卵巢功能衰退过程中卵巢大小和窦状卵泡数变化的研究

【作者】 孙宁；

【导师】 林守清；

【作者基本信息】 北京协和医学院 ， 护理学， 2011， 博士

【摘要】 [背景]超声检查因其直观、无创、可重复等特点,受到妇产科临床工作者的关注。最早多应用于观察多囊性卵巢综合征患者的卵巢情况。1970年开始使用超声指标描述多囊卵巢,1981年Swanson等人首先应用高分辨率实时经腹超声测量多囊卵巢的卵巢体积(Ovarian Volume,OV)(?)口窦状卵泡数(Antral Follicle Counts, AFC),研究多囊卵巢OV和AFC的直径。1992年Takahashi等人采用经阴超声测量多囊卵巢的卵巢面积(Ovary Area,OA),研究发现多囊卵巢与正常卵巢相比OA增大。Sample等人1977年最早超声(经腹)下使用椭圆体积公式来分析45名1-20岁正常女性的OV,研究女性发育过程的OV。Andolf等人1987年超声下研究377名40-70岁女性OV与年龄间的关系,研究结果发现OV随年龄增长而缩小。随着研究的不断深入,辅助生殖技术研究中利用OV和AFC来反映卵巢储备能力,研究结果表明随OV的缩小和AFC的减少,卵巢储备能力降低。2000-2004年5篇文献研究发现OV的改变是反映生殖衰老或绝经状态敏感且特异性的指标,Giacobbe等人2004年超声下研究192名40-55岁妇女反映绝经状态OV的特异度和敏感度,采用工作特征曲线分析结果发现OV≤4cm3时敏感度和特异度最高。国内学者1993年超声下观察359名13-71岁正常女性一生各期：青春期、生育期不同月经周期和绝经期的OV,研究结果发现生育期的排卵期OV最大,绝经期OV最小,OV随月经周期而改变。1997年协和妇科内分泌学者研究卵巢功能衰退过程中子宫面积、OA以及血E2水平的改变,结果发现MT早期与生育期妇女卵泡期相比,子宫面积增大38%,OA缩小30%,E2水平无明显下降。2008年妇科内分泌学者继续前面的研究,采用STRAW分期,前瞻性(1年)研究卵巢功能衰退过程中OA的变化,研究发现OA随卵巢功能衰退而缩小。研究认为AFC (2-10mm),与卵巢大小不同,不随月经周期的时相而变化,与年龄相关性好,研究者认为将来可能用于生殖分期的修正。2001年Flaws等人研究年龄40-54岁妇女的AFC,共59例,绝经前34例,绝经后25例,研究发现绝经前AFC(2.5±1.7)明显多于绝经后(1.1±1.3)。国内生殖衰老过程中该指标研究较少。关于超声下卵巢形态的变化多用OV,而临床目前观察卵巢大小多用两条径线,从中可以计算OA,实际应用以卵巢径线为主,检测较方便,省时。现未有在同一群病例中对OA和OV的比较,来说明OV反应卵巢大小较OA的敏感性和特异性好。AFC的临床应用也较为广泛和方便。研究表明年龄和FSH水平、月经周期的改变与生殖衰老密切相关,尤其后二者已用于生殖衰老分期。本论文基于生殖衰老的STRAW分期,较全面、系统地观察社区女性卵巢大小与AFC在生殖衰老过程中的改变,探讨其临床应用价值。本论文分三个部分第一部分卵巢功能衰退过程中卵巢大小和窦状卵泡数变化的横断面研究第二部分卵巢功能衰退过程中卵巢大小和窦状卵泡数变化的一年随访研究第三部分卵巢功能衰退过程中卵巢面积变化的四年随访研究第一部分卵巢功能衰退过程中卵巢大小和窦状卵泡数变化的横断面研究[研究目的]探讨卵巢功能衰退过程中卵巢大小和窦状卵泡数的变化。[研究内容]1.描述研究对象卵巢径线、OA、OV、AFC和FSH、E2水平的分布情况。2.分析研究对象卵巢径线、OA、OV和AFC在不同年龄之间的变化情况及与年龄的相关性。3.按照STRAW生殖衰老分期系统进行分组,比较不同绝经状态之间FSH水平、E2水平、卵巢径线、OA、OV和AFC的变化对妇女卵巢功能衰退的提示作用。4.探讨可能适于临床应用的,对卵巢功能衰退有提示价值的卵巢径线、OA、OV和AFC的界值。[研究方法]研究设计：横断面研究研究对象：年龄在17-65岁之间的女性,在过去的12个月中未使用激素治疗和口服避孕药；可以阅读和理解中文；自愿参加本研究。研究时间：2009年7月至2010年5月。研究地点：北京某高校住校女生；北京市西城区某社区。信息收集：一般人口学资料、月经史和疾病史、个人史、家族史；月经周期第3-7天的血清FSH和E2水平；月经周期第3至7天行盆腔超声检查,显示最大切面,测其纵径和前后径,探头在原位旋转90度,显示横径并测量。计算OA和OV,并动态观察双侧卵巢内AFC。 LMC≥60天者,在任意天进行检查。月经记录：采用统一的月经日记表,记录月经及可能的生活事件连续记录。质量控制：按研究开始前制定质量控制方法执行。[统计分析方法]1.研究对象一般情况及人口统计学特征的描述,计量资料采用均数及标准差来描述；计数资料用频数、百分比描述。2.研究对象卵巢径线、OA、OV和AFC及各项指标的情况采用均数及标准差描述。3.评估连续变量的个体内差异采用配对样本的Wilcoxon符号秩检验。4.研究对象各种卵巢大小和窦状卵泡数在不同年龄之间的变化情况采用Kruskal Wallis Test分析。5.研究对象卵巢大小和窦状卵泡数与年龄的相关性使用Pearson相关分析。6.按照STRAW生殖衰老分期系统进行分组,调整混杂变量后的协方差分析比较不同STRAW分期卵巢大小、卵泡数和性激素水平的变化。7.使用ROC曲线探讨卵巢大小、卵泡数、年龄和FSH水平反映绝经状态的cut-off值,将卵巢纵径、卵巢横径、卵巢前后径、OA、OV、AFC、年龄和FSH水平分别划分成7个、7个、8个、7个、6个、4个、9个和8个cut-off值,采用闭经≥12个月为绝经后,闭经<12个月为绝经前作为绝经状态的金标准。[结果]1.一般情况研究符合条件、自愿参加并完成检查480人。研究对象平均年龄为42.54±13.02岁(17.67-63.75)。平均卵巢纵径、横径和前后径分别为2.59±0.55cm、1.91±0.42cm和1.64±0.36cm;MOA为3.49±1.40cm2; MOV为4.86±2.79cm3; MAFC为3.47±1.76个；FSH和E2水平分别为29.06±31.23IU/L和50.38±71.48pg/ml。2.卵巢大小和窦状卵泡数在不同年龄变化情况(1)平均卵巢纵径、横径、前后径、MOA、MOV和MAFC在不同年龄存在统计学差异(P＜0.001)。平均卵巢纵径、横径、前后径、MOA和MOV在45-岁组下降明显,50-岁组进一步下降,最小在55～岁组；AFC从30岁开始降低,37岁呈显著下降趋势,50岁后卵泡几乎衰竭。(2) Pearson相关分析显示,平均卵巢纵径、横径、前后径、MOA、MOV和MAFC均与年龄呈显著负相关(r=-0.677；r=-0.676；r=-0.565；r=-0.618；r=-0.603；r=-0.628；P<0.01)；平均卵巢纵径和横径与年龄关系最密切。3.根据STRAW生殖衰老分期系统,将研究对象分为生育早期、生育峰期、生育晚期、MT早期、MT晚期、绝经早期和绝经晚期,对FSH、E2水平、平均卵巢纵径、横径、前后径、MOA、MOV和MAFC进行比较。(1)经调整年龄和体重指数后,七组间FSH和E2水平均存在统计学差异(p＜0.001),对各组FSH和E2比较显示：E2在生育早期组、生育峰期组分别与MT早期组、MT晚期组之间存在统计学差异(p＜0.05)；生育晚期组、MT早期组、MT晚期组分别与绝经早期、绝经晚期之间存在统计学差异(p＜0.05)。FSH水平在生育早期组、生育峰期组、生育晚期组、MT早期组分别与MT晚期组、绝经早期组、绝经晚期组之间有统计学差异(p＜0.001)。(2)经调整年龄和体重指数后,七组间平均卵巢径线、MOA、MOV和MAFC均存在统计学差异(p＜0.001),对各组卵巢大小和窦状卵泡数指标两两比较显示：平均卵巢纵径在生育早期组(3.09±0.37cm)、生育峰期组(2.97±0.33cm)、生育晚期组(2.72±0.32cm)、MT早期组(2.65±0.39cm)分别与MT晚期组(2.30±0.37cm)、绝经早期组(1.88±0.31cm)、绝经晚期组(1.77±0.24cm)之间存在统计学差异(p＜0.05)；MT晚期组与绝经早期组、绝经晚期组之间存在统计学差异(p<0.001)。平均卵巢横径在生育早期组(2.29±0.24cm)与绝经早期组(1.35±0.23cm)、绝经晚期组(1.25±0.17cm)之间存在统计学差异(p＜0.05)；在生育峰期(2.18±0.20cm)、生育晚期组(2.01±0.27cm).MT早期组(1.95±0.29cm)分别与MT晚期组(1.74±0.34cm)、绝经早期组、绝经晚期组之间存在统计学差异(p<0.05)；MT晚期组与绝经早期组、绝经晚期组之间存在统计学差异(p<0.001)。平均卵巢前后径在生育早期组(1.87±0.22cm)与生育峰期组(1.92±0.21cm)、绝经早期组(1.20±0.23cm)、绝经晚期组(1.11±0.18cm)之间存在统计学差异(p＜0.05)；在生育峰期组、生育晚期组(1.75±0.23cm)、MT早期组(1.71±0.30cm)分别与MT晚期组(1.50±0.35cm)、绝经早期组、绝经晚期组之间存在统计学差异(p<0.05); MT晚期组与绝经早期组、绝经晚期组之间存在统计学差异(p＜0.001)。MOA和MOV在生育早期组(MOA:4.60±0.99cm2;MOV:7.13±2.11cm3)与绝经早期组(MOA:1.81±0.75cm2;MOV:1.74±1.24cm3)、绝经晚期组(MOA:1.59±0.48cm2;MOV:1.36±0.66cm3)之间存在统计学差异(p＜0.05)；在生育峰期组(MOA:4.52±0.90cm2;MOV:6.66±1.79cm3)、生育晚期组(MOA:3.80±0.92cm2;MOV:5.31±2.16cm3)、MT早期组(MOA:3.66±1.19cm2; MOV:5.06±2.49cm3)分别与MT晚期组(MOA:2.81±1.17cm2;MOV:3.56±2.47cm3)、绝经早期组、绝经晚期组之间存在统计学差异(p＜0.05)；MT晚期组与绝经早期组、绝经晚期组之间存在统计学差异(p＜0.001)。MAFC在生育早期组(4.79±1.57个)与生育峰期组(4.71±1.16个)之间存在统计学差异(p=0.002)；在生育晚期组(3.15±1.39个)与MT晚期组(1.4±0.78个)之间存在统计学差异(p=0.015)。4.反映绝经状态的卵巢径线、OA、OV、AFC、年龄和FSH水平的界值卵巢纵径、横径和前后径反映绝经最好的敏感度和特异度的结合分别为≤2.1cm、≤1.6cm和≤1.4cm(纵径：敏感度86.8%,特异度为90.9%；横径：敏感度96.1%,特异度为90.3%；前后径：敏感度92.1%,特异度为86.6%)；OA、OV和AFC反映绝经最好的敏感度和特异度的结合分别为≤2.3cm2、≤3.0cm3和≤2个(OA：敏感度为88.2%,特异度为91.5%；OV：敏感度为94.7%,特异度为85.5%；AFC：敏感度为100%,特异度为84.2%)。年龄和FSH水平反映绝经最好的敏感度和特异度的结合分别为≥51岁和≥30IU/L(年龄：敏感度为94.2%,特异度为91.1%；FSH：敏感度为96.7%,特异度为85.2%)。卵巢纵径、横径、前后径、OA、OV、AFC、年龄和FSH水平ROC下的面积分别为0.925、0.978、0.971、0.955、0.974、0.933、0.976和0.949。[结论]1.卵巢径线、OA、OV和AFC在本研究人群中变化明显。2.平均卵巢径线、MOA、MOV和MAFC在不同年龄存在差异。AFC在30岁后开始下降,37岁开始明显减少。卵巢大小和窦状卵泡数与年龄相关性分析中,卵巢纵径和横径与年龄相关性最高,其次为AFC; OA与OV相比,OA与年龄相关性更高。3.按照STRAW生殖衰老分期系统进行分组,卵巢径线、OA、OV在MT早期开始变化,AFC在生育晚期开始变化。4.卵巢径线、OA、OV和AFC与年龄和FSH水平一样可以反映绝经状态。第二部分卵巢功能衰退过程中卵巢大小和窦状卵泡数变化的一年随访研究[研究目的]探讨一年内卵巢功能衰退过程中卵巢大小和窦状卵泡数的变化。[研究内容]1.描述一年内研究对象卵巢径线、OA、OV、AFC及各项指标的变化情况。2.分析一年内研究对象卵巢径线、OA、OV和AFC在不同年龄之间的变化情况。3.根据研究对象一年中月经周期的变化,按照STRAW生殖衰老分期系统进行分组,比较不同绝经状态之间激素水平、卵巢径线、OA、OV和AFC的变化。4.描述绝经时间与OA、OV、FSH和E2水平的关系。[研究方法]研究设计：前瞻性队列研究设计,随访时间1年。研究对象：同第一部分研究时间：2009年10月至2011年7月。符合条件的研究对象在入组时完成基线问卷调查和基线检查,于12个月±15天内完成随诊问卷调查和检查。研究地点：北京市西城区某社区。基线信息：同第一部分随诊信息：有关基线调查问卷内容的变化情况；血清FSH和E2水平以及盆腔超声检查,检查时间与基线相同。月经记录和质量控制：同第一部分[统计分析方法]1.研究对象一般情况及人口统计学特征的描述,计量资料采用均数及标准差来描述；计数资料用频数、百分比描述。2.基线和随访研究对象卵巢径线、OA、OV和AFC及各项指标的情况采用均数及标准差描述；绝经时间与OA、OV、FSH和E2水平的关系采用均数及标准差描述。3.一年内研究对象卵巢大小和窦状卵泡数在不同年龄间变化情况采用Kruskal Wallis Test分析。4.根据研究对象一年中月经周期的变化,按照STRAW生殖衰老分期系统进行分组,调整混杂变量后的协方差分析比较基线和随访不同STRAW分期卵巢大小和窦状卵泡数的变化。5.不同STRAW分期基线和随访之间卵巢大小、卵泡数的变化采用配对样本的Wilcoxon符号秩检验。[结果]1.一般情况研究符合条件、自愿参加并完成基线检查400人,完成随访的有349人,随访率为87.2%。研究对象基线时平均年龄为47.77±8.16岁(19.42-62.58)。基线检查平均卵巢纵径、横径和前后径分别为2.46±0.51cm、1.81±0.40cm和1.58±0.36cm,随访时分别为2.40±0.55cm、1.73±0.43cm和1.51±0.36cm。基线检查时的MOA为3.20±1.32cm2,随诊时为3.00±1.34cm2。基线检查时的MOV为4.25±2.62cm3,随诊时为3.85±2.55cm3。基线检查时的MAFC为3.05±1.64个,随诊时为2.96±1.87个。基线检查时的FSH和E2水平分别为34.0±32.2IU/L和55.8±81.1pg/ml,随诊时分别为38.2±33.0IU/L和51.2±71.4pg/ml;平均卵巢纵径、横径、前后径、MOA、MOV和FSH水平在基线和随诊之间均存在统计学差异(P<0.05)。基线MOA在4.5cm2以上的有44例(12.7%),随诊时为42例(12.1%)；基线MOA在2.0cm2以下的有71例(20.5%),随诊时为97例(28.0%)。基线MOV在8.0cm3以上的有27例(7.8%),随诊时为19例(5.5%)；基线MOV在2.0cm3以下的有73例(21.1%),随诊时为101例(29.2%)。基线MAFC≤1个的为30例(8.7%),随诊时为37例(10.7%),MAFC在随诊时缺失的更多。2.卵巢大小和窦状卵泡数随年龄的改变情况根据每位参加研究的妇女一年基线和随诊平均卵巢纵径、横径、前后径、MOA、MOV和MAFC所得的平均卵巢纵径、横径、前后径、MOA、MOV和MAFC均随年龄增长有逐渐下降趋势(P<0.001)。平均卵巢纵径、横径、前后径、MOA和MOV在45～岁组下降明显,50～岁组进一步下降,最小在55～岁组；MAFC在35～岁组下降明显,40～岁组进一步下降,最小在50～岁组。3.随访结束时,将月经周期的长度根据STRAW生殖衰老分期系统,将研究对象分为生育期组、MT早期组、MT晚期组、绝经早期组和绝经晚期组,对平均FSH、E2水平、卵巢纵径、横径、前后径、MOA、MOV和MAFC进行比较。(1)对基线和随诊各分期FSH、E2、卵巢径线、MOA、MOV和MAFC比较显示：基线和随诊的E2和FSH水平在生育期组与MT早期组之间无统计学差异(P>0.05)；绝经早期组与绝经晚期组之间无统计学差异(P>0.05)；其余各组之间均有统计学差异(p<0.001)。基线平均卵巢纵径在生育期组(2.81±0.36cm)和MT早期组(2.64±0.31cm)之间无统计学差异(p=0.286)；MT早期组和MT晚期组(2.50±0.47cm)之间无统计学差异(p=0.132)；绝经早期组(1.98±0.31cm)和绝经晚期组(1.77±0.24cm)之间无统计学差异(p=0.088)；其余各组间均存在统计学差异(p<0.001)。基线平均卵巢横径在生育期组(2.09±0.26cm)和MT早期组(1.93±0.21cm)、MT晚期组(1.91±0.40cm)之间无统计学差异(p=0.114,p=0.270)；MT早期组和MT晚期组之间无统计学差异(p=0.825)；其余各组间均存在统计学差异(p＜0.001)。基线平均卵巢前后径在生育期组(1.80±0.23cm)和MT早期组(1.70±0.25cm)、MT晚期组(1.64±0.41cm)之间无统计学差异(p=0.430,p=0.180)；MT早期组和MT晚期组之间无统计学差异(p=0.433)；绝经早期组(1.26±0.23cm)和绝经晚期组(1.10±0.15cm)之间无统计学差异(p=0.072)；其余各组间均存在统计学差异(p<0.001)。随诊平均卵巢纵径、横径和前后径均在生育期组(纵径：2.85±0.34cm；横径：2.07±0.27cm；前后径：1.79±0.23cm)和MT早期组(纵径：2.63±0.35cm；横径：1.91±0.27cm；前后径：1.66±0.27cm)之间无统计学差异(p=0.115；p=0.079；p=0.172)；绝经早期组(纵径：1.80±0.26cm；横径：1.27±0.20cm；前后径：1.14±0.20cm)和绝经晚期组(纵径：1.74±0.28cm；横径：1.22±0.21cm；前后径：1.09±0.17cm)之间无统计学差异(p=0.071；p=0.937;p=0.929)；其余各组间均存在统计学差异(p＜0.001)。基线平均MOA和MOV在生育期组(MOA:4.04±0.93cm2; MOV:5.80±2.02cm3)、MT早期组(MOA:3.58±0.92cm2; MOV:4.78±1.83cm3)、MT晚期组(MOA:3.40±1.50cm2;MOV：4.84±3.38cm3)分别与绝经早期组(MOA:2.00±0.74cm2; MOV:2.01±1.22cm3)、绝经晚期组(MOA:1.56±0.43cm2; MOV:1.35±0.62cm3)存在统计学差异(p<0.001)。基线MAFC在各组间不存在统计学差异(p->0.05)。随诊MOA和MOV在生育期组(MOA：4.06±0.99cm2；MOV：5.82±2.20cm3)和MT早期组(MOA:3.51±0.99cm2;MOV:4.67±2.00cm3)之间无统计学差异(p=0.109；p=0.076)；绝经早期组(MOA:1.65±0.54cm2;MOV:1.46±0.81cm3)和绝经晚期组(MOA:1.53±0.53cm2;MOV:1.31±0.89cm3)之间无统计学差异(p=0.190；p=0.508)；其余各组间均存在统计学差异(p<0.001)。随诊MAFC在各组不存在统计学差异(p＞0.05)。(2)经调整年龄和体重指数后,五组间FSH、E2水平、卵巢径线、MOA、MOV(?)(?)MAFC在基线和随诊之间的比较显示：MT晚期组的随诊FSH明显高于基线FSH水平(p＜0.001)；生育期组和绝经晚期组的E2水平随诊时明显高于基线水平(p＜0.05)；MT晚期组的E2水平随诊时明显低于基线水平(p=0.033)；MT晚期组和绝经早期组的随诊的平均卵巢纵径、横径、前后径、MOA、MOV和MAFC明显较基线减少(p＜0.05)；生育期组、MT早期和MT晚期组的MAFC在基线和随诊之间无统计学差异(p=0.819,p=0.077,p=0.279)。4.绝经时间与OA、OV、FSH和E2水平的关系以生育期为对照组,MOA和MOV从MT早期开始缩小,在MT晚期显著缩小,MT晚期(停经≤0.9年)和绝经后妇女与正常月经妇女比较,MOA分别缩小33.9%和58.4%,MOV分别缩小43.8%和73.5%,绝经3-5年后两者无明显继续缩小。FSH水平从MT晚期显著增加,MT晚期(停经≤0.9年)和绝经后妇女与正常月经妇女比较,FSH水平分别增加466%和662%,绝经1-5年仍处于波动状态。E2水平在MT晚期(停经≤0.9年)与正常月经妇女相比无明显变化,绝经1年后无明显降低。[结论]1.随诊一年内卵巢径线、OA、OV和AFC在本研究人群中变化明显。2.随诊一年内平均卵巢径线、MOA和MOV随年龄增长而缩小；MAFC随年龄增长而减少；MAFC在35岁后明显下降。3.根据研究对象一年中月经周期的变化,按照STRAW生殖衰老分期系统进行分组,卵巢径线、OA、OV在MT晚期明显变化,提示在MT早期开始变化,AFC从生育期开始变化。4.MT晚期与生育期妇女卵泡期相比,OA和OV显著缩小,E2水平无明显下降。第三部分卵巢功能衰退过程中卵巢面积变化的四年随访研究[研究目的]探讨卵巢功能衰退过程中卵巢面积的变化。[研究内容]1.描述基线时妇女不同STRAW分期OA的变化。2.比较基线和第四年随访不同STRAW分期OA的变化。3.分析五年所有观察对象不同STRAW分期OA的变化。[研究方法]研究设计：前瞻性队列研究设计,随访时间4年研究对象：年龄30-54岁之间；在20—30岁之间月经规律,范围在21—35天之间；在过去12个月中有月经来潮；在过去12个月中未使用激素治疗和口服避孕药；可以阅读和理解中文；在研究所涉及的社区内至少再居住1年以上；自愿参加本研究。研究时间：根据入选标准和排除标准先后于2005年6月～2005年12月和2007年4月～2007年7月,选取北京市西城区月坛街道办事处8居民委员会,愿意参加调查且签署知情同意书的妇女。符合条件的研究对象在入组时完成基线问卷调查和基线检查,于12个月±15天内完成每年随诊的问卷调查和检查。研究地点：北京市西城区某社区。基线信息和随诊信息：同第二部分月经记录和质量控制：同第一部分[统计分析方法]1.研究对象一般情况及人口统计学特征的描述,计量资料采用均数及标准差来描述；计数资料用频数、百分比描述。2.根据研究对象月经周期的变化,按照STRAW生殖衰老分期系统分组,调整混杂变量后的协方差分析比较基线和五年所有观察对象不同STRAW分期OA的差异。3.重复测量协方差分析比较基线和第四年随访不同STRAW分期者OA的差异。[结果]1.基线卵巢面积的情况根据纳入和排除标准,349人纳入基线数据分析。基线时有103人处于生育期(29.5%),有154人处于MT早期(44.1%),另有92人处于MT晚期(26.4%)；基线MOA为3.54±0.98cm2。调整年龄和BMI后,卵巢纵径、前后径、MOA在各组之间均无统计学差异(P＞0.05)。2.延续前人的工作成果,随访四年结束后,根据STRAW生殖衰老分期系统,将研究对象分为生育期组、MT早期组、MT晚期组、绝经早期组和绝经晚期组,分析随时间变化的不同时期的OA的改变。(1)基线时生育期共有65人,第四年随访时有29人过渡到MT早期,6人过渡到MT晚期。基线时MT早期104人,随访时有68人仍处于MT早期,33人过渡到MT晚期,3人绝经。基线时MT晚期有73人,第四年随访时仍处于MT晚期者33人,另外40人绝经。(2)完成四年随访的研究对象从基线到第四次随访的5次MOA在不同时间点存在显著统计学差异(P<0.001)。(3)基线时生育期的妇女平均随访3.59年后,仍然处于生育期者的MOA(4.03±1.23cm2),较基线(3.61±0.81cm2)升高(P＞0.05)；过渡至MT早期者的MOA(3.59±0.97cm2),较基线(3.29±0.81cm2)升高(P＞0.05)。MOA在生育期和MT早期之间无统计学差异(P=0.067)。基线时MT早期的妇女平均随访3.59年后,仍然处于MT早期者的MOA(3.56±0.84cm2),较基线(3.62±0.86cm2)降低(P＜0.05)。MT晚期者MOA(3.03±1.27cm2),较基线(3.55±0.69cm2)降低(P＜0.05)。MOA在MT早期和MT晚期之间无统计学差异(P=0.703)。基线MT晚期者平均随访3.59年后,仍然处于MT晚期者的MOA(2.96±1.26cm2),较基线(3.66±1.44cm2)降低(P＜0.001)。过渡至绝经早期者的MOA(1.61±0.56cm2),较基线(2.93±1.23cm2)降低(P＜0.001)。MOA在MT晚期和绝经后早期之间有统计学意义(P=0.001)。3.调整年龄和BMI后,1427个观察值的MOA从生育期到绝经早期存在不断缩小趋势(生育期：3.64±0.98cm2；MT早期：3.51±1.09cm2；MT晚期：3.05±1.33cm2；绝经早期：1.80±0.74cm2),MOA在各组之间存在显著统计学差异(P＜0.001)。[结论]1.MOA随时间的推移而缩小2.根据研究对象月经周期的变化,按照STRAW生殖衰老分期系统分组,MOA从生育期到绝经期存在不断缩小的趋势,MOA在MT早期开始变化,MT晚期显著降低。3.OA是反映卵巢大小的较好指标。更多还原

【Abstract】 Background:The ovary aging is dynamic process. The main body changes during the process include:decrease of ovary size and amounts of follicular, decrease of the fertility, the change of sexual hormone, and the menstruation changes. The increasing FSH is one of the earliest sign of ovary aging, but it may lead the increase of medical cost. STRAW system considered the changes of menstrual cycle as one the important standard of different stages of ovary aging process. Ovarian area, ovarian volume and antral follicle counts are used to assess the results of pregnant in IVF-ET. Although is one the popular receipted aging system. It still had some conflict. Ultrasound is easily to obtain results which are the response of the ovary ageing.Section one:To analyze the changes of ovarian form during the process of ovary aging.Section two:To analyze the changes of ovarian form during the process of ovary aging follow1year.Section three:To analyze the changes of OA during the process of ovary aging follow4years.Section one:The changes of ovarian form during the process of ovary agingObjective:To analyze the changes of ovarian form during the process of ovary aging.1. To describe the changes of ovarian form and hormone level.2. To analyze the changes of ovarian form with age increasing.3. To analyze the changes of ovarian form according the STRAW staging system..4. To choose the cut-off of the changes of ovarian form that can describe ovary aging used in clinics.Materials and methodsCross section study design was used in the present study. The study belonged to Community Perimenopausal Women’s Health Promotion Project.480women aged17-70years who lived Beijing community attended our survey by the purposive sample method. We conducted the survey by face-to-face interview with the questionnaire. The items of the questionnaire are detailed as follow:the basic conditions (such as age, career, education, income, etc), illness medical history, sex hormone treatment history, menstruation condition.Examination items included: 1.Serum E2and FSH:Using the electrochemiluminescence (Elecsys2010automatic electrochemiluminescence instrument made of American Roche Company). The cv for E2and FSH are6%,1.4%of interest and6.4%,4.6%of intraset respectively as baseline, and43%,0.74%of interest and5.8%.3.6%of intraset respectively as the follow up.2. OA, OV and AFC:They were assessed by transvaginal ultrasound (LOGIQ5Expert, GE) to measure the two or three diameters of ovary and count the number on a number of levels in ovary dynamically.Statistics:All data were entered into database Epidata3.02and were analyzed by SPSS15.0(Statistics Software Package for Social Science). Qualitative data were analyzed by frequency, proportion; quantitative data were analyzed by mean and standard deviation. Kruskal Wallis Test was used to analyze the changes of ovarian form in different age groups. Pearson correlation was used to analyze the relationship between ovarian form and age. Convariance was used to analyze the changes of ovarian form among different stages according STRAW staging system. ROC was used to analyze the cut-off of ovarian form to predict the menopause status.Results1. The distribution of general information480women aged17-70years participated in the data collection. The average age is42.54±13.02years (range17.67-63.75). The average length, breadth and anteroposterior diameter of ovarian are2.59±0.55cm,1.91±0.42cm and1.64±0.36cm separately. The average area of ovarian is3.49±1.40cm2.The average volume of ovarian is4.86±2.79cm3. The average AFC of ovarian is3.47±1.76. The average FSH and E2level is29.06±31.23IU/L and50.38±71.48pg/ml separately.2. The changes of ovarian form(1) The ovarian diameter, OA,OV and AFC decrease by age (P<0.001). Ovarian diameter, OA and OV decrease sharply after50years. The ovarian form is smallest between55-years. The AFC decrease sharply after35years, the AFC is smallest between50-years.(2)There is statistically negative correlation between ovarian length, breadth, anteroposterior diameter、MOA、MOV、MAFC and age (r=-0.675; r=-0.674; r=-0.566; r=-0.617; r=-0.600; r=-0.627;P<0.01)3. Participants were divided in to different groups based on STRAW aging system.(1) Compare the serum FSH and E2level in each group adjusted age and BMI.Statistically difference was found in serum E2between early reproductive, peak reproductiveand and early MT, late MT (p<0.05); between late reproductive, early MT, late MT and early postmenopause(early post-), late postmenopause(late post-) group (p<0.05). Statistically difference was found in serum FSH between early reproductive,peak reproductive, late reproductive, early MT and late MT,(early post-), late post-group (p<0.05).(2) Compare the ovarian length, breadth, anteroposterior diameter、MOA、MOV and MAFC in each group convariance adjusted age and BML.Statistically difference was found in ovarian length diameter between early reproductive, peak reproductive, late reproductive, early MT and late MT, early post-, late post-group (p<0.05); between late MT and early post-, late post-group (p<0.05).Statistically difference was found in ovarian breadth diameter between early reproductive and early pos-, late post-group (p<0.05); between peak reproductive, late reproductive, early MT and late MT, early post-, late post-group (p<0.05); between late MT and early post-, late post-group (p<0.05).Statistically difference was found in ovarian anteroposterior diameter between early reproductive and peak reproductive, early post-, late post-group (p<0.05); between peak reproductive, late reproductive, early MT and late MT, early pos-late post-group (p<0.05); between late MT and early post-, late post-group (p<0.05).Statistically difference was found in MOA and MOV between early reproductive and early post-, late post-group (p<0.05); between peak reproductive, late reproductive, early MT and late MT, early post-, late post-group (p<0.05); between late MT and early post-, late post-group (p<0.05).Statistically difference was found in MAFC between early reproductive and peak reproductive(p=0.002); between late reproductive and late MT (p=0.015).4.The cut-off of ovarian form、age and FSH level to predict menopause statusThe best sensitivity and specificity of ovarian length, breadth and diameter anteroposterior is less than2.1cm,1.6cm andl.4cm; The best sensitivity and specificity of MOA, MOV and MAFC is less than2.3cm2,3.0cm3and2; The best sensitivity and specificity of age and FSH level is more than51years and40IU/L.Conclusion1. The ovarian form changed obviously.2. The variability of Mean ovarian diameter、MOA、MOV and MAFC was decrease with the increase of age.The MAFC decrease sharply after30years. The correlation is highest between ovarian length、breadth diameter and age.3. The changes of Mean ovarian diameter、MOA、MOV and MAFC is obvious in different groups according the STRAW staging system.4. The ovarian form is similar with age and FSH level in predicting menopause.Section two:The changes of ovarian form during the process of ovary aging follow1year.Objective:To analyze the changes of ovarian form during the process of ovary aging follow1year..1. To describe the changes of ovarian form follow1year.2. To analyze the changes of ovarian form with age increasing.3. To analyze the changes of ovarian form according the STRAW staging system.4.To describe the relationship between menopausal time and OA、OV、FSH and E2Materials and methodsPerspective longitudinal study design was used in the present study. The baseline information is the same with section one. We analysis data of the baseline investigation and12months±15days follow up.400women aged17-70years who lived Beijing community attended our survey by the purposive sample method.12months±15days later these women were investigated again for changes of the above situations and re-measured the indexes below.Examination items included:the same with the section oneStatistics:Qualitative data were analyzed by frequency, proportion; quantitative data were analyzed by mean and standard deviation. Kruskal Wallis Test was used to analyze the changes of ovarian form in different age groups. Convariance was used to analyze the changes of ovarian form among different stages according STRAW staging system.Results1. The distribution of general information400women aged17-70years participated in the baseline data collection, among which349women finished the follow-up, with the follow-up rate at87.2%. The average age is47.77±8.16years (range19.42-62.58). The average length, breadth, anteroposterior diameter of ovarian are2.46±0.51cm,1.81±0.40cm,1.58±0.36cm on baseline and2.40±0.55cm,1.73±0.43cm,1.51±0.36cm on follow-up separately. The average OA,OV are3.20±1.32cm2,4.25±2.62cm3on baseline and3.00±1.34cm2,3.85±2.55cm3on follow-up separately. The average AFC are3.05±1.64and2.98±1.87on baseline and follow-up separately. The average FSH, E2level are30.12±31.60IU/L,54.8±80.5pg/ml on baseline and38.8±33.3IU/L,51.9±71.6pg/ml follow-up separately. There is statistically significance in mean ovarian diameter、MOA、MOV、MAFC、FSH and E2on baseline and follow-up (P<0.05)The percentage of ovarian area more than4.5cm2and less than2.0cm2at baseline is12.7%(44) and20.5%(71). At the12th month, the percentage of ovarian area more than4.5cm2and less than2.0cm2is12.1%(42) and28.0%(97). The percentage of ovarian volume more than8.0cm3and less than2.0cm3at baseline is7.8%(27) and21.1%(73). The percentage of ovarian volume more than8.0cm3and less than2.0cm3at follow-up is5.5%(19) and29.2%(101). The percentage of AFC less than1at baseline is8.7%(30). The percentage of AFC less than1at follow-up is10.7%(37).2. The changes of ovarian formThe mean ovarian diameter,OA,OV and AFC decrease by age (P<0.05).Ovarian diameter, OA and OV decrease sharply after50years. The ovarian form is smallest between55-years The AFC decrease sharply after35years, the AFC is smallest between50-years.3. Participants were divided in to different groups based on STRAW aging system after1year follow-up.(1)Compare the serum FSH、E2、ovarian length, breadth, anteroposterior diameter、 MO A、MOV and MAFC in each group convariance adjusted age and BMI on baseline and follow up seperately.Statistically difference was not found in serum E2and FSH level between premenopause and early MT (P>0.05); between early post-and late post-group (P>0.05) on baseline and follow-up.Statistically difference was not found in ovarian length diameter between premenopause and early MT (p=0.286); between early MT and late MT (P=0132);between early post-and late post-group (p=0.088) on baseline. Statistically difference was not found in ovarian breadth diameter between premenopause and early MT, late MT(p=0.114,p=0.270); between early MT and late MT (P=0.825) on baseline. Statistically difference was not found in ovarian anteroposterior diameter between premenopause and early MT、late MT (p=0.430,p=0.180); between early MT and late MT (P=0.433);between early post-and late post-group(p=0.072)on baseline.Statistically difference was not found in ovarian length, breadth, anteroposterior diameter between premenopause and early MT (P>0.05); between early post-and late post-group (P>0.05) on follow-up.Statistically difference was found in MO A, MOV between premenopause、early MT、 late MT and early post-, late post-group (p<0.001) on baseline. Statistically difference was not found in MAFC among different groups (p>0.05) on baseline.Statistically difference was not found in MOA,MOV between premenopause and early MT (p=0.109;p=0.076); between early post-and late post-group (p=0.190;p=0.508) on follow-up. Statistically difference was not found in MAFC among different groups (p>0.05) on follow-up.(2) Compare the ovarian length diameter、ovarian breadth diameter、ovarian anteroposterior diameter、MOA、MOV and MAFC between baseline and follow-up in each group convariance adjusted age and BML.The follow-up level on FSH is higher than the baseline level in late MT (p<0.001) The follow-up level on E2is higher than the baseline level in premenopause and late post-(p<0.05). The follow-up level on E2is lower than the baseline level in late MT (p=0.033)Statistical differences of Baseline and Follow up ovarian length diameter、breadth diameter、anteroposterior diameter、MOA、MOV and MAFC were found in late MT and early post-group (p<0.05). No Statistical difference was found between Baseline and follow-up AFC in premenopause、early MT and late MT (p<0.05).4.The relationship between menopausal time and OA、OV、FSH and E2The OA decrease sharply on late MT(33.9%) and postmenopause(58.4%) comparing with the reproductive women. The OV decrease sharply on late MT(43.8%) and postmenopause(73.5%) comparing with the reproductive women. The OA and OV did not decrease after3-5years amenorrhea. The FSH level increase sharply on late MT(466%) and postmenopause(662%) comparing with the reproductive women. The FSH level fluctuate between1and5year after menopause. The E2level have no change on late MT.Conclusion1.The ovarian form changed obviously after1year follow-up.2.The variability of mean ovarian length,breadth,anteroposterior diameter、OA、OV and AFC was decrease with the increase of age. The AFC decrease sharply after35years.3.The changes of Mean ovarian diameter、MOA、MOV and MAFC is obvious in different groups according the STRAW staging system.4.The OA and OV decrease sharply on late MT; E2level did not change obviously comparing with reproductive women. Section three:The changes of ovarian area during the process of ovary aging follow4year.Objective:To analyze the changes of ovarian area during the process of ovary aging follow4year..1. To describe the changes of ovarian area on baseline.2. To analyze the changes of ovarian area between baseline and the fourth follow-up according the STRAW staging system.3. To analyze the changes of ovarian area using all observations according the STRAW staging system.Materials and methodsPerspective longitudinal study design was used in the present study. We analysis data of the baseline investigation and4years follow up.377women aged30-54years who lived Beijing community attended our survey by the purposive sample method. The baseline and follow-up information is the same with the section two. Examination items included is the same with section one.Statistics:Qualitative data were analyzed by frequency, proportion; quantitative data were analyzed by mean and standard deviation. Convariance was used to analyze the changes of ovarian area among different stages according STRAW staging system. Repeated measure was used to analyze the changes of MOA between baseline and the fourth year follow-up.1. The distribution of MOA at baselineThe percentage of premenopause at baseline is29.5%(103). The percentage of early MT at baseline is44.1%(154). The percentage of late MT at baseline is26.4%(92). The MOA is3.54±0.98cm2(95%CI:3.34-3.73).There is no statistically significance in MOA at baseline after adjusted age and BMI (P>0.05)2. Participants were divided into different groups based on STRAW aging system.(1)There are65subjects at premenopause on baseline.29subjects enter into early MT and6subjects enter into late MT on the fourth follow-up. There are104subjects at early MT on baseline.41subjects are also in early MT,33subjects enter into late MT and3subjects enter into postmenopause on the fourth follow-up. There are73subjects at late MT on baseline.23subjects are also in late MT and40subjects enter into postmenopause on the fourth follow-up.(2)The MOA changes obviously with the time from baseline to the fourth follow-up (P< 0.001)(3)The MOA in premenopause and early MT at the fourth year follow-up is smaller than baseline after3.59years follow-up. The MOA in early MT、late MT and postmenopause at the fourth year follow-up is smaller than baseline after3.59years follow-up (P<0.05). The MOA in late MT and postmenopause at the fourth year follow-up is smaller than baseline after3.59years follow-up (P<0.05).3.The MOA of1427observations is statistically different among different groups according STRAW staging system (P<0.001).Conclusion1. The MOA have no changed obviously according the STRAW staging system.2. The variability of MOA was decrease with time3. The variability of MOA was decrease with menopause status.更多还原