-15 in follicular fluid was positively correlated with the basal estradiol (E₂). Conclusion DHEA improved the ovarian reserve of DOR women via increasing AFC and decreasing basal FSH. DHEA also increased the level of BMP-15 in follicular fluid, which was correlated with the basal E₂.