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北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (1): 167-173. doi: 10.19723/j.issn.1671-167X.2023.01.026

• 论著 • 上一篇    下一篇

不孕女性维生素D水平与抗苗勒氏管激素的相关性及对妊娠结局的预测

孙希雅1,陈艺璐1,2,曾琳3,闫丽盈1,乔杰1,李蓉1,智旭1,*()   

  1. 1. 北京大学第三医院妇产科生殖医学中心，国家妇产疾病临床医学研究中心(北京大学第三医院)，辅助生殖教育部重点实验室(北京大学)，生殖内分泌与辅助生殖技术北京市重点实验室，北京 100191
    2. 青岛大学附属妇女儿童医院，山东青岛 266000
    3. 北京大学第三医院临床流行病学研究中心，北京 100191
  • 收稿日期:2021-11-16 出版日期:2023-02-18 发布日期:2023-01-31
  • 通讯作者: 智旭 E-mail:zhixujp@163.com
  • 基金资助:
    国家自然科学基金(81971440);北京市自然科学基金(7212129)

Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome

Xi-ya SUN1,Yi-lu CHEN1,2,Lin ZENG3,Li-ying YAN1,Jie QIAO1,Rong LI1,Xu ZHI1,*()   

  1. 1. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital); Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
    2. Women and Children's Hospital, Qingdao University, Shandong, Qingdao 266000, China
    3. Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing 100191, China
  • Received:2021-11-16 Online:2023-02-18 Published:2023-01-31
  • Contact: Xu ZHI E-mail:zhixujp@163.com
  • Supported by:
    the National Natural Science Foundation of China(81971440);the Beijing Municipal Natural Science Foundation(7212129)

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摘要：

目的: 探讨不孕女性血清25(OH)D水平与抗苗勒氏管激素(anti-Müllerian hormone, AMH)间的关系及二者对体外受精和胚胎移植妊娠结局的预测作用。方法: 纳入2018年11月至2019年9月间756例应用体外受精和胚胎移植助孕的不孕女性，根据体内维生素D水平将入组人群分为3组(血清25(OH)D≤10 μg/L为A组，10 μg/L < 血清25(OH)D < 20 μg/L为B组，血清25(OH)D≥20 μg/L为C组)，检测患者血清AMH水平，分析组间差异并探讨各不孕类型[输卵管/男方因素、多囊卵巢综合征(polycystic ovary syndrome, PCOS)、排卵障碍(非PCOS原因)、子宫内膜异位症、不明原因不孕、其他]中维生素D水平与血清AMH水平之间的相关性，以及在全部不孕女性中血清25(OH)D水平和血清AMH水平对妊娠结局的独立/协同预测作用。结果: (1) 87.7%的入组研究对象处于维生素D不足或缺乏的状态；(2) A、B、C三个不同维生素D水平组的血清AMH分别为1.960 (1.155, 3.655) μg/L、2.455(1.370, 4.403) μg/L、2.360(1.430, 4.780) μg/L，组间差异无统计学意义(P>0.05)；(3) 血清25(OH)D和AMH水平呈现季节性变化(P < 0.05)；(4) 利用多重线性回归分析，调整潜在混杂因素后，各不孕类型女性的血清AMH水平与血清25(OH)D水平之间无明显相关性(P>0.05)；(5) 二元Logistics回归模型分析发现所有不孕女性中，血清AMH水平是预测生化妊娠结局的独立影响因素(P < 0.05)，血清25(OH)D无法单独预测妊娠结局(P>0.05)，但能够与血清AMH协同预测生化妊娠结局(P < 0.05)。结论: 按照目前诊断标准，不孕女性维生素D缺乏或不足较为普遍，但未发现血清25(OH)D水平与卵巢储备功能相关。血清25(OH)D无法独立预测不孕女性妊娠结局，但AMH能够独立或与血清25(OH)D共同预测不孕女性的生化妊娠结局。

关键词: 维生素D, 抗苗勒氏管激素, 不孕女性, 妊娠结局

Abstract:

Objective: To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome. Methods: Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 μg/L, group B with serum (10-20) μg/L, and group C with serum ≥20 μg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed. Results: (1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) μg/L, 2.455 (1.370, 4.403) μg/L, 2.360 (1.430, 4.780) μg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05). Conclusion: Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

Key words: Vitamin D, anti-Müllerian hormone (AMH), Infertile female, Pregnancy outcome

中图分类号: 

  • R714.8

表1

3组不同维生素D水平的临床特征"

Characteristic Group A Group B Group C P valuea
Total, n 85 578 93
Age/years, $\bar x \pm s$ 32.2±4.4 31.8±4.2 33.5±4.1 0.001
BMI/(kg/m2), $\bar x \pm s$ 22.70±3.60 22.73±3.21 22.09±3.26 0.211
Serum 25(OH)D/(μg/L), $\bar x \pm s$ 8.384±1.038 14.395±2.645 22.96±2.89 < 0.001
Duration of infertility/years, M(P25, P75) 3.0 (1.0, 4.0) 3.0 (2.0, 5.0) 3.0 (1.0, 6.0) 0.123
AFC, $\bar x \pm s$ 10.4±5.8 11.3±6.2 11.9±5.9 0.267
AMH/(μg/L), M(P25, P75) 1.960 (1.155, 3.655) 2.455 (1.370, 4.403) 2.360 (1.430, 4.780) 0.242
Basal FSH levels/(IU/L), $\bar x \pm s$ 6.845±2.202 6.801±2.753 7.282±2.065 0.321
Infertility factor, n(%) 0.069
  Fallopian tube/Male factor 36 (42.4) 231 (40.0) 37(39.8)
  PCOS 8 (9.4) 107 (18.5) 18(19.4)
  Ovulation disorders excluded PCOS 18 (21.2) 90 (15.6) 19(21.3)
  Endometriosis 5 (5.9) 19 (3.3) -
  Unexplained infertility 5 (5.9) 67 (11.6) 13(14.0)
  Others 13 (15.3) 64 (11.1) 6(6.5)
Season of blood draw, n(%) < 0.001
  Spring 60 (70.6%) 312 (54.0%) 44 (47.3%)
  Summer 9 (10.6%) 183 (31.7%) 33 (35.5%)
  Autumn - 4 (0.7%) 4 (4.3%)
  Winter 16 (18.8%) 79 (13.7%) 12 (12.9%)
Duration of treatment/d, $\bar x \pm s$ 11.0±2.2 10.9±2.5 10.2±2.9 0.015
Total dose of Gn used/IU，M(P25, P75) 2 700.0 (2 012.5, 3 375.0) 2 475.0 (1 743.8, 3 375.0) 2 400.0 (1 828.1, 3 150.0) 0.258
Number of oocytes retrieved, M(P25, P75) 10.0 (7.5, 16.5) 12.0 (8.0, 18.0) 12.0 (7.0, 17.5) 0.343

表2

采血季节对血清25(OH)D和血清AMH的影响"

Items Season of blood draw P valuea
Spring Summer Autumn Winter
Serum 25(OH)D/(μg/L), $\bar x \pm s$ 14.317±4.167 15.711±4.008 20.320±5.474 14.153±5.400 < 0.001
AMH/(μg/L), M(P25, P75) 2.245 (1.360, 3.958) 2.540 (1.315, 4.805) 3.430 (2.900, 5.060) 2.590 (1.310, 5.230) 0.046

表3

不同不孕类型的AMH相关性分析"

Infertility factor Items B SE P value
Fallopian tube/Male factor (n=304) Serum 25(OH)D －0.039 0.029 0.186
Age －0.079 0.035 0.024
BMI －0.013 0.042 0.767
AFC 0.144 0.027 < 0.001
Constant 5.326 1.580 0.001
PCOS (n=133) Serum 25(OH)D 0.122 0.095 0.201
Age －0.008 0.120 0.947
BMI －0.389 0.111 0.001
AFC 0.357 0.057 < 0.001
Constant 9.012 4.771 0.061
Ovulation disorders excluded PCOS (n=127) Serum 25(OH)D －0.005 0.014 0.734
Age 0.025 0.014 0.088
BMI －0.010 0.021 0.621
AFC 0.159 0.022 < 0.001
Constant －0.100 0.778 0.898
Endometriosis (n=24) Serum 25(OH)D 0.106 0.107 0.336
Age －0.050 0.101 0.624
BMI －0.122 0.106 0.263
AFC 0.081 0.074 0.289
Constant 5.249 4.111 0.218
Unexplained infertility (n=85) Serum 25(OH)D 0.049 0.056 0.391
Age 0.017 0.068 0.799
BMI －0.172 0.089 0.057
AFC 0.105 0.057 0.071
Constant 4.608 2.886 0.114
Others (n=83) Serum 25(OH)D －0.007 0.046 0.885
Age 0.006 0.048 0.904
BMI －0.031 0.061 0.619
AFC 0.168 0.038 < 0.001
Constant 2.009 2.241 0.373

表4

血清25(OH)D水平与血清AMH水平对不孕女性妊娠结局的预测作用"

Items Biochemical pregnancy Clinical pregnancy
OR 95%CI P value OR 95%CI P value
AMH 1.503 1.083-2.086 0.015 1.310 0.957-1.791 0.092
Serum 25(OH)D 1.044 0.974-1.119 0.223 1.039 0.970-1.114 0.276
25(OH)D*AMH 0.978 0.958-0.997 0.027 0.982 0.962-1.002 0.071
Age 0.948 0.905-0.992 0.022 0.949 0.907-0.993 0.024
BMI 1.018 0.962-1.078 0.531 1.019 0.963-1.079 0.515
AFC 1.024 0.979-1.070 0.302 1.019 0.975-1.064 0.403
Number of embryos transferred 1.052 0.670-1.652 0.827 1.051 0.674-1.641 0.826
Constant 1.122 - 0.924 1.242 - 0.857
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CN 11-4691/R
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