控制性超促排卵中卵巢低反应诊断标准研究进展

控制性超促排卵中卵巢低反应是困扰临床医生的一个难题,目前国内外对卵巢低反应的诊断标准尚未达成共识。本文将从年龄、生殖发育调节因子、促性腺激素(Gn)用量、hCG注射日优势卵泡数、窦卵泡数及获卵数等方面对控制性超促排卵中卵巢低反应诊断标准进行综述。     

抗米勒管激素在妇产科的应用

正抗米勒管激素(AMH)又被称为米勒管激素的抑制物质或抗缪勒管激素,是一种二聚体糖蛋白,属于多肽生长因子和组织生长因子β家族的一个成员。在女性,从胚胎3个月起由卵巢粒层细胞产生,从青春期开始分泌增加,在卵泡发育过程中发挥自分泌和旁分泌功能[1]。AMH反映的是卵巢中小卵泡非周期性连续生长状态。可作为临床上评估卵巢储备功能及女性生育能力的指标[2]。目前评价卵巢储备的指标有窦卵泡计数(AFC)、基础卵泡刺激素(FSH)、基础黄体生成激素(LH)、FSH/LH、AMH等。大量研究表明,AMH与年龄、促性腺激素(Gn)负相关,与AFC、获卵数、受精数、优胚数正相关,目前AMH已被认为是评价     

基础FSH/LH比值对预测年轻不孕患者IVF-ET周期卵巢反应性的影响

目的:探讨基础FSH和LH比值预测基础FSH水平正常且年轻不孕患者卵巢反应性的临床价值。方法:回顾分析2004年6月至2005年5月因男方因素或输卵管因素行体外受精-胚胎移植(in-vitrofertilization-embryotransfer,IVF-ET)治疗的年轻(年龄≤35岁)且基础FSH水平正常(≤8.5IU/L)不孕患者237例的临床资料,共计237个治疗周期,依据FSH/LH不同比例分为3组,A组(n=44)FSH/LH<1;B组(n=143)FSH/LH12;C组(n=50)FSH/LH>2。比较各组间的年龄、激素水平、卵巢反应、IVF的实验室结果以及妊娠情况。结果:3组患者的年龄、窦卵泡数、基础E2值、受精率、卵裂率和妊娠率两两相比无统计学差异(P>0.05),但A、B两组间的基础FSH值、基础LH值、E2峰值和成熟卵泡数差异有统计学意义(P<0.05);A、C两组间基础FSH值、基础LH值、E2峰值、促性腺激素(gonadotropin,Gn)总用量、Gn平均每日用量、Gn用药时间及获卵数和成熟卵泡数的差异有统计学意义(P<0.05);B、C两组间基础LH值、E2峰值、促性腺激素总用量、Gn平均每日用量和Gn用药时间比较也有明显差异(P<0.05)。结论:FSH正常的年轻妇女,FSH/LH>2的卵巢反应性明显低于FSH/LH<1者;FSH/LH比值是预测基础FSH正常且年轻不孕者卵巢反应性的一项较好指标。     

抗苗勒管激素在辅助生殖技术中预测卵巢反应性的价值

目的:探讨抗苗勒管激素(anti-Mllerian hormone,AMH/MIS)在辅助生殖技术中预测卵巢反应性的价值。方法:按纳入标准选择80例第一次接受IVF-ET治疗的患者,于启动周期月经第2天用酶联免疫吸附法(ELISA)测定血清AMH水平;电化学免疫发光法测定基础血清FSH、LH、E2、T、PRL。同时用超声诊断仪为卵巢窦卵泡计数。记录促性腺激素总量、获卵数等。结果:(1)卵巢低反应组(n=14)与正常反应组(n=66)基础AMH水平分别为0.38±0.27ng/ml、2.10±1.25ng/ml,差异有统计学意义(P<0.05);(2)获卵数与基础血清AMH、窦状卵泡数(AFC)呈正相关,相关系数分别为0.776,0.577,与FSH、FSH/LH呈负相关,相关系数分别为-0.405,-0.528。多元线性回归分析各项指标对获卵数的影响按序依次为基础血清AMH、AFC、FSH、FSH/LH、年龄;(3)基础血清AMHROCAUC为0.961。卵巢低反应的基础血清AMHCut-off值为0.562ng/ml时,其灵敏度可达96%、特异性86%,阳性预测值92.3%,阴性预测值97%。结论:辅助生殖技术中基础血清AMH水平与目前临床常用指标相比,预测卵巢反应性的诊断价值最高,且灵敏、简便、经济。     

抗苗勒氏管激素(AMH)预测卵巢储备功能及反应性的研究

目的:探讨抗苗勒氏管激素(AMH)对卵巢储备功能及卵巢反应性的预测价值。方法:利用ELISA法对228例不孕症患者基础血清AMH蛋白水平(bAMH)进行检测,其中71例初次接受IVF-ET治疗的患者,分别检测IVF周期中FSH注射后各阶段的血清及卵泡液中AMH蛋白水平,分离并采用RT-PCR检测卵巢颗粒细胞AMH mRNA相对含量。结果:①228例不孕症患者bAMH水平与窦卵泡计数成正相关(r=0.907,P<0.01),与患者年龄、初潮年龄、初潮至就诊的年数成负相关(r=-0.833,P<0.01;r=-0.580,P<0.01;r=-0.783,P<0.01)。②71例接受IVF-ET治疗的患者,bAMH与在FSH注射后各阶段血清AMH水平无明显差异(t=0.042,P>0.05;t=0.278,P>0.05;t=0.255,P>0.05)。③血清、卵泡液AMH蛋白表达及颗粒细胞AMH mRNA相对含量与卵巢反应性有关,卵巢低反应组(获卵数≤5个)与正常组(获卵数>5个)比较,差异有统计学意义(P<0.05)。④获卵数与bAMH水平均呈显著正相关(r=0.527,P<0.01)。颗粒细胞AMH mRNA相对含量与成熟卵数、受精卵数显著相关(r=0.479,P<0.01,r=0.529,P<0.01)。⑤发生卵巢过度刺激综合征患者的bAMH蛋白水平较其他患者显著增高(t=3.173,P<0.01)。结论:AMH的表达不受促性腺激素作用的影响,bAMH水平与患者卵巢的储备功能及卵巢反应性有关,可以作为评价卵巢储备功能及预测促排卵中卵巢反应性的血清学标记物。     

早卵泡期血清抗苗勒管激素水平在预测卵巢低反应中的价值探讨

目的:探讨早卵泡期血清抗苗勒管激素(AMH)水平对卵巢储备功能低下患者在控制性超排卵(COH)中预测卵巢低反应的应用价值及前景。方法:分析2013年10月至2015年6月在昆明医科大学第四附属医院接受体外受精/单精子卵母细胞内注射-胚胎移植(IVF/ICSI-ET)205个周期的患者,其中包括卵巢低反应患者70例(获卵数5个)和卵巢正常反应患者135例(15个获卵数≥5个)。在患者月经第二天或第三天清晨抽空腹静脉血,测定抗苗勒管激素(AMH)、基础卵泡刺激素(b FSH)、基础黄体生成素(b LH)及基础雌二醇(b E2)水平,同时行阴道B超检查测定窦卵泡数(AFC),以获卵数为评价标准。结果:年龄、AMH、AFC、b FSH及b FSH/b LH和获卵数存在相关性(P0.05),其中AMH相关性最强(r=0.597,P=0.000),其余相关性由强到弱为:AFCb FSH水平b FSH/b LH比值年龄。预测卵巢低反应ROC曲线下面积AMH最大,其余次序和相关性一致。预测卵巢低反应的AMH水平界值1.275μg/L(ROC曲线下面积0.823,灵敏度0.786,特异度0.852)。结论:血清AMH水平是反映卵巢储备能力的理想指标,可预测COH中卵巢低反应,用于指导临床选择合适的治疗方案。     

预测体外受精中卵巢反应性相关因素分析

目的:比较基础抑制素B(basal inhibin B,bINHB)、基础卵泡刺激素(bFSH)、年龄、窦卵泡计数(AFC)对于体外受精中卵巢反应的预测价值。方法:选取首次施行体外受精/卵胞质内单精子注射-胚胎移植(IVF/ICSI-ET)患者796例,于促排卵开始前1个月,测定月经第3日血清bINHB、bFSH水平,B超测定当日卵巢内AFC,分别比较其与获卵数的相关性。结果:bINHB、AFC与获卵数呈正相关性,相关系数(r)分别为0.147和0.661;bFSH、年龄与获卵数呈负相关,r分别为-0.239和-0.355,均P<0.001。按|r|值行相关性排序,bINHB、bFSH、年龄、AFC与获卵数相关性递增。结论:bINHB、bFSH、年龄、AFC均可以预测卵巢反应性,AFC是预测卵巢反应最好的指标。     

促性腺激素释放激素激动剂降调节后血清抑制素B水平对体外受精-胚胎移植结局的预测价值

目的 探讨促性腺激素释放激素激动剂(GnRH-a)降调节后,血清抑制素B(INHB)对体外受精-胚胎移植(IVF-ET)中卵巢反应性和IVF-ET结局的预测价值.方法 前瞻性观察124例行IVF-ET患者.超促排卵均采用GnRH-a+重组卵泡刺激素(rFSH)+人绒毛膜促性腺激素(hCG)黄体期长方案.观察指标:年龄、基础卵泡刺激素(bFSH)水平、卵泡刺激素(FSH)与黄体生成素(LH)比值、GnRH-a降调节后INHB水平、双侧卵巢内总窦卵泡数(AFC)及双侧卵巢体积.卵巢反应性评价指标为获卵数.通过多元线性回归分析、logistic同归分析评价各激素水平与卵巢反应性及IVF-ET结局的关系,计算受试者工作特征(ROC)曲线下面积(AUC),评价INHB水平预测获卵数的准确率,通过敏感度、特异度计算并确定其诊断临界值.结果 INHB水平与AFC呈显著正相关关系(r=0.435,P<0.01);多元回归分析显示,INHB水平与bFSH水平呈显著负相关关系(r=-0.239,P<0.01),与AFC(r=0.435,P<0.01)、获卵数(r=0.861,P<0.01)呈显著正相关关系,而与年龄、FSH/LH比值、卵巢体积无相关性(P>0.05).ROC曲线分析显示,GnRH-a降调节后,INHB水平的最大AUC为0.933(95%CI为0.878～0.988),将INHB水平为15 ng/L作为临界值时,其预测卵巢反应性的敏感度为95.5%,特异度为50.0%.结论 INHB水平足预测IVF-ET中卵巢反应性的最佳指标之一,INHB水平下降是卵巢储备功能下降的早期指标,但对IVF-ET结局无预测价值.     

控制性超排卵治疗中卵巢高反应影响因素分析

目的:筛选影响卵巢反应性的相关因素,用以指导临床制定合理的超排卵方案。方法:回顾性分析183例进行长方案降调下行控制性超排卵治疗者,按获卵数>15枚和4～15枚且使用Gn起步≤3支/d分为高反应组(n=96)和正常反应组(n=87)。结果:与低反应组比,高反应组窦卵泡数较多(P<0.05)、注射hCG日E2水平高(P<0.01)、基础FSH水平较低(P<0.05)。Logistic分析示基础FSH水平为保护因素(B=-0.608,P<0.01),窦卵泡数(B=1.675,P<0.01)、降调后LH水平(B=0.98,P=0.01)为危险因素。使用Gn 2支/d(75 IU/支)和3支/d起步发生高反应的几率分别是1支/d起步的7.4倍和6.7倍,而两者本身无显著差异。治疗结局:高反应组冷冻胚胎率和卵巢过度刺激综合症(OHSS)发生率均高于正常反应组(P<0.05)。结论:对于窦卵泡数多、基础FSH水平低或降调后LH水平较高的患者应尽量采用Gn 1支/d起步。     

基础窦卵泡数在评价卵巢的反应性及预测人类辅助生殖技术(ART)结局中的作用

目的:探讨基础总窦卵泡数(tAFC)在评价卵巢功能和预测ART结局中的作用。方法:回顾性分析1 353例接受常规体外受精(IVF)/卵母细胞质内单精子显微注射(ICSI)治疗的不孕患者早卵泡期窦卵泡计数的资料,按tAFC分组:A组<5个,B组5~10个,C组11~15个,D组>15个,分别统计各组促性腺激素(Gn)用量、hCG注射日直径≥14 mm卵泡数、获卵数、2原核(2PN)数、可利用胚胎数及妊娠结局。结果:tAFC对卵巢反应性和卵巢储备功能的预测价值优于年龄和基础卵泡刺激素(bFSH),tAFC<10个预示卵巢低反应性,>12个则预示卵巢高反应性;tAFC对ART结局的预测价值稍优于年龄和bFSH,tAFC>10个则预示临床妊娠可能性大,tAFC>15个或<5个则预示周期取消率增加。新鲜周期妊娠率随tAFC增多而上升(C组最高42.3%),周期取消率随tAFC增多而下降,但tAFC>15个时,周期取消率上升至24.2%,主要原因是卵巢过度刺激综合征(OHSS)。结论:基础tAFC与影响ART结局的各种因素密切相关,可作为预测ART结局的参考指标,并且直接有效地评价卵巢储备功能和卵巢反应性,是患者接受ART前的首选检查,临床应用中值得推广。     

单侧输卵管切除术对体外受精-胚胎移植周期卵巢反应性和结局的影响

目的:研究单侧输卵管切除术对体外受精-胚胎移植(IVF-ET)周期卵巢反应性和妊娠结局的影响。方法:以行IVF-ET单侧输卵管切除的106例不孕患者为研究组,同期双侧输卵管梗阻的患者360例为对照组,比较研究组输卵管切除后术侧和健侧超促排卵启动日卵巢的大小和窦卵泡数、hCG注射日卵巢的大小、≥12mm卵泡数和获卵数,同时比较研究组和对照组≥12mm卵泡数、获卵数、受精数、优质胚胎数以及Gn用量、用药天数、妊娠率。结果:研究组中术侧和健侧启动日卵巢的大小无显著性差异,然而超促排卵启动日窦卵泡数、hCG注射日双侧卵巢大小、≥12mm卵泡数和获卵数均有统计学差异。研究组无论是hCG注射日≥12mm卵泡数、获卵数、Gn用量、用药天数,还是受精数、优胚数和妊娠率与对照组比较,均无显著性差异。结论:单侧输卵管切除术降低同侧卵巢的反应性,但总体上不影响卵巢对Gn的反应和IVF-ET妊娠结局。     

Three-dimensional ultrasonographic ovarian measurements and in vitro fertilization outcome are related to age

OBJECTIVE: To evaluate whether the number of ovarian antral follicles, ovarian volume, and ovarian stromal blood flow change with age and to prospectively analyze whether three-dimensional ultrasonographic measurements predict ovarian response and IVF outcome. DESIGN: Prospective analysis. SETTING: Assisted reproductive unit. PATIENT(S): Fifty-six consecutive women 22 to 43 years of age with normal basal serum FSH concentrations who were undergoing their first IVF cycle. MAIN OUTCOME MEASURE(S): Number of ovarian antral follicles, ovarian volume, and ovarian stromal flow index were determined by three-dimensional and power Doppler ultrasonography. Pretreatment measurements were compared with number of recovered oocytes, fertilization rates, and pregnancy rates. RESULT(S): As patient age increased, significant trends in ovarian volume, number of follicles, and stromal vascularity decreased. Three-dimensional ovarian measurements and fertilization rates differed significantly among age groups. For each age group, a higher number of antral follicles, greater ovarian volume, and favorable ovarian stromal vascularity was associated with higher number of retrieved oocytes and increased pregnancy rates. CONCLUSION(S): Increasing patient age is associated with poor ovarian response, as represented by smaller ovarian volume, lower antral follicle count, and poor stromal vascularity. Three-dimensional power Doppler ultrasonography can help to individualize IVF in patients regardless of age.     

Basal antral follicle number and mean ovarian diameter predict cycle cancellation and ovarian responsiveness in assisted reproductive technology cycles

OBJECTIVE: To determine the predictive value and define threshold levels for basal antral follicle number and mean ovarian diameter in patients undergoing ART cycles. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS: Two hundred seventy-eight patients who had ovarian measurements performed on cycle day 3 before beginning treatment with gonadotropins. INTERVENTION: Pretreatment ovarian ultrasound measurements. MAIN OUTCOME MEASURE: Number of oocytes retrieved, hormone levels, and cycle outcomes. RESULTS: A direct linear correlation was observed between mean ovarian diameter and basal follicle number. Both measures demonstrated a positive linear correlation with recovered oocytes, basal E(2), and peak E(2). Both demonstrated a negative linear correlation with ampules of gonadotropins administered, days of stimulation, patient age, cycle day 3 FSH, and FSH:LH ratio. An antral follicle count of 相似文献   

Ultrasonographical predictive factors of ovarian response to stimulation prior to in vitro fertilization

OBJECTIVE: Evaluate whether ovarian antral follicles number, ovarian volume and ovarian area are predictive of ovarian response. PATIENTS AND METHODS: Prospective cohort analysis of 41 women with normal basal serum FSH concentration, who were undergoing their IVF cycle. The ovarian antral follicle number, the ovarian volume and area were determined by transvaginal ultrasonography on the third menstrual day for 20 women, and after pituitary suppression for 21 women. The main outcome measures are the number of follicles the day of HCG with a diameter >or=14 mm, the number of oocytes retrieved and the number of embryos. RESULTS: The antral follicle count was significantly correlated to the number of follicles (R=0.7; P<0.001), to the number of oocytes retrieved (R=0.46; P=0.008) and to the number of embryos (R=0.44; P=0.01). The ovarian volume and area was significantly correlated to the number of follicles. DISCUSSION AND CONCLUSION: The total antral follicle number on day 3 has a predictive value for favourable IVF outcome. Because this sonographic count is easy, safe and inexpensive it should be performed prior every IVF cycle.     

卵巢及输卵管手术对卵巢反应性的影响

目的:探讨卵巢肿瘤剔除术,输卵管手术对卵巢功能的影响。方法:以曾做卵巢肿瘤剔除术、输卵管妊娠行输卵管手术者为实验组,输卵管阻塞性不孕患者为对照组,回顾性分析两组因不孕行体外受精-胚胎移植患者的卵巢对控制性超排卵的反应。结果:实验组窦卵泡数,hCG日直径≥14mm、<14 mm的卵泡数,取卵数均明显少于对照组,促性腺激素(FSH)用量明显多于对照组;卵巢肿瘤剔除术组hCG日直径≥14 mm的卵泡数、取卵数明显少于输卵管切除术组和输卵管修补组;输卵管切除术组hCG日直径≥14 mm,<14 mm的卵泡数,取卵数均明显少于输卵管修补术组。三实验组术侧卵巢对比,卵巢肿瘤剔除术组除各项参数均明显低于输卵管切除术组及输卵管修补术组。结论:卵巢及输卵管手术均影响卵巢功能,减低卵巢储备能力,手术范围越大,损伤越大。     

The effect of aging on ovarian volume measurements in infertile women.

OBJECTIVE: To test the hypothesis that aging is associated with a decrease in ovarian volume, and that the FSH level and volume are correlated inversely. METHODS: One hundred nine women who had 73 in vitro fertilization cycles and 36 ovulation induction cycles were analyzed. Basal FSH and estradiol (E2) levels were measured on cycle day 3, and ovarian volume was measured and antral follicles were counted on the day of starting gonadotropin. RESULTS: The mean age (+/- standard deviation) was 32.6+/-4.7 years. The mean FSH was 6.9+/-2.4 IU/L. The mean ovarian volume was 6.0+/-4.7 cm3. There were no significant differences between the median volumes of the left and right ovaries in individual subjects (4.6 and 4.8 cm3, respectively; interquartile range 3.0-7.3 and 3.1-7.9; P = .79). There was a significant positive correlation between age and FSH level (R = .372, P<.001), but not between age and ovarian volume (R = .039, P = .69). A significant relation was noted between FSH and the number of follicles (H = 20.8, P<.001), but not between FSH and volume (R = .102, P = .29). There was a significant decrease in the number of follicles and a higher cycle cancellation rate in women with volume smaller than 3 cm3 compared with those with volume greater than 3 cm3. CONCLUSION: Women with small ovarian volumes, low number of antral follicles, and normal basal FSH and E2 levels may have diminished ovarian reserve.     

Sonographic assessment of ovarian reserve. Its correlation with outcome of in vitro fertilization cycles

Ovarian reserve is a crucial factor for normal ovarian response and the achievement of pregnancy after in vitro fertilization (IVF). Recently, the study of morphological markers by means of ultrasonographic counting of antral follicles (AFC) has proved useful. The present prospective study included 327 consecutive IVF patients who had a basal ultrasound scan of their ovarian reserve during the early follicular phase and had a first IVF cycle between 1 and 3 months later. We performed 313 ovum pick-ups with a mean of 11.1 ± 7.9 oocytes retrieved. The pregnancy rate per aspiration was 34.5%. Clear and significant differences were observed between normal and low response with respect to AFC, follicle-stimulating hormone (FSH) level and age. We also found that AFC correlated negatively and significantly with age, FSH and LH, and positively and also significantly with the total number of follicles, estradiol level and the number of oocytes retrieved. Using receiver operating characteristic curves, the cut-off value of AFC for poor response was 7 follicles. The value of AFC for predicting pregnancy was lower, although patients with AFC of 8 or more follicles obtained significantly higher pregnancy rates. We consider that AFC should be included in the study of the infertile patient.