Effects of antibiotic exposure on human fertility: a systematic review
GAO Yaya1,2, XIA Luobin1,2, PAN Guixia1, TAO Fangbiao1,2, SHAO Shanshan1,2
1. School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China; 2. Key Laboratory of Population Health Across Life Cycle, Ministry of Education, Hefei, Anhui 230032, China
Abstract：Objective To explore the impact of antibiotic exposure on human fertility, so as to provide the reference for related research on risk factors and prevention of infertility. Methods Publications pertaining to antibiotic exposure and human fertility were retrived in CNKI, Wanfang Data, VIP, PubMed, Embase and Web of Science from inception to March 2024. Two reviewers independently conducted literature screening, data extraction, and quality assessment. A qualitative analysis was performed to investigate the effect of antibiotic exposure on human fertility. Results A total of 11 623 articles were retrieved, and 31 of them were finally included. Among them, 19 were quasi-experimental studies (4 high-quality and 15 medium-quality), 6 were observational studies (5 high-quality and 1 medium-quality), and 6 were randomized controlled trials (RCTs) with high risks of implementation bias and measurement bias. Sixteen quasi-experimental studies and five RCTs found that the use of sensitive antibiotics such as doxycycline for the treatment of reproductive system infections improved female pregnancy rates or male semen quality. Two quasi-experimental studies and one RCT suggested that antibiotics (such as sirolimus or sulfasalazine) used to treat other systemic diseases might cause adverse effects on the reproductive system. Four observational studies indicated that exposure to antibiotics such as sulfonamides, macrolides, and tetracyclines increased the risk of infertility or prostate cancer. Two observational studies found a dual effect of antibiotics on infertility. Conclusions Antibiotic exposure appears to have either beneficial or harmful effects on fertility, depending on the antibiotic types, doses, and indication. However, these studies have limitations such as small sample size, selection bias, and the inability to achieve randomization and blind methods. Further research with optimized designs is necessary to explore the relationship between antibiotic exposure and fertility.
[1] ZHOU Z,ZHENG D,WU H,et al.Epidemiology of infertility in China:a population-based study[J].BJOG,2018,125(4):432-441. [2] BAUD A,HILLION K H,PLAINVERT C,et al.Microbial diversity in the vaginal microbiota and its link to pregnancy outcomes[J].Sci Rep,2023,13(1):9061-9072. [3] SHAO S S,PAN W J,WANG B L,et al.Association between antibiotic exposure and the risk of infertility in women of childbearing age:a case-control study[J/OL].Ecotoxicol Environ Saf,2023,249[2024-05-16].https://doi.org/10.1016/j.ecoenv.2022.114414. [4] 曾宪涛,包翠萍,曹世义,等.Meta分析系列之三:随机对照试验的质量评价工具[J].中国循证心血管医学杂志,2012,4(3):183-185. [5] STANG A.Critical evaluation of the Newcastle-Ottawa Scale for the assessment of the quality of nonrandomized studies in meta-analyses[J].Eur J Epidemiol,2010,25(9):603-605. [6] 曾宪涛,庄丽萍,杨宗国,等.Meta分析系列之七:非随机实验性研究、诊断性试验及动物实验的质量评价工具[J].中国循证心血管医学杂志,2012,4(6):496-499. [7] BRAUN M,YOUNG J,REINER C S,et al.Ovarian toxicity from sirolimus[J].N Engl J Med,2012,366(11):1062-1064. [8] MIKKELSEN E M,ULRICHSEN S P,JOHANNESEN B R,et al.Preconception use of antibiotics and fecundability:a Danish prospective cohort study[J].Fertil Steril,2023,120(3 Pt 2):650-659. [9] SCHAUMBURG I,OLSEN J.Time to pregnancy among Danish pharmacy assistants[J].Scand J Work Environ Health,1989,15(3):222-226. [10] 罗琼秀,袁金兰,杨岚.多西环素联合甲硝唑对慢性子宫内膜炎合并不孕患者氧化应激指标和免疫功能的影响[J].当代医学,2023,29(16):59-62. [11] 孙擎擎,曹义娟,顾娟,等.左氧氟沙星联合宫腔灌注甲硝唑治疗不孕症伴慢性子宫内膜炎患者的临床效果[J].中国综合临床,2023,39(3):228-232. [12] 李霞,依力米努尔·阿布拉,宁冰雪,等.不同治疗方式对合并慢性子宫内膜炎的反复种植失败患者妊娠结局的影响[J].新疆医科大学学报,2022,45(9):992-997. [13] 郑圣霞,胡美红,栾红兵,等.宫腔灌注治疗慢性子宫内膜炎对反复种植失败患者妊娠结局的影响[J].实用医学杂志,2019,35(15):2434-2437. [14] 陈泽城,吴红梅.孕期解脲支原体感染状况及妊娠预后分析[J].承德医学院学报,2017,34(5):373-375. [15] 任平,章晓梅,马艳萍,等.沙眼衣原体、支原体感染的不孕症抗生素治疗后临床观察[J].中国抗感染化疗杂志,2003,3(1):16-18. [16] CROWE H M,WESSELINK A K,WISE L A,et al.Antibiotics and fecundability among female pregnancy planners:a prospective cohort study[J].Hum Reprod,2021,36(10):2761-2768. [17] TOOVEY S,HUDSON E,HENDRY W F,et al.Sulphasalazine and male infertility:reversibility and possible mechanism[J].Gut,1981,22(6):445-451. [18] O'MORÁIN C,SMETHURST P,DORE C J,et al.Reversible male infertility due to sulphasalazine:studies in man and rat[J].Gut,1984,25(10):1078-1084. [19] BOURSI B,MAMTANI R,HAYNES K,et al.Recurrent antibiotic exposure may promote cancer formation:another step in understanding the role of the human microbiota?[J].Eur J Cancer,2015,51(17):2655-2664. [20] TAMIM H M,HAJEER A H,BOIVIN J F,et al.Association between antibiotic use and risk of prostate cancer[J].Int J Cancer,2010,127(4):952-960. [21] 钟恺欣,张欣宗,叶桂芳,等.捐精志愿者支原体感染后用药对精液质量的影响[J].广东医学,2021,42(8):888-891. [22] 唐许,龚成,刘慧.卞星青霉素联合多西环素治疗对男性早期梅毒患者皮损、免疫功能及性功能的影响[J].中国性科学,2019,28(8):136-139. [23] 姜卫国,周兵.西地那非治疗前列腺炎相关的性功能障碍患者65例效果评价[J].中国医药指南,2012,10(11):152-153. [24] 张建国,王艳丽,周四维.慢性非细菌性前列腺炎患者精液质量改变和抗生素治疗效果[J].中华男科学杂志,2004,10(8):598-600. [25] AHMADI M H,MIRSALEHIAN A,SADIGHI G M,et al.Association of asymptomatic Chlamydia trachomatis infection with male infertility and the effect of antibiotic therapy in improvement of semen quality in infected infertile men[J/OL].Andrologia,2018,50(4)[2024-05-16].https://doi.org/10.1111/and.12944. [26] AHMADI M H,MIRSALEHIAN A,GILANI M,et al.Improvement of semen parameters after antibiotic therapy in asymptomatic infertile men infected with Mycoplasma genitalium[J].Infection,2018,46(1):31-38. [27] AHMADI M H,MIRSALEHIAN A,SADIGHI G M,et al.Asymptomatic infection with Mycoplasma hominis negatively affects semen parameters and leads to male infertility as confirmed by improved semen parameters after antibiotic treatment[J].Urology,2017,100:97-102. [28] 胡雷,王俊豪,巢杏慧,等.短期口服抗生素对伴白细胞精子症畸形精子不育患者的治疗效果[J].中国性科学,2022,31(4):14-18. [29] ZHANG Q F,ZHANG Y J,WANG S,et al.The effect of screening and treatment of Ureaplasma urealyticum infection on semen parameters in asymptomatic leukocytospermia:a case-control study[J].BMC Urol,2020,20(1):165-172. [30] 刘伟刚,白杰,张保,等.联合应用消痈散结汤与盐酸左氧氟沙星注射液治疗附睾炎患者效果及对精浆中性α-葡糖苷酶和精液质量的影响[J].中国性科学,2019,28(6):9-13. [31] 刘鹏,孙建明,练锋,等.解脲脲原体感染男性不育症患者精液质量分析[J].临床检验杂志,2015,33(4):277-278. [32] PAJOVIC B,RADOJEVIC N,VUKOVIC M,et al.Semen analysis before and after antibiotic treatment of asymptomatic Chlamydia- and Ureaplasma-related pyospermia[J].Andrologia,2013,45(4):266-271. [33] 钱余,江河,姜洋.慢性前列腺炎患者治疗前后精液参数改变[J].吉林医学,2013,34(8):1426-1428. [34] HAMADA A,AGARWAL A,SHARMA R,et al.Empirical treatment of low-level leukocytospermia with doxycycline in male infertility patients[J].Urology,2011,78:1320-1325. [35] MAGRI V,MONTANARI E,SKERK V,et al.Fluoroquinolone-macrolide combination therapy for chronic bacterial prostatitis:retrospective analysis of pathogen eradication rates,inflammatory findings and sexual dysfunction[J].Asian J Androl,2011,13(6):819-827. [36] 郑汝强,王新生,王沛涛.高压氧配合抗生素治疗慢性细菌性前列腺炎不育的临床观察[J].中国男科学杂志,2006,12(11):25-28. [37] VAZQUEZ-LASLOP N,MANKIN A S.How macrolide antibiotics work[J].Trends Biochem Sci,2018,43(9):668-684. [38] MILLER M,SINGER M.Do antibiotics cause mitochondrial and immune cell dysfunction?A literature review[J].J Antimicrob Chemother,2022,77(5):1218-1227.
