多囊卵巢综合征女性IVF助孕中同型半胱氨酸水平与卵子质量关系的研究
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摘要
目的探讨接受体外受精助孕的多囊卵巢综合征(polycystic ovary syndrome,PCOS)女性患者的卵泡液同型半胱氨酸(homocysteine,Hcy)浓度与卵子及胚胎质量的关系。方法收集77对准备行IVF助孕夫妇的女性患者的取卵日卵泡液及月经周期第3天的血液标本。其中45例患者为PCOS,32例患者为输卵管因素,并且男方精液检测均在正常范围。采用酶联免疫吸附试验(ELISA)测定血清与卵泡液中Hcy的浓度;分析卵泡液、血清Hcy浓度与卵母细胞及胚胎参数之间的关系。结果 PCOS组患者血清及卵泡液Hcy浓度显著高于输卵管因素组;PCOS组患者MⅡ卵率、正常受精率及优质胚胎率均显著低于输卵管因素组;在PCOS组,按照卵泡液Hcy浓度不同将患者分成三组,MⅡ卵和MⅠ卵之间卵泡液Hcy浓度存在显著差异(P<0.001),不同组间正常受精率存在显著差异(P<0.001),1级和2级胚胎的卵泡液Hcy浓度显著低于3级胚胎(P<0.001)。结论卵泡液Hcy浓度可能对准备接受IVF助孕的PCOS女性的卵子成熟度、正常受精率及胚胎质量有一定影响。
Objective To investigate the influence of homocysteine(Hcy)in follicular fluid on oocyte and embryo qualities in polycystic ovary syndrome patients undergoing IVF.Methods The blood and follicular fluid were obtained for the determination of Hcy levels from 77 women of couples undergoing IVF treatment.The serum was obtained on the third day of menstruation,and the follicular fluid was obtained on the day of oocyte retrieval.Totally 45 patients of them were diagnosed with PCOS,other 32 patients were diagnosed with tube infertility.The sperm test results of the male were all normal.The concentration of follicular fluid and serum Hcy were measured with ELISA.The correlation between ovular,embryonic parameters and follicular fluid or serum Hcy levels were all analyzed with the statistical methods.Results The follicular fluid and serum Hcy level of the PCOS group were significant higher than those of the tube infertility group.But the MII oocyte rate,fertilization rate and high quality embryo rate of the PCOS group were significant lower than those of the tube infertility group.In the PCOS group,the patients were divided into three subgroups in accordance with the concentration of follicular fluid Hcy.There were significant difference of the follicular fluid Hcy between the MⅡoocyte group and MI oocyte group(P<0.001),and there were significant difference on the fertilization rate among the three subgroups(P<0.001).The follicular fluid Hcy level in Grade 1-2 embryos were lower than that in Grade 3 embryos.Conclusion Concentration of follicular fluid Hcy may be an influence factor on fertilization rate,oocyte and embryo quality in PCOS patients undergoing IVF.
Objective To investigate the influence of homocysteine(Hcy)in follicular fluid on oocyte and embryo qualities in polycystic ovary syndrome patients undergoing IVF.Methods The blood and follicular fluid were obtained for the determination of Hcy levels from 77 women of couples undergoing IVF treatment.The serum was obtained on the third day of menstruation,and the follicular fluid was obtained on the day of oocyte retrieval.Totally 45 patients of them were diagnosed with PCOS,other 32 patients were diagnosed with tube infertility.The sperm test results of the male were all normal.The concentration of follicular fluid and serum Hcy were measured with ELISA.The correlation between ovular,embryonic parameters and follicular fluid or serum Hcy levels were all analyzed with the statistical methods.Results The follicular fluid and serum Hcy level of the PCOS group were significant higher than those of the tube infertility group.But the MII oocyte rate,fertilization rate and high quality embryo rate of the PCOS group were significant lower than those of the tube infertility group.In the PCOS group,the patients were divided into three subgroups in accordance with the concentration of follicular fluid Hcy.There were significant difference of the follicular fluid Hcy between the MⅡoocyte group and MI oocyte group(P<0.001),and there were significant difference on the fertilization rate among the three subgroups(P<0.001).The follicular fluid Hcy level in Grade 1-2 embryos were lower than that in Grade 3 embryos.Conclusion Concentration of follicular fluid Hcy may be an influence factor on fertilization rate,oocyte and embryo quality in PCOS patients undergoing IVF.
引文
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[9]Kilic-Okman T,Guldiken S,Kucuk M.Relationship between homocysteine and insulin resistance in women with polycystic ovary syndrome[J].Endocr J,2004,51:505-508
[10]杨春伟,王晓涛,李秋云,等.不同方案超促排卵过程中黄体生成素水平对多囊卵巢综合征患者排卵的影响[J].中国煤炭工业医学杂志,2017,20(12):1411-1414
[11]黄影,王蔼明,赵勇,等.多囊卵巢综合征与高同型半胱氨酸血症相关性的研究进展[J].生殖医学杂志,2013,22(8):626-632
[12]徐彬,付建平,张羽.缺血修饰白蛋白、同型半胱氨酸对老年急性冠状动脉综合征患者早期诊疗的影响[J].中国煤炭工业医学杂志,2017,20(11):1296-1300
[13]Forges T,Monnier-Barbarino P,Alberto JM,et al.Impact of folate and homocysteine metabolism on human reproductive health[J].Hum Reprod Update,2007,13:225-238
[14]Palep-Singh M,Picton HM,Yates ZR,et al.polycystic ovary syndrome and the single nucleoti-de polymorphisms of methylenetetrahydrofolate reductase:apilot observational study[J].Hum Fertil(Camb),2007,10:33-41
[15]Palep-Singh M,Picton HM,Yates ZR,et al.Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene:Association with the polycystic ovary syndrome An observational study[J].Eur J Obstet Gynecol Reprod Biol,2008,138:180-186
[16]Boxmeer JC.The homocysteine pathway in human subfertility[M].Rotterdam:Erasmus University Rotterdam Publisher,2008:13
[17]宁艳春,王婧瑶,赵铭佳,等.卵巢子宫内膜异位症患者卵泡液炎症因子水平和卵丘颗粒细胞的变化及其与体外受精-胚胎移植结局的关系[J].中国医药,2018,13(6):910-913
[18]Ebisch IM,Peters WH,Thomas CM,et al.Homocysteine,glutathione and related thiols affect fertility parameters in the(sub)fertile couple[J].Hum Reprod,2006,21:1725-1733
[19]Berker B,Kaya C,Aytac R,et al.Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction[J].Hum Reprod,2009,24(9):2293-2302
[20]De la Calle M,Usandizaga R,Sancha M,et al.Homocysteine,folic acid and B-grou Pvitamins in obstetrics and gynaecology[J].Eur J Obster Gynecol Reprod Biol,2003,107:125-134
[21]Boxmeer JC,Brouns RM,Lindemans J,et al.Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans[J].Fertil Steril,2008,89(6):1766-1770
[22]Riley JC,Behrman HR.Oxygen radicals and reactive oxygen species in reproduction[J].Proc Soc Exp Biol Med,1991,198(3):781-791
[23]Miyazaki T,Sueoka K,Dharmarajan AM,et al.Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary[J].J Reprod Fertil,1991,91(1):207-212
[24]Cagnacci A,Generali M,Pirillo D,et al.Effects of lowor high dose hormone therapy on fasting and post methionine homocysteine levels in postmenopausal women[J].Climacteric,2006,9(5):388-395
[25]Berger PB,Herrmann RR,Dumesic DA.The effect of estrogen replacement therapy on total plasma homocysteine in healthy postmenopausal women[J].Mayo Clin Proc,2000,75(1):18-23
[2]Schacter M,Raziel A,Friedler S,et al.Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine[J].Hum Reprod,2003,8:721-727
[3]Kaya C,Cengiz SD,Berker B,et al.Comparative effects of atorvastatin and simvastatin on the plasma total homocysteine levels in women with polycystic ovary syndrome:aprospective,randomized study[J].Fertil Steril,2009,92(2):635-642
[4]Boxmeer JC,Smit M,Utomo E,et al.Low folate in seminal plasma is associated with increased sperm DNA damage[J].Fertil Steril,2009,92(2):548-556
[5]Boxmeer JC,Steegers-Theunissen RP,Lindemans J,et al.Homocysteine metabolism in the pre-ovulatory follicle during ovarian stimulation[J].Hum Reprod.2008,23(11):2570-2576
[6]Molloy AM,Brody LC,Mills JL,et al.The search for genetic polymorphisms in the homocysteine/folate pathway that contribute to the etiology of human neural tube defects[J].Birth Defects Research,2009,85:285-294
[7]Ebisch IM,Thomas CM,Peters WH,et al.The importance of folate,zinc and antioxidants in the pathogenesis and prevention of subfertility[J].Hum Reprod Update,2007,13:163-174
[8]陈子江,刘嘉茵.多囊卵巢综合征-基础理论与临床[M].第3版.北京:人民卫生出版社,2009:2-10
[9]Kilic-Okman T,Guldiken S,Kucuk M.Relationship between homocysteine and insulin resistance in women with polycystic ovary syndrome[J].Endocr J,2004,51:505-508
[10]杨春伟,王晓涛,李秋云,等.不同方案超促排卵过程中黄体生成素水平对多囊卵巢综合征患者排卵的影响[J].中国煤炭工业医学杂志,2017,20(12):1411-1414
[11]黄影,王蔼明,赵勇,等.多囊卵巢综合征与高同型半胱氨酸血症相关性的研究进展[J].生殖医学杂志,2013,22(8):626-632
[12]徐彬,付建平,张羽.缺血修饰白蛋白、同型半胱氨酸对老年急性冠状动脉综合征患者早期诊疗的影响[J].中国煤炭工业医学杂志,2017,20(11):1296-1300
[13]Forges T,Monnier-Barbarino P,Alberto JM,et al.Impact of folate and homocysteine metabolism on human reproductive health[J].Hum Reprod Update,2007,13:225-238
[14]Palep-Singh M,Picton HM,Yates ZR,et al.polycystic ovary syndrome and the single nucleoti-de polymorphisms of methylenetetrahydrofolate reductase:apilot observational study[J].Hum Fertil(Camb),2007,10:33-41
[15]Palep-Singh M,Picton HM,Yates ZR,et al.Plasma homocysteine concentrations and the single nucleotide polymorphisms in the methionine synthase gene:Association with the polycystic ovary syndrome An observational study[J].Eur J Obstet Gynecol Reprod Biol,2008,138:180-186
[16]Boxmeer JC.The homocysteine pathway in human subfertility[M].Rotterdam:Erasmus University Rotterdam Publisher,2008:13
[17]宁艳春,王婧瑶,赵铭佳,等.卵巢子宫内膜异位症患者卵泡液炎症因子水平和卵丘颗粒细胞的变化及其与体外受精-胚胎移植结局的关系[J].中国医药,2018,13(6):910-913
[18]Ebisch IM,Peters WH,Thomas CM,et al.Homocysteine,glutathione and related thiols affect fertility parameters in the(sub)fertile couple[J].Hum Reprod,2006,21:1725-1733
[19]Berker B,Kaya C,Aytac R,et al.Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction[J].Hum Reprod,2009,24(9):2293-2302
[20]De la Calle M,Usandizaga R,Sancha M,et al.Homocysteine,folic acid and B-grou Pvitamins in obstetrics and gynaecology[J].Eur J Obster Gynecol Reprod Biol,2003,107:125-134
[21]Boxmeer JC,Brouns RM,Lindemans J,et al.Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans[J].Fertil Steril,2008,89(6):1766-1770
[22]Riley JC,Behrman HR.Oxygen radicals and reactive oxygen species in reproduction[J].Proc Soc Exp Biol Med,1991,198(3):781-791
[23]Miyazaki T,Sueoka K,Dharmarajan AM,et al.Effect of inhibition of oxygen free radical on ovulation and progesterone production by the in-vitro perfused rabbit ovary[J].J Reprod Fertil,1991,91(1):207-212
[24]Cagnacci A,Generali M,Pirillo D,et al.Effects of lowor high dose hormone therapy on fasting and post methionine homocysteine levels in postmenopausal women[J].Climacteric,2006,9(5):388-395
[25]Berger PB,Herrmann RR,Dumesic DA.The effect of estrogen replacement therapy on total plasma homocysteine in healthy postmenopausal women[J].Mayo Clin Proc,2000,75(1):18-23