Effect of body mass index on assisted reproductive outcomes in patients with polycystic ovary syndrome complicated with infertility
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摘要:
目的 分析BMI对多囊卵巢综合征(PCOS)合并不孕症患者胚胎质量和临床妊娠结局的影响。
方法 回顾性分析2022年1月至2024年11月在海军军医大学第一附属医院生殖医学中心接受体外受精助孕的PCOS合并不孕症患者的新鲜移植周期临床资料。共纳入198个新鲜移植周期,根据BMI的不同分为3组:正常组(BMI 18.5~23.9 kg/m2)102个、超重组(BMI 24.0~27.9 kg/m2)49个和肥胖组(BMI≥28.0 kg/m2)47个,比较3组的促排卵情况、胚胎质量和临床妊娠结局。
结果 3组患者的促性腺激素(Gn)使用总量差异有统计学意义(
P <0.001),肥胖组最多,超重组次之,正常组最少。Gn使用天数随着BMI的升高逐渐增加,其中肥胖组与正常组相比差异有统计学意义(P <0.01)。正常组的人绒毛膜促性腺激素(hCG)日雌二醇水平高于超重组和肥胖组(均P <0.01),肥胖组的hCG日孕酮水平低于正常组(P <0.016 7)。3组hCG日子宫内膜厚度随着BMI的升高呈下降趋势,但差异无统计学意义(P >0.05)。3组获卵数随着BMI的升高逐渐下降(P <0.01)。3组间正常卵裂率、新鲜胚胎移植周期种植率和新鲜移植周期临床妊娠率差异均无统计学意义(均P >0.05),后2个指标随着BMI升高呈下降趋势。正常组的正常受精率和优质囊胚形成率均高于超重组和肥胖组,差异有统计学意义(均P <0.016 7),而超重组与肥胖组之间差异无统计学意义(均P >0.05)。肥胖组的第3天可用胚胎率、第3天优质胚胎率和囊胚形成率均低于正常组与超重组,差异有统计学意义(均P <0.01),而正常组与超重组之间差异均无统计学意义(均P >0.05)。结论 在PCOS合并不孕症患者辅助生殖中,随着BMI的升高,Gn用量增加及获卵数、受精率和囊胚形成率下降。虽然种植率和临床妊娠率3组间差异无统计学意义,但随着BMI的升高有下降趋势。在临床工作中,对于PCOS合并不孕症患者,在启动促排卵治疗前注意控制其BMI在合理范围内。
Abstract:Objective To analyze the effect of body mass index (BMI) on embryo quality and clinical pregnancy outcomes in patients with polycystic ovary syndrome (PCOS) complicated with infertility.
Methods Clinical data of PCOS patients complicated with infertility who underwent
in vitro fertilization at Reproductive Medicine Center of The First Affiliated Hospital of Naval Medical University between Jan. 2022 and Nov. 2024 were retrospectively analyzed. A total of 198 fresh transfer cycles were included and assigned to 3 groups based on BMI: normal group (102 cycles, BMI 18.5-23.9 kg/m2), overweight group (49 cycles, BMI 24.0-27.9 kg/m2), or obese group (47 cycles, BMI≥28.0 kg/m2). The ovulation induction outcomes, embryo quality, and clinical pregnancy outcomes were compared among the 3 groups.Results Total gonadotropin (Gn) consumption differed significantly among the 3 groups (
P < 0.001): highest in the obese group, intermediate in the overweight group, and lowest in the normal group. The duration of Gn administration gradually increased with the elevation of BMI, with a significant difference between the obese group and the normal group (P < 0.01). The estradiol level on human chorionic gonadotropin (hCG) trigger day was significantly higher in the normal group than that in the overweight and obese groups (bothP < 0.01), whereas the progesterone level on hCG day was significantly lower in the obese group than in the normal group (P < 0.016 7). The endometrial thickness on hCG day showed a downward trend with the increase of BMI, but the difference was not significant (P > 0.05). The number of eggs obtained in the 3 groups decreased significantly with the increase of BMI (P < 0.01). There were no significant differences in the normal cleavage rate, implantation rate, or clinical pregnancy rate among the 3 groups (allP > 0.05). However, the latter 2 indicators showed a decreasing trend with increasing BMI. Normal fertilization rate and high-quality blastocyst formation rate in the normal group were significantly higher than those in the overweight and obese groups (allP < 0.016 7), but there was no significant difference between the overweight and obese groups (bothP > 0.05). The rates of D3 available embryos, high-quality embryos and blastocyst formation in the obese groups were significantly lower than those in the normal and overweight groups (allP < 0.01), but there was no significant difference between the normal and overweight groups (allP > 0.05).Conclusion In assisted reproduction for PCOS patients with infertility, as BMI increases, the dosage of Gn increases, along with decreases in the number of eggs obtained, normal fertilization rate, and blastocyst formation rate. Although there was no significant difference in implantation rate or clinical pregnancy rate among the 3 groups, there was a downward trend with the increase of BMI. It is suggested that we should control BMI in a reasonable range before ovulation induction for PCOS patients with infertility in clinical practice.
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多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期女性非常普遍和复杂的内分泌疾病,其发病原因尚不清楚,可能涉及到多基因和环境的相互作用。据预测,全球育龄女性PCOS的患病率为8%~13%[1]。PCOS以慢性排卵功能障碍、高雄激素和黄体生成素升高及胰岛素抵抗、肥胖等为特征,是导致女性不孕的主要因素之一。目前PCOS的诊断是排除性诊断,国际上先后制定了多个标准,如美国国立卫生研究院(National Institutes of Health,NIH)提出的NIH标准、欧洲人类生殖与胚胎学学会和美国生殖医学学会提出的鹿特丹标准以及美国雄激素过多协会(Androgen Excess Society,AES)提出的AES标准等。为规范PCOS的临床诊治和管理,成年PCOS的诊断采用鹿特丹标准[2]:(1)稀发排卵或者无排卵;(2)高雄激素的临床表现和/或高雄激素血症;(3)卵巢多囊改变(超声下表现为一侧或双侧卵巢内直径2~9 mm的卵泡≥12个,和/或卵巢体积≥10 mL);(4)上述项中符合2项并排除其他高雄激素病因。
已有研究表明,肥胖女性无论采取自然受孕还是辅助生殖技术助孕,其生殖结局均较差,包括生育能力下降甚至不孕、流产风险增加及不良的新生儿和孕产妇结局等[3-4]。这一现象主要由下丘脑-垂体-卵巢轴、卵母细胞质量和子宫内膜容受性之间的相互作用介导[4]。虽然其具体机制目前尚未完全阐明,但肥胖对生育能力有着直接与间接的负面影响已毫无疑问。由肥胖、不孕症和PCOS组成的三联征不可避免地相互联系。据估计,育龄妇女受PCOS影响的比例可能仍在上升[5]。在处理与PCOS相关的不孕症时,若排卵诱导治疗无效,体外受精-胚胎移植(in vitro fertilization and embryo transfer,IVF-ET)技术仍被认为是一种重要且有效的解决方法[6]。大多数确诊PCOS的患者其BMI普遍较高,统计数据显示,中国PCOS患者超重或肥胖的比例为34.0%~43.3%;在其他一些国家和地区,这一比例可高达50%~80%[7]。超重或肥胖女性PCOS的发病率是正常体重女性的4倍[8]。但目前关于肥胖对PCOS患者辅助生殖技术助孕结局影响的研究结论尚存争议,这主要与研究的样本量、研究对象等存在差异有关。另一方面,鉴于种族人口的不同,国内外对于依据BMI划分肥胖和超重的标准并不统一。本研究依据国内对BMI的划分标准,探讨BMI对PCOS合并不孕症患者辅助生殖技术助孕的影响,以完善PCOS妇女的个体风险评估,并为后续的治疗策略和方案提供信息,从而进一步优化不同BMI类别的PCOS合并不孕症患者助孕的妊娠结局。
1 资料和方法
1.1 研究对象与分组
回顾性分析2022年1月至2024年11月在海军军医大学第一附属医院生殖医学中心因女方PCOS合并不孕症行体外受精(in vitro fertilization,IVF)助孕的198例患者的新鲜移植周期临床资料。纳入标准:(1)根据欧洲人类生殖与胚胎学学会和美国生殖医学学会提出的鹿特丹标准[2]诊断为PCOS;(2)女方年龄≤38岁;(3)女方患有不孕症且接受IVF助孕治疗。排除标准:(1)女方仅出现卵巢多囊状态;(2)女方采用供卵或冻卵周期;(3)男方采用供精或冻精;(4)采用卵细胞质内单精子注射(intracytoplasmic sperm injection,ICSI)周期助孕,包括补救ICSI;(5)夫妻一方或双方合并有染色体问题或者单基因病行胚胎植入前筛查技术助孕。共纳入198个新鲜移植周期,依据亚洲BMI划分标准[9]分为3组:正常组(BMI 18.5~23.9 kg/m2)102个、超重组(BMI 24.0~27.9 kg/m2)49个和肥胖组(BMI≥28.0 kg/m2)47个。
1.2 研究方法
1.2.1 控制性促排卵和取卵
月经来潮第3天检测血清激素并行阴道超声检查,以评估卵巢基础状态,条件适宜时开始应用促排卵药物控制性促排卵。促排卵期间监测阴道超声及雌二醇、孕酮和促黄体生成素,卵泡直径增长至12 mm以上时加用促性腺激素(gonadotropin,Gn)释放激素拮抗剂,持续应用至触发日,待卵泡直径>18 mm时予以人绒毛膜促性腺激素(human chorionic gonadotropin,hCG)或注射用重组绒促性素扳机,触发后36~37 h取卵。
1.2.2 精液收集及处理
采用WHO标准进行精液的常规分析。男方禁欲3~7 d,取卵当天上午男方来院用手淫法取精,收集全部精液于无菌无毒容器内。收集的精液置室温液化后根据精液质量采用密度梯度离心法或直接离心法进行洗涤。
1.2.3 受精及胚胎培养
在恒温倒置显微镜下观察受精情况,以出现双原核作为正常受精标志。将正常受精的合子移入新鲜的培养液微滴中继续单独培养,并在授精后继续观察胚胎发育情况。第3天根据卵裂球数目、形态、大小是否均匀及碎片多少对胚胎进行质量评估,分为Ⅰ、Ⅱ、Ⅲ、Ⅳ级。正常受精卵在发育至第3天时,如形成6个或以上大小均一的卵裂球,且胚胎碎片在15%以内,视为优质胚胎。结合患者意愿及胚胎情况,决定是否进行囊胚培养。如果继续体外培养,在第5天和第6天观察囊胚的形成并根据Garden评分系统对囊胚进行评估,3期或者3期以上且内细胞团和囊胚滋养层评分不含C级的囊胚视为优质囊胚。
1.2.4 妊娠结局的确定
移植术后第12~14天检测血清β-hCG呈阳性、第4~7周超声下观察到宫腔内孕囊和原始心管搏动,判定为临床妊娠,之后定期随访。
1.2.5 观察指标的计算
正常受精率(%)=双原核卵子数/卵子总数×100%;正常卵裂率(%)=正常卵裂胚胎数/正常受精卵子数×100%;第3天可用胚胎率(%)=第3天可利用胚胎数/正常受精卵子数×100%;第3天优质胚胎率(%)=第3天优质胚胎数/正常受精卵子数×100%;囊胚形成率(%)=2期及2期以上囊胚数/行囊胚培养的卵裂期胚胎总数×100%;优质囊胚形成率(%)=优质囊胚数/行囊胚培养的卵裂期胚胎总数×100%;新鲜胚胎移植周期种植率(%)=着床胚胎数/新鲜移植胚胎数×100%;新鲜移植周期临床妊娠率(%)=临床妊娠周期数/新鲜移植周期总数×100%。
1.3 统计学处理
应用SPSS 20.0软件进行统计学分析。计数资料以频数和百分数表示,组间比较采用χ2检验。符合正态分布的计量资料以x±s表示,多组间比较采用方差分析;不符合正态分布的计量资料以M(Q1,Q3)表示,采用非参数检验。采用Bonferroni法进行两组间多重比较。检验水准(α)为0.05。
2 结果
2.1 3组患者间一般情况比较
3组PCOS合并不孕症患者之间平均年龄和新鲜移植第3天卵裂期胚胎个数的差异无统计学意义(均P>0.05)。不孕年限在超重组和正常组之间差异无统计学意义(P>0.05),但肥胖组明显高于正常组和超重组,差异有统计学意义(均P<0.016 7)。3组之间BMI和获卵数的差异均有统计学意义(均P<0.01),且随着BMI的升高,获卵数逐渐下降。见表 1。
表 1 3组PCOS合并不孕症患者一般情况比较Table 1 Comparison of general characteristics among 3 groups of PCOS patients with infertilityx±s Parameter Normal n=102 Overweight n=49 Obese n=47 F value P value Infertility age/year 30.55±3.19 31.39±2.69 30.66±3.76 1.165 0.314 Infertility duration/year 2.81±1.86 2.88±2.09 4.07±2.29*△ 6.705 0.002 Maternal BMI/(kg·m-2) 21.07±1.43 25.53±1.17* 31.85±3.82*△ 390.814 <0.001 Number of eggs obtained 17.18±8.58 14.50±11.27* 10.68±10.07*△ 7.362 0.001 Number of embryos transferred 1.75±0.44 1.46±0.52 1.68±0.48 1.692 0.193 *P<0.016 7 vs normal group; △P<0.016 7 vs overweight group. PCOS: Polycystic ovary syndrome; BMI: Body mass index. 2.2 3组患者控制性促排卵情况比较
3组PCOS合并不孕症患者的Gn使用总量随着BMI的升高而增加,且肥胖组与正常组和超重组之间差异均有统计学意义(均P<0.01)。随着BMI的升高,3组Gn使用天数相应增加,但超重组与正常组、肥胖组之间差异无统计学意义(均P>0.05),仅正常组与肥胖组之间差异有统计学意义(P<0.01)。3组之间hCG日子宫内膜厚度差异无统计学意义(P>0.05),但随着BMI的升高呈下降趋势。hCG日雌二醇和孕酮水平随着BMI的升高而下降,其中正常组的雌二醇水平与超重组、肥胖组相比差异均有统计学意义(均P<0.01),但超重组和肥胖组之间差异无统计学意义(P>0.05);孕酮水平仅肥胖组与正常组之间差异有统计学意义(P<0.016 7)。见表 2。
表 2 3组PCOS合并不孕症患者控制性促排卵情况比较Table 2 Comparison of controlled ovarian hyperstimulation among 3 groups of PCOS patients with infertilityParameter Normal n=102 Overweight n=49 Obese n=47 F/Z value P value Total amount of Gn/U, x±s 1 598.85±510.64 1 791.85±665.67 2 365.22±803.16**△△ 23.663 <0.001 Gn duration/d, x±s 9.54±1.91 10.10±2.80 11.00±3.13** 5.569 0.004 Endometrial thickness on hCG day/mm, x±s 11.02±2.23 10.62±2.43 10.20±2.60 1.678 0.190 Estradiol level on hCG day/(pg·mL-1), M(Q1,Q3) 3 276.00(1 949.00, 6 423.00) 3 017.00(893.60, 4 652.50)** 1 886.00(946.60, 4 013.00)** 11.599 0.003 Progesterone level on hCG day/(ng·mL-1), M(Q1,Q3) 0.83 (0.41, 1.43) 0.54 (0.30, 0.99) 0.46 (0.27, 0.78)* 12.460 0.002 *P<0.016 7, **P<0.01 vs normal group; △△P<0.01 vs overweight group. PCOS: Polycystic ovary syndrome; Gn: Gonadotropin; hCG: Human chorionic gonadotropin. 2.3 3组患者胚胎结局和临床妊娠情况比较
3组PCOS合并不孕症患者的正常卵裂率比较差异无统计学意义(P>0.05)。除正常卵裂率外,其余统计指标大多随着BMI的升高而呈下降趋势。正常组的正常受精率和优质囊胚形成率均高于超重组和肥胖组,差异有统计学意义(均P<0.016 7),而超重组与肥胖组之间差异无统计学意义(P>0.05)。肥胖组的第3天可用胚胎率、第3天优质胚胎率和囊胚形成率均低于正常组与超重组,差异有统计学意义(均P<0.01),而正常组与超重组之间差异均无统计学意义(均P>0.05)。所有移植均为新鲜第3天卵裂期胚胎移植,3组间新鲜胚胎移植周期种植率和新鲜移植周期临床妊娠率之间差异均无统计学意义(均P>0.05)。见表 3。
表 3 3组PCOS合并不孕症患者胚胎结局和临床妊娠情况比较Table 3 Comparison of embryo quality and pregnancy outcomes among 3 groups of PCOS patients with infertility% (n/N) Parameter Normal Overweight Obese χ2 value P value Normal fertilization rate 72.74 (1 145/1 574)*△ 62.11 (423/681) 58.37 (293/502) 47.829 <0.001 Normal cleavage rate 98.25 (1 125/1 145) 97.64 (413/423) 98.29 (288/293) 0.695 0.706 D3 available embryo rate 80.00 (916/1 145)△△ 78.72 (333/423)△△ 63.82 (187/293) 35.405 <0.001 D3 high-quality embryo rate 68.91 (789/1 145)△△ 69.74 (295/423)△△ 52.56 (154/293) 30.543 <0.001 Blastocyst formation rate 81.90 (552/674)△△ 78.28 (191/244)△△ 63.41 (78/123) 21.389 <0.001 High-quality blastocyst formation rate 47.77 (322/674)*△ 38.52 (94/244) 36.59 (45/123) 8.964 0.011 Implantation rate 48.98 (24/49) 47.37 (9/19) 34.38 (11/32) 1.784 0.410 Clinical pregnancy rate 67.86 (19/28) 53.85 (7/13) 52.63 (10/19) 1.355 0.508 *P<0.016 7 vs overweight group; △P<0.016 7, △△P<0.01 vs obese group. PCOS: Polycystic ovary syndrome; D3: Day 3. 3 讨论
PCOS患者中超重或肥胖现象较为常见,其会进一步加重内在的胰岛素抵抗及PCOS的临床表现[10]。然而PCOS并不局限于超重或肥胖的人群,体重正常甚至体重过轻的女性也可能患病。因此,PCOS可见于所有BMI类别的人群,但与BMI较高的人群相比,低BMI人群的发病率通常较低[11]。与非PCOS女性相比,患有PCOS的女性更易出现焦虑、抑郁、生育力低下以及生活质量下降的现象[12]。为深入研究BMI对接受IVF-ET治疗的PCOS患者促排卵和胚胎结局的影响,并为临床实践中针对不同类型PCOS患者的治疗提供参考,本研究按照亚洲BMI分类,将PCOS合并不孕症患者分为正常组、超重组和肥胖组,结果发现在促排卵方面,随着BMI的升高,不孕年限、Gn使用总量、Gn使用天数也随之增加,其中正常组的不孕年限和Gn使用天数明显低于肥胖组,且差异有统计学意义(均P<0.016 7)。3组之间获卵数的差异有统计学意义(P=0.001),肥胖组患者的Gn使用总量比正常组高,获得的卵子数反而最少。结果表明较高的BMI不利于排卵,肥胖的PCOS女性通常需要更高剂量的Gn和更长的促排周期诱发排卵[13]。研究显示,一方面BMI升高会降低血清Gn的有效浓度,另一方面脂肪组织作为一种高度特化的内分泌与旁分泌器官,能促使瘦素、脂联素等脂肪细胞因子分泌增加。这些药代动力学的改变可能导致相应的Gn抵抗[14],使得超重和肥胖PCOS女性Gn用量和使用天数往往多于BMI正常的PCOS患者。因此,肥胖的PCOS患者在促排卵前适当减重有利于促排卵,维持BMI在正常范围可减少Gn用量和使用时间,且能增加获卵数目。本研究结果与大多数研究[15-16]相符。
本研究结果显示,3组新鲜胚胎平均移植个数差异无统计学意义(P>0.05),而hCG日子宫内膜厚度和hCG日的雌二醇、孕酮水平随着BMI升高呈下降趋势,正常组hCG日雌二醇水平明显高于超重组和肥胖组,差异有统计学意义(均P<0.01)。在胚胎结局和临床妊娠方面,3组正常卵裂率相对一致,较为固定,表明卵裂率是与BMI无关的一个指标。其余相关胚胎和临床妊娠结局统计指标随着BMI升高一致呈下降趋势。近年来有越来越多的研究表明女性PCOS的发生、发展与系统性低分化慢性炎症状态及细胞因子的水平相关,如IL-6、IL-18、TNF等[17]。低分化慢性炎症状态主要是与体内脂肪的聚集有关,其会影响PCOS患者的卵巢功能、受精和胚胎的发育及后续植入潜能等[18]。卵泡液中细胞因子的改变会影响颗粒细胞功能,干扰卵子的生长发育[19]。超重或肥胖的PCOS患者,其体内过多的脂肪组织可以促使细胞因子和脂肪因子大量释放,影响卵子和胚胎的发育。此外,肥胖女性卵母细胞纺锤体容易异常和排列紊乱,在一定程度上也干扰了卵母细胞的质量[20],导致相关统计指标随着BMI的升高呈逐渐降低趋势,在囊胚形成率这一指标上尤为凸显。Zhou等[15]分析了1 782例35岁以下接受IVF/ICSI治疗的PCOS患者,低BMI(<18.5 kg/m2)组42例、正常BMI(18.5 kg/m2≤BMI<25 kg/m2)组800例、超重(25 kg/m2≤BMI<30 kg/m2)组742例、肥胖组(≥30 kg/m2)198例。结果发现Gn使用剂量和使用天数在低BMI和正常BMI组患者间差异均无统计学意义(均P>0.05),但均低于超重组和肥胖组(均P<0.008);hCG注射日雌二醇水平及获卵数却与之相反,正常BMI组明显高于超重组和肥胖组(均P<0.008);4组间hCG日子宫内膜厚度、种植率和临床妊娠率差异均无统计学意义(均P>0.05)。Li等[21]的研究共纳入966例接受IVF治疗的PCOS女性,根据取卵前一天血液样本的甘油三酯血糖-体重指数(triglyceride glucose-body mass,TyG-BMI)对患者进行四分位数分组,比较了4组患者的临床和实验室结果的差异,发现Q1到Q4组患者的获卵数、双原核卵子数和触发日雌二醇及孕酮水平逐渐下降(均P<0.05),4组卵裂率均衡在99.82%~99.39%之间,Q1到Q4组的Gn起始剂量和总剂量及持续天数逐渐增加。本研究样本量虽小于这些已有研究,但本研究结果与这些大样本回顾性研究基本一致。后续将在适当扩大样本量的基础上,进一步分析不同BMI类别的PCOS患者孕产期和子代围生期结局。
总的来说,在处理肥胖PCOS合并不孕症患者促排卵时,需综合考虑采取生活方式干预、药物治疗、代谢管理及个体化的促排卵方案,逐步调整促排卵药物的剂量,并结合超声密切监测卵泡发育情况。通过这些综合策略,可在控制肥胖及相关代谢风险的同时,有效促进排卵,从而优化整体健康状况及妊娠结局。
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表 1 3组PCOS合并不孕症患者一般情况比较
Table 1 Comparison of general characteristics among 3 groups of PCOS patients with infertility
x±s Parameter Normal n=102 Overweight n=49 Obese n=47 F value P value Infertility age/year 30.55±3.19 31.39±2.69 30.66±3.76 1.165 0.314 Infertility duration/year 2.81±1.86 2.88±2.09 4.07±2.29*△ 6.705 0.002 Maternal BMI/(kg·m-2) 21.07±1.43 25.53±1.17* 31.85±3.82*△ 390.814 <0.001 Number of eggs obtained 17.18±8.58 14.50±11.27* 10.68±10.07*△ 7.362 0.001 Number of embryos transferred 1.75±0.44 1.46±0.52 1.68±0.48 1.692 0.193 *P<0.016 7 vs normal group; △P<0.016 7 vs overweight group. PCOS: Polycystic ovary syndrome; BMI: Body mass index. 表 2 3组PCOS合并不孕症患者控制性促排卵情况比较
Table 2 Comparison of controlled ovarian hyperstimulation among 3 groups of PCOS patients with infertility
Parameter Normal n=102 Overweight n=49 Obese n=47 F/Z value P value Total amount of Gn/U, x±s 1 598.85±510.64 1 791.85±665.67 2 365.22±803.16**△△ 23.663 <0.001 Gn duration/d, x±s 9.54±1.91 10.10±2.80 11.00±3.13** 5.569 0.004 Endometrial thickness on hCG day/mm, x±s 11.02±2.23 10.62±2.43 10.20±2.60 1.678 0.190 Estradiol level on hCG day/(pg·mL-1), M(Q1,Q3) 3 276.00(1 949.00, 6 423.00) 3 017.00(893.60, 4 652.50)** 1 886.00(946.60, 4 013.00)** 11.599 0.003 Progesterone level on hCG day/(ng·mL-1), M(Q1,Q3) 0.83 (0.41, 1.43) 0.54 (0.30, 0.99) 0.46 (0.27, 0.78)* 12.460 0.002 *P<0.016 7, **P<0.01 vs normal group; △△P<0.01 vs overweight group. PCOS: Polycystic ovary syndrome; Gn: Gonadotropin; hCG: Human chorionic gonadotropin. 表 3 3组PCOS合并不孕症患者胚胎结局和临床妊娠情况比较
Table 3 Comparison of embryo quality and pregnancy outcomes among 3 groups of PCOS patients with infertility
% (n/N) Parameter Normal Overweight Obese χ2 value P value Normal fertilization rate 72.74 (1 145/1 574)*△ 62.11 (423/681) 58.37 (293/502) 47.829 <0.001 Normal cleavage rate 98.25 (1 125/1 145) 97.64 (413/423) 98.29 (288/293) 0.695 0.706 D3 available embryo rate 80.00 (916/1 145)△△ 78.72 (333/423)△△ 63.82 (187/293) 35.405 <0.001 D3 high-quality embryo rate 68.91 (789/1 145)△△ 69.74 (295/423)△△ 52.56 (154/293) 30.543 <0.001 Blastocyst formation rate 81.90 (552/674)△△ 78.28 (191/244)△△ 63.41 (78/123) 21.389 <0.001 High-quality blastocyst formation rate 47.77 (322/674)*△ 38.52 (94/244) 36.59 (45/123) 8.964 0.011 Implantation rate 48.98 (24/49) 47.37 (9/19) 34.38 (11/32) 1.784 0.410 Clinical pregnancy rate 67.86 (19/28) 53.85 (7/13) 52.63 (10/19) 1.355 0.508 *P<0.016 7 vs overweight group; △P<0.016 7, △△P<0.01 vs obese group. PCOS: Polycystic ovary syndrome; D3: Day 3. -
[1] ALENEZI S A, KHAN R, AMER S. The impact of high BMI on pregnancy outcomes and complications in women with PCOS undergoing IVF-a systematic review and meta-analysis[J]. J Clin Med, 2024, 13(6): 1578. DOI: 10.3390/jcm13061578. [2] Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome[J]. Fertil Steril, 2004, 81(1): 19-25. DOI: 10.1016/j.fertnstert.2003.10.004. [3] SEBIRE N J, JOLLY M, HARRIS J P, et al. Maternal obesity and pregnancy outcome: a study of 287, 213 pregnancies in London[J]. Int J Obes Relat Metab Disord, 2001, 25(8): 1175-1182. DOI: 10.1038/sj.ijo.0801670. [4] TALMOR A, DUNPHY B. Female obesity and infertility[J]. Best Pract Res Clin Obstet Gynaecol, 2015, 29(4): 498-506. DOI: 10.1016/j.bpobgyn.2014.10.014. [5] MARCH W A, MOORE V M, WILLSON K J, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria[J]. Hum Reprod, 2010, 25(2): 544-551. DOI: 10.1093/humrep/dep399. [6] BUYALOS R P, LEE C T. Polycystic ovary syndrome: pathophysiology and outcome with in vitro fertilization[J]. Fertil Steril, 1996, 65(1): 1-10. DOI: 10.1016/s0015-0282(16)58017-0. [7] LIM S S, DAVIES M J, NORMAN R J, et al. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis[J]. Hum Reprod Update, 2012, 18(6): 618-637. DOI: 10.1093/humupd/dms030. [8] ALVAREZ-BLASCO F, BOTELLA-CARRETERO J I, SAN MILLÁN J L, et al. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women[J]. Arch Intern Med, 2006, 166(19): 2081-2086. DOI: 10.1001/archinte.166.19.2081. [9] 孙长颢. 营养与食品卫生学[M]. 6版. 北京: 人民卫生出版社, 2011: 183-189. [10] BAHRI KHOMAMI M, SHORAKAE S, HASHEMI S, et al. Systematic review and meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome[J]. Nat Commun, 2024, 15(1): 5591. DOI: 10.1038/s41467-024-49749-1. [11] MOHAPATRA I, SAMANTARAY S R. BMI and polycystic ovary syndrome: demographic trends in weight and health[J]. Cureus, 2024, 16(3): e55439. DOI: 10.7759/cureus.55439. [12] YIN X, JI Y, CHAN C L W, et al. The mental health of women with polycystic ovary syndrome: a systematic review and meta-analysis[J]. Arch Womens Ment Health, 2021, 24(1): 11-27. DOI: 10.1007/s00737-020-01043-x. [13] OZGUN M T, ULUDAG S, ONER G, et al. The influence of obesity on ICSI outcomes in women with polycystic ovary syndrome[J]. J Obstet Gynaecol, 2011, 31(3): 245-249. DOI: 10.3109/01443615.2010.546906. [14] O'ROURKE R W. Adipose tissue and the physiologic underpinnings of metabolic disease[J]. Surg Obes Relat Dis, 2018, 14(11): 1755-1763. DOI: 10.1016/j.soard.2018.07.032. [15] ZHOU H, ZHANG D, LUO Z, et al. Association between body mass index and reproductive outcome in women with polycystic ovary syndrome receiving IVF/ICSI-ET[J]. Biomed Res Int, 2020, 2020: 6434080. DOI: 10.1155/2020/6434080. [16] BAILEY A P, HAWKINS L K, MISSMER S A, et al. Effect of body mass index on in vitro fertilization outcomes in women with polycystic ovary syndrome[J]. Am J Obstet Gynecol, 2014, 211(2): 163.e1-163.e6. DOI: 10.1016/j.ajog.2014.03.035. [17] RUDNICKA E, SUCHTA K, GRYMOWICZ M, et al. Chronic low grade inflammation in pathogenesis of PCOS[J]. Int J Mol Sci, 2021, 22(7): 3789. DOI: 10.3390/ijms22073789. [18] SHANG J, WANG S, WANG A, et al. Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment[J]. Reprod Biol Endocrinol, 2024, 22(1): 11. DOI: 10.1186/s12958-023-01183-6. [19] LIU Y, LIU H, LI Z, et al. The release of peripheral immune inflammatory cytokines promote an inflammatory cascade in PCOS patients via altering the follicular microenvironment[J]. Front Immunol, 2021, 12: 685724. DOI: 10.3389/fimmu.2021.685724. [20] MACHTINGER R, COMBELLES C M H, MISSMER S A, et al. The association between severe obesity and characteristics of failed fertilized oocytes[J]. Hum Reprod, 2012, 27(11): 3198-3207. DOI: 10.1093/humrep/des308. [21] LI X, LUAN T, WEI Y, et al. The association between triglyceride glucose-body mass index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study[J]. J Ovarian Res, 2024, 17(1): 90. DOI: 10.1186/s13048-024-01416-1.