多囊卵巢综合征患者反复妊娠丢失的因素

doi:10.12280/gjszjk.20220075

摘要/Abstract

摘要：

多囊卵巢综合征（PCOS）的多种病理改变与反复妊娠丢失相关。PCOS患者的高胰岛素血症和胰岛素抵抗可通过干扰正常的胎盘附着导致妊娠丢失;临床常用二甲双胍纠正胰岛素代谢异常,也可减少妊娠丢失。PCOS患者雄激素过多可能导致不孕、妊娠丢失及妊娠期并发症,尚需要更多高质量的临床研究探讨。此外,肥胖和血脂异常会增加PCOS患者发生RPL的概率,通过饮食结构调整、生活方式干预及体质量管理,以减少肥胖的不良影响,改善妊娠结局。本文从胰岛素代谢、糖脂代谢、雄激素、同型半胱氨酸和维生素D等多方面分析PCOS患者反复妊娠丢失的因素,以期为PCOS患者的生育和辅助生殖治疗提供指导。

关键词: 多囊卵巢综合征, 胚胎丢失, 胰岛素抗药性, 同型半胱氨酸, 维生素D

Abstract:

Multiple pathological factors of polycystic ovary syndrome (PCOS) are associated with recurrent pregnancy loss (RPL). Hyperinsulinemia and insulin resistance in PCOS patients can lead to pregnancy loss by interfering with the normal placental attachment. Metformin is clinically used to correct the abnormal metabolism related to hyperinsulinemia, and to reduce pregnancy loss. Excessive androgen in PCOS patients may lead to infertility, RPL and pregnancy complications. However, more high-quality clinical studies are needed to understand the relationship between excessive androgen and RPL. In addition, obesity and dyslipidemia increase the probability of RPL in PCOS patients. Dietary structure adjustment, lifestyle intervention and body weight management will reduce the adverse effects of obesity, and improve pregnancy outcomes. In this paper, we analyzed the factors of RPL in PCOS patients from insulin metabolism, glucolipid metabolism, androgen, homocysteine and vitamin D, in order to provide a clinical guidance for the fertility and assisted reproductive therapy of PCOS patients.

Key words: Polycystic ovary syndrome, Embryo loss, Insulin resistance, Homocysteine, Vitamin D

叶子, 马翔. 多囊卵巢综合征患者反复妊娠丢失的因素[J]. 国际生殖健康/计划生育, 2022, 41(3): 225-229.

YE Zi, MA Xiang. Factors of Recurrent Pregnancy Loss in Patients with Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(3): 225-229.

参考文献 37

[1]	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. doi: 10.3390/ijms22073789 URL
[2]	Bender Atik R, Christiansen OB, Elson J, et al. ESHRE guideline: recurrent pregnancy loss[J]. Hum Reprod Open, 2018, 2018(2): hoy004. doi: 10.1093/hropen/hoy004. doi: 10.1093/hropen/hoy004
[3]	多囊卵巢综合征相关不孕治疗及生育保护共识专家组,中华预防医学会生育力保护分会生殖内分泌生育保护学组. 多囊卵巢综合征相关不孕治疗及生育保护共识[J]. 生殖医学杂志, 2020, 29(7):843-851. doi: 10.3969/j.issn.1004-3845.2020.07.002. doi: 10.3969/j.issn.1004-3845.2020.07.002
[4]	Asanidze E, Kristesashvili J, Andguladze S. Correlation Between Levels Of Homocysteine, Anti-Müllerian Hormone And Insulin Resistance In PCOS Patients With Recurrent Miscarriage[J]. Georgian Med News, 2019,(290):25-29. pmid: 31322509
[5]	Bahri Khomami M, Boyle JA, Tay CT, et al. Polycystic ovary syndrome and adverse pregnancy outcomes: Current state of knowledge, challenges and potential implications for practice[J]. Clin Endocrinol(Oxf), 2018, 88(6):761-769. doi: 10.1111/cen.13579. doi: 10.1111/cen.13579 URL
[6]	Abdalla MA, Shah N, Deshmukh H, et al. Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials[J]. Clin Endocrinol(Oxf), 2022, 96(3):371-394. doi: 10.1111/cen.14623. doi: 10.1111/cen.14623 URL
[7]	Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: a comprehensive review[J]. Hum Reprod Update, 2021, 27(3):584-618. doi: 10.1093/humupd/dmaa051. doi: 10.1093/humupd/dmaa051 URL
[8]	Zhai J, Li Z, Zhou Y, et al. The role of plasminogen activator inhibitor-1 in gynecological and obstetrical diseases: An update review[J]. J Reprod Immunol, 2022, 150:103490. doi: 10.1016/j.jri.2022.103490. doi: 10.1016/j.jri.2022.103490 URL
[9]	Jerzak M, Szafarowska M. Preliminary Results for Personalized Therapy in Pregnant Women with Polycystic Ovary Syndrome During the COVID-19 Pandemic[J]. Arch Immunol Ther Exp(Warsz), 2022, 70(1):13. doi: 10.1007/s00005-022-00650-z. doi: 10.1007/s00005-022-00650-z
[10]	Newman C, Dunne FP. Metformin for pregnancy and beyond: the pros and cons[J]. Diabet Med, 2022, 39(3):e14700. doi: 10.1111/dme.14700. doi: 10.1111/dme.14700
[11]	Wei D, Zhang B, Shi Y, et al. Effect of Preconception Impaired Glucose Tolerance on Pregnancy Outcomes in Women With Polycystic Ovary Syndrome[J]. J Clin Endocrinol Metab, 2017, 102(10):3822-3829. doi: 10.1210/jc.2017-01294. doi: 10.1210/jc.2017-01294 URL
[12]	Romero ST, Sharshiner R, Stoddard GJ, et al. Correlation of serum fructosamine and recurrent pregnancy loss: Case-control study[J]. J Obstet Gynaecol Res, 2016, 42(7):763-768. doi: 10.1111/jog.12974. doi: 10.1111/jog.12974 URL
[13]	Koivuaho E, Laru J, Ojaniemi M, et al. Age at adiposity rebound in childhood is associated with PCOS diagnosis and obesity in adulthood-longitudinal analysis of BMI data from birth to age 46 in cases of PCOS[J]. Int J Obes(Lond), 2019, 43(7):1370-1379. doi: 10.1038/s41366-019-0318-z. doi: 10.1038/s41366-019-0318-z URL
[14]	Yang J, He Y, Wu Y, et al. Association between abnormal body mass index and pregnancy outcomes in patients following frozen embryo transfer: a systematic review and meta-analysis[J]. Reprod Biol Endocrinol, 2021, 19(1):140. doi: 10.1186/s12958-021-00809-x. doi: 10.1186/s12958-021-00809-x URL
[15]	Sermondade N, Huberlant S, Bourhis-Lefebvre V, et al. Female obesity is negatively associated with live birth rate following IVF: a systematic review and meta-analysis[J]. Hum Reprod Update, 2019, 25(4):439-451. doi: 10.1093/humupd/dmz011. doi: 10.1093/humupd/dmz011 pmid: 30941397
[16]	Cena H, Chiovato L, Nappi RE. Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists[J]. J Clin Endocrinol Metab, 2020, 105(8):e2695-e2709. doi: 10.1210/clinem/dgaa285. doi: 10.1210/clinem/dgaa285
[17]	Chen R, Chen S, Liu M, et al. Pregnancy outcomes of PCOS overweight/obese patients after controlled ovarian stimulation with the GnRH antagonist protocol and frozen embryo transfer[J]. Reprod Biol Endocrinol, 2018, 16(1):36. doi: 10.1186/s12958-018-0352-z. doi: 10.1186/s12958-018-0352-z URL
[18]	Cocksedge KA, Li TC, Saravelos SH, et al. A reappraisal of the role of polycystic ovary syndrome in recurrent miscarriage[J]. Reprod Biomed Online, 2008, 17(1):151-160. doi: 10.1016/s1472-6483(10)60304-5. doi: 10.1016/s1472-6483(10)60304-5 pmid: 18616903
[19]	Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics[J]. Metabolism, 2019, 92:108-120. doi: 10.1016/j.metabol.2018.11.002. doi: 10.1016/j.metabol.2018.11.002 URL
[20]	Arya S, Hansen KR, Peck JD, et al. Metabolic syndrome in obesity: treatment success and adverse pregnancy outcomes with ovulation induction in polycystic ovary syndrome[J]. Am J Obstet Gynecol, 2021, 225(3):280.e1-280.e11. doi: 10.1016/j.ajog.2021.03.048. doi: 10.1016/j.ajog.2021.03.048
[21]	李宣, 丁卫, 刘嘉茵, 等. 血脂异常对多囊卵巢综合征患者IVF/ICSI妊娠结局的影响[J]. 中华妇产科杂志, 2018, 53(6):402-408. doi: 10.3760/cma.j.issn.0529-567x.2018.06.008. doi: 10.3760/cma.j.issn.0529-567x.2018.06.008
[22]	Ye W, Xie T, Song Y, et al. The role of androgen and its related signals in PCOS[J]. J Cell Mol Med, 2021, 25(4):1825-1837. doi: 10.1111/jcmm.16205. doi: 10.1111/jcmm.16205 URL
[23]	Cocksedge KA, Saravelos SH, Wang Q, et al. Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage?[J]. Hum Reprod, 2008, 23(4):797-802. doi: 10.1093/humrep/den022. doi: 10.1093/humrep/den022 URL
[24]	Kazerooni T, Ghaffarpasand F, Asadi N, et al. Correlation between thrombophilia and recurrent pregnancy loss in patients with polycystic ovary syndrome: a comparative study[J]. J Chin Med Assoc, 2013, 76(5):282-288. doi: 10.1016/j.jcma.2013.01.009. doi: 10.1016/j.jcma.2013.01.009 pmid: 23683262
[25]	Rahman TU, Ullah K, Guo MX, et al. Androgen-induced alterations in endometrial proteins crucial in recurrent miscarriages[J]. Oncotarget, 2018, 9(37):24627-24641. doi: 10.18632/oncotarget.24821. doi: 10.18632/oncotarget.24821 URL
[26]	Bahri Khomami M, Joham AE, Boyle JA, et al. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-A systematic review, meta-analysis, and meta-regression[J]. Obes Rev, 2019, 20(5):659-674. doi: 10.1111/obr.12829. doi: 10.1111/obr.12829 pmid: 30674081
[27]	Makieva S, Saunders PT, Norman JE. Androgens in pregnancy: roles in parturition[J]. Hum Reprod Update, 2014, 20(4):542-559. doi: 10.1093/humupd/dmu008. doi: 10.1093/humupd/dmu008 pmid: 24643344
[28]	Sun L, Ye J, Wang Y, et al. Elevated basal luteinizing hormone does not impair the outcome of human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles[J]. Sci Rep, 2018, 8(1):13835. doi: 10.1038/s41598-018-32128-4. doi: 10.1038/s41598-018-32128-4 URL
[29]	Coyle C, Campbell RE. Pathological pulses in PCOS[J]. Mol Cell Endocrinol, 2019, 498:110561. doi: 10.1016/j.mce.2019.110561. doi: 10.1016/j.mce.2019.110561 URL
[30]	申路路, 赵志梅. 同型半胱氨酸与不良妊娠结局的关系[J]. 国际生殖健康/计划生育杂志, 2021, 40(4):339-343. doi: 10.12280/gjszjk.20200737. doi: 10.12280/gjszjk.20200737
[31]	Chang H, Xie L, Ge H, et al. Effects of hyperhomocysteinaemia and metabolic syndrome on reproduction in women with polycystic ovary syndrome: a secondary analysis[J]. Reprod Biomed Online, 2019, 38(6):990-998. doi: 10.1016/j.rbmo.2018.12.046. doi: S1472-6483(19)30024-0 pmid: 30979610
[32]	Wang J, You D, Wang H, et al. Association between homocysteine and obesity: A meta-analysis[J]. J Evid Based Med, 2021, 14(3):208-217. doi: 10.1111/jebm.12412. doi: 10.1111/jebm.12412 URL
[33]	Gözüküçük M, Gürsoy AY, Destegül E, et al. Homocysteine and C-reactive Protein Levels in Women with Polycystic Ovary Syndrome[J]. Gynecol Minim Invasive Ther, 2021, 10(4):210-214. doi: 10.4103/GMIT.GMIT_30_20. doi: 10.4103/GMIT.GMIT_30_20 pmid: 34909377
[34]	王研, 丁旭, 黄艳红. 维生素D对多囊卵巢综合征患者生育影响的研究进展[J]. 中华临床医师杂志(电子版), 2021, 15(5): 393-396. doi: 10.3877/cma.j.issn.1674-0785.2021.05.015. doi: 10.3877/cma.j.issn.1674-0785.2021.05.015
[35]	Zhao JF, Li BX, Zhang Q. Vitamin D improves levels of hormonal, oxidative stress and inflammatory parameters in polycystic ovary syndrome: a meta-analysis study[J]. Ann Palliat Med, 2021, 10(1):169-183. doi: 10.21037/apm-20-2201. doi: 10.21037/apm-20-2201 URL
[36]	Fernando M, Ellery SJ, Marquina C, et al. Vitamin D-Binding Protein in Pregnancy and Reproductive Health[J]. Nutrients, 2020, 12(5):1489. doi: 10.3390/nu12051489. doi: 10.3390/nu12051489 URL
[37]	Pilz S, Zittermann A, Obeid R, et al. The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data[J]. Int J Environ Res Public Health, 2018, 15(10):2241. doi: 10.3390/ijerph15102241. doi: 10.3390/ijerph15102241 URL