Corona and Reproduction, or Why the Corona Vaccination Does Not Result in Infertility

Anne-Sophie Braun; Katharina Feil; Elisabeth Reiser; Guenter Weiss; Thore von Steuben; Germar Michael Pinggera; Frank-Michael Köhn; Bettina Toth

doi:10.1055/a-1750-9284

Geburtshilfe und Frauenheilkunde, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2022; 82(05): 490-500
DOI: 10.1055/a-1750-9284

GebFra Science

Review/Übersicht

Corona and Reproduction, or Why the Corona Vaccination Does Not Result in Infertility

Artikel in mehreren Sprachen: English | deutsch

Anne-Sophie Braun

¹Universitätsklinik für Gynäkologische Endokrinologie u. Reproduktionsmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria

,

Katharina Feil

¹Universitätsklinik für Gynäkologische Endokrinologie u. Reproduktionsmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria

,

Elisabeth Reiser

¹Universitätsklinik für Gynäkologische Endokrinologie u. Reproduktionsmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria

,

Guenter Weiss

²Universitätsklinik für Innere Medizin II, Medizinische Universität Innsbruck, Innsbruck, Austria

,

Thore von Steuben

¹Universitätsklinik für Gynäkologische Endokrinologie u. Reproduktionsmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria

,

Germar Michael Pinggera

³Universitätsklinik für Urologie, Medizinische Universität Innsbruck, Innsbruck, Austria

,

Frank-Michael Köhn

⁴Andrologicum, München, Germany

,

Bettina Toth

¹Universitätsklinik für Gynäkologische Endokrinologie u. Reproduktionsmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria

› Institutsangaben

Abstract

Background As the COVID-19 pandemic persists and new vaccines are developed, concerns among the general public are growing that both infection with the SARS-CoV-2 virus and vaccinations against the coronavirus (mRNA vaccines) could lead to infertility or higher miscarriage rates. These fears are voiced particularly often by young adults of reproductive age. This review summarizes the current data on the impact of SARS-CoV-2 infection and corona vaccinations on female and male fertility, based on both animal models and human data.

Method A systematic literature search (PubMed, Embase, Web of Science) was carried out using the search terms “COVID 19, SARS-CoV-2, fertility, semen, sperm, oocyte, male fertility, female fertility, infertility”. After the search, original articles published between October 2019 and October 2021 were selected and reviewed.

Results Despite the use of very high vaccine doses in animal models, no negative impacts on fertility, the course of pregnancy, or fetal development were detected. In humans, no SARS-CoV-2 RNA was found in the oocytes/follicular fluid of infected women; similarly, no differences with regard to pregnancy rates or percentages of healthy children were found between persons who had recovered from the disease, vaccinated persons, and controls. Vaccination also had no impact on live-birth rates after assisted reproductive treatment. No viral RNA was detected in the semen of the majority of infected or still infectious men; however, a significant deterioration of semen parameters was found during semen analysis, especially after severe viral disease. None of the studies found that corona vaccines had any impact on male fertility.

Discussion Neither the animal models nor the human data presented in recent studies provide any indications that fertility decreases after being vaccinated against coronavirus. However, there is a growing body of evidence that severe SARS-CoV-2 infection has a negative impact on male fertility and there is clear evidence of an increased risk of complications among pregnant women with SARS-CoV-2 infection. The counseling offered to young adults should therefore take their fears and concerns seriously as well as providing a structured discussion of the current data.

Key words

COVID-19 - corona vaccine - SARS-CoV-2 - reproduction - sperm - oocyte - embryo - infertility

Volltext

Referenzen

References/Literatur
1 WHO. WHO Coronavirus (Covid-19) Dashboard. Accessed January 17, 2022 at: https://covid19.who.int/
2 Andersen KG, Rambaut A, Lipkin WI. et al. The proximal origin of SARS-CoV-2. Nat Med 2020; 26: 450-452
3 Jin J-M, Bai P, He W. et al. Gender Differences in Patients With COVID-19: Focus on Severity and Mortality. Front Public Health 2020;
4 Chauvin M, Larsen M, Quirant B. et al. Elevated Neopterin Levels Predict Fatal Outcome in SARS-CoV-2-Infected Patients. Front Cell Infect Microbiol 2021;
5 Nguyen NT, Chinn J, De Ferrante M. et al. Male gender is a predictor of higher mortality in hospitalized adults with COVID-19. PLoS One 2021; 16: e0254066
6 Mauvais-Jarvis F, Klein SL, Levin ER. Estradiol, Progesterone, Immunomodulation, and COVID-19 Outcomes. Endocrinology 2020;
7 Lanser L, Burkert FR, Thommes L. et al. Testosterone Deficiency Is a Risk Factor for Severe COVID-19. Front Endocrinol (Lausanne) 2021; 12: 694083
8 Lund LC, Hallas J, Nielsen H. et al. Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study. Lancet Infect Dis 2021; 21: 1373-1382
9 Sonnweber T, Sahanic S, Pizzini A. et al. Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial. Eur Respir J 2021; 57: 2003481
10 Sudre CH, Murray B, Varsavsky T. et al. Attributes and predictors of long COVID. Nat Med 2021; 27: 626-631
11 Groff D, Sun A, Ssentongo AE. et al. Short-term and Long-term Rates of Postacute Sequelae of SARS-CoV-2 Infection: A Systematic Review. JAMA Netw Open 2021; 4: e2128568
12 Ho FK, Petermann-Rocha F, Gray SR. et al. Is older age associated with COVID-19 mortality in the absence of other risk factors? General population cohort study of 470,034 participants. PLoS One 2020; 15: e0241824
13 Xu Y, Chen Y, Tang X. Guidelines for the diagnosis and treatment of coronavirus disease 2019 (COVID-19) in China. Glob Health Med 2020; 2: 66-72
14 Kim L, Garg S, OʼHalloran A. et al. Risk Factors for Intensive Care Unit Admission and In-hospital Mortality Among Hospitalized Adults Identified through the US Coronavirus Disease 2019 (COVID-19)-Associated Hospitalization Surveillance Network (COVID-NET). Clin Infect Dis 2021; 72: e206-e214
15 Cunningham JW, Vaduganathan M, Claggett BL. et al. Clinical Outcomes in Young US Adults Hospitalized With COVID-19. JAMA Intern Med 2021; 181: 379
16 Gacci M, Coppi M, Baldi E. et al. Semen impairment and occurrence of SARS-CoV-2 virus in semen after recovery from COVID-19. Hum Reprod 2021; 36: 1520-1529
17 Holtmann N, Edimiris P, Andree M. et al. Assessment of SARS-CoV-2 in human semen–a cohort study. Fertil Steril 2020; 114: 233-238
18 Hajizadeh Maleki B, Tartibian B. COVID-19 and male reproductive function: a prospective, longitudinal cohort study. Reproduction 2021; 161: 319-331
19 Demirel C, Tulek F, Celik HG. et al. Failure to Detect Viral RNA in Follicular Fluid Aspirates from a SARS-CoV-2-Positive Woman. Reprod Sci 2021; 28: 2144-2146
20 Klaritsch P, Ciresa-König A, Pristauz-Telsnigg G. et al. COVID-19 During Pregnancy and Puerperium – A Review by the Austrian Society of Gynaecology and Obstetrics (OEGGG). Geburtshilfe Frauenheilkd 2020; 80: 813-819
21 Gao L, Ren J, Xu L. et al. Placental pathology of the third trimester pregnant women from COVID-19. Diagn Pathol 2021;
22 Wong YP, Khong TY, Tan GC. The Effects of COVID-19 on Placenta and Pregnancy: What Do We Know So Far?. Diagnostics 2021; 11: 94
23 Mandò C, Savasi VM, Anelli GM. et al. Mitochondrial and Oxidative Unbalance in Placentas from Mothers with SARS-CoV-2 Infection. Antioxidants 2021;
24 Stumpfe FM, Titzmann A, Schneider MO. et al. SARS-CoV-2 Infection in Pregnancy – a Review of the Current Literature and Possible Impact on Maternal and Neonatal Outcome. Geburtshilfe Frauenheilkd 2020; 80: 380-390
25 Delahoy MJ, Whitaker M, OʼHalloran 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. MMWR Morb Mortal Wkly Rep 2020; 69: 1347-1354
26 Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies. Acta Obstet Gynecol Scand 2020; 99: 823-829
27 Medeiros KS, Sarmento ACA, Martins ES. et al. Impact of SARS-CoV-2 (COVID-19) on pregnancy: a systematic review and meta-analysis protocol. BMJ Open 2020; 10: e039933
28 Magee LA, Von Dadelszen P, Kalafat E. et al. COVID-19 vaccination in pregnancy–number needed to vaccinate to avoid harm. Lancet Infect Dis 2021;
29 Polack FP, Thomas SJ, Kitchin N. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med 2020; 383: 2603-2615
30 Chalupka A, Handra N, Richter L. et al. Estimates of COVID-19 Vaccine Effectiveness against SARS-CoV-2 infections following a nationwide vaccination campaign. AGES; 2021. Accessed November 19, 2021 at: https://www.ages.at/fileadmin/Corona/Immunschutz/Impfeffektivität_der_in_Österreich_eingesetzten_COVID19-Impfstoffe_Ergebnisse_einer_populatonsbasierten_Kohortenstudie__KW_05-35.pdf
31 Baden LR, El Sahly HM, Essink B. et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med 2021; 384: 403-416
32 Voysey M, Clemens SAC, Madhi SA. et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021; 397: 99-111
33 Karlsson LC, Soveri A, Lewandowsky S. et al. Fearing the disease or the vaccine: The case of COVID-19. Pers Individ Dif 2021; 172: 110590
34 Diaz P, Reddy P, Ramasahayam R. et al. COVID-19 vaccine hesitancy linked to increased internet search queries for side effects on fertility potential in the initial rollout phase following Emergency Use Authorization. Andrologia 2021;
35 Tatsis N, Ertl HCJ. Adenoviruses as vaccine vectors. Mol Ther 2004; 10: 616-629
36 Pardi N, Hogan MJ, Porter FW. et al. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov 2018; 17: 261-279
37 Bowman CJ, Bouressam M, Campion SN. et al. Lack of effects on female fertility and prenatal and postnatal offspring development in rats with BNT162b2, a mRNA-based COVID-19 vaccine. Reprod Toxicol 2021; 103: 28-35
38 Stebbings R, Maguire S, Armour G. et al. Developmental and reproductive safety of AZD1222 (ChAdOx1 nCoV-19) in mice. Reprod Toxicol 2021; 104: 134-142
39 Stanley KE, Thomas E, Leaver M. et al. Coronavirus disease-19 and fertility: viral host entry protein expression in male and female reproductive tissues. Fertil Steril 2020; 114: 33-43
40 Barragan M, Guillén JJ, Martin-Palomino N. et al. Undetectable viral RNA in oocytes from SARS-CoV-2 positive women. Hum Reprod 2021; 36: 390-394
41 Wang M, Yang Q, Ren X. 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 Orvieto R, Noach-Hirsh M, Segev-Zahav A. et al. Does mRNA SARS-CoV-2 vaccine influence patientsʼ performance during IVF-ET cycle?. Reprod Biol Endocrinol 2021; 19: 69
43 Kolanska K, Hours A, Jonquière L. et al. Mild COVID-19 infection does not alter the ovarian reserve in women treated with ART. Reprod Biomed Online 2021;
44 Li K, Chen G, Hou H. et al. Analysis of sex hormones and menstruation in COVID-19 women of child-bearing age. Reprod Biomed Online 2021; 42: 260-267
45 Bentov Y, Beharier O, Moav-Zafrir A. et al. Ovarian follicular function is not altered by SARS-CoV-2 infection or BNT162b2 mRNA COVID-19 vaccination. Hum Reprod 2021; 36: 2506-2513
46 Girardi G, Bremer AA. Scientific Evidence Supporting Coronavirus Disease 2019 (COVID-19) Vaccine Efficacy and Safety in People Planning to Conceive or Who Are Pregnant or Lactating. Obstet Gynecol 2022; 139: 3-8
47 Chen F, Zhu S, Dai Z. et al. Effects of COVID-19 and mRNA vaccines on human fertility. Hum Reprod 2021;
48 Wainstock T, Yoles I, Sergienko R. et al. Prenatal maternal COVID-19 vaccination and pregnancy outcomes. Vaccine 2021; 39: 6037-6040
49 Köhn F-M, Schuppe H-C. Auswirkungen von COVID-19 auf die männliche Fertilität. J Reproduktionsmed Endokrinol 2021; 18: 45-47
50 Sergerie M, Mieusset R, Croute F. et al. High risk of temporary alteration of semen parameters after recent acute febrile illness. Fertil Steril 2007; 88: 970.e1-970.e7
51 Yang M, Chen S, Huang B. et al. Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications. Eur Urol Focus 2020; 6: 1124-1129
52 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. Cells 2020; 9: 920
53 Verma S, Saksena S, Sadri-Ardekani H. ACE2 receptor expression in testes: implications in coronavirus disease 2019 pathogenesis†. Biol Reprod 2020; 103: 449-451
54 Borges E, Setti AS, Iaconelli A. et al. Current status of the COVID-19 and male reproduction: A review of the literature. Andrology 2021; 9: 1066-1075
55 Pascolo L, Zito G, Zupin L. et al. Renin Angiotensin System, COVID-19 and Male Fertility: Any Risk for Conceiving?. Microorganisms 2020; 8: 1492
56 Vishvkarma R, Rajender S. Could SARS-CoV-2 affect male fertility?. Andrologia 2020;
57 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 Metab 2020; 318: E878-E880
58 Seymen CM. The other side of COVID-19 pandemic: Effects on male fertility. J Med Virol 2021; 93: 1396-1402
59 Shen Q, Xiao X, Aierken A. et al. The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS-CoV-2 infection. J Cell Mol Med 2020; 24: 9472-9477
60 Illiano E, Trama F, Costantini E. Could COVID-19 have an impact on male fertility?. Andrologia 2020; 52: e13654
61 Kalra S, Bhattacharya S, Kalhan A. Testosterone in COVID-19 – Foe, Friend or Fatal Victim?. Eur Endocrinol 2020; 16: 88
62 Paoli D, Pallotti F, Nigro G. et al. Sperm cryopreservation during the SARS-CoV-2 pandemic. J Endocrinol Invest 2021; 44: 1091-1096
63 Temiz MZ, Dincer MM, Hacibey I. et al. Investigation of SARS-CoV-2 in semen samples and the effects of COVID-19 on male sexual health by using semen analysis and serum male hormone profile: A cross-sectional, pilot study. Andrologia 2021; 53: e13912
64 Pazir Y, Eroglu T, Kose A. et al. Impaired semen parameters in patients with confirmed SARS-CoV-2 infection: A prospective cohort study. Andrologia 2021; 53: e14157
65 Li H, Xiao X, Zhang J. et al. Impaired spermatogenesis in COVID-19 patients. EClinicalMedicine 2020;
66 Guo T-H, Sang M-Y, Bai S. et al. Semen parameters in men recovered from COVID-19. Asian J Androl 2021; 23: 479-483
67 Erbay G, Sanli A, Turel H. et al. Short-term effects of COVID-19 on semen parameters: A multicenter study of 69 cases. Andrology 2021; 9: 1060-1065
68 Koç E, Keseroğlu BB. Does COVID-19 Worsen the Semen Parameters? Early Results of a Tertiary Healthcare Center. Urol Int 2021; 105: 743-748
69 Best JC, Kuchakulla M, Khodamoradi K. et al. Evaluation of SARS-CoV-2 in Human Semen and Effect on Total Sperm Number: A Prospective Observational Study. World J Mens Health 2021; 39: 489
70 Pan F, Xiao X, Guo J. et al. No evidence of severe acute respiratory syndrome–coronavirus 2 in semen of males recovering from coronavirus disease 2019. Fertil Steril 2020; 113: 1135-1139
71 Song C, Wang Y, Li W. et al. Absence of 2019 novel coronavirus in semen and testes of COVID-19 patients†. Biol Reprod 2020; 103: 4-6
72 Li D, Jin M, Bao P. et al. Clinical Characteristics and Results of Semen Tests Among Men With Coronavirus Disease 2019. JAMA Netw Open 2020; 3: e208292
73 Paoli D, Pallotti F, Colangelo S. et al. Study of SARS-CoV-2 in semen and urine samples of a volunteer with positive naso-pharyngeal swab. J Endocrinol Invest 2020; 43: 1819-1822
74 Safrai M, Reubinoff B, Ben-Meir A. BNT162b2 mRNA Covid-19 vaccine does not impair sperm parameters. medRxiv 2021;
75 Gonzalez DC, Nassau DE, Khodamoradi K. et al. Sperm Parameters Before and After COVID-19 mRNA Vaccination. JAMA 2021; 326: 273
76 Huang C, Zhou S-F, Gao L-D. et al. Risks associated with cryopreserved semen in a human sperm bank during and after the COVID-19 pandemic. Reprod Biomed Online 2021; 42: 589-594
77 Ruan Y, Hu B, Liu Z. et al. No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation. Andrology 2021; 9: 99-106
78 Burke CA, Skytte AB, Kasiri S. et al. A cohort study of men infected with COVID-19 for presence of SARS-CoV-2 virus in their semen. J Assist Reprod Genet 2021; 38: 785-789
79 Kayaaslan B, Korukluoglu G, Hasanoglu I. et al. Investigation of SARS-CoV-2 in Semen of Patients in the Acute Stage of COVID-19 Infection. Urol Int 2020; 104: 678-683
80 Ma L, Xie W, Li D. et al. Evaluation of sex-related hormones and semen characteristics in reproductive-aged male COVID-19 patients. J Med Virol 2021; 93: 456-462
81 Pavone C, Giammanco GM, Baiamonte D. et al. Italian males recovering from mild COVID-19 show no evidence of SARS-CoV-2 in semen despite prolonged nasopharyngeal swab positivity. Int J Impot Res 2020; 32: 560-562
82 Nieschlag E, Schlatt S, Kliesch S, Behre HM. WHO-Laborhandbuch zur Untersuchung und Aufarbeitung des menschlichen Ejakulates. 5. Aufl.. Berlin, Heidelberg:: Springer;; 2012
83 Carto C, Nackeeran S, Ramasamy R. COVID-19 vaccination is associated with a decreased risk of orchitis and/or epididymitis in men. Andrologia 2021;
84 World Health Organization. WHO Laboratory Manual for the Examination and Processing of human Sperm. 5th ed. Geneva: WHO; 2010