【协和医学杂志】新型冠状病毒感染对生育力的影响研究进展

时间:2023-11-28 21:29:27   热度:37.1℃   作者:网络

新型冠状病毒(SARS-CoV-2)引发的新型冠状病毒感染(COVID-19)疫情给全球带来了挑战。截至2023年4月12日,全球已累计报告确诊病例超过7.6亿例,死亡病例超过689万例[1]。SARS-CoV-2感染会对人体多个脏器造成破坏,其对生育力的影响目前已成为人们关注的热点问题。本文就SARS-CoV-2攻击人体的机制、对生育力的影响及对女性妊娠的影响等方面进行综述,以期为临床医生提供参考和借鉴。

1 SARS-CoV-2攻击人体的机制

SARS-CoV-2是一种有包膜的单链RNA病毒,属于β-冠状病毒亚群,由RNA和4种结构蛋白组成,包括协助病毒进入细胞的刺突蛋白(又称“S蛋白”),协助病毒组装的膜蛋白(又称“M蛋白”)和包膜蛋白(又称“E蛋白”),以及形成核衣壳的核衣壳蛋白 (又称“N蛋白”)[2]

其中S蛋白由S1、S2两个亚基构成,S1亚基主要介导病毒与宿主细胞膜的结合与附着,宿主细胞膜表面的血管紧张素转化酶2(ACE2)受体是与S1亚基结合的主要受体之一,其在Ⅱ型肺泡上皮、上支气管上皮、小肠、结肠、肾脏、心肌等均有广泛表达[3],S1亚基与宿主细胞表面的ACE2受体结合后,在宿主细胞的跨膜丝氨酸蛋白酶2(TMPRSS2)或溶酶体内组织蛋白酶的作用下,S蛋白被激活,释放S2亚基促进病毒与宿主细胞膜相融合,最终使病毒基因进入到宿主细胞内[3-4]

除Ⅱ型肺泡上皮细胞、鼻杯状细胞外[3],心脏、肠道、大脑、睾丸、输卵管均能检测到ACE2和TMPRSS2的高表达[5],提示这些组织器官易被SARS-CoV-2攻击。

2 SARS-CoV-2对生育力的影响

2.1 男性生殖系统

男性和女性对于SARS-CoV-2的易感性相似,但与女性相比,男性感染SARS-CoV-2后的重症率和死亡率更高[6]。研究显示,睾酮可上调ACE2和TMPRSS2的表达[7],而雄激素受体在TMPRSS2的转录中起关键作用[8],这些机制可能与男性感染SARS-CoV-2后疾病严重程度相关。

不同男性生殖器官对于SARS-CoV-2的易感性不同:

1 ACE2和TMPRSS2广泛存在于内皮细胞,而感染SARS-CoV-2会损伤内皮细胞,影响阴茎血管完整性,同时SARS-CoV-2可能直接损伤海绵体内皮细胞,进而导致男性勃起功能障碍[9]

2 在前列腺和精囊组织中可检测到ACE2和TMPRSS2的共表达,其中前列腺上皮细胞中分别有0.32%和18.65%的细胞表达ACE2和TMPRSS2,不足1%的细胞中发现共表达且共表达水平较低[10]

3 在睾丸组织中,ACE2和TMPRSS2高水平表达,ACE2主要在精原细胞、支持细胞及间质细胞中表达,TMPRSS2在精原细胞和精细胞中富集表达[11],因此睾丸被认为是SARS-CoV-2攻击的靶器官之一。

但这一观点目前仍存在争议,有研究显示ACE2和TMPRSS2在睾丸组织中的共表达水平较低[12]。Stanley等[13]对睾丸细胞进行单细胞RNA测序(scRNA-seq)分析显示,ACE2和TMPRSS2的共表达率<0.05%,但男性患者感染SARS-CoV-2后仍出现睾丸炎或精子产量下降,因此SARS-CoV-2可能通过其他机制影响精原细胞发育和精子形成。

此外,对感染SARS-CoV-2的男性患者睾丸进行活检,镜下可见急性睾丸损伤的征象,包括Sertoli细胞肿胀和空泡化、精原细胞脱落、Leydig细胞减少、睾丸间质水肿、炎性细胞聚集等现象[14],进一步提示SARS-CoV-2感染会引起睾丸炎,导致男性生育力减弱。

重症男性患者的精液中SARS-CoV-2检测为阳性,而处于感染急性期、鼻咽拭子检测仍为阳性的无症状男性患者及处于感染恢复期的轻症男性患者,其精液中SARS-CoV-2 RNA检测为阴性,提示SARS-CoV-2通过精液传播的可能性较低[15-18]

研究表明,COVID-19患者SARS-CoV-2平均检出率为7%(范围:5%~11%),这与患者诊断COVID-19和进行精液检测的时间间隔有关,与患者年龄、疾病严重程度以及相关合并症无关[19]

Holtmann 等[20]研究显示,感染SARS-CoV-2的男性患者精液中精子总数、浓度及活力低于未感染组,提示男性患者在感染急性期精子质量会受到影响,且影响程度与疾病严重程度相关,但这种现象也可能由发热或者药物引起。感染后精子质量在整个生精周期可能会持续下降,但随着恢复时间的增加,精子质量逐渐恢复正常[17,21]

综上,感染SARS-CoV-2后男性生育力可能会出现下降,但对于精子质量的影响可能为一过性。

2.2 女性生殖系统

研究表明, SARS-CoV-2可能会影响女性生殖功能,进而影响其生育力。目前的scRNA-seq数据显示,输卵管ACE2和TMPRSS2的共表达水平较高[5],而在子宫、卵巢组织中二者共表达水平很低[22],因此子宫和卵巢组织感染SARS-CoV-2的风险较低。

另有研究显示,ACE2和TMPRSS2在卵巢皮质、髓质和卵母细胞中存在共表达,其中卵母细胞中ACE2和TMPRSS2的共表达程度随着卵母细胞成熟而增加,但由于这些卵母细胞在月经周期中或排卵或萎缩,因此很难对女性配子产生长期影响[13,23],且在SARS-CoV-2 RNA检测阳性的女性卵母细胞中未发现病毒RNA[24]

子宫内膜组织中也可检测到ACE2和TMPRSS2的表达,且二者的表达随月经周期发生变化,从分泌早期到分泌中期表达增加,但由于二者的表达程度较低,内膜感染SARS-CoV-2的可能性很小[25]。对感染者的子宫内膜样本进行监测,尚未发现SARS-CoV-2 RNA[26]

SARS-CoV-2 对排卵的影响目前尚不明确,但有研究显示,COVID-19女性患者的月经周期和月经量出现异常,在两项研究中,分别有16%和28%的患者存在月经不规律[27-28]

Khan等[27]研究显示,该症状与COVID-19疾病严重程度相关,而Li等[28]研究显示,在出院后1~2个月内84% 的患者月经量恢复正常,99%的患者月经周期恢复正常,提示SARS-CoV-2对月经的影响是短暂的[28]

此外,月经的改变还可能与患病期间的压力或焦虑情绪相关[29]。但也存在感染SARS-CoV-2后出现闭经或卵巢早衰的个案报道,2例年龄分别为27岁和34岁的女性患者在感染SARS-CoV-2后7~8个月出现闭经和与卵巢早衰一致的激素水平[30-31]

目前研究表明,SARS-CoV-2对女性生育力影响较小。

3 SARS-CoV-2对妊娠的影响

3.1 妊娠女性是SARS-CoV-2感染的高危人群

既往研究显示,与同龄非妊娠女性患者相比,妊娠不会增加SARS-CoV-2的感染风险,COVID-19妊娠女性患者发生重症的风险(8%)低于非妊娠女性患者(13.8%)[32-34]

但近期美国疾控与预防中心(CDC)的一项研究显示,COVID-19妊娠女性患者ICU入住率[调整风险比(aRR)=3.0,95% CI:2.6~3.4]、需要机械通气(aRR=2.9,95% CI:2.2~3.8)或体外膜肺氧合(aRR=2.4,95% CI:1.5~4.0)以及死亡(aRR=1.7,95% CI:1.2~2.4)的发生风险均高于非妊娠女性患者,即与非妊娠女性患者相比,妊娠女性患者感染SARS-CoV-2后更易发展为重症[35],危险因素包括高龄、肥胖、高血压、糖尿病、哮喘等合并症[36-37],这表明妊娠女性可能是SARS-CoV-2感染的高危人群,需予以重点关注。

目前虽有COVID-19妊娠女性患者在孕早期发生流产的相关报道,但无法确定是否与SARS-CoV-2感染相关[38-39],其症状严重程度与非妊娠女性患者相似[40],而孕中期及孕晚期COVID-19妊娠女性患者不良妊娠结局(包括子痫前期、早产、死胎以及剖宫产)的发生风险可能与疾病严重程度相关[36,41]

Delahoy等[36]报道,有症状的COVID-19妊娠女性患者早产率高于无症状者(23% 比 8%);另有研究表明COVID-19妊娠女性患者的早产率为25%,其中80%(48%为SARS-CoV-2感染, 14%为胎儿因素,18%为其他产科疾病因素)由医源性因素导致[42],尽管COVID-19妊娠女性患者早产率较高,但新生儿并发症的发生风险并未增加[43-44]

一项队列研究显示,COVID-19妊娠女性患者剖宫产率高于非感染者,且剖宫产率与疾病严重程度呈正相关(有症状者为46.7%,无症状者为45.5%,未感染者为30.9%,P=0.044)、死产率增加(3.2%)且为基线水平(0.6%)的5倍以上,但目前尚不清楚具体剖宫产指征(病情恶化、垂直传播风险或其他产科指征)[45-46]。因此,对于COVID-19妊娠女性患者,应密切关注其疾病严重程度,避免妊娠不良结局的发生,相关剖宫产指征有待进一步研究。

3.2 SARS-CoV-2存在垂直传播

2020年11月,Vivanti等[47]报道了1例23岁初产妇,在妊娠35周时感染SARS-CoV-2且症状严重,因胎儿指征行剖宫产手术,在该患者鼻咽部、羊水、胎盘拭子以及新生儿血液和呼吸道样本中SARS-CoV-2检测结果均为阳性,且在新生儿出生后1 h、3 d、18 d时再次进行鼻咽及直肠拭子SARS-CoV-2检测,结果仍为阳性,这表明SARS-CoV-2存在垂直传播,但发生垂直传播的时间和风险目前尚不明确,有待进一步研究。2021年,SARS-CoV-2成为继寨卡病毒后又一个被WHO列为存在垂直传播的病原体[48]

垂直传播包括宫内传播、产时传播以及产后传播:

(1)宫内传播:胎盘组织中可检测到ACE2和TMPRSS2的表达[49],尽管其共表达程度在不同报道中存在差异[50],但依旧为SARS-CoV-2的宫内传播提供了可能路径。一项Meta分析显示胎盘及羊水中SARS-CoV-2检测阳性率分别为7.7%(2/26)、0(0/17),3.7%(3/82)[51]。大多数存在宫内传播的COVID-19妊娠女性的胎盘均出现严重炎症反应,典型特征为弥漫性慢性绒毛间炎、坏死以及绒毛周围大量纤维蛋白沉积(>50%的胎盘),这一现象目前被认为是典型的“SARS-CoV-2胎盘炎”[52],导致胎盘血流灌注不良,且与胎儿宫内窘迫、死产、酸中毒以及转入NICU的发生率升高相关[53],但胎儿生长受限的发生风险是否与之相关目前尚不明确,有待进一步研究。

(2)产时传播:尽管COVID-19妊娠女性患者阴拭子中SARS-CoV-2检出率很低(3%)[54],但其粪便中的SARS-CoV-2检出率较高 (43%)[55],产妇在分娩期间产生的粪便、飞沫或气溶胶中SARS-CoV-2病毒均有可能对周围环境造成污染[56],从而导致产时传播。

(3)产后传播:可能与接触感染SARS-CoV-2的产妇或其他照护者相关[54],目前在母乳中尚未检测出具有复制能力的病毒[57],但存在SARS-CoV-2特异性IgG、IgM和IgA抗体[58],这些抗体能否为婴儿提供抵抗力尚不清楚。

虽然SARS-CoV-2对女性生育力的影响相对较小,妊娠女性感染SARS-CoV-2后易发展为重症,不良妊娠结局发生风险增加,且可能导致垂直传播,但目前研究提示母乳喂养的益处大于潜在风险[59],建议疑似或确诊COVID-19的哺乳期女性可进行母乳喂养。

4 SARS-CoV-2对辅助生育的影响

COVID-19疫情对人类辅助生殖技术(ART)在临床中的应用产生了巨大冲击。但随着人们对SARS-CoV-2研究的深入,ART的临床诊疗目前正逐渐恢复。

目前尚未在人类胚胎细胞中发现SARS-CoV-2的RNA,但已有多项研究证实,人类胚胎中存在感染SARS-CoV-2的受体,在植入前第6日胚胎的滋养外胚层细胞中可检测到ACE2和TMPRSS2的共表达,提示胚胎可能对SARS-CoV-2易感[60-61]

一项针对121例既往感染SARS-CoV-2患者的回顾性研究显示,近期感染(感染时间<180 d)对新鲜周期ART治疗结果无影响,感染组与对照组在获卵数、受精和成熟卵率、优质胚胎数量和临床妊娠率方面差异无统计学意义,但感染时间>180 d可能对获卵数产生长期负面影响[62]

而在冷冻胚胎移植周期中,既往感染SARS-CoV-2的患者与对照组的妊娠率比较无统计学差异(29% 比49%, P=0.070),但感染时间<60 d时,感染组较对照组妊娠率下降(21% 比 55%,P=0.006)[63]。目前SARS-CoV-2对ART的影响研究大多集中于女性患者,未来可在SARS-CoV-2对于男性患者ART的影响方面开展相关研究。

5 小结

SARS-CoV-2感染会导致男性生育力下降,尤其是处于急性感染期的男性患者。尽管SARS-CoV-2对女性生育力的影响相对较小,但妊娠女性感染后不仅易发展为重症,不良妊娠结局发生的风险亦将增加,且可能导致垂直传播,但母乳喂养的获益仍大于潜在风险,因此建议感染SARS-CoV-2的哺乳期女性可进行母乳喂养。

虽然人类胚胎存在感染SARS-CoV-2的风险,但其对ART的负面影响较小。目前研究针对SARS-CoV-2对生育力的影响进行了初步探索,但其造成的长期影响尚不明确,导致育龄人群对于感染SARS-CoV-2产生担忧,未来仍需高质量的研究数据进一步明确这一问题,从而更好地指导临床医师为育龄人群提供合适的建议与指导。

参考文献

[1]WHO. COVID-19 Weekly Epidemiological Update[Z]. 2021.

[2]Ashour HM, Elkhatib WF, Rahman MM, et al. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks[J]. Pathogens, 2020, 9: 186.

[3]Jackson CB, Farzan M, Chen B, et al. Mechanisms of SARS-CoV-2 entry into cells[J]. Nat Rev Mol Cell Biol, 2022, 23: 3-20.

[4]Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor[J]. Cell, 2020, 181: 271-280.e278.

[5]Qi J, Zhou Y, Hua J, et al. The scRNA-seq Expression Profiling of the Receptor ACE2 and the Cellular Protease TMPRSS2 Reveals Human Organs Susceptible to SARS-CoV-2 Infection[J]. Int J Environ Res Public Health, 2021, 18: 284.

[6]Jin JM, Bai P, He W, et al. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality[J]. Front Public Health, 2020, 8: 152.

[7]Fricke-Galindo I, Falfán-Valencia R. Genetics Insight for COVID-19 Susceptibility and Severity: A Review[J]. Front Immunol, 2021, 12: 622176.

[8]Mukherjee S, Pahan K. Is COVID-19 Gender-sensitive?[J]. J Neuroimmune Pharmacol, 2021, 16: 38-47.

[9]Kresch E, Achua J, Saltzman R, et al. COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction: Histopathological, Immunohistochemical, and Ultrastructural Study of the Human Penis[J]. World J Mens Health, 2021, 39: 466-469.

[10]Song H, Seddighzadeh B, Cooperberg MR, et al. Expression of ACE2, the SARS-CoV-2 Receptor, and TMPRSS2 in Prostate Epithelial Cells[J]. Eur Urol, 2020, 78: 296-298.

[11]Wang Z, Xu X. scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells[J]. Cells, 2020, 9: 920.

[12]Borges E, Setti AS, Iaconelli A, et al. Current status of the COVID-19 and male reproduction: A review of the literature[J]. Andrology, 2021, 9: 1066-1075.

[13]Stanley KE, Thomas E, Leaver M, et al. Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues[J]. Fertil Steril, 2020, 114: 33-43.

[14]Flaifel A, Guzzetta M, Occidental M, et al. Testicular Changes Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)[J]. Arch Pathol Lab Med, 2021, 145: 8-9.

[15]Patel DP, Punjani N, Guo J, et al. The impact of SARS-CoV-2 and COVID-19 on male reproduction and men's health[J]. Fertil Steril, 2021, 115: 813-823.

[16]Fraietta R, de Carvalho RC, Camillo J, et al. SARS-CoV-2 is not found in human semen during mild COVID-19 acute stage[J]. Andrologia, 2022, 54: e14286.

[17]Donders GGG, Bosmans E, Reumers J, et al. Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: a prospective, observational study and validation of the SpermCOVID test[J]. Fertil Steril, 2022, 117: 287-296.

[18]Saylam B, Uguz M, Yarpuzlu M, et al. The presence of SARS-CoV-2 virus in semen samples of patients with COVID-19 pneumonia[J]. Andrologia, 2021, 53: e14145.

[19]Corona G, Vena W, Pizzocaro A, et al. Andrological effects of SARS-CoV-2 infection: a systematic review and meta-analysis[J]. J Endocrinol Invest, 2022, 45: 2207-2219.

[20]Holtmann N, Edimiris P, Andree M, et al. Assessment of SARS-CoV-2 in human semen-a cohort study[J]. Fertil Steril, 2020, 114: 233-238.

[21]Guo L, Zhao S, Li W, et al. Absence of SARS-CoV-2 in semen of a COVID-19 patient cohort[J]. Andrology, 2021, 9: 42-47.

[22]Goad J, Rudolph J, Rajkovic A. Female reproductive tract has low concentration of SARS-CoV2 receptors[J]. PLoS One, 2020, 15: e0243959.

[23]Wu M, Ma L, Xue L, et al. Co-expression of the SARS-CoV-2 entry molecules ACE2 and TMPRSS2 in human ovaries: Identification of cell types and trends with age[J]. Genomics, 2021, 113: 3449-3460.

[24]Barragan M, Guillén JJ, Martin-Palomino N, et al. Undetectable viral RNA in oocytes from SARS-CoV-2 positive women[J]. Hum Reprod, 2021, 36: 390-394.

[25]Henarejos-Castillo I, Sebastian-Leon P, Devesa-Peiro A, et al. SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle[J]. Fertil Steril, 2020, 114: 223-232.

[26]Boudry L, Essahib W, Mateizel I, et al. Undetectable viral RNA in follicular fluid, cumulus cells, and endometrial tissue samples in SARS-CoV-2-positive women[J]. Fertil Steril, 2022, 117: 771-780.

[27]Khan SM, Shilen A, Heslin KM, et al. SARS-CoV-2 infection and subsequent changes in the menstrual cycle among participants in the Arizona CoVHORT study[J]. Am J Obstet Gynecol, 2022, 226: 270-273.

[28]Li K, Chen G, Hou H, et al. Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age[J]. Reprod Biomed Online, 2021, 42: 260-267.

[29]Demir O, Sal H, Comba C. Triangle of COVID, anxiety and menstrual cycle[J]. J Obstet Gynaecol, 2021, 41: 1257-1261.

[30]Puca E, Puca E. Premature Ovarian Failure Related to SARS-CoV-2 Infection[J]. J Med Cases, 2022, 13: 155-158.

[31]Wilkins J, Al-Inizi S. Premature ovarian insufficiency secondary to COVID-19 infection: An original case report[J]. Int J Gynaecol Obstet, 2021, 154: 179-180.

[32]World Health Organization.Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) [EB/OL].(2020-02-28)[2023-06-12].https://reliefweb.int/report/china/report-who-china-joint-mission-coronavirus-disease-2019-covid-19.

[33]Cheng B, Jiang T, Zhang L, et al. Clinical Characteristics of Pregnant Women With Coronavirus Disease 2019 in Wuhan, China[J]. Open Forum Infect Dis, 2020, 7: ofaa294.

[34]Wei L, Gao X, Chen S, et al. Clinical Characteristics and Outcomes of Childbearing-Age Women With COVID-19 in Wuhan: Retrospective, Single-Center Study[J]. J Med Internet Res, 2020, 22: e19642.

[35]Zambrano LD, Ellington S, Strid P, et al. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status-United States, January 22-October 3, 2020[J]. MMWR Morb Mortal Wkly Rep, 2020, 69: 1641-1647.

[36]Delahoy MJ, Whitaker M, O'Halloran A, et al. Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19-COVID-NET, 13 States, March 1-August 22, 2020[J]. MMWR Morb Mortal Wkly Rep, 2020, 69: 1347-1354.

[37]Ellington S, Strid P, Tong VT, et al. Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status-United States, January 22-June 7, 2020[J]. MMWR Morb Mortal Wkly Rep, 2020, 69: 769-775.

[38]WAPM (World Association of Perinatal Medicine) Working Group on COVID-19. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection[J]. Ultrasound Obstet Gynecol, 2021, 57: 232-241.

[39]Rana MS, Usman M, Alam MM, et al. First trimester miscarriage in a pregnant woman infected with COVID-19 in Pakistan[J]. J Infect, 2021, 82: e27-e28.

[40]Zhang L, Jiang Y, Wei M, et al. Analysis of the pregnancy outcomes in pregnant women with COVID-19 in Hubei Province[J]. Zhonghua Fu Chan Ke Za Zhi, 2020, 55: 166-171.

[41]Khoury R, Bernstein PS, Debolt C, et al. Characteristics and Outcomes of 241 Births to Women With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers[J]. Obstet Gynecol, 2020, 136: 273-282.

[42]Knight M, Bunch K, Vousden N, et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study[J]. BMJ, 2020, 369: m2107.

[43]Flaherman VJ, Afshar Y, Boscardin WJ, et al. Infant Outcomes Following Maternal Infection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): First Report From the Pregnancy Coronavirus Outcomes Registry (PRIORITY) Study[J]. Clin Infect Dis, 2021, 73: e2810-e2813.

[44]Yang H, Sun G, Tang F, et al. Clinical features and outcomes of pregnant women suspected of coronavirus disease 2019[J]. J Infect, 2020, 81: e40-e44.

[45]Panagiotakopoulos L, Myers TR, Gee J, et al. SARS-CoV-2 Infection Among Hospitalized Pregnant Women: Reasons for Admission and Pregnancy Characteristics-Eight U.S. Health Care Centers, March 1-May 30, 2020[J]. MMWR Morb Mortal Wkly Rep, 2020, 69: 1355-1359.

[46]Joseph NT, Rasmussen SA, Jamieson DJ. The effects of COVID-19 on pregnancy and implications for reproductive medicine[J]. Fertil Steril, 2021, 115: 824-830.

[47]Vivanti AJ, Vauloup-Fellous C, Prevot S, et al. Transplacental transmission of SARS-CoV-2 infection[J]. Nat Commun, 2020, 11: 3572.

[48]WHO. Definition and categorization of the timing of mother-to-child transmission of SARS-CoV-2[Z]. 2021.

[49]Levy A, Yagil Y, Bursztyn M, et al. ACE2 expression and activity are enhanced during pregnancy[J]. Am J Physiol Regul Integr Comp Physiol, 2008, 295: R1953-1961.

[50]Pique-Regi R, Romero R, Tarca AL, et al. Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?[J]. Elife, 2020, 9: e58716.

[51]Kotlyar AM, Grechukhina O, Chen A, et al. Vertical transmission of coronavirus disease 2019: a systematic review and meta-analysis[J]. Am J Obstet Gynecol, 2021, 224: 35-53.e33.

[52]Vivanti AJ, Vauloup-Fellous C, Escourrou G, et al. Factors associated with SARS-CoV-2 transplacental transmission[J]. Am J Obstet Gynecol, 2022, 227: 541-543.e11.

[53]Narang K, Miller M, Trinidad C, et al. Impact of asymptomatic and mild COVID-19 infection on fetal growth during pregnancy[J]. Eur J Obstet Gynecol Reprod Biol, 2023, 281: 63-67.

[54]Yap M, Debenham L, Kew T, et al. Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol[J]. BMJ Open, 2020, 10: e041868.

[55]van Doorn AS, Meijer B, Frampton CMA, et al. Systematic review with meta-analysis: SARS-CoV-2 stool testing and the potential for faecal-oral transmission [J]. Aliment Pharmacol Ther, 2020, 52: 1276-1288.

[56]Carosso A, Cosma S, Borella F, et al. Pre-labor anorectal swab for SARS-CoV-2 in COVID-19 pregnant patients: is it time to think about it?[J]. Eur J Obstet Gynecol Reprod Biol, 2020, 249: 98-99.

[57]Centeno-Tablante E, Medina-Rivera M, Finkelstein JL, et al. Transmission of SARS-CoV-2 through breast milk and breastfeeding: a living systematic review[J]. Ann N Y Acad Sci, 2021, 1484: 32-54.

[58]Demers-Mathieu V, Do DM, Mathijssen GB, et al. Difference in levels of SARS-CoV-2 S1 and S2 subunits-and nucleocapsid protein-reactive SIgM/IgM, IgG and SIgA/IgA antibodies in human milk[J]. J Perinatol, 2021, 41: 850-859.

[59]World Health Organization.Clinical management of COVID-19: living guideline, 13 January 2023[EB/OL].(2023-01-13)[2023-06-12] https://apps.who.int/iris/handle/10665/365580.

[60]Colaco S, Chhabria K, Singh D, et al. Expression map of entry receptors and infectivity factors for pan-coronaviruses in preimplantation and implantation stage human embryos[J]. J Assist Reprod Genet, 2021, 38: 1709-1720.

[61]Weatherbee BAT, Glover DM, Zernicka-Goetz M. Expres-sion of SARS-CoV-2 receptor ACE2 and the protease TMPRSS2 suggests susceptibility of the human embryo in the first trimester[J]. Open Biol, 2020, 10: 200162.

[62]Youngster M, Avraham S, Yaakov O, et al. IVF under COVID-19: treatment outcomes of fresh ART cycles[J]. Hum Reprod, 2022, 37: 947-953.

[63]Youngster M, Avraham S, Yaakov O, et al. The impact of past COVID-19 infection on pregnancy rates in frozen embryo transfer cycles[J]. J Assist Reprod Genet, 2022, 39: 1565-1570.

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