Wang Tzu-Hao, Chang Chia-Lin, Wu Hsien-Ming, Chiu Ya-Ming, Chen Chun-Kai, Wang Hsin-Shih
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Lin-Kou Medical Center, Taoyuan, Taiwan.
Fertil Steril. 2006 Nov;86(5):1392-401. doi: 10.1016/j.fertnstert.2006.03.064.
The objective of this study was to investigate the association between follicular fluid (FF) levels of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and pregnancy-associated plasma protein-A (PAPP-A), which is a protease for IGFBP-4, and the quality of subsequent embryo development from in vitro fertilized oocytes aspirated from the same follicle.
Prospective study.
University infertility clinic and academic research laboratory.
PATIENT(S): One hundred sixty-two infertile women undergoing controlled ovarian hyperstimulation for IVF and embryo transfer were recruited in a university hospital.
INTERVENTION(S): During oocyte retrieval, samples of 225 FFs and matched mature oocytes were collected and studied.
MAIN OUTCOME MEASURE(S): Concentrations of FF IGF-I, IGF-II, IGFBP-1, IGFBP-3, IGFBP-4, and PAPP-A were determined using ELISA. Progesterone secretion by cultured granulosa cells (GC) was measured by RIA.
RESULT(S): Levels of IGF-II, IGFBP-3, and IGFBP-4 in FF on the day of oocyte retrieval were significantly correlated with embryo scores on day 3 (72 hours after oocyte retrieval). Levels of IGF-II, IGFBP-3, and IGFBP-4 in FF from follicles in which oocytes developed into day 2 embryos (48 hours after oocyte retrieval; 20 >or= embryo score >or= 6) after fertilization were significantly higher than those from follicles in which oocytes were unable to be fertilized and were arrested in embryo development on day 2, whereas the levels of PAPP-A were significantly lower in the former than the latter group. Using multiple regression analysis, we found that high levels of IGFBP-3 and IGFBP-4 combined with low levels of PAPP-A in FF were significantly correlated with successful fertilization and early development into day 2 embryos. In contrast, high FF IGFBP-1 and IGFBP-4 in combination with low FF IGF-I were significantly correlated with a later (day 2-day 3) embryo development. A significant stimulation of P secretion in cultured GCs by the combination of recombinant IGF-II, IGFBP-3, and IGFBP-4 further strengthened these proteins' functional roles in promoting late follicular development.
CONCLUSION(S): High IGF-II, IGFBP-3, IGFBP-4, and low PAPP-A levels in FF at the time of oocyte retrieval suggest better oocyte maturation and early embryo development (within 48 hours after oocyte retrieval), whereas high IGFBP-1, IGFBP-4, and low FF IGF-I levels may favor later embryo development (between 48 and 72 hours after oocyte retrieval).
本研究的目的是调查卵泡液（FF）中胰岛素样生长因子（IGF）、IGF结合蛋白（IGFBP）以及妊娠相关血浆蛋白-A（PAPP-A，一种IGFBP-4的蛋白酶）的水平与从同一卵泡抽吸的体外受精卵母细胞随后的胚胎发育质量之间的关联。
前瞻性研究。
大学不孕不育诊所和学术研究实验室。
在一家大学医院招募了162名接受控制性卵巢过度刺激以进行体外受精和胚胎移植的不孕女性。
在卵母细胞采集过程中，收集并研究了225份卵泡液样本及配对的成熟卵母细胞。
使用酶联免疫吸附测定法（ELISA）测定卵泡液中IGF-I、IGF-II、IGFBP-1、IGFBP-3、IGFBP-4和PAPP-A的浓度。通过放射免疫分析法（RIA）测量培养的颗粒细胞（GC）的孕酮分泌。
卵母细胞采集当天卵泡液中IGF-II、IGFBP-3和IGFBP-4的水平与第3天（卵母细胞采集后72小时）的胚胎评分显著相关。受精后卵母细胞发育成第2天胚胎（卵母细胞采集后48小时；胚胎评分20≥胚胎评分≥6）的卵泡液中IGF-II、IGFBP-3和IGFBP-4的水平显著高于卵母细胞未受精且在第2天胚胎发育停滞的卵泡液，而前者的PAPP-A水平显著低于后者。使用多元回归分析，我们发现卵泡液中高水平的IGFBP-3和IGFBP-4与低水平的PAPP-A与成功受精和早期发育成第2天胚胎显著相关。相反，卵泡液中高水平的IGFBP-1和IGFBP-4与低水平的IGF-I与较晚（第2天至第3天）的胚胎发育显著相关。重组IGF-II、IGFBP-3和IGFBP-4联合对培养的颗粒细胞孕酮分泌有显著刺激作用，进一步强化了这些蛋白在促进卵泡晚期发育中的功能作用。
卵母细胞采集时卵泡液中高IGF-II、IGFBP-3、IGFBP-4和低PAPP-A水平提示卵母细胞成熟度较好和早期胚胎发育（卵母细胞采集后48小时内）良好，而高IGFBP-1、IGFBP-4和低卵泡液IGF-I水平可能有利于后期胚胎发育（卵母细胞采集后48至72小时）。
