A survey of fertility patients’ attitudes towards the COVID-19 vaccine
Fertility patients, particularly if pregnant or hoping to conceive, are hesitant to accept COVID-19 vaccination and unlikely to delay their fertility treatment plans.
Jenna Turocy, M.D. Alex Robles, M.D., Evan Reshef, M.D., Mary D’Alton, M.D., Eric J. Forman, M.D. Zev Williams, M.D., Ph.D.
Columbia University Fertility Center
Department of Obstetrics & Gynecology
Columbia University Irving Medical Center
Objective: To survey fertility patients’ perception and willingness to receive vaccination against COVID-19
Design: An online survey sent to current fertility patients
Setting: A large academic fertility practice
Patient(s): Fertility patients seen within the last year
Main Outcome Measures(s): Patient acceptance of the mRNA COVID-19 vaccination and associated concerns
Result(s): A total of 284 patients completed the survey for a response rate of 9.6% of those emailed and 18.8% of those who opened the email. Among all fertility patients, 119 (41.9%) would accept a mRNA COVID-19 vaccine if offered. Pregnant fertility patients and those hoping to conceive in the next 6 months were less likely to accept a mRNA COVID-19 vaccine (17.3% vs 47.3% pregnant vs non-pregnant, p=0.00001 and 41.3% vs 65.2% planning vs not planning to conceive, p= 0.0062), citing fears of birth defects, unknown long-term health effects on children and risk of pregnancy loss. Among fertility patients who plan to accept the vaccine, 80 (89.9%) are not planning on changing their fertility plans based on vaccination. Vaccination acceptance did not vary based on a history of high-risk chronic medical conditions or being a high-risk frontline worker. Patients who did not receive the influenza vaccine this year were less likely to accept a COVID-19 vaccine (21.7% vs 48.4%, p = 0.0001).
Conclusion(s): Fertility patients, particularly if pregnant or hoping to conceive in the next 6 months, are hesitant to accept the currently available mRNA COVID-19 vaccines.
The COVID-19 pandemic, a global medical crisis and socio-economic catastrophe, spurred the scientific community and pharmaceutical industry to develop vaccines in unprecedented time. While research and development of a vaccine only began in early 2020, the TN162b2 mRNA vaccine produced by Pfizer-BioNTech became the first vaccine against SARS-COV-2 (COVID-19) authorized by the FDA to be distributed in the United States on December 11th, 2020.  This was closely followed by the authorization of the mRNA-1273 vaccine produced by Moderna on December 18, 2020.  Both vaccines utilize a novel mRNA platform, with published reports demonstrating a high efficacy against COVID-19.  However, pregnant and lactating women were excluded from the initial phase III trials of these two vaccines. Specific safety data in these populations are not yet available and further studies are planned.
“Vaccine hesitancy” as defined by the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization in 2015 is a “delay in acceptance or refusal of vaccination despite availability of vaccination services.”  The speed with which the COVID-19 vaccines were developed, the use of novel and never before used mRNA technology, and the current political climate, have made skepticism in the general population toward COVID-19 vaccines particularly high.  Although the mechanism of action of mRNA vaccines and existing safety data are reassuring, studies of mRNA vaccines in ongoing pregnancy are currently lacking.  For patients who are pregnant or contemplating conceiving, a lack of safety and efficacy data in pregnancy makes it very difficult to know whether or not to recommend COVID-19 vaccination. Currently, the FDA Emergency Use Authorization (EUA) permits the vaccination of pregnant and breastfeeding individuals with a requirement biopharmaceutical companies engage in post-authorization observational studies in pregnancy.
Previous studies have shown that women are particularly hesitant to receive vaccinations in pregnancy, citing concerns of fetal safety as the main reason.  At the same time, pregnant women are at greater risk for severe disease when infected by other respiratory viruses such H1N1 and influenza, [8, 9] with recent studies suggesting that pregnancy is a risk factor for severe COVID-19 disease. [10 - 14]
At the time of this publication, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal Fetal Medicine (SMFM) have issued statements recommending that COVID-19 vaccines should not be withheld from pregnant or lactating individuals while also supporting those who choose not to receive the vaccine. [15,16] Regulators in the United Kingdom do not recommend vaccinating pregnant women or women planning a pregnancy within three months of receiving the vaccine. 
The questions regarding vaccinating women suffering from infertility are especially complex. In addition to the stress of an ongoing global pandemic, fertility patients are also experiencing the stress of infertility. Many are hoping to conceive in the near future and may have the option to choose when to undergo treatments such as frozen embryo transfers. While deciding if they wish to continue fertility treatment during the pandemic, fertility patients may also be in the position to choose if they wish to be vaccinated. The American Society for Reproductive Medicine (ASRM) issued a statement recommending that all patients who are trying to conceive and/or undergoing fertility treatments be encouraged to receive a vaccine against COVID-19. 
In this study, we surveyed patients at a large academic fertility center in New York City to determine patient perception and willingness to receive vaccination against COVID-19 and if it will impact their plans to conceive. This information can be helpful in assisting providers and professional societies with patient counseling and education.
Materials and Methods
Study setting and population
A 25-item survey was constructed to assess fertility patients’ views on the novel mRNA COVID-19 vaccine. The survey was sent to all patients seen at a New York academic fertility practice between December 2019 to May 2020. The survey was sent using Qualtrics platform and all respondents were anonymous with no unique identifiers collected. The survey was sent as a follow-up to the study of the emotional impact of the ASRM guidelines on fertility patients during the COVID-19 pandemic and was approved by Columbia University Institutional Review Board for research and publication purposes.
The data collected including demographic characteristics of respondents such as age, sex, parity and fertility plans. Patients’ concerns surrounding the COVID-19 infection and vaccination were rated on a Likert scale. Ordinal data was compared using Fisher exact or chi-square test as appropriate, with significance at p<0.05.
The survey was sent to 2,970 recipients electronically. Fifty one percent (n= 1509) opened the email and 328 clicked on the survey link. A total of 284 patients, 92.6% female and 7.4% male, completed the survey for a response rate of 9.6% of the total emailed and 18.8% of those who opened the email. The average age was 37.4 (range 24 - 54 ) [Table 1]. Of the respondents, 100 (37.9%) had children and 67 (23.6%) suffered from recurrent pregnancy loss, defined as 2 or more losses. Seventy-five (26.4%) were currently pregnant with additional 133 (46.8%) hoping to conceive in the next 6 months. A large number of respondents, 130 (69.1%), were planning on undergoing fertility treatment in the next 6 months. Of those who were planning on fertility treatment, 11 (8.5%) planned for intrauterine insemination, 60 (46.1%) planned for in vitro fertilization (IVF), 5 (3.8%) planned for an egg freeze cycle and 45 (34.6%) planned for frozen embryo transfer (FET).
Among all fertility patients, 119 (41.9%) would accept the COVID-19 vaccine if offered [Fig 1, Fig 2]. One hundred and sixty-five (58.1%) would not and or were unsure if they would accept the vaccine. Among pregnant fertility patients, 62 (82.7%) would not or were unsure if they would accept the vaccine. Pregnant fertility patients were significantly less likely to accept the vaccine than non-pregnant fertility patients (17.3% vs 47.3% respectively, p=.00001). Fifty-eight (93.6%) said the pregnancy affected their decision. Twenty-two (34.5%) cited the risk of birth defects as their biggest concern. Other fears included pregnancy loss (11, 17.7%) and long-term health effects on children (10, 16.1%).
Among non-pregnant fertility patients, 89 (47.3%) would accept the vaccine if offered. For those who did not accept the vaccine (n = 99), 74 (74.7%) reported their fertility plans affected this decision, with 24 (24.2%) citing the risk of birth defects as their biggest concern. Other fears included long term health effects on children (16, 16.2%), risk of pregnancy loss (14, 14.1%) and difficulty conceiving (6, 6.1%). Of those who were planning on accepting the vaccine, the majority (n= 80, 89.9%) are not planning on changing their fertility plans based on vaccination. After COVID-19 vaccination, nine patients (10.1%) plan to cancel or delay frozen embryo transfer (n = 3), IVF (n = 2), egg freezing (n = 1) or timed intercourse (n = 1). Patients who plan to conceive in the next 6 months (n = 133) were less likely to accept COVID-19 vaccination than those without plans to conceive (41.3% vs. 65.2% respectively, p = 0.0062) [Table 2].
Twenty-five (8.8%) of the patients surveyed reported that they already contacted COVID-19 virus and 61 (21.5%) had lost a close friend or relative to COVID-19. No significant difference in vaccine acceptance was seen between patients who had lost a close friend or relative (p = .3788), had an underlying high-risk medical condition (p = .2171), or were considered a high-risk worker in healthcare facility or first responder (p= .8637). Patients who did not receive the influenza vaccine this year (n = 54) were less likely to accept the COVID-19 vaccine than those who did receive the influenza vaccine (21.7% vs 48.4%, respectively, p= .0001). Respondents were more concerned for the risk of COVID-19 infection than the risk of vaccination [Fig. 3], citing risk of COVID-19 infection to family members as their biggest concern.
We conducted a survey of fertility patients at a large academic fertility center in New York City to determine their perceptions and willingness to receive vaccination against COVID-19 as well as the impact the vaccine will have on their plans to conceive. We found that while the rate of COVID-19 acceptance among fertility patients was comparable to the general population (41.9% vs 46%) , those who were either pregnant, planning to conceive or planning fertility treatment in the next 6 months were less likely to respond they would accept a mRNA COVID-19 vaccine if offered. While 74.7% of respondents reported that their fertility plans affected their decision, the vast majority of patients (89.9%) would not alter their plans based on the vaccine, highlighting the time-sensitive and non-elective nature of fertility treatment. This finding is similar to our prior study showing that most fertility patients did not want to cancel or postpone fertility treatments in the setting of COVID-19 . Pregnancy or planning to conceive were significant predictors of hesitancy towards the COVID-19 vaccine. Respondents’ primary concern was the potential harm to a fetus or child, an area for which there is currently no data. Those who did not receive an influenza vaccine this year were also far less likely to receive a COVID-19 vaccine, possibly reflecting a hesitancy to receive vaccines in general.
A strength of the study is the timeliness; the study was conducted during the COVID-19 pandemic and within two weeks after the FDA first authorized the use of a COVID-19 vaccine in the United States. Thus the study reflects how fertility patients felt in real-time without recall bias.
This study had limitations as well. The survey data represented a snapshot at one point in time. As the mRNA COVID-19 vaccines are further studied and become more widely distributed, more data relating to the safety in pregnancy will accumulate. The additional safety data as well as changes in disease prevalence, severity and treatment options will likely shift the perceptions and willingness of fertility patients and pregnant patients to receive the vaccine. Indeed, the proportion of the general public willing to receive the vaccine has nearly doubled from 34% to 63% between July 2020 to November 2020 . This suggests public perceptions are likely to change. Another limitation of the study was the low response rate, as only 9.6% of those sent the survey responded. This could cause sampling bias, although which direction results would be skewed is unknown at this time. The limited number of respondents is likely to due to the short window the survey was available. Those emailed had 3 days to complete the survey and no reminder email or incentive was provided. Given the anonymity of the study, no information on non-responders is available.
This study reflects the current attitudes, concerns and perception of fertility patients shortly after the mRNA COVID-19 vaccine was first authorized for emergency use in the United States. Fertility patients, particularly those pregnant or hoping to conceive, are hesitant to accept a mRNA COVID-19 vaccine at this time. Those who do plan to accept a COVID-19 vaccine are unlikely to change their fertility treatment plans. Collectively, this data can help providers counsel patients while highlighting areas for future investigation.
 FDA. FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine. Available at. https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19. Accessed on December 23, 2020
 FDA. Moderna COVID-19 Vaccine Available at: https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine Accessed on December 23, 2020
 Polack F, Thomas S, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez J, et. al. C4591001 Clinical Trial Group. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 10:NEJMoa2034577.
 MacDonald NE; SAGE Working Group on Vaccine Hesitancy. Vaccine hesitancy: Definition, scope and determinants. Vaccine. 2015;33(34):4161-4164.
 Fisher KA, Bloomstone SJ, Walder J, Crawford S, Fouayzi H, Mazor KM. Attitudes Toward a Potential SARS-CoV-2 Vaccine : A Survey of U.S. Adults. Ann Intern Med. 2020;173(12):964-973. doi:10.7326/M20-3569
 Pardi, N., Hogan, M., Porter, F, Weissman, D. mRNA vaccines — a new era in vaccinology. Nat Rev Drug Discov (2018) 17, 261–279).
 O'Shea A, Cleary B, McEntee E, Barrett T, O'Carroll A, Drew R, O'Reilly F. To vaccinate or not to vaccinate? Women's perception of vaccination in pregnancy: a qualitative study. BJGP Open. 2018 Apr 4;2(2):bjgpopen18X101457. doi: 10.3399/bjgpopen18X101457. PMID: 30564712; PMCID: PMC6184095
 Ellington S, Strid P, Tong VT, Woodworth K, Galang RR, Zambrano LD, 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. MMWR Morb Mortal Wkly Rep. 2020;69:769-75 (https://www.cdc.gov/mmwr/volumes/69/wr/mm6925a1.htm).
 Zambrano LD, Ellington S, Strid P, Galang RR, Oduyebo T, Tong VT, 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. CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team. MMWR Morb Mortal Wkly Rep. 2020;69:1641-7 (https://www.cdc.gov/mmwr/volumes/69/wr/mm6944e3.htm).
 Collin J, Byström E, Carnahan A, Ahrne M. Public Health Agency of Sweden's Brief Report: pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 infection in intensive care in Sweden. Acta Obstet Gynecol Scand. 2020;99:819- 22
 Delahoy MJ, Whitaker M, O'Halloran A, Chai SJ, Kirley PD, Alden N, 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. COVID-NET Surveillance Team. MMWR Morb Mortal Wkly Rep. 2020;69:1347-54 (https://www.cdc.gov/mmwr/volumes/69/wr/mm6938e1.htm).
 Panagiotakopoulos L, Myers TR, Gee J, Lipkind HS, Kharbanda EO, Ryan DS, 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. MMWR Morb Mortal Wkly Rep. 2020;69:1355-9 (https://www.cdc.gov/mmwr/volumes/69/wr/mm6938e2.htm).
 The American College of Obstetrics and Gynecology. Vaccinating Pregnant and Lactating Patients Against COVID-19. Available at: (https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2020/12/vaccinating-pregnant-and-lactating-patients-against-covid-19 https://s3.amazonaws.com/cdn.smfm.org/media/2591/SMFM_Vaccine_Statement_12-1-20_(final).pdf Accessed on December 23, 2020
 The Society for Maternal Fetal Medicine. Society for Maternal-Fetal Medicine (SMFM) Statement: SARS-CoV-2 Vaccination in Pregnancy. Available at. https://s3.amazonaws.com/cdn.smfm.org/media/2591/SMFM_Vaccine_Statement_12-1-20_(final).pdf Accessed on December 23, 2020
 Joint Committee on Vaccination and Immunisation: advice on priority groups for COVID-19 vaccination. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/940936/Priority_groups_for_coronavirus__COVID-19__vaccination_-_advice_from_the_JCVI__2_December_2020.pdf Accessed on December 23, 2020
 American Society For Reproductive Medicine. AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE (ASRM) PATIENT MANAGEMENT AND CLINICAL RECOMMENDATIONS DURING THE CORONAVIRUS (COVID-19) PANDEMIC. Available at: https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/covid-19/covidtaskforceupdate11.pdf Accessed on December 23, 2020
 Page S, Elbeshbishi S. EXCLUSIVE: AMERICANS’ READINESS TO TAKE THE COVID-19 VACCINE SPIKES AFTER THE START OF SHOTS. Available at: https://www.usatoday.com/story/news/politics/2020/12/22/more-americans-ready-take-covid-19-vaccine-suffolk-poll-shows/3925900001/ Accessed on December 23, 2020
 Turocy JM, Robles A, Hercz D, D'Alton M, Forman EJ, Williams Z. THE EMOTIONAL IMPACT OF THE ASRM GUIDELINES ON FERTILITY PATIENTS DURING THE COVID-19 PANDEMIC. Available at: https://www.fertstertdialog.com/posts/65837-the-emotional-impact-of-the-asrm-guidelines-on-fertility-patients-during-the-covid-19-pandemic Accessed December 23, 2020
 Brenan, M. WILLINGNESS TO GET COVID-19 VACCINE TICKS UP TO 63% IN U.S. Available at: https://news.gallup.com/poll/327425/willingness-covid-vaccine-ticks.aspx Accessed December 23, 2020