网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
单纯性肥胖患者卵泡液中骨形态发生蛋白-15水平对胚胎质量的影响和初步预测价值
作者:王祁1  梁慧2 
单位:1. 徐州医科大学, 江苏 徐州 221006;
2. 徐州医科大学附属徐州妇幼保健院, 江苏 徐州 221009
关键词:骨形态发生蛋白-15 身体质量指数 卵泡液 体外受精/胞浆内单精子注射 胚胎质量 
分类号:R714.8
出版年·卷·期(页码):2024·43·第十期(1526-1534)
摘要:

目的: 探究单纯性肥胖患者取卵日卵泡液中骨形态发生蛋白-15(BMP-15)水平对体外受精/胞浆内单精子注射(IVF/ICSI)胚胎质量的影响和预测价值。方法: 选取2022年6月至2023年6月于我院生殖医学中心行IVF/ICSI助孕的118例不孕症患者为研究对象,按身体质量指数(BMI)分为对照组(18.5 kg·m-2≤BMI<24 kg·m-2)、超重组(24 kg·m-2≤BMI<28 kg·m-2)、肥胖组(BMI≥28 kg·m-2,)3组。所有患者均采用拮抗剂方案促排卵,收集月经第3天静脉血清,采用酶联免疫吸附试验法(ELISA)检测取卵日卵泡液中BMP-15含量。结果: 与对照组相比,肥胖组抗苗勒氏管激素(AMH)和基础黄体酮(bP)显著降低,肥胖组基础促卵泡生成素(bFSH)较对照组和超重组均降低,超重组bP较对照组明显降低(P<0.05)。随着BMI增加,患者促性腺激素(Gn)用量显著增加,卵泡液BMP-15水平显著降低(P<0.05)。与对照组和超重组相比,肥胖组获卵总数、MetaphaseⅡ(MⅡ)率、囊胚形成率和优质胚胎率均减少(P<0.05)。非肥胖患者BMP-15高水平组受精率、优质胚胎率和囊胚形成率较低水平组均升高(P<0.05)。肥胖患者BMP-15高水平组MⅡ率、受精率、优质胚胎率和囊胚形成率较低水平组均升高(均P<0.05)。肥胖患者卵泡液BMP-15水平与MⅡ率、受精率、优质胚胎率和囊胚形成率均呈正相关。多因素逻辑回归分析显示BMP-15、AMH和bFSH是肥胖患者胚胎质量的独立影响因素(P<0.05)。BMP-15、AMH和bFSH对肥胖患者胚胎质量结局均具有较好的预测价值,且BMP-15联合bFSH组的检测效能明显高于单独检测(P<0.05)。结论: 肥胖会降低育龄期妇女的卵泡液BMP-15表达,对胚胎质量产生负面影响,卵泡液BMP-15联合血清bFSH检测对单纯性肥胖女性胚胎质量的预测有较好效能。

Objective: To investigate the impact and predictive value of bone morphogenetic protein-15(BMP-15) levels in follicular fluid on the quality of embryos in patients with simple obesity undergoing in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI). Methods: A total of 118 infertile patients who underwent IVF/ICSI at the Reproductive Medicine Center of our hospital from June 2022 to June 2023 were enrolled. Based on body mass index(BMI), patients were divided into 3 groups: control group(18.5 kg·m-2≤BMI<24 kg·m-2), overweight group(24 kg·m-2≤BMI<28 kg·m-2), and obese group(BMI≥28 kg·m-2). All patients underwent ovarian stimulation using the antagonist protocol. Serum was collected on day 3 of menstruation, and BMP-15 levels in follicular fluid on the day of oocyte retrieval were measured using enzyme-linked immunosorbent assay(ELISA). Results: Compared to the control group, anti-Müllerian hormone(AMH) and baseline progesterone(bP) levels were significantly lower in the obese group, while baseline follicle-stimulating hormone(bFSH) levels were lower in both the obese and overweight groups(P<0.05). The amount of gonadotropins(Gn) required significantly increased with BMI, and BMP-15 levels in follicular fluid significantly decreased(P<0.05). The total number of retrieved oocytes, Metaphase Ⅱ(MⅡ) rate, blastocyst formation rate, and high-quality embryo rate were all lower in the obese group compared to the control and overweight groups(P<0.05). In non-obese patients, the high BMP-15 group had higher fertilization, high-quality embryo, and blastocyst formation rates compared to the low BMP-15 group(P<0.05). Among obese patients, the high BMP-15 group had higher MⅡ, fertilization, high-quality embryo, and blastocyst formation rates than the low BMP-15 group(all P<0.05). In obese patients, BMP-15 levels in follicular fluid were positively correlated with MⅡ rate, fertilization rate, high-quality embryo rate, and blastocyst formation rate. Multivariate Logistic regression analysis showed that BMP-15, AMH, and bFSH were independent influencing factors for embryo quality in obese patients(P<0.05). The combined detection of BMP-15 and bFSH demonstrated better predictive performance for embryo quality outcomes than individual detection(P<0.05). Conclusion: Obesity reduces BMP-15 expression in follicular fluid of women of reproductive age, negatively affecting embryo quality. The combined detection of follicular fluid BMP-15 and serum bFSH has reliable predictive value for embryo quality in women with simple obesity.

参考文献:

[1] BROUGHTON D E,MOLEY K H.Obesity and female infertility:potential mediators of obesity's impact[J].Fertil Steril,2017,107(4):840-847.
[2] 中国营养学会肥胖防控分会,中国营养学会临床营养分会,中华预防医学会行为健康分会,等.中国居民肥胖防治专家共识[J].中华流行病学杂志,2022,43(5):609-626.
[3] VAHRATIAN A.Prevalence of overweight and obesity among women of childbearing age:results from the 2002 National Survey of Family Growth[J].Matern Child Health J,2009,13(2):268-273.
[4] KNIGHT M,KURINCZUK J J,SPARK P,et al.Extreme obesity in pregnancy in the United Kingdom[J].Obstet Gynecol,2010,115(5):989-997.
[5] RAMLAU-HANSEN C H,THULSTRUP A M,NOHR E A,et al.Subfecundity in overweight and obese couples[J].Hum Reprod,2007,22(6):1634-1637.
[6] SHAH D K,MISSMER S A,BERRY K F,et al.Effect of obesity on oocyte and embryo quality in women undergoing in vitro fertilization[J].Obstet Gynecol,2011,118(1):63-70.
[7] DUBE J L,WANG P,ELVIN J,et al.The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes[J].Mol Endocrinol,1998,12(12):1809-1817.
[8] PERSANI L,ROSSETTI R,DI PASQUALE E,et al.The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders[J].Hum Reprod Update,2014,20(6):869-883.
[9] BELLI M,SHIMASAKI S.Molecular aspects and clinical relevance of GDF9 and BMP15 in ovarian function[J].Vitam Horm,2018,107:317-348.
[10] GODE F,GULEKLI B,DOGAN E,et al.Influence of follicular fluid GDF9 and BMP15 on embryo quality[J].Fertil Steril,2011,95(7):2274-2278.
[11] WU Y T,TANG L,CAI J,et al.High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development[J].Hum Reprod,2007,22(6):1526-1531.
[12] 陆菲菲,孙海翔,王玢,等.体外受精-胚胎移植者体重指数对最终妊娠结局的影响[J].现代医学,2015,43(3):300-303.
[13] 何敏,李朋粉,赵冬梅,等.人卵丘细胞PROK1表达与IVF-ET后胚胎发育及妊娠结局的关系[J].东南大学学报(医学版),2019,38(3):471-477.
[14] 黄剑磊,孙丹,马媛,等.多囊卵巢综合征患者IVF助孕卵母细胞质量及胚胎发育指标分析[J].宁夏医科大学学报,2020,42(12):1201-1205.
[15] 李华锋,顾玉婷,武传叶.染色体多态性对IVF/ICSI-ET妊娠结局的影响[J].生殖医学杂志,2024,33(2):174-179.
[16] 中国肥胖问题工作组数据汇总分析协作组.我国成人体重指数和腰围对相关疾病危险因素异常的预测价值:适宜体重指数和腰围切点的研究[J].中华流行病学杂志,2002,23(1):5-10.
[17] RACHON D,TEEDE H.Ovarian function and obesity--interrelationship,impact on women's reproductive lifespan and treatment options[J].Mol Cell Endocrinol,2010,316(2):172-179.
[18] JUNGHEIM E S,MOLEY K H.Current knowledge of obesity's effects in the pre-and periconceptional periods and avenues for future research[J].Am J Obstet Gynecol,2010,203(6):525-530.
[19] TORTORIELLO D V,MCMINN J,CHUA S C.Dietary-induced obesity and hypothalamic infertility in female DBA/2J mice[J].Endocrinology,2004,145(3):1238-1247.
[20] VAN DER STEEG J W,STEURES P,EIJKEMANS M J,et al.Obesity affects spontaneous pregnancy chances in subfertile,ovulatory women[J].Hum Reprod,2008,23(2):324-328.
[21] BROUGHTON D E,JUNGHEIM E S.A focused look at obesity and the preimplantation trophoblast[J].Semin Reprod Med,2016,34(1):5-10.
[22] 张艳,劳凯雪,李易倩,等.不同体重指数对年龄小于35岁多囊卵巢综合征患者IVF/ICSI-ET 助孕结局的影响[J].中国现代医药杂志,2022,24(8):44-47.
[23] LEARY C,LEESE H J,STURMEY R G.Human embryos from overweight and obese women display phenotypic and metabolic abnormalities[J].Hum Reprod,2015,30(1):122-132.
[24] CAO L Y,ZHANG Z Q,LIU P P,et al.Aberrant BMP15/HIF-1alpha/SCF signaling pathway in human granulosa cells is involved in the PCOS related abnormal follicular development[J].Gynecol Endocrinol,2022,38(11):971-977.
[25] SUN R Z,LEI L,CHENG L,et al.Expression of GDF-9,BMP-15 and their receptors in mammalian ovary follicles[J].J Mol Histol,2010,41(6):325-332.
[26] ARIKAN F B,SAGSOZ N.Effects of obesity on the serum BMP15,GDF9,and kisspeptin concentrations in women of reproductive age[J].J Med Biochem,2023,42(3):392-400.
[27] WU Y T,WANG T T,CHEN X J,et al.Bone morphogenetic protein-15 in follicle fluid combined with age may differentiate between successful and unsuccessful poor ovarian responders[J].Reprod Biol Endocrinol,2012,10:116.
[28] OTSUKA F,YAMAMOTO S,ERICKSON G F,et al.Bone morphogenetic protein-15 inhibits follicle-stimulating hormone(FSH) action by suppressing FSH receptor expression[J].J Biol Chem,2001,276(14):11387-11392.
[29] YAO Y L,WANG Y L,WANG F P,et al.BMP15 modulates the H19/miR-26b/SMAD1 axis influences yak granulosa cell proliferation,autophagy,and apoptosis[J].Reprod Sci,2023,30(4):1266-1280.
[30] BURATINI J,DELLAQUA T T,CANTO M D,et al.The putative roles of FSH and AMH in the regulation of oocyte developmental competence:from fertility prognosis to mechanisms underlying age-related subfertility[J].Hum Reprod Update,2022,28(2):232-254.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 839057 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

本系统由北京博渊星辰网络科技有限公司设计开发 技术支持电话:010-63361626

苏ICP备09058541