Farname Inc. in collaboration with Iranian Society of Gynecology Oncology


1 School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 School of Medicine, Guilan University of Medical Sciences, Rasht, Iran

3 Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran,

4 School of medicine, Iran University of Medical Sciences, Tehran, Iran

5 Reproductive Health Research Center, Guilan University of Medical Sciences, Guilan, Iran


Background/objective: The COVID-19 pandemic has disrupted people’s lives all over the world and vaccination is one of the best ways to eradicate this pandemic and save people’s lives. Despite this, vaccines have many known and unknown side effects like fever, fatigue, headache, etc. Fertility is an important aspect of human life with too many concerns about its relation with COVID-19 and its vaccines. Women are complaining of menstrual irregularities like postmenopausal bleeding, heavy menstrual bleeding, polymenorrhea and fertility concerns after receiving the second dose of COVID-19 vaccine. The immunologic reactions between vaccines’ ingredients and immune system of the body, seem to be responsible for this global issue. Angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG) are the receptors for SARS-COV-2. ACE2 is expressed in human respiratory system, kidney, vagina, uterus and particularly widely in the ovaries; and BSG is expressed in the uterus, ovary stroma and granulosa cells. Therefore, SARS-COV-2 can invade the target cells by attachment to ACE2 and BSG, and modulate their expression and through these probable mechanisms, it can disturb female reproduction and menstruation.
Conclusion: According to these accumulated evidences, in this study, we aimed at summarizing the recent studies with focus on probable mechanisms which SARS-COV-2 and COVID-19 vaccines affect menstruation irregularities and reproduction complications.


  1. 1. Haryalchi K, Heidarzadeh A, Abedinzade M, Olangian-Tehrani S, Ghazanfar Tehran S. The Importance of Happy Hypoxemia in COVID-19. Anesthesiology and pain medicine. 2021;11(1):e111872. 2. Haryalchi K, Olangian-Tehrani S, Asgari Galebin SM, Mansour-Ghanaie M. The importance of myocarditis in Covid-19. Health Science Reports. 2022;5(1):e488. 3. Havers FP, Reed C, Lim T, Montgomery JM, Klena JD, Hall AJ, et al. Seroprevalence of antibodies to SARS-CoV-2 in 10 sites in the United States, March 23-May 12, 2020. JAMA internal medicine. 2020;180(12):1576-86. 4. Luyten J, Beutels P. The social value of vaccination programs: beyond cost-effectiveness. Health Affairs. 2016;35(2):212-8. 5. Thiyagarajan DK, Basit H, Jeanmonod R. Physiology, menstrual cycle. StatPearls [Internet]. 2020. 6. Huang H-H, Wang P-H, Yang Y-P, Chou S-J, Chu P-W, Wu G-J, et al. A review of severe acute respiratory syndrome coronavirus 2 infection in the reproductive system. Journal of the Chinese Medical Association. 2020;83(10):895. 7. Li F, Lu H, Zhang Q, Li X, Liu Q, Yang Q, et al. Impact of COVID-19 on female fertility: a systematic review and meta-analysis protocol. BMJ open. 2021;11(2):e045524. 8. Schaler L, Wingfield M. COVID-19 vaccine—can it affect fertility? Irish Journal of Medical Science (1971-). 2021:1-3. 9. Umakanthan S, Sahu P, Ranade AV, Bukelo MM, Rao JS, Abrahao-Machado LF, et al. Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Postgraduate medical journal. 2020;96(1142):753-8. 10. Li K, Chen G, Hou H, Liao Q, Chen J, Bai H, et al. Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age. Reprod Biomed Online. 2021;42(1):260-7. 11. 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 (Lausanne). 2021;8:635255. 12. Wilkins J, Al-Inizi S. Premature ovarian insufficiency secondary to COVID-19 infection: An original case report. Int J Gynaecol Obstet. 2021;154(1):179-80. 13. Pan PP, Zhan QT, Le F, Zheng YM, Jin F. Angiotensin-converting enzymes play a dominant role in fertility. International journal of molecular sciences. 2013;14(10):21071-86. 14. Reis FM, Bouissou DR, Pereira VM, Camargos AF, dos Reis AM, Santos RA. Angiotensin-(1-7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertility and sterility. 2011;95(1):176-81. 15. Segars J, Katler Q, McQueen DB, Kotlyar A, Glenn T, Knight Z, et al. Prior and novel coronaviruses, Coronavirus Disease 2019 (COVID-19), and human reproduction: what is known? Fertility and sterility. 2020;113(6):1140-9. 16. Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Frontiers of medicine. 2020;14(2):185-92. 17. Jing Y, Run-Qian L, Hao-Ran W, 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. 18. 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. The Journal of pathology. 2004;203(2):622-30. 19. Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA neurology. 2020;77(6):683-90. 20. Özdin S, Bayrak Özdin Ş. Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender. The International journal of social psychiatry. 2020;66(5):504-11. 21. Haleem A, Javaid M, Vaishya R. Effects of COVID-19 pandemic in daily life. Curr Med Res Pract. 2020;10(2):78-9. 22. Anifandis G, Messini CI, Daponte A, Messinis IE. COVID-19 and fertility: a virtual reality. Reproductive BioMedicine Online. 2020;41(2):157-9. 23. 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. 24. Blumenfeld Z. Possible impact of COVID-19 on fertility and assisted reproductive technologies. Fertility and sterility. 2020;114(1):56-7. 25. Li F, Lu H, Zhang Q, Li X, Wang T, Liu Q, et al. Impact of COVID-19 on female fertility: a systematic review and meta-analysis protocol. BMJ Open. 2021;11(2):e045524. 26. Mahdian S, Shahhoseini M, Moini A. COVID-19 Mediated by Basigin Can Affect Male and Female Fertility. Int J Fertil Steril. 2020;14(3):262-3. 27. Hikmet F, Mear L, Edvinsson A, Micke P, Uhlen M, Lindskog C. The protein expression profile of ACE2 in human tissues. Mol Syst Biol. 2020;16(7):e9610. 28. Saeed BQ, Al-Shahrabi R, Alhaj SS, Alkokhardi ZM, Adrees AO. Side Effects and Perceptions Following Sinopharm COVID-19 Vaccination. International Journal of Infectious Diseases. 2021. 29. Merchant H. CoViD-19 post-vaccine menorrhagia, metrorrhagia or postmenopausal bleeding and potential risk of vaccine-induced thrombocytopenia in women. The BMJ. 2021:bmj. n958/rr-2. 30. Bentov Y, Beharier O, Moav-Zafrir A, Kabessa M, Godin M, Greenfield C, et al. Ovarian follicular function is not altered by SARS-Cov-2 infection or BNT162b2 mRNA Covid-19 vaccination. medRxiv. 2021. 31. Menni C, Klaser K, May A, Polidori L, Capdevila J, Louca P, et al. Vaccine side-effects and SARS-CoV-2 infection after vaccination in users of the COVID Symptom Study app in the UK: a prospective observational study. The Lancet Infectious Diseases. 2021. 32. Jamieson M, Hughes BL, Swamy G, O’Neal L, Eckert M, Turrentine M, et al. COVID-19 Vaccination Considerations for Obstetric–Gynecologic Care. 33. Male V. Menstrual changes after covid-19 vaccination. British Medical Journal Publishing Group; 2021. 34. Harrison M, Hoover K, Kaufman S, McCracken K, Robillard D, Romano M, et al. NASPAG Position Statement on COVID-19 Vaccines and Gynecologic Concerns in Adolescents and Young Adults. 35. Kurdoğlu Z. Do the COVID-19 Vaccines Cause Menstrual Irregularities? 36. Edelman A, Boniface ER, Benhar E, Han L, Matteson KA, Favaro C, et al. Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination: A U.S. Cohort. Obstetrics & Gynecology. 9900:10.1097/AOG.0000000000004695. 37. Karagiannis A, Harsoulis F. Gonadal dysfunction in systemic diseases. European journal of endocrinology. 2005;152(4):501-13. 38. Komorowska B. Autoimmune premature ovarian failure. Przeglad menopauzalny = Menopause review. 2016;15(4):210-4. 39. Monin L, Whettlock EM, Male V. Immune responses in the human female reproductive tract. Immunology. 2020;160(2):106-15. 40. Krishna UR. Reproductive Health During the COVID-19 Pandemic. The Journal of Obstetrics and Gynecology of India. 2021:1-5. 41. Wang M, Yang Q, Ren X, Hu J, Li Z, Long R, et al. Investigating the impact of asymptomatic or mild SARS-CoV-2 infection on female fertility and in vitro fertilization outcomes: A retrospective cohort study. EClinicalMedicine. 2021;38:101013. 42. Sajjadi NB, Nowlin W, Nowlin R, Wenger D, Beal JM, Vassar M, et al. United States internet searches for "infertility" following COVID-19 vaccine misinformation. Journal of osteopathic medicine. 2021;121(6):583-7. 43. Fauzia M. Fact Check: a False Post on Social Media Claims covid-19 Vaccine Causes Infertility in Women. USA Today. 2020. 44. Morris RS. SARS-CoV-2 spike protein seropositivity from vaccination or infection does not cause sterility. F&S reports. 2021;2(3):253-5. 45. Markert UR, Szekeres-Bartho J, Schleußner E. Adverse effects on female fertility from vaccination against COVID-19 unlikely. Journal of reproductive immunology. 2021;148:103428. 46. Laufer G, Mayer J, Mueller BF, Mueller-Lantzsch N, Ruprecht K. Analysis of transcribed human endogenous retrovirus W env loci clarifies the origin of multiple sclerosis-associated retrovirus env sequences. Retrovirology. 2009;6:37. 47. Kornmann G, Curtin F. Temelimab, an IgG4 Anti-Human Endogenous Retrovirus Monoclonal Antibody: An Early Development Safety Review. Drug safety. 2020;43(12):1287-96. 48. Bowman CJ, Bouressam M, Campion SN, Cappon GD, Catlin NR, Cutler MW, et al. Lack of effects on female fertility and prenatal and postnatal offspring development in rats with BNT162b2, a mRNA-based COVID-19 vaccine. Reproductive toxicology (Elmsford, NY). 2021;103:28-35. 49. Orvieto R, Noach-Hirsh M, Segev-Zahav A, Haas J, Nahum R, Aizer A. Does mRNA SARS-CoV-2 vaccine influence patients' performance during IVF-ET cycle? Reproductive biology and endocrinology : RB&E. 2021;19(1):69. 50. Safrai M, Rottenstreich A, Herzberg S, Imbar T, Reubinoff B, Ben-Meir A. Stopping the misinformation: BNT162b2 COVID-19 vaccine has no negative effect on women’s fertility. medRxiv. 2021:2021.05.30.21258079. 51. Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, et al. Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. New England Journal of Medicine. 2021;384(24):2273-82. 52. Thakur V, Ratho RK, Kumar P, Bhatia SK, Bora I, Mohi GK, et al. Multi-Organ Involvement in COVID-19: Beyond Pulmonary Manifestations. Journal of Clinical Medicine. 2021;10(3).