多囊卵巢综合征不孕患者药物促排卵的风险与防治进展

曹佳城; 肖扬; 王素霞

doi:10.16766/j.cnki.issn.1674-4152.002997

多囊卵巢综合征不孕患者药物促排卵的风险与防治进展

doi: 10.16766/j.cnki.issn.1674-4152.002997

1.
浙江中医药大学附属杭州市中医院中医妇科, 浙江杭州 310053
2.
浙江中医药大学第二临床医学院中医妇科, 浙江杭州 310053
3.
杭州市中医院中医妇科, 浙江杭州 310053

基金项目:

浙江省中医药科技计划项目 2022ZZ025

详细信息

通讯作者:
王素霞，E-mail：wangsuxiahz@163.com

中图分类号: R711.75 R711.6
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- 被引次数: 0
出版历程
- 收稿日期: 2022-05-12

Research progress on the risk and prevention of ovulation induction in infertile patients with polycystic ovary syndrome

1.
Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China

摘要

摘要: 本文全面检索知网、万方、PubMed等电子数据库中关于多囊卵巢综合征(PCOS)不孕患者药物促排卵治疗的相关文献，对近10年的文献进行系统评价，全面了解其风险，阐述其发病机制，并总结相应的防治措施，以期为该病的临床治疗提供依据。结果显示如下。(1)多胎妊娠：促性腺激素的多胎妊娠风险明显高于口服促排卵药物，联合来曲唑或克罗米芬并不能改善其多胎妊娠结局。(2)卵巢过度刺激综合征(OHSS)：人绒毛膜促性腺激素(HCG)的OHSS风险最高，临床用药时应严格掌握其剂量、注射时机；OHSS高危患者建议采用促性腺激素释放激素(GnRH)诱导排卵，但需警惕黄体功能不足的风险。(3)未破裂卵泡黄素化综合征(LUFs)：GnRH联合HCG或克罗米芬可以有效降低这一风险，但目前仍缺乏足够大的样本量。(4)空卵泡综合征(EFS)：多见于HCG或GnRH诱导排卵后的患者，有研究认为可以通过监测遗传标志物进行预防。(5)早期流产：二甲双胍单独使用或联合促排卵药物均不能降低早期流产风险，来曲唑和克罗米芬在早期流产风险上差异也无统计学意义。(6)卵巢功能减退：抗缪勒管激素或可为PCOS不孕伴卵巢功能减退的良好诊断指标，但需要进一步去证实。基于各种促排卵药物的风险，希望临床医师在PCOS不孕患者的治疗上选择更适合的方案，从而规避相关风险，减轻PCOS不孕患者的生理以及经济方面的负担。
- 多囊卵巢综合征 /
- 促排卵 /
- 风险 /
- 研究进展
Abstract: This study aimed to explore the risk with its mechanism and prevention measures of infertile patients with polycystic ovary syndrome (PCOS) after ovulation induction therapy. Literature was searched from several online databases, including CNKI, WanFang and PubMed, which were systematically evaluated to comprehensively understand its risks and pathogenesis, and the corresponding prevention and treatment measures were summarised to provide a basis for clinical treatment of the disease. Results are as follows, (1) Multiple pregnancy: the risk of multiple pregnancy with gonadotropin is significantly higher than that with oral ovulation stimulants, and the combination of letrozole or clomiphene with gonadotropin could not improve the outcome of multiple pregnancy. (2) Ovarian hyperstimulation syndrome (OHSS): human chorionic gonadotropin (HCG) has the highest risk of OHSS, and its dose and injection timing should be strictly controlled in clinical administration. Ovulation induction with gonadotropin releasing hormone (GnRH) is recommended for patients at high risk of OHSS, but the risk of luteal insufficiency should be monitored. (3) Luteinised unruptured follicle syndrome (LUFs): GnRH combined with HCG or clomiphene can effectively reduce this risk, but a large sample size is still lacking. (4) Empty follicle syndrome (EFS): it is commonly found in patients after ovulation induction by HCG or GnRH, and some studies suggest that prevention can be achieved by monitoring genetic markers. (5) Early abortion: metformin alone or in combination with ovulation induction drugs cannot reduce the risk of early abortion, and no significant difference in the risk of early abortion was observed between letrozole and clomiphene. (6) Diminished ovarian reserve (DOR): Anti-Müllerian hormone may be a good diagnostic indicator of PCOS infertility with DOR, however, further confirmation is needed. Based on the risk of various ovulation induction drugs, we hope that clinicians can select a more suitable treatment for infertile patients with PCOS to avoid the related risks and reduce the physiological and economic burden of infertile patients with PCOS.
- Polycystic ovary syndrome /
- Ovulation induction /
- Risk /
- Research progress
利益冲突 无

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参考文献(45)

[1]	COSTELLO M, GARAD R, HART R, et al. A review of first line infertility treatments and supporting evidence in women with polycystic ovary syndrome[J]. Med Sci, 2019, 7(9): 95.
[2]	张巧利, 贾婵维, 周丽颖, 等. 2018 SOGC多囊卵巢综合征诱导排卵实践指南(No. 362)解读[J]. 中华生殖与避孕杂志, 2020, 40(8): 695-700. https://www.cnki.com.cn/Article/CJFDTOTAL-HDXK202306011.htm ZHANG Q L, JIA C W, ZHOU L Y, et al. Interpretation to SOGC clinical practice guideline: No. 362-Ovulation Induction in Polycystic Ovary Syndrome[J]. Chinese Journal of Reproduction and Contraception, 2020, 40(8): 695-700. https://www.cnki.com.cn/Article/CJFDTOTAL-HDXK202306011.htm
[3]	孙丽, 张钰. 来曲唑序贯治疗来曲唑促排卵失败多囊卵巢综合征的疗效观察[J]. 现代药物与临床, 2020, 35(10): 2051-2056. https://www.cnki.com.cn/Article/CJFDTOTAL-GWZW202010026.htm SUN L, ZHANG Y. Clinical observation of letrozole sequential therapy in treatment of polycystic ovary syndrome due to letrozole induced ovulation failure[J]. Drugs & Clinic, 2020, 35(10): 2051-2056. https://www.cnki.com.cn/Article/CJFDTOTAL-GWZW202010026.htm
[4]	纵艳艳. 氯米芬联合人绝经期促性腺激素对多囊卵巢综合征患者促排卵的效果分析[J]. 中华全科医学, 2017, 15(5): 820-822. doi: 10.16766/j.cnki.issn.1674-4152.2017.05.028 ZONG Y Y. Effect of clomiphene citrate with human menopausal gonadotropin on ovulation induction in women with polycystic ovary syndrome[J]. Chinese Journal of General Practice, 2017, 15(5): 820-822. doi: 10.16766/j.cnki.issn.1674-4152.2017.05.028
[5]	PONTRE J, LANGDON F, MURRAY K, et al. The cumulative success of ovulation induction therapy with gonadotrophins in therapy-naïve anovulatory women: an observational study[J]. Aust N Z J Obstet Gynaecol, 2020, 60(2): 271-277. doi: 10.1111/ajo.13123
[6]	GARTHWAITE H, STEWART J, WILKES S. Multiple pregnancy rate in patients undergoing treatment with clomifene citrate for WHO group Ⅱ ovulatory disorders: a systematic review[J]. Hum Fertil, 2021, 15: 1-10.
[7]	王蕊, 张岩, 孙旸, 等. 二甲双胍联合克罗米芬在多囊卵巢综合征患者诱导排卵中疗效的Meta分析[J]. 武警后勤学院学报(医学版), 2020, 29(4): 1-7. doi: 10.16548/j.2095-3720.2020.04.001 WANG R, ZHANG Y, SUN Y, et al. Therapeutic efficacy of metformin combined with clomiphene for ovulation induction in patients with polycystic ovary syndrome: a Meta-analysis[J]. Journal of Armed Police Logistics College (Medical Edition), 2020, 29(4): 1-7. doi: 10.16548/j.2095-3720.2020.04.001
[8]	BANSAL S, GOYAL M, SHARMA C, et al. Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: a randomized controlled trial[J]. Int J Gynaecol Obstet, 2020, 152(3): 345-350. https://pubmed.ncbi.nlm.nih.gov/32920843/
[9]	HU S F, YU Q, WANG Y Y, et al. Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials[J]. Arch Gynecol Obstet, 2018, 297(5): 1081-1088. doi: 10.1007/s00404-018-4688-6
[10]	ABBARA A, CLARKE S A, DHILLO W S. Novel concepts for inducing final oocyte maturation in In Vitro fertilization treatment[J]. Endocr Rev, 2018, 39(5): 593-628. doi: 10.1210/er.2017-00236
[11]	DU D F, LI M F, LI X L. Ovarian hyperstimulation syndrome: a clinical retrospective study on 565 inpatients[J]. Gynecol Endocrinol, 2020, 36(4): 313-317. doi: 10.1080/09513590.2019.1653275
[12]	张希奇, 杨美琼. 不同剂量HCG控制性促排卵诱导卵泡成熟及对胚胎移植妊娠结局影响[J]. 中国计划生育学杂志, 2020, 28(12): 2045-2048. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202012029.htm ZHANG X Q, YANG M Q. Effects of different doses of HCG used in the induction of follicular maturation of controlled ovulation induction and its influence on pregnancy outcomes of embryo transfer[J]. Chinese Journal of Family Planning, 2020, 28(12): 2045-2048. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202012029.htm
[13]	黄欣慰, 徐璞. 多囊卵巢综合征不孕患者应用GnRH-a与HCG诱导卵泡成熟促排卵效果比较[J]. 中国计划生育学杂志, 2021, 29(5): 899-902. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202105012.htm HUANG X W, XU P. Comparison of effect of GnRH-a and hCG used for induced follicle maturation and ovulation induction in infertility women with polycystic ovary syndrome[J]. Chinese Journal of Family Planning, 2021, 29(5): 899-902. https://www.cnki.com.cn/Article/CJFDTOTAL-JHSY202105012.htm
[14]	FISCHER D, REISENBUCHLER C, ROSNER S, et al. Avoiding OHSS: controlled ovarian low-dose stimulation in women with PCOS[J]. Geburtshilfe Frauenheilkd, 2016, 76(6): 718-726. doi: 10.1055/s-0042-100206
[15]	SHI S Q, HONG T, JIANG F F, et al. Letrozole and human menopausal gonadotropin for ovulation induction in clomiphene resistance polycystic ovary syndrome patients: a randomized controlled study[J]. Medicine, 2020, 99(4): e18383. DOI: 10.1097/MD.0000000000018383.
[16]	WEISS N S, KOSTOVA E, NAHUIS M, et al. Gonadotrophins for ovulation induction in women with polycystic ovary syndrome[J]. Cochrane Database Syst Rev, 2019, 1(1): CD010290. DOI: 10.1002/14651858.CD010290.pub3.
[17]	药维之, 彭文. 人绝经期促性腺素联合曲普瑞林治疗多囊卵巢综合征患者排卵障碍的效果及对激素水平的影响[J]. 海南医学, 2018, 29(7): 952-954. doi: 10.3969/j.issn.1003-6350.2018.07.020 YAO W Z, PENG W. Effect of human menopausal gonadotropin combined with triamcinolone on ovulation dysfunction in polycystic ovary syndrome women and its influence on hormone levels[J]. Hainan Medical Journal, 2018, 29(7): 952-954. doi: 10.3969/j.issn.1003-6350.2018.07.020
[18]	GADALLA M A, NORMAN R J, TAY C T, et al. Medical and surgical treatment of reproductive outcomes in polycystic ovary syndrome: an overview of systematic reviews[J]. Int J Fertil Steril, 2020, 13(4): 257-270.
[19]	FRANIK S, ELTROP S M, KREMER J A, et al. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome[J]. Cochrane Database Syst Rev, 2018, 5(5): CD010287. DOI: 10.1002/14651858.CD010287.pub3.
[20]	HUBKA P, VISNOVA H, SEHNAL B, et al. Current possibilities in the prevention and therapy of ovarian hyperstimulation syndrome[J]. Ceska Gynekol, 2021, 86(2): 124-127. doi: 10.48095/cccg2021124
[21]	郭瑶, 杨金娜, 于跃辉. 来曲唑与克罗米芬治疗多囊卵巢综合征不孕症临床疗效比较[J]. 临床军医杂志, 2018, 46(3): 359-361. https://www.cnki.com.cn/Article/CJFDTOTAL-JYGZ201803038.htm GUO Y, YANG J N, YU Y J. Clinical efficacy of letrozole and Clomiphene in the treatment of polycystic ovary syndrome infertility[J]. Clinical Journal of Medical Officers, 2018, 46(3): 359-361. https://www.cnki.com.cn/Article/CJFDTOTAL-JYGZ201803038.htm
[22]	AZMOODEH A, PEJMAN M M, AKBARI A F, et al. Effects of letrozole-HMG and clomiphene-HMG on incidence of luteinized unruptured follicle syndrome in infertile women undergoing induction ovulation and intrauterine insemination: a randomised trial[J]. Glob J Health Sci, 2015, 8(4): 244-252.
[23]	吕松林, 李坤朋. 曲普瑞林联合氯米芬对多囊卵巢综合征不孕患者促黄体生成素、促卵泡雌激素、睾酮水平的影响[J]. 临床医学研究与实践, 2020, 5(28): 147-148. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS202028056.htm LYU S L, LI K P. Effect of triptorelin combined with clomiphene on the levels of luteinizing hormone, follicle stimulating estrogen and testosterone in infertile patients with polycystic ovarian syndrome[J]. Clinical Research and Practice, 2020, 5(28): 147-148. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS202028056.htm
[24]	刘阳. 促性腺激素释放激素激动剂联合人绒毛膜促性腺激素在多囊卵巢综合征患者促排中的应用效果[J]. 临床医学研究与实践, 2019, 4(14): 105-106, 109. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS201914042.htm LIU Y. Application effect of gonadotropin releasing hormone agonist combined with human chorionic gonadotropin in promoting ovulation of patients with polycystic ovary syndrome[J]. Clinical Research and Practice, 2019, 4(14): 105-106, 109. https://www.cnki.com.cn/Article/CJFDTOTAL-YLYS201914042.htm
[25]	SHIBATA T, MAKINODA S, WASEDA T, et al. Granulocyte colony-stimulating factor as a potential inducer of ovulation in infertile women with luteinized unruptured follicle syndrome[J]. Transl Res, 2016, 171: 63-70. https://www.sciencedirect.com/science/article/pii/S1931524415003369
[26]	殷晓雪, 刘金星. 针药联合治疗未破裂卵泡黄素化综合征的Meta分析[J]. 湖北中医杂志, 2021, 43(1): 62-66. https://www.cnki.com.cn/Article/CJFDTOTAL-HBZZ202101019.htm YIN X X, LIU J X. Meta-analysis of acupuncture combined with drug therapy for luteinization syndrome of unruptured follicles[J]. Hubei Journal of Traditional Chinese Medicine, 2021, 43(1): 62-66. https://www.cnki.com.cn/Article/CJFDTOTAL-HBZZ202101019.htm
[27]	焦亚男, 蔡平平. 未破裂卵泡黄素化综合征中西医诊疗进展[J]. 中国中西医结合杂志, 2019, 39(9): 1148-1152. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201909036.htm JIAO Y N, CAI P P. Advances in Diagnosis and Treatment of Luteinized Unruptured Follicle Syndrome[J]. Chinese Journal of Integrated Traditional and Western Medicine, 2019, 39(9): 1148-1152. https://www.cnki.com.cn/Article/CJFDTOTAL-ZZXJ201909036.htm
[28]	DEEPIKA K, SINDHUMA D, KIRAN B, et al. Empty follicle syndrome following GnRHa trigger in PCOS patients undergoing IVF cycles[J]. J Reprod Infertil, 2018, 19(1): 16-25.
[29]	YAKOVI S, IZHAKI I, BEN-AMI M, et al. Does the empty follicle syndrome occur in cases of low number of maturing follicles in assisted reproduction?[J]. Gynecol Endocrinol, 2019, 35(4): 305-308.
[30]	SINGH N, DALAL V, KRIPLANI A, et al. Empty follicle syndrome: a challenge to physician[J]. J Hum Reprod Sci, 2018, 11(3): 274-278.
[31]	SONG J Y, SUN Z G. A borderline form of empty follicle syndrome treated with a double-trigger of gonadotropin-releasing hormone agonist and human chorionic gonadotropin: a case report[J]. Medicine, 2019, 98(27): e16213. DOI: 10.1097/MD.0000000000016213.
[32]	ZHANG Z H, WU L, DIAO F Y, et al. Novel mutations in LHCGR (luteinizing hormone/choriogonadotropin receptor): expanding the spectrum of mutations responsible for human empty follicle syndrome[J]. J Assist Reprod Genet, 2020, 37(11): 2861-2868. doi: 10.1007/s10815-020-01931-2.pdf
[33]	YANG P, CHEN T L, LIU Y Q, et al. The critical role of ZP genes in female infertility characterized by empty follicle syndrome and oocyte degeneration[J]. Fertil Steril, 2020, 115(5): 1259-1269.
[34]	覃晓, 黎枝, 覃卫玲, 等. 不同促排卵方案对多囊卵巢综合征不孕症患者的治疗效果[J]. 生殖医学杂志, 2021, 30(2): 175-178. https://www.cnki.com.cn/Article/CJFDTOTAL-SZYX202102010.htm QIN X, LI Z, QIN W L, et al. Therapeutic effects of different ovulation induction protocols on infertile patients with polycystic ovary syndrome[J]. Journal of Reproductive Medicine, 2021, 30(2): 175-178. https://www.cnki.com.cn/Article/CJFDTOTAL-SZYX202102010.htm
[35]	MORLEY L C, TANG T, YASMIN E, et al. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility[J]. Cochrane Database Syst Rev, 2017, 11(11): CD003053. DOI: 10.1002/14651858.CD003053.pub6.
[36]	YU Q J, WANG Z H, SU F F, et al. Effectiveness and safety of aspirin combined with letrozole in the treatment of polycystic ovary syndrome: a systematic review and meta-analysis[J]. Ann Palliat Med, 2021, 10(4): 4632-4641.
[37]	SONG S Y, YANG J B, SONG M S, et al. Effect of pretreatment with combined oral contraceptives on outcomes of assisted reproductive technology for women with polycystic ovary syndrome: a meta-analysis[J]. Arch Gynecol Obstet, 2019, 300(3): 737-750.
[38]	EL SHARKWY I A, ABD EL AZIZ W M. Randomized controlled trial of N-acetylcysteine versus l-carnitine among women with clomiphene-citrate-resistant polycystic ovary syndrome[J]. Int J Gynaecol Obstet, 2019, 147(1): 59-64.
[39]	谢琦, 刘丽婷. 抗苗勒管激素对多囊卵巢综合征不孕患者促排卵结局的影响[J]. 海南医学, 2021, 32(14): 1843-1845. https://www.cnki.com.cn/Article/CJFDTOTAL-HAIN202114020.htm XIE Q, LIU L T. Effect of anti-mullerian hormone on ovulation induction outcome in infertile patients with polycystic ovary syndrome[J]. Hainan Medical Journal, 2021, 32(14): 1843-1845. https://www.cnki.com.cn/Article/CJFDTOTAL-HAIN202114020.htm
[40]	WANG C J, DI W, GU Z W. Endocrine and glycolipid metabolism characteristics of diminished ovarian reserve in Chinese women with polycystic ovary syndrome[J]. J Int Med Res, 2020. DOI: 10.1177/0300060520912982.
[41]	ZHOU S, JI Y P, WANG H M. The risk factors of gestational hypertension in patients with polycystic ovary syndrome: a retrospective analysis[J]. BMC Pregnancy Childbirth, 2021, 21(1): 336.
[42]	张鸥, 易建平, 樊桂玲, 等. GnRHa、HCG在促排卵治疗多囊卵巢综合征不孕患者中的应用效果比较[J]. 吉林医学, 2016, 37(10): 2454-2456. https://www.cnki.com.cn/Article/CJFDTOTAL-JLYX201610030.htm ZHANG O, YI J P, FAN G L, et al. Comparison of the effects of GnRHa and hCG in the treatment of PCOS infertility patients with ovulation induction[J]. Jilin Medical Journal, 2016, 37(10): 2454-2456. https://www.cnki.com.cn/Article/CJFDTOTAL-JLYX201610030.htm
[43]	宋晓霞, 孙林. 促性腺激素释放激素激动剂在多囊卵巢综合征患者促排卵治疗中的应用效果[J]. 中国当代医药, 2020, 27(5): 134-136, 139. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGUD202005040.htm SONG X X, SUN L. Application effect of gonadotropin-releasing hormone agonist in ovulation induction therapy of patients with polycystic ovary syndrome[J]. China Modern Medicine, 2020, 27(5): 134-136, 139. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGUD202005040.htm
[44]	LIN L H, FUSHIDA K, HASE E A, et al. Gestational tubal choriocarcinoma presenting as a pregnancy of unknown location following ovarian induction[J]. Case Rep Obstet Gynecol, 2018, 2018: 4705192. DOI: 10.1155/2018/4705192.
[45]	PETRANGELO A, CZUZOJ-SHULMAN N, TULANDI T, et al. Ovulation induction for infertility the risk of breast cancer: a population-based case-control study[J]. Int J Gynecol Obstet, 2018, 131(1): 22S.