Pragmatic coping with COVID-19 pandemic for running an in vitro fertilization laboratory: Egyptian perspective
This report summarizes recommendations on how in vitro fertilization laboratory should pragmatically practice during the current and future waves of COVID-19 pandemic.
Mohamed Fawzy, M.D.,ab Mohamed H. Zidan, M.Sc.,c Mohamed M. Elzayat, Ph.D.,d Momen Abdelkhalik, M.Sc.ef Mohamed Mahmoud, M.Sc.,g Yasmin Magdi, M.Sc.,h Niveen Ahmed, M.Sc.,j Ahmed Nasr, M.Sc.,k Abdelhamid Wafik, Ph.D.,m Ragaa Monsour, M.D., Ph.D.n
aIbnSina IVF Center, IbnSina Hospital, Sohag, Egypt
bBanoon IVF Center, Asyut, Egypt
cGannah IVF Hospital, Cairo, Egypt
dRoyal Fertility Center, Mansoura, Egypt
eEl-Nada Fertility Centers, Banisuif, Egypt
fEl-Nile Fertility Center, Menia, Egypt
gNour Al Hayah Fertility Center, Cairo, Egypt
hAl-Yasmeen Fertility and Gynecology Center, Benha, Egypt
jDar El Maraa IVF Center, Cairo, Egypt
kMadina Women’s Hospital, Alexandria, Egypt
mAl-Azhar University, Cairo, Egypt
nEgyptian IVF-ET Center, Cairo, Egypt
Around 80% of COVID-19 patients are asymptomatic but shedding SARS-CoV-2 virus, which is extremely dangerous as COVID-19 leads to a higher rate of mortality than usual influenzas with no curative treatment or vaccine thus far (1,2). In addition, SARS-CoV-2 has an infection rate (R0) of up to 5.6 (3), rendering it extremely infectious. To reduce the risk of transmission COVID-19, many authorities have recommended suspension of all non-urgent but lifesaving procedures (4,5), and the IVF is no exception (6). However, the “one-size-fits-all” approach is not necessarily suitable for all communities as there is no prediction as to when this pandemic status will end. Therefore, we should prepare for this “new normal”.
A task force established by the Egyptian Society of Embryology and Assisted Reproductive Technology (ESEART) performed a survey on how the Egyptian IVF laboratories are coping with COVID-19 pandemic. Professional experts managing IVF laboratories discussed the results of the survey for 32 hours of web-based meetings. These findings were the motivation to develop pragmatic recommendations dealing with a range of scenarios with the aim of keeping IVF laboratory teams safe during the COVID-19 pandemic.
Around 40% of IVF facilities in Egypt responded to a survey conducted between March 25, 2020 and April 3, 2020 about their plans to coping with COVID-19 pandemic.
The survey revealed a 52% decrease in IVF cycles due to COVID-19 than previous times. A 13% of surveyed centers would shut down completely, 49% would decide based on patients’ decisions after counselling, 20% had stopped treating patients except for fertility preservation and ongoing cycles, and 18% have continued to function as usual. Only 36% of centers had plans for how to deal if one or more of the team contracted SARS-CoV-2, while 64% had no plans in place. A 45% of responders had no testing in place to detect if a team member was infected, while 55% of facilities regularly check team members regularly.
It appeared that suspending IVF service as recommended by ASRM and ESHRE, although safe, did not have agreement from all.
Prevention and safety
As many as 80% of COVID-19 patients are asymptomatic shedders of SARS-CoV-2 (2,7,8), so preventing the introduction of COVID-19 into the lab is a priority. IVF laboratory staff is mandatory to follow a rigorous protocol for hand hygiene by regular washing with soap and water before entering the laboratory, after encountering patients, and after removal of gloves. Members using contact lenses must replace them with prescription glasses. All staff members must undergo daily screening of temperature using a non-touch infrared thermometer and use a proper set of personal protective equipment (PPE) including disposable laboratory coats, gloves, cap, eye protectors, shoe covers, and face mask, during working hours, and wear a face mask everywhere outside the facility as SARS-CoV-2 is airborne (9–11).
The staff reorganization during COVID-19 should be designed to reduce the overall working hours, such as by assigning those with the highest skills to take over during this period. Complications of COVID-19 are very serious for older people, pregnant women and those with chronic conditions, which mandates their exclusion during this reorganization.
Supplies, stock, and equipment
As a shortage of supplies could occur, it seems logical, then, for IVF facilities to establish a collaboration policy to ensure enough stocks of supplies including PPE that can be transferred to any center if needed. There must also be practical plans ready to be enacted should equipment maintenance arise.
The cryopreserved biological materials must be safely maintained throughout the duration of the pandemic, and so it is critical to ensure the availability of sufficient amounts of liquid nitrogen (LN2).
Cross contamination in liquid nitrogen
While there is no clear evidence in relation to SARS-CoV-2 transmission via nitrogen vapor or LN2, we cannot entirely rule out this possibility. As SARS-CoV-2 is airborne, it could be introduced into the LN2 itself during its production and transportation to IVF laboratories, or through exposure to infected persons during the cryopreservation process or long-term storage (12–14). This again mandates the use of a full set of PPE by staff. It appears logical to specify certain tanks for the pandemic period to easily track any future genetic or epigenetic effects.
Sterilization and disinfectants
COVID-19 remains on surfaces from hours to days, which mandates the daily intensive disinfection of the lab and equipment. Hydrogen peroxide (H2O2; 6%), a safe disinfectant for gametes and embryos (15), is recommended when fighting SARS-CoV-2 (16). Although 70% ethanol is effective against SARS-CoV-2 (17), it can adversely affect embryo development (15). Sodium hypochlorite (0.1%) also showed effectiveness against SARS-CoV2 (17), although its safety in IVF setting has been questioned. In this exceptional time, the effectiveness of ethanol and sodium hypochlorite can outweigh their possible risk when used cautiously and in certain circumstances such as an infected member or when preparing for shutdown.
IVF laboratories are equipped with a heating, ventilation, and air conditioning (HVAC) system to maintain clean air flow under positive pressure (15), which can prompt COVID-19 transmission (18). Thus, although strange, it appears safer to switch off HVAC systems along with all other direct or indirect air flow including the workstations during the working hours to minimize the risk of COVID-19. Operating theatres, intensive care units, and hospitals for COVID-19 patients use negative pressure as standard to reduce the viral load (19). Whether the negative pressure can be applied safely in the IVF setting for higher protection to personnel remains an open question.
Although we generally recommend against initiating unurgent IVF cycles during the COVID-19 period, we should still have pragmatic recommendations for facilities that face difficulties suspending IVF cycles.
Each IVF laboratory must have an updated lab phone tree and written emergency instructions dealing with all possible scenarios for maintenance at full capacity through complete shutdown (either gradual or urgent), or in the case of an infected member. IVF lab teams must be train through mock stimulatory situations to ensure those plans can be effected. Maximum care must be taken to protect embryos from exposure to SARS-CoV-2, as the data regarding the virus’s effect on embryos is still limited.
A clear, written, emergency plan on how to deal with shortages including stocks of hygiene and cleaning supplies, as well as PPE, and laboratory consumables must be available and regularly updated.
These instructions would include, but are not limited to, restriction of movement for patients and staff in, out and around the facility, proper physical distancing between persons within the facility, and restriction to one accompanying person with each patient.
IVF laboratories should group their staff into rotating teams to work sequentially with no overlap or meetings. Meetings should be held more frequently through web-based platforms to review working protocols and update plans.
The team should arrive earlier to allow time for temperature and other checks by a medical staff wearing PPE, and in the case of appearance of any symptom, they must remotely report this to the facility and the health authorities, and enter immediate self-isolation.
Set of blood examinations should be done every two weeks for all staff, and must be under surveillance and continuous revision. Laboratory staff aged 55 years or older, pregnant women, and those with chronic diseases are advised to stay home.
Patients must provide complete data about their general state of health for the past two weeks and continue to do so until cycle completion, and they must be counseled about the risk of cancelation anytime.
All staff and patients should wear face masks everywhere. Within the facility, all staff must wear a full set of PPE as described above. Vigorous hand washing using soap and water must be performed as mentioned above. Persons who wear contact lenses in laboratories should replace them with medical glasses or may wear protective glasses.
The supply of liquid nitrogen must be maintained at all times, including the worst-case scenario of a total country lockdown. A written plan to cope with this situation is mandatory. One or more lab members must be designated as responsible for the nitrogen tanks, and as the contact for the electronic monitoring system.
In the case of one or more lab members contracting COVID-19 and entering self-isolation, an emergency plan assigning collaborative staff to take over the job or transferring the entire tanks to those facilities is essential.
Most COVID-19 patients are asymptomatic shedders of the virus, which suggests that maintaining negative pressure would be prudent in the operating theatre at least. For the IVF lab, as no data exists on whether negative pressure is embryo safe, switching on the HVAC system is only recommended when there are no team members in place. We also recommend stopping all direct and indirect air flow including the workstations.
As high relative humidity discourages the spread of viruses (20), we recommend maintaining it at the highest level accepted for IVF laboratories. Using humidified incubators across this period is in line with the main concept of “higher humidity is safer”. We recommend each lab to specify certain incubators (where possible) to be used across the pandemic.
SARS-CoV-2 is likely to have similar susceptibilities as other coronaviruses; therefore, sodium hypochlorite (0.1%) for general surface disinfection, 70% ethanol, 6% hydrogen peroxide, and quaternary ammonium compounds are likely effective disinfectants. We must prioritize their use according to embryo safety and area of use within the facility.
Sterilization must include all laboratory surfaces and equipment, and all disposables and media bottles must be wiped with disinfectant. Sterilization must be done with higher precision for doorknobs, cameras, monitors, benchtops, and chairs, and light switches.
While no data is available for gamete contamination, sperm preparation protocols must follow those used for HIV-positive patients. Multiple washing for the oocytes and embryos is also advisable to dilute any possible contaminants. Although it might sound logical to use a single culture protocol by placing each embryo in one droplet, there is no evidence to recommend this and so the decision is left to each facility or practice.
The risk of cross contamination with previously cryopreserved samples, although theoretical, cannot be ruled out. Also, it is unknown if there will be any genetic and epigenetic effects associated with this crisis. Therefore, it is advisable to specify certain tanks for cryopreservation across the pandemic.
Recommendations if COVID-19 is suspected for staff
Individuals should not be allowed to enter the facility if they are suffering, or have suffered, a fever and/or a defined set of newly present symptoms indicative of COVID-19, and must self-isolate for four weeks, while keeping the facility updated with their progress. Quarantined personnel can only return to work according to the advice from responsible authorities. The entire facility must undergo the most aggressive sterilization protocol as outlined above.
If SARS-CoV-2 infection is detected in more than one staff member, we have to take immediate advice from the health authorities on how to deal with either immediate shutdown or aggressive sterilization and assigning the duties to the backup team.
Steps for complete shutdown
IVF laboratories must have plans to implement a controlled shutdown. Each lab needs to backup all critical data before shutdown, and to the cryopreserved samples safe during the shutdown.
The plan must consider protecting equipment, materials, and disposables from destruction or loss during the shutdown.
Next, all equipment must be disinfected, the micromanipulators’ pressure released, switched off and unplugged, and auto-start functions disabled, before being covered.
Next, all containers and media bottles must be properly labelled and stored safely. Gas cylinders must be properly closed and secured and stored in an upright position. Ensure that critical equipment are plugged into the emergency electrical outlets.
All doors must be properly closed and secured. If available, electronic monitoring systems have to be effectuated.
When the decision to reopen is taken, the facility has to follow all the same steps as are used when opening a new unit.
1. Ye F, Xu S, Rong Z, Xu R, Liu X, Deng P, et al. Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster. Int J Infect Dis 2020;
2. Day M. Covid-19: four fifths of cases are asymptomatic, China figures indicate. Bmj 2020;m1375.
3. Sanche S, Lin YT, Xu C, Romero-Severson E, Hengartner N, Ke R. High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2. Emerg Infect Dis [Internet] 2020;26(7). Available from: http://www.ncbi.nlm.nih.gov/pubmed/32255761
4. Iacobucci G. Covid-19: all non-urgent elective surgery is suspended for at least three months in England. BMJ 2020;368:m1106.
5. Stahel PF. How to risk-stratify elective surgery during the COVID-19 pandemic? Patient Saf Surg 2020;14(1).
6. American Society for Reproductive Medicine. Patient Management and Clinical Recommendations During The Coronavirus (COVID-19) Pandemic | ASRM [Internet]. 2020 [cited 2020 Apr 17];1:1–3. Available from: https://www.asrm.org/news-and-publications/covid-19/statements/patient-management-and-clinical-recommendations-during-the-coronavirus-covid-19-pandemic/
7. Bai Y, Yao L, Wei T, Tian F, Jin DY, Chen L, et al. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA - J. Am. Med. Assoc. 2020;
8. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395(10223):507–13.
9. De Santis L, Anastasi A, Cimadomo D, Klinger FG, Licata E, Pisaturo V, et al. COVID-19: the perspective of Italian embryologists managing the IVF laboratory in pandemic emergency. Hum Reprod [Internet] 2020;Available from: https://doi.org/10.1093/humrep/deaa074
10. Xiao Y, Torok ME. Taking the right measures to control COVID-19. Lancet Infect. Dis. 2020;0(0).
11. Leung CC, Lam TH, Cheng KK. Mass masking in the COVID-19 epidemic: people need guidance. Lancet. 2020;
12. Bielanski A, Vajta G. Risk of contamination of germplasm during cryopreservation and cryobanking in IVF units. Hum. Reprod. 2009;24(10):2457–67.
13. Pomeroy KO, Harris S, Conaghan J, Papadakis M, Centola G, Basuray R, et al. Storage of cryopreserved reproductive tissues: Evidence that cross-contamination of infectious agents is a negligible risk. Fertil Steril 2010;94(4):1181–8.
14. Schafer TW, Everett J, Silver GH, Came PE. Biohazard: Virus-contaminated liquid nitrogen . Science (80-. ). 1976;191(4222):24–6.
15. Mortimer D, Cohen J, Mortimer ST, Fawzy M, McCulloh DH, Morbeck DE, et al. Cairo consensus on the IVF laboratory environment and air quality: report of an expert meeting. In: Reproductive BioMedicine Online. 2018. p. 658–74.
16. Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J. Hosp. Infect. 2020;104(3):246–51.
17. Chin AWH, Chu JTS, Perera MRA, Hui KPY, Yen H-L, Chan MCW, et al. Stability of SARS-CoV-2 in different environmental conditions. The Lancet Microbe 2020;
18. Lu J, Gu J, Li K, Xu C, Su W, Lai Z, et al. COVID-19 Outbreak Associated with Air Conditioning in Restaurant, Guangzhou, China, 2020. Emerg Infect Dis 2020;26(7).
19. Chow TT, Kwan A, Lin Z, Bai W. Conversion of operating theatre from positive to negative pressure environment. J Hosp Infect 2006;64(4):371–8.
20. Wang J, Tang K, Feng K, Lv W. High Temperature and High Humidity Reduce the Transmission of COVID-19. SSRN Electron J 2020