Impact of SARS-CoV-2 infection on fertility: concerns in Reproductive Medicine

Authors

  • Ana Beatriz de Almeida Department of Women’s and Reproductive Health, Centro Materno-Infantil do Norte; Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Centro Hospitalar Universitário do Porto https://orcid.org/0000-0002-7898-5132
  • Tiago Meneses Alves Department of Women’s and Reproductive Health, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto; Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto https://orcid.org/0000-0002-4402-8836
  • Rosa Zulmira Macedo Department of Women’s and Reproductive Health, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto; Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto; Centre of Assisted Medical Procriation (CPMA), Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto
  • Márcia Barreiro Department of Women’s and Reproductive Health, Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto; Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto; Centre of Assisted Medical Procriation (CPMA), Centro Materno-Infantil do Norte, Centro Hospitalar Universitário do Porto https://orcid.org/0000-0002-8849-0862

DOI:

https://doi.org/10.25753/BirthGrowthMJ.v31.i3.27747

Keywords:

COVID-19, fertility, reproductive medicine

Abstract

The coronavirus disease 2019 pandemic brought repercussions on health services providing fertility treatments. Approximately 0.3% of the overall livebirth rate corresponds to infants conceived using assisted reproductive technology treatments every year. Besides its negative impact relative to cycle cancelations, it is thought that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may affect the human reproductive system through angiotensin-converting enzyme 2 (ACE2) receptor, and consequently lead to infertility. The SARS-CoV-2 infection may disrupt the hypothalamus-pituitary-ovary (HPO) axis, and hence oocyte quality. Moreover, the endometrial ACE2 expression raises concerns about endometrial and placental dysfunctions related to obstetrical complications when pregnancy is achieved. Furthermore, an association between COVID-19 and changes in menstrual patterns was observed. However, in men, ACE2 expression levels on testicular cells is low and presence of SARS-CoV-2 mRNA in semen is controversial. Still, imaging signs of orchitis and epididymitis in COVID-19 recovered patients and clinical hypogonadism may be responsible for impairing male fertility during the pandemic. The international recommendations firstly encouraged the gradual re-establishment of fertility treatments by identifying those patients who should be prioritized. Therefore, we assessed the importance of fertility preservation during coronavirus disease 2019 pandemic to urgent subgroups of patients (mainly oncological patients and autoimmune diseases) that are usually submitted to gonadotoxic and teratogenic treatments that cannot be deferred indefinitely awaiting for the pandemic to end. The implications of SARS-CoV-2 effects on assisted reproductive technology (ART) outcomes are also explored in this review.

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References

Lee WY, Mok A, Chung JPW. Potential effects of COVID-19 on reproductive systems and fertility; assisted reproductive technology guidelines and considerations: a review. Hong Kong Med J. 2021; 27(2): 118-26. https://doi.org/10.12809/hkmj209078.

Yüce M, Filiztekin E, Ozkaya KG. COVID-19 diagnosis — A review of current methods. Biosens Bioelectron. 2021;172:112752. https://doi.org/10.1016/j.bios.2020.112752.

The ESHRE COVID-19 Working Group: Vermulen N, Ata B, Gianaroli L, Lundin K, Mocanu E, Rautakallio-Hokkanen S, et al. A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe. Hum Reprod Open. 2020;2020(3):hoaa035. https://doi.org/10.1093/hropen/hoaa035.

Veiga A, Gianaroli L, Ory S, Horton M, Feinberg E, Penzias A. Assisted reproduction and COVID-19: A joint statement of ASRM, ESHRE and IFFS. Fertil Steril. 2020;114(3):484-485. https://doi.org/10.1016/j.fertnstert.2020.06.044.

Seymen CM. The other side of COVID‐19 pandemic: Effects on male fertility. J Med Virol. 2020;93(3):1396-402. https://doi.org/10.1002/jmv.26667.

Younis JS, Abassi Z, Skorecki K. Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection. Am J Physiol Endocrinol Metabol. 2020: 318:6. https://doi.org/10.1152/ajpendo.00183.2020.

Stanley KE, Thomas E, Leaver M, Wells D. Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertil Steril. 2020;114 (1):33-43. https://doi.org/10.1016/j.fertnstert.2020.05.001.

Mali AS, Magdum M, Novotny J. COVID-19 impact on reproduction and fertility. JBRA Assist Reprod. 2021;25(2):310-3. https://doi.org/10.5935/1518-0557.20200103.

Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, et al. Angiotensinconverting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. 2020;251(3):228-48. https://doi.org/10.1002/path.5471.

Pan PP, Zhan QT, Le F, Ming YM, Jin F. Angiotensin-Converting Enzymes Play a Dominant Role in Fertility. Int J Mol Sci. 2013; 14 (10): 21071-86; https://doi.org/10.3390/ijms14102107.

Verma S, Saksena S, Sadri‐Ardekani H. ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis. Biol Reprod. 2020;103(3):449-451. https://doi.org/10.1093/biolre/ioaa080.

Li H, Xiao X, Zhang J, Zafar MI, Wu C, Long Y, et al. Impaired spermatogenesis in COVID-19 patients. E Clinical Med. 2020;28:100604. https://doi.org/10.1016/j.eclinm.2020.100604.

Chandi A, Jain N. State of assisted reproduction technology in the coronavirus disease 2019 era and consequences on human reproductive system. Biol Reprod. 2021;105(4):808–21. https://doi.org/10.1093/biolre/ioab122.

Pan F, Xiao X, Guo J, Song Y, Li H, Patel DP, et al. No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril. 2020;113:1135-9. https://doi.org/10.1016/j.fertnstert.2020.04.024.

Li D, Jin M, Bao P, Zhao W, Zhang S. Clinical characteristics and results of semen tests among men with coronavirus disease 2019. JAMA Netw Open. 2020;3(5):e208292. https://doi.org/10.1001/jamanetworkopen.2020.8292.

Cirillo M, Rizzello F,Badolato L, Angelis D, Evangelisti P, Coccia ME, et al. The effects of COVID-19 lockdown on lifestyle and emotional state in women undergoing assisted reproductive technology: Results of an Italian survey. J Gynecol Obstet Hum Reprod. 2021;50(8):102079. https://doi.org/10.1016/j.jogoh.2021.102079.

Illiano E, Trama F, Costantini E. Could COVID-19 have an impact on male fertility? Andrologia. 2020;52(6):e13654. https://doi.org/10.1111/and.13654.

Yan J, Li RQ, Wang HR, Hao-Ran C, Ya-Bin L, Yang G, et al. Potential influence of COVID-19/ACE2 on the female reproductive system. Mol Hum Reprod. 2020;26(6):367-73. https://doi.org/10.1093/molehr/gaaa030.

Ding T, Wang T, Zhang J, Cui P, Chen Z, Zhou S, et al. Analysis of ovarian injury associated with COVID-19 disease in reproductive-aged women in Wuhan, China: an observational study. Front Med 2021;8:635255. https://doi.org/10.3389/fmed.2021.635255.

Ding Y, He L, Zhang Q, Huang Z, Che X, Hou J, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS- CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 2004;203(2):622–30. https://doi.org/10.1002/path.1560.

Herr D, Bekes I, Wulff C. Local renin-angiotensin system in the reproductive system. Front Endocrinol (Lausanne). 2013;4:150. https://doi.org/10.3389/fendo.2013.00150.

Li R, Yin T, Fang F, Li Q, Chen J, Wang Y, et al. Potential risks of SARS-CoV-2 infection on reproductive health. Reprod Biomed Online. 2020;41(1):89-95. https://doi.org/10.1016/j.rbmo.2020.04.018.

Henarejos-Castillo I, Sebastian-Leon P, Devesa-Peiro A, Pellicer A, Diaz-Gimeno P. SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle. Fertil Steril. 2020;114(2):223-32. https://doi.org/10.1016/j.fertnstert.2020.06.026.

Li K, Chen G, Hou H, Liao Q, Chen J, Bai H, Lee S, et al. Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age. Reprod Biomed Online. 2021;42(1):260-7. https://doi.org/10.1016/j.rbmo.2020.09.020.

Lebar V, Laganà AS, Chiantera V, Kunicˇ T, Lukanovic ́ D. The Effect of COVID-19 on the Menstrual Cycle: A Systematic Review. J. Clin. Med. 2022;11(13):3800. https://doi.org/10.3390/jcm11133800.

Khan S, Shilen A, Heslin K, Ishimwe P, Allen A, Jacobs E, et al. SARS-CoV-2 infection and subsequent changes in the menstrual cycle among participants in the Arizona CoVHORT study. Am. J. Obstet. Gynecol. 2022; 226(2): 270–3. https://doi.org/10.1016/j.ajog.2021.09.016.

Selek A, Güçlü M, Bolu SE. COVID-19 pandemic: what about the gonads? Hormones. 2021;20(2):259-68. https://doi.org/10.1007/s42000-021-00277-3.

Alviggi C, Esteves S, Orvieto R, Conforti A, Marca A, Fischer R, et al. COVID-19 and assisted reproductive technology services: repercussions for patients and proposal for individualized clinical management. Reprod Biol Endocrinol. 2020;18(1):45. https://doi.org/10.1186/s12958-020-00605-z.

Dellino M, Minoia C, Paradiso AV, De Palo R, Silvestris E. Fertility Preservation in Cancer Patients During the Coronavirus (COVID-19) Pandemic. Front Oncol. 2020;10:1009. https://doi.org/10.3389/fonc.2020.01009.

Telfer EE, McLaughlin M. In vitro development of ovarian follicles. Semin Reprod Med. 2011;29(1):15–23. https://doi.org/10.1055/s-0030-1268700.

Sirohi B, Buckshee Rohatgi T, Lambertini M. Oncofertility and COVID-19-cancer does not wait. Ecancermedicalscience. 2020;14: ed101. https://doi.org/10.3332/ecancer.2020.ed101.

Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer - Full Text View - ClinicalTrials.gov [Internet]. [cited 2022 Jul 16]. Available from: https://clinicaltrials.gov/ct2/ show/NCT02308085.

Invernizzi P, Pasini S, Selmi C, Gershwin ME, Podda M. Female predominance and X chromosome defects in autoimmune diseases. J Autoimmun. 2009;33(1):12-6. https://doi.org/10.1016/j.jaut.2009.03.005.

Madjunkov M, Dviri M, Librach C. A comprehensive review of the impact of COVID-19 on human reproductive biology, assisted reproduction care and pregnancy: a Canadian perspective. J Ovarian Res. 2020;13(1):140. https://doi.org/10.1186/s13048-020-00737-1.

Lawson AK, McQueen DB, Swanson AC, Confino R, Feinberg EC, Pavone ME. Psychological distress and postponed fertility care during the COVID-19 pandemic. J Assis Reprod Gen. 2021;38(2):333-41. https://doi.org/10.1007/s10815-020-02023-x.

Esteves SC, Yarali H, Ubaldi FM, Carvalho JF, Bento FC, Vaiarelli A, et al. Validation of ART calculator for predicting the number of metaphase II oocytes required for obtaining at least one euploid blastocyst for transfer in couples undergoing in vitro fertilization/intracytoplasmic sperm injection. Front Endocrinol (Lausanne). 2020;10:917. https://doi.org/10.3389/fendo.2019.00917.

American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and Practice Committee. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014;101(3):633–4. https://doi.org/10.1016/j.fertnstert.2013.12.032.

Cirillo M, Rizzello F,Badolato L, Angelis D, Evangelisti P, Coccia ME, et al. The effects of COVID-19 lockdown on lifestyle and emotional state in women undergoing assisted reproductive technology: Results of an Italian survey. J Gynecol Obstet Hum Reprod. 2021;50(8):102079. https://doi.org/10.1016/j.jogoh.2021.102079.

Tokgoz VY, Kaya Y, Tekin AB. The level of anxiety in infertile women whose ART cycles are postponed due to the COVID-19 outbreak. J Psychosom Obstet Gynaecol. 2020:1–8. https://doi.org/10.1080/0167482X.2020.1806819.

Chen L, Huang X, Yi Z, Deng Q, Jiang N, Feng C, et al. Ultrasound imaging findings of acute testicular infection in patients with coronavirus disease 2019. J Ultrasound Med 2020;40(9):1787-94. https://doi.org/10.1002/jum.15558.

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Published

2022-10-19

How to Cite

1.
de Almeida AB, Meneses Alves T, Zulmira Macedo R, Barreiro M. Impact of SARS-CoV-2 infection on fertility: concerns in Reproductive Medicine. REVNEC [Internet]. 2022Oct.19 [cited 2024Mar.29];31(3):212-9. Available from: https://revistas.rcaap.pt/nascercrescer/article/view/27747