Please note that the questions asked via email and live within the session have been consolidated to remove duplicate questions and redundancies

 

Theme 1: Viral mechanisms of action/infectability and Immunity:

 

We know that COVID-19 stays on surfaces for various periods of time after exposure. Are there any studies on how long it retains its “infectability” on these surfaces? Since most of the IVF consumables and media are internationally shipped, should we be concerned about contaminated surfaces like package materials etc?

“Most data were described with the endemic human coronavirus strain (HCoV-) 229E. On different types of materials it can remain infectious for from 2 hours up to 9 days. A higher temperature such as 30ºC or 40ºC reduced the duration of persistence of highly pathogenic MERS-CoV, TGEV and MHV. However, at 4ºC persistence of TGEV and MHV can be increased to 28 days. Few comparative data obtained with SARS-CoV indicate that persistence was longer with higher inocula (Table I). In addition it was shown at room temperature that HCoV-229E persists better at 50% compared to 30% relative humidity [8].” (Kampf et al., 2020)

 

You mentioned we develop Immunoglobulins after contact with CoV 19, do we really know once you are negative for virus RNA, and you get IgG positive, are you safe from reinfection?

Immunity after infection – under constant current investigation, not fully known, we hope so….see  Wu et al and M. Lipsitch (April 13th, Nature News)

 

Does Covid 19 has a specific host cell or receptors? What are the first cytokines activated in the immune Response against covid 19?

Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To devise therapeutic strategies to counteract SARS-CoV-2 infection, it is crucial to develop a comprehensive understanding of how this coronavirus hijacks the host during the course of infection, and to apply this knowledge towards developing both new drugs and repurposing existing ones.” (Gordon et al, 2020)

Specific host cell = a cell that has the ACE2 receptor and human dipeptidyl peptidase 4 (hDPP4.   Serine protease TMPRSS2 is important for SARS-CoV-2 S activation

Type II bronchiolar alveolar cells, GI system, heart, kidney. 

ACE receptors on Endometrium, eggs, embryos, seminal plasma, FF? – unknown

 

Pathway of immune response/cytokines etc:

“ Some people who were critically ill with COVID-19 had high blood levels of proteins called cytokines, some of which can ramp up immune responses. These include a small but potent signaling protein called interleukin-6 (IL-6). IL-6 is a call-to-arms for some components of the immune system, including cells called macrophages. Macrophages fuel inflammation and can damage normal lung cells as well. The release of those cytokines, known as a cytokine storm, can also occur with other viruses, such as HIV.” (Ledford, Nature News April 9th)

 

How stable are viruses in sunlight? Does UV light kill the virus? What about virus stability in warmer climates?. 

Dr. Parmegiani’s response:

An adequate UV-C Dose decontaminates any microorganism for surfaces. UV-C germicidal effectiveness and use is influenced by wavelength, temperature and UV intensity, which is affected by distance (https://www.cdc.gov/infectioncontrol/pdf/guidelines/disinfection-guidelines-H.pdf) So, forLN2/NV (low temperature) we need to use proper methods for UV-C irradiation. Please note that UV-C from sunlight are completely absorbed by the ozone layer and atmosphere.

 

Dr. Elder’s response:

I haven’t seen any reports.  I wouldn’t count on UV alone, better to adhere strictly to protocols of regular cleaning and decontamination procedures: 

·         Kampf et al., 2020(1) 

·         Van Dormalen et al, 2020(2) 

(Note that the majority of these studies were carried out using other coronaviruses, not SARS CoV-2.)

“The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.

Spread in hot dry climates?  Probably more dependent on other factors in those particular communities than on environmental factors…. wait and see, but on surfaces: At a temperature of 30ºC or more the duration of persistence is shorter (Kampf et al, 2020)

What is the required temperature to kill COVID19?

"60 degrees Celsius (140 degrees Fahrenheit) for an hour, researchers have found. To kill the virus in a laboratory setting, the team had to heat it to 92 degrees Celsius (197 degrees Fahrenheit) for 15 minutes" - https://www.newsweek.com/coronavirus-heat-kill-virus-1498074

How big is the virus?

70-90nm

 

Is someone on ACE inhibitors at increased risk of infection

controversial, conflicting reports, this is from Royal Brompton cardiologist:

 “There is no sound scientific basis or evidence to support this speculation and, based on all the current evidence, we advise all patients who have been prescribed these medications to continue taking them unless they are specifically advised to stop by their medical team.”

Also see Editorial in BMJ, Ferrer & Aaronson: Clinical effects are unpredictable, so treatment decisions must be tailored and pragmatic”

 

Why WHO Now doesn't recommend avoiding Ibuprofen for Covid?

Ibuprofen:  MRHA statement March 23rd:

“There is some debate suggesting NSAIDs may increase complications from simple acute respiratory infections or slow recovery. The product information of many NSAIDs already contains warnings that their anti-inflammatory effects may hide the symptoms of a worsening infection. However, the evidence is not conclusive.

There is currently no research into ibuprofen and the new coronavirus.

Patients who have confirmed COVID-19, or believe they have COVID-19, should be advised to take paracetamol in preference to ibuprofen. Patients already being treated with ibuprofen do not need to stop treatment”

How could hydroxychloroquine affect COVID-19?

It has anti-inflammatory properties and can have serious severe side-effects. Multiple mechanisms of antiviral activity, including:

·         Interference with the cellular receptor ACE2 (potentially making it particularly effective against SARS and COVID-19).

·         Impairment of acidification of endosomes, which interferes with virus trafficking within cells.

·         These agents also have immunosuppressive properties.  Activity against many pro-inflammatory cytokines (e.g., IL-1 and IL-6) might be helpful in prevention or treatment of cytokine storm.  (Internet Book of Critical Care, April 8th)

A laboratory study of hydroxychloroquine showed that it could prevent SARS-CoV-2, the virus behind Covid-19, from entering cells in a petri dish. While it shows a plausible mechanism for the drug, the effects on cells in a dish can be different from those in living people.

 

“The data are really just, at best, suggestive,” Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, told CBS’s Face the Nation on April 5. “There have been cases that show there may be an effect, and there are others to show there’s no effect. So I think, in terms of science, I don’t think we could definitively say it works.”

 

How does one interpret a positive serum antibody result? Is there any significant risk for transmission? 

 Currently unknown, under investigation (see M. Lipsich, April 13th)

 

Theme 2: COVID- 19 as it relates to fertility patients, gametes and embryos

 

Is it true that covid19 has a link with Male infertility or DNA sperm fragmentation?

There is no data to suggest that so far.

See Pan et al, 2013: This article refers to expression of the ACE2 gene/enzyme, NOT the virus:

“The ACE2 gene, which was recently cloned, has an expression pattern that is restricted to endothelial cells in the heart and kidney, epithelial cells in the distal tubule of the kidney, and adult Leydig cells in the testis [36,44]. The full-length human ACE2 cDNA predicts an endothelium-bound carboxypeptidase of 805 amino acids, which has 42% homology with the N-terminal catalytic domain of ACE1 (Figure 2) and contains the following two domains: an amino-terminal catalytic domain and a carboxy-terminal domain [45]. The expression of ACE2 in the ovaries and testes suggests that this enzyme plays a regulatory role in steroidogenesis and thus affects germ cells and reproductive health

In the male reproductive tract, ACE2 is selectively expressed by adult Leydig cells in the testis. In addition, the ACE2-producing Ang-(1–7) and its receptor Mas have also been detected in the testis, and these are mainly located in the interstitial compartment and cytoplasm of the Leydig cells [26]. Reis et al. further demonstrated the strong influence of ACE2 in the male reproductive system by showing that humans with severe spermatogenesis impairment have lower levels of ACE2, Ang-(1–7), and Mas compared with fertile subjects [26]. Because the sex steroid hormone is one of the major products secreted from Leydig cells, it is suggested that ACE2 participates in the modulation of spermatogenesis”

“Increasing data have demonstrated that ACE2 is present in human and rat ovaries [26,32]. The Ang-(1–7) peptides, which are produced by ACE2, are also located in several ovarian compartments and may be quantified in follicular fluid (FF) [27]. Gonadotropin induces changes in the ovarian expression of ACE2, Ang-(1–7), and the Mas receptor, which implies that ACE2 participates in ovarian physiology mediated by Ang-(1–7) [32] The ACE2/Ang-(1–7)/Mas axis was recently verified to promote meiotic resumption, which is highly regulated by luteinizing hormone, likely as a gonadotrophin intermediate [61].”

 

Does COVID-19 impact pregnancy? Are the mother or baby at higher risk for anything short or long-term? Increased risk of miscarriage? Can we be sure or is it too soon to confidently assess?

ECDC Update, April 8th: “There is limited scientific evidence on the severity of illness in pregnant women after COVID-19 infection. It seems that pregnant women appear to experience similar clinical manifestations as non-pregnant women who have progressed to COVID-19 pneumonia and to date (as of 25 March), there have been no maternal deaths, no pregnancy losses and only one stillbirth reported. No current evidence suggests that infection with COVID-19 during pregnancy has a negative effect on the foetus. At present, there is no evidence of transmission of COVID-19 from mother to baby during pregnancy and only one confirmed COVID-19 neonatal case has been reported to date.”

 

ACE2 presence has been confirmed in ovarian tissue. How can it influence IVF treatment?

Expression of the gene for the ACE2 ENZYME, not the receptor has been confirmed in ovarian tissue. There is no data to suggest that the ACE2 receptor is in ovarian tissue. This on its own is unlikely to influence IVF treatment.

Do we have any data about miscarriage and fetal malformation caused by coronavirus in the first trimester of pregnancy?

Being that this virus was only realized in December, data on exposure in early pregnancy is lacking. We need to see what effect there may be if any.

 

Do you think we should suggest after healing PCR RNA for the presence of the virus in the sperm?

                Sperm PCR won’t be possible for a while, wait & see

 

Is there a possibility the semen could be contaminated with COVID-19 through the processes of collection?

The expectation is that it is. Viruses can be present in biological fluids.

 

What long term effects do you think COVID will have on fertility treatments

See Jan Tesarik  (April 1st)

 

Because SARS-CoV-2 appears to not be transmitted sexually the biggest effect will be on just ensuring that patients and healthcare workers do not infect each other.

 

Any new information re: when antibody testing will be available for our staff and patients?

Many different types of assay/kit are under development & testing, availability will be hIghly variable between countries/regions/areas….

 

Antibody testing is already available from the CDC and several commercial groups. What we need to do though, is complete testing on selected populations so that we can better interpret the tests.

 

Hypertension and gestational diabetes may make patients more vulnerable to COVID-19, until vaccination release would it be better to avoid pregnancy altogether?

Each patient should be assessed carefully for risk and counselled accordingly

 

Is there any study showing any evidence of SARS-CoV2 in seminal plasma and follicular fluid?

Song et al (April 2020):” No positive RT-PCR result was found in the semen or testicular biopsy specimen. The results from this study show no evidence of sexual transmission of

2019-nCov from males.”

 

What effect would the pyrexia or hypoxemia from COVID-19 have on the sperm/oocytes/pregnancy?

Probably similar to the effects of any other illness causing those symptoms

 

Leydig cells present ACE receptors, it could be possible that other cells in the male reproductive system present the receptors?

It is not established at this time

 

Would the blood gonadal barrier prevent the infection of gametes?

It is not established at this time. 

 

Yes, there are blood tissue barriers but some viruses can penetrate these barriers. For example, the viruses that cause encephalitis (Japanese Encephalitis Virus, Rabies Virus, HIV-1, Herpes Simplex Virus, etc.) can breach this barrier. Most viruses though, are impeded by the blood tissue barriers.

 

Clinics that are still up and running have they seen any difference in pregnancy rates and specifically biochemicals?

This data is not available

 

Since coronavirus affects the hypothalamus, is there a possibility it could affect the secretion of GnRH in the hypothalamus?

It may affect, but again, no data

 

Do you think it is acceptable to treat and vitrify oocytes for cancer patients when otherwise shutdown? Should we treat minor (under 18) cancer patients any differently?

“Cancer” patients egg cryopreservation is considered “high priority” in most countries, and it may be performed but local rules may regulate this.  If a minor (under 18) has menstrual cycle (peri- post-pubertal), then IVF/egg cryopreservation is an option (see PMID: 25214440)

 

The major risk to cancer patients would be the risk that a side-effect of treatment (severe ovarian hyperstimulation syndrome, for example) could place them into the hospital with potentially infectious patients and that resources necessary to treat these infected patients could be used on a case that initially was not life-threatening. There is also the risk of patients and healthcare workers infecting each other. There is no reason to suspect that the Covid virus will affect the oocytes or the resulting embryos.

 

Theme 3: COVID-19 and the IVF lab

 

Would trypsin wash be useful or practical to use in an IVF Lab?

NO – the spike/receptor interaction is activated by protease-dependent cleavage – see Wu et al (2020):

 

“Trypsin could also activate SARS-CoV-2 S protein efficiently and induce large syncytium formation. To our surprise, we found that, even without trypsin, SARS-CoV-2 S protein could trigger syncytium formation on 293/hACE2 cells, a phenomena similar to what was observed in MHV S protein in certain aspect51. This led us to speculate that SARS-CoV-2 S protein is capable of triggering protease-independent and receptor-dependent syncytium formation. Such a mechanism might enhance virus spreading through cell–cell fusion and this might partially explain rapid progress of the diseases”

 

Should we be doing semen analysis during the shutdown period?

Many clinics will have to take advice from their authorities. Fertility and sterility:Fert/Steril website: Tissue Storage from coronavirus infected to uninfected samples.

 

Each clinic should develop and/or review their written emergency plans for tank storage and maintenance and ensure that tank maintenance continues without interruption. It is unknown whether cross-contamination may occur between stored tissues from coronavirus infected to uninfected samples. However, until proven otherwise, it is recommended that samples from coronavirus infected patients be handled in the same manner as tissues from patients who are seropositive for other infectious diseases: https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/62122-patient-management-and-clinical-recommendations-during-the-coronavirus-covid-19-pandemic

 

Can this virus be found in spent culture medium?

There is currently no evidence to show this.

 

Can we use ultraviolet light for decontamination of the IVF lab? Do we have to use UV light to sterilize the laminar hoods before we restart receiving cases at IVF lab?

Yes, you absolutely can use UV-C. The suggestion is to calculate the proper UV-C dose  (µWs/cm2) necessary to deactivate the virus. UV-C is used also to sterilize Liquid Nitrogen, which should be considered a potential vector of infection (Parmegiani et al, 2009). Please note, UV light is very dangerous for embryos and other cells. We cannot expose gametes and embryos to UV.

 

Do you believe it may be useful to use Nidacon ProInsert device to process IUI and IVF sperm during this time period and the coming months to minimize viral transmission risk? What other precautions should be made for sperm preps?

Have the partner bring in the specimen, then process using the Nidacon Proinsert tubes per protocol - see Loskutoff references for viral patient processing using these tubes.

 

Can you recommend effective cleaning protocols that would be effective on COVID-19 but minimize embryo toxicity for ivf labs?

Please see Kampf 2020 paper but CRB advise: Consider augmenting your SOPs on sanitizing surfaces and work areas. Review CDC recommendations on sanitizing. Instruct staff on frequency of regular and additional sanitizing (e.g. after liquid nitrogen has been delivered). Exercise caution when choosing cleaning supplies – 7x soap and/or 70% ethanol are effective against COVID-19 virus

 

Kampf G et al (2020) Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J of Hospital Infections 104:246-251

 

Also see WHO guidelines: Laboratory biosafety guidance related to coronavirus disease (COVID-19), Feb 2020 : 

 

When you mention PPEs, to what extent. Does that include goggles, masks, impervious hats, and gowns?

That will have to depend on your own risk analysis. But from a recent talk about experience in China we have this....Notes from experiences in China have suggested: Differences in ppe according to risks of exposure, outpatients( masks) follicle monitoring, Egg collection, IVF lab perhaps goggles, N95 mask/surgical masks, gloves and gowns

 

Interesting Checklist: Lab management: https://www.aab.org/aab/IVF_Laboratory_Management_During_COVID-19_Pandemi.asp

 

Do you recommend transferring embryos or freeze-all only for practices still currently open?

The majority of societies would recommend freezing. This is not only a safety issue can be done for not increasing the strain on the health services if complications occur.

 

What do you think to add Nukleosidanalogon to the culture media

Nucleoside analogues?  I wouldn’t!

 

What about the air pressure during a pandemic? Usually positive pressure in IVF lab but in ICU for COVID-19 negative pressure is recommended. What do you think is safer for laboratory staff?

                better to make sure no pathogens get in the lab!

 

What about the possible injection of the virus into the oocyte during ICSI, is there some information on whether the virus, if injected in the oocyte, could integrate into the oocyte’s genome and get activated.

Dr Parker addressed this question during the second session - as CoV-2 is a +RNA virus, the scenario is unlikely

 

Should we worry about embryos with zonae breached and then left in culture for PGT, since the zona is now open?

Best approach is to take all possible steps to avoid the risk of any virus entering the lab/culture system

 

What to do if a patient is in cycle and tested covid 2019 positive? Or if a patient ends up being positive, what protocols should be put in place with their samples?

If a patient tested positive for Coronavirus, then IVF treatment is advised not to start. If a patient test positive after starting IVF/FET cycle, then it is advised to cancel cycle.

 

For labs that are open (or that will reopen) what safety measures should be taken to protect lab staff as well as all samples? Please be specific

 refer you to the documents published by AAB/CRB, that is very detailed and specific

https://www.aab.org/images/CRB/2020/PAMF%20and%20COLLEGE%20OF%20REPRODUCTIVE%20BIOLOGY%20REPORT%20on%20COVID19%20%20%20procedures%20FINAL%20%2020200403%20copyright4.pdf

 

With the amount of washing and we perform during the laboratory IVF process, is the theoretical covid-19 viral load in the transfer media a realistic possible risk to the patient? What about gradient sperm preps?

It is unlikely that patient specimen (egg, sperm, embryo) would carry Coronavirus if adequate laboratory procedures are applied

 

 One estimation of the dilution factor from performing standard IVF with a 1 ul drop containing the oocyte/embryo being placed into 25 ul drops is 1:1 million. If vitrification is then performed it would be 1:6.6 trillion. Warming of the embryo would dilute it even further. It is not known whether the Covid virus is found in semen. If it is, a gradient prep would most likely reduce its concentration and the use of centrifugation systems for processing semen from HIV positive semen could reduce it further. It should be noted though, that these systems would need to be validated on each type of virus. Viruses that bind the zona pellucida may be more difficult to remove.

 

We are running an egg bank and I am wondering what would be a recommendation for the oocytes donor screening? Anything additional to a regular scheme, specific for COVID?

Donors should be tested for Coronavirus and those tested positive should be cancelled (as a recommendation - but you need to establish your own SOP and follow it)

 

Does nanofiltration completely eliminate the virus from any fluid?

Nanofilters (depending pore size) would possibly remove/eliminate virus after filtration, but this would likely not be a practical application in IVF

 

What would be a practical and economic protocol for utilizing UV in the lab to help kill the virus without harming any gametes or embryos?

Applying UV in IVF laboratories is generally not used; - instead cleaning surfaces with adequate disinfection may be recommended

 

What is your opinion on the filters action that can be used in the lab?

Probably not very practical

 

Theme 4: COVID-19, Cryopreservation and cryostorage

 

Does the sars-cov2 survive -196 c in cryostorage? Risk of COVID infection within the dewars? Should they be kept apart from other hazardous samples as well?

 

According to Lodo's talk last week the LN2 carries pathogens. Very little is known about viral survival in LN2. NO evidence of transmission so many believe no special precautions need to be taken otherwise it is up to each Sci director to do his/her own risk assessment and if the conservative opinion is formed then to store separately.

 

However Fert/Steril Tissue Storage - Each clinic should develop and/or review their written emergency plans for tank storage and maintenance and ensure that tank maintenance continues without interruption. It is unknown whether cross-contamination may occur between stored tissues from coronavirus infected to uninfected samples. However, until proven otherwise, it is recommended that samples from coronavirus infected patients be handled in the same manner as tissues from patients who are seropositive for other infectious diseases.

Dr. Parmegiani’s response:

This depends on our SOP. I would recommend "dilute risks"" with appropriate vitrification-carriers and procedures for handling/ vitrification/ warming". An easy-to-implement and straightforward procedure is the vitrification-carrier washing with sterile liquid nitrogen before warming (Parmegiani et al, 2009). 

 

Could you share details for sterilizing LN2? How do you confirm sterilization?

This is explained in Parmegiani et al Fertil Steril 2009 and 2012. Specific devices have been developed and optimized for UV-C liquid nitrogen sterilization (www.nterilizer.com). Disclosure of conflict of interest: I’m shareholder of Nterilizer srl (L.Parmegiani).

 

See also : Joaquim et al (2017)

 

Will the potential viral load of a frozen embryo / egg or associated cryomedia be sufficient to cause infection ?

We don’t currently know what viral load  represents an infective dose

 

LN2 temperature is -196°c. so can u tell me how contamination occurred? Can the virus survive in LN2?

The hypothetical risk of contamination throughout LN2 was described in slide 10 of my presentation (Parmegiani et al RBMO 2011)

 

Yes the virus can survive in LN2 like all other viruses

 

Would it be prudent to periodically test detritus from our LN2 storage dewars for a battery of most concerning pathogens? But then, to what end?

This was addressed ‘live’ during the second session (Dr Pomeroy)

 

All nitrogen tanks (including vapor tanks) will most likely have microbes in their detritus. Most comes from the atmosphere as the moisture containing air condenses on the exposed inner surfaces and then forms ice which is dislodged into the tank. Cross-contamination is not likely, so it would not probably be useful to culture the detritus.

 

Please specify, Dewars are in aluminum so hypochlorite (bleach) will destroy the tank.

                That is why UV is a better option for this purpose

 

Do you believe that using only closed devices for vitrification for human samples should be the standard procedure?

Closed systems can also be contaminated from the outside

 

Vials storing sperm will have liquid nitrogen and it is unclear whether risks are lessened by vapour phase storage?

 Any microorganism accidentally present in the LN2 can also pass to the N vapour phase (Parmegiani, Fertil Steril 2011) 

 

 Vapor phase storage is mainly used to reduce cross-contamination, the transfer of a contaminant in one vial to another. Cross-contamination is unlikely. The only working conditions case where cross-contamination was found was in large bags used to store bone marrow. One study (Cobo et al, 2012) looked at IVF from patients that had HIV, Hep B or Hep C. They found no evidence of viruses in follicular fluid, culture media or liquid nitrogen where embryos were stored despite some patients having viral loads of up to 2 million/ml . They found no evidence of cross-contamination using PCR. Another study (Bielanski et al, 2003) spiked a liquid nitrogen tank with high titers of virus and examined straws that were closed or open for evidence of cross-contamination. They found some cross-contamination in straws left open and none in closed straws.

 

How are water aerosols different from the ones generated by the fumes of liquid N2? Is the persistence and diffusion the same as with water vapour?

Liquid N2 “fumes” is the result of water molecules suspended in the air change from invisible gas to tiny visible water droplets (caused by sudden cooling); therefore, technically, it has the same characteristics.

 

Theme 5: Restarting IVF cycles 

 

How long should labs wait before reopening? Should labs be open now? Should we continue doing emergency medical egg freezing? When we could restart the IVF activity?

 

The timing of this will be dependent on ongoing Government advice. Undefined lockdown, Undefined interruption. Unfortunately, different countries will have their own dates to commence word. This depends on many things and the spread of the virus.

Please see checklists here: https://www.aab.org/images/CRB/2020/PAMF%20and%20COLLEGE%20OF%20REPRODUCTIVE%20BIOLOGY%20REPORT%20on%20COVID19%20%20%20procedures%20FINAL%20%2020200403%20copyright4.pdf

Dr. Parmegiani’s response:

I would say that we have no information regarding the virus in oocyte or

spermatozoa, so… if the virus is hypothetically in biological fluids (follicular fluid in

this case) we should dilute the contamination titer. We can add washing steps with

clean medium and tips after decumulation, before starting the equilibration procedure.

We must have very strict Standard Operational Procedures to avoid environment

and liquid nitrogen contamination. This utmost risk should be considered, after this

pandemic, for any kind of contaminant.

 

Is money or business stability a major influence in whether IVF units are choosing to operate or not?

There are different and severe affected areas in the US. The guidelines are from ASRM The American Society for Reproductive Medicine (ASRM) has advised that as of 17th March suspension of all-new, non-urgent fertility treatments in the midst of a public health emergency. They aim to review their recommendations no later than 30 March 2020 with the aim of resuming usual patient care as soon as possible. Since these are only guidelines and suggestions, different clinics may have different reasons for deciding not to follow them.

 

Any idea of how many US IVF centers are following ARSM guidelines?

The most recent data shared by ASRM suggested approximately 80% of the clinics in the US are adhering to the ASRM guidelines

 

Should from now on patients have a positive serology for sars-cov2 antibodies so only patients vaccinated (or those that have had the virus) be accepted for treatment?

We have not reached a time/status where this is a realistic possibility (addressed ‘live’ by Dr.  Morbeck during 2nd session)

 

Do you think a second wave of infection can come next fall/winter and how this can affect IVF treatments and clinics again?

There is currently a great deal of discussion/speculation/theoretical projection -answer as yet unknown

 

In case the patient becomes positive one day before the oocyte retrieval do you still recommend performing the retrieval?

                Cancel the cycle (probably the safest option)

 

The stay at home orders that are in place are for non essential procedures. but since infertility is a disease would you consider fertility treatments as essential? If so should ivf treatments continue at any stage in these uncertain times?

                See Jan Tesarik, April 1st 

 

For a patient with COVID 19 who was discharged recently, how much time must we wait before performing IVF?

Depends on results of testing (at least 3 viral RNA tests, + serology)

 

With so many citizens not working or furloughed around the world. Do you expect to have a delay in patients returning as they may not have the funds for maybe a couple of months or so?

This is hard to predict; but in countries (regions) where IVF is not paid by health insurance, there may be a decreased volume initially.

 

Do you expect government incentives to be removed after COVID-19 considering the fact health funds will be directed to the crisis?

This is not known, depending on the different governments, and their priorities

 

Are you at all concerned about the potential supply chain shortages of PPE, media, and/or consumable lab equipment? If so, what strategies can labs use to mitigate risk?

This is a concern indeed, and not sure if anyone can do anything about it, except using existing consumables in the most rational way

 

Do you believe that we have to make changes in surgical rooms in order to decrease the aerosol virus spread and the risk in the anesthesia .. for example negative pressure rooms?

Negative pressure room is great if you are treating infectious/symptomatic patients; however, for IVF, it is recommended not to treat (or stop the treatment) if a patient test positive.

 

This is the debate. We all agree that Infertility is a disease and not an elective procedure. But in the time when other non-life threatening procedures are being postponed, should we limit IVF procedures to only those that a delay of several months would be detrimental. Don’t forget that it is very difficult to demonstrate that one month of delay can be detrimental for a woman aged or with bad ovarian reserve and so really we think that a bad prognosis for these patients can change?

This is a notion that many agrees in most part, and for instance ASRM guideline is reflective of it in part

 

What about patients with hyperstimulation syndrome or further problems after Ivf that are overloading health cares systems? Has anyone been thinking also at this problem or considering this factor when deciding when and how to restart?

This is a good point.  However, in “principle” when treating infertile patients, a stimulation protocol should be (and can be) used that avoids (or minimizes) the risk of OHSS (that is independent of the Coronavirus pandemic)

 

Theme 6: Restarting IVF cycles - Staff considerations

 

What are the best ways to protect staff contamination during egg collection (or other procedures) from an infected patient?

Each clinic will have to revise all of its protocols. Lessons from clinics greatly affected by the virus must be disseminated. Infection control and risk analysis should be performed for all stages of treatment. Please see checklists here: https://www.aab.org/images/CRB/2020/PAMF%20and%20COLLEGE%20OF%20REPRODUCTIVE%20BIOLOGY%20REPORT%20on%20COVID19%20%20%20procedures%20FINAL%20%2020200403%20copyright4.pdf

 

Is there a strategy for testing laboratory personnel despite them not having symptoms? Should all staff be tested? If so, how often?

There are some groups starting to coordinate testing for laboratory staff.

 

What do you do when one member of your lab team tests positive for Covid -19?

                This was discussed live during the 2nd session (Lodo and others)

 

I would be interested to know how the clinics are managing their workforce as they reintroduce treatments- keeping split teams?

Creating a “split team” is an option to try to avoid having everyone in “quarantine” if one gets infected.

 

Usually there is a common seminar or conference area, where every employee congregates. Do we have to close that area?

This is a very good consideration.

 

Theme 7: Restarting IVF cycles - COVID-19 testing of IVF patients

 

How do we deal with patients that are asymptomatic for COVID 19?

This is important question; 1 positive (asymptomatic) patient should not start IVF treatment (or FET); and 2, if a patient becomes positive during treatment, then it is recommended to cancel the treatment cycle

 

In the future should all of our patients be tested for COVID19? What about those not undergoing IVF but having other less invasive treatments?

Probably all patients should be tested, independently how “invasive” is the treatment (before the treatment is initiated); - IF adequate testing capability is available

 

What type of COVID-19 testing should be done on infertility patients? PCR? ELISA? Both?

Probably both the virus testing and the antibody testing - if adequate testing capability is available

 

How can antibody screening be utilized to allow treatments to resume?

Antibody testing alone is not sufficient, it should be combined with the virus testing

 

Should we test all patients for the new virus before re-starting IVF cycles?

The recommendation is “yes”

 

Who to treat? Who to treat first; recontacting patients

There may be local/regional (or society ) guidelines available that should be followed, but the highest priority is likely for medically indicated fertility preservation (typically cancer patients), followed by patients with advanced reproductive age and low ovarian reserve

 

Social distancing for Patients? See Chinese experience

This is recommended to distance patients (as much as possible)



ADDITIONAL REFERENCES:

 

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