COMMENTARY

COVID-19 screening during fertility treatment: how do guidelines

compare against each other?

Athanasios Papathanasiou

Received: 20 May 2020 /Accepted: 8 July 2020

Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract

Various fertility scientific societies have published pathways and recommendations for COVID-19 screening during fertility

treatments. As there is currently very limited research evidence on how to best deliver this screening, it is not surprising that there

are noticeable differences between their recommendations. This paper compares the screening pathways recommended by these

guidelines, in the light of the emerging evidence. It proposes the more liberal use of viral testing for improving detection of

asymptomatic or mildly symptomatic fertility patients. It also argues that a negative test result on symptomatic individuals should

not be over-relied upon for allowing the treatment to proceed. In these cases, a low threshold for cancellation may still need to be

maintained.

Keywords Covid-19

Sars

Fertility

IVF

Guideline

Introduction

Developing risk assessment strategies against COVID-19 for the

fertility services presents with unique challenges. The very natu re

of fertility treatment involves a number of necessary face-to-face

interactions which extend over a timeframe of weeks. This re-

quires continual reaffirming of good health, not just a single

assessment. It also demands prompt investigation of the potential

risk, followed by decisions—to conclude o r cancel the

treatment—which are often backed by limited evidence.

Ideally, a reliable and sensitive point-of-care diagnostic tool for

COVID-19 could address most of these challenges effectively.

However, at the time of writing this paper, no such tool is readily

available for use in the reproductive medicine field [1]. As a

result, fertility scientific societies currently suggest combining

tools for assessing the risk of exposure to the virus, with some

noticeable differences among their recommendations.

The aim of this paper is to discuss the guidance on COVID-

19 screening that is specific to the delivery of fertility treat-

ment. Differences within the existing guidelines will help

highlight gaps and limitations in current knowledge, which

future guidance should try to address. Moreover, studying

these differences will increase preparedness among clinicians,

in anticipation of challenging, yet unexplored, clinical scenar-

ios that may be encountered in everyday fertility practice.

Search for COVID-19 fertility guidelines

COVID-19-related fertility guidance was expected to be avail-

able online within the dedicated scientific societies’ websites,

as this would facilitate instant publication and dissemination,

as well as regular updating of the guidance. Therefore, an

online search was conducte d using relevant keywords

(‘covid-19′, ‘sars’, ‘fertility’, ‘reproductive’, ‘society’, ‘asso-

ciation’, ‘college’, ‘guidance’ and ‘guideline’) in two popular

search engines (‘ Google’ and ‘ Bing’ ). This was

complemented by directly searching within the websites of

known fertility societies for the latest updates (search per-

formed on 16 May 2020, English language only).

Four national/international societies have published clini-

cal guidance that addresses COVID-19 screening during fer-

tility treatments (European Society of Human Reproduction

andEmbryology(ESHRE),AmericanSocietyfor

Reproducti ve Medicine (ASRM), British Fertility Society/

Association of Reproductive and Clinical Scientists (BFS/

ARCS) and Canadian Fertility and Andrology Society

(CFAS)) (Table 1)[2–5].

* Athanasios Papathanasiou

linktothanos@gmail.com

Bourn Hall Clinic, Farrier Close, Wymondham Norwich NR18 0WF

Journal of Assisted Reproduction and Genetics

https://doi.org/10.1007/s10815-020-01885-5

The screening process

Triage by self-assessment

All scientific societies advocate a ‘triage’ approach to as-

certaining patient risk of exposure to the virus. This is

based on self-reporting, which is performed via remote

means of communication such as phone or email.

Interestingly, there are differences in the nature of ques-

tions each society recommends asking. Overall, the topics

covered by the triage assessments are:

i) Symptoms suggestive of COVID-19 infection (all 4

guidelines)

ii) Episodes of exposure to a potentially infected individ-

ual (all 4 guidelines)

iii) Lifestyle-related risk of exposure (such as high-risk

profession al grou ps or t ravel hist ory) (ESHRE,

ASRM and CFAS)

iv) Viral prevalence locally (depending where the individ-

ual resides) (ASRM only)

The differences in the covered triage topics likely reflect

the still limited—though growing—knowledge around the

risk factors for acquiring COVID-19 infection. Exposure to

a potentially infected individual is well recognised as one of

these factors by authoritative sources [6]. Other risk factors,

such as working in healthcare, are emerging; however, the

odds of acquiring the virus occupationally are difficult to

quantify and are influenced by type of activity, use of protec-

tive equipment and opportunity [7]. Only the ASRM guideline

comments that the risk of exposure is also influenced by geo-

graphical differences in viral prevalence. However, geograph-

ical variations in the prevalence of the virus are not limited to

the USA but prevail worldwide [8]. Interestingly, a COVID-

19 self-assessment electronic application already incorporates

the geographical factor (within the USA) in the decision-

making [9]. Similar tools designed with fertility processes in

mind could be soon integrated into fertility practice. Until

then, reproductive medicine clinics may need to monitor and

react to trends in viral prevalence within their catchment area.

Existing guidance also supports repeating the triage assess-

ment during treatment, which reflects the ongo ing risk of

Table 1 Summary of recommendations for COVID-19 screening during fertility treatment by national/international scientific reproductive medicine

societies

European Society of

Human Reproduction

and Embryology

(ESHRE)

American Society for

Reproductive Medicine

(ASRM)

British Fertility Society/Association of

Reproductive and Clinical Scientists (BFS/

ARCS)

Canadian Fertility

and Andrology

Society (CFAS)

Risk triage by

self-assessment

Yes Yes Yes Yes

Triage is based on ◦ Symptoms

◦ Episode of possible

exposure

◦ Lifestyle risk

(healthcare provider,

travel history)

◦ Symptoms Episode of

possible exposure

◦ Lifestyle risk (risk at

workplace, travel

history)

◦ Virus prevalence locally

◦ Symptoms

◦ Episode of possible exposure

◦ Symptoms

◦ Episode of possible

exposure

◦ Lifestyle risk

(travel history)

How often to triage Before treatment

During stimulation

Before every clinic visit Before treatment

Before every clinic visit

Before every clinic

visit

Advocate COVID-19

testing

Yes Refer to authoritative

sources

Yes Refer to local public

health services

COVID-19 testing

policy

Selective (if

symptomatic or

high-risk self--

assessment)

Unclear (refer to

authoritative sources,

such as the Centers for

Disease Control)

One routine test just before starting treatment and

consider repeat before a procedure and

selective (if symptomatic or high-risk self--

assessment)

Selective (refer to

local public health

services)

Decision to cancel is

based on

‘Typical’ self-reported

symptoms or

Positive testing

Refer to authoritative

sources

Positive testing or self-reported symptoms (if no

time to test)

Positive testing

If Covid-19 test is

negative

Continue with

treatment

Refer to authoritative

sources

Continue with treatment Continue with

treatment

(depending on

individual

assessment)

Temperature checks

in clinic

No Optional No Optional

J Assist Reprod Genet

exposure to the virus. The importance of a cautious approach of

reaffirming rather than assuming continuous good health is thus

emphasised. The ASRM, BFS/ARCS and CAFS recommend

re-triaging before every clinic visit, while ESHRE applies the

more laconic appr oach of a single triage during stimulation.

Although one could argue that the more checks the better,

COVID-19 triaging will inevitably place an extra burden on

staff resources, on top of other restrictions already imposed on

staffing levels (social distancing, staff sickness, etc.).

COVID-19 testing

Although most guidelines refer to some form of COVID-19

testing as an adjuvant to triage screening, only the European

guidelines detail when testing should be performed. Two ap-

proaches to testing are being proposed. ESHRE recommends

testing only in the presence of symptoms or risk (selective

testing). In contrast, BFS/ARCS advocates a more cautious

approach, by recommending routine testing at the beginning

of treatment as well as before any procedure, with added

(selective) testing in the presence of symptoms or risk.

The latter guidance from BFS/ARCS is more in line with

the emerging knowledge about transmission of the virus,

aiming to detect the subgroups of infected patients who have

very mild or no symptoms. Some of the asymptomatic ones

will be at the ‘incubating’ stage, only to become symptomatic

during or just after the completion of fertility treatment. These

‘incubators’ may already shed a high viral load [10]. Other

patients may be asymptomatic throughout but obviously still

be contagious. Early reports indicate 18–31% to be truly

asymptomatic [11–13].

At least some of these surreptitious patients (incubating,

asymptomatic or mildly symptomatic) will be missed by a

selec tive approach to COVID-19 testing (as suggested by

ESHRE). Obviously, testing technology is still evolving, and

currently, it cannot guarantee to detect all the carriers [1].

There are also resource and financial considerations, particu-

larly if the test is to be frequently repeated. Moreover, the

absolute benefit—extra number of positive cases detected—

may be arguably limited if routine testing is applied on a low-

risk population (although this can only be proven retrospec-

tively). Notwithstanding the aforementioned uncertainties,

regular viral testing (as supported by the BFS/ARCS) has

the potential to achieve higher and earlier detection of infected

cases, thereby reducing the overall risk of transmission.

Taking into account the relatively high morbidity and mortal-

ity from COVID-19, this could translate to saving more lives.

This technology is expected to become even more reliable in

the near future.

American guidelines (ASRM and CFAS) refrain from pro-

posing a testing pathway but instead refer to guidance from

other (authoritative or local) sources. Although this is an hon-

est and ‘safe’ approach, it de prives reproductive medicine

clinicians of much needed practical guidance how to tackle

the screening issue. Consequently, it is expected that clinics

will do their own research and even consult with local experts

on how to set up their own screening programmes.

Cancellation

A higher than usual cancellation rate is expected after intro-

ducing COVID-19 screening. The importance of performing a

viral detection test before cancelling the cycle is highlighted

by all guidelines (Table 1). In principle, a positive result

should prompt cancellation, while a negative result should

allow treatment to continue— but remain vigilant.

Interestingly, there is difference of opinion on how symptoms

should be managed. BFS/ARCS advocates that symptoms

should prompt viral testing—as long as time allows—with

the result of this test determining whether to cancel or not.

ESHRE places more emphasis on symptoms; they advise can-

cellation if the patient develops ‘typical’ COVID-19 symp-

toms, without need for confirmation by testing.

There is an accumulating evidence that a minority of pa-

tients with confirmed COVID-19 infection will have an initial

negative test (PCR) [14]. In these patients, repeated testing

over the next few days tends to become positive (an average

of 5 days is required) [14, 15]. On the basis of this evidence,

the ESHRE recommendation to cancel on the basis of typical

symptoms alone appears to be the safer approach.

On the other hand, the ESHRE guidance does not

specify what ‘typical’ symptoms are. One would expect

that these would be a fever (over 37.8 °C) and a new,

persistent cough [16]. Realistically, it would be difficult

to justify allowing a febrile coughing patient to enter

the fertility clinic or have a fertility-rel ated procedure.

Non-specific symptoms, such as a sore throat, nasal dis-

charge, feeling unwell, loss of smell and taste or mildly

elevated temperature, may still be challenging to man-

age though. In these more subtle cases, the guidance

supports performing a viral detection test to guide the

decision-making. However, as already argued, a single

negative result should not exclude infection. Therefore,

in symptomatic patients, it may be safer to cancel a

cycle altogether regardless of the severity of symptoms,

unless perhaps there is time f or repeated testing. The

guidelines do not elaborate on this uncomfortable sce-

nario but imply that the decision should be based on an

individual risk assessment [4]. In practical terms, repro-

ductive medicine clinicians may not feel confident about

quantifying the risk of an individual patient being in-

fected, and there may be no ready access to an experi-

enced physician. In these cases, it may come down to

the ‘flexibil ity’ of individual clinic policies and the con-

fidence clinicians place on their locally available

COVID-19 testing.

J Assist Reprod Genet

Temperature checks

Temperature checks at the point of entry have been widely

implemented in certain settings (country borders, airports,

etc.), in an attempt to detect a nd isolate symptomatic

COVID-19 patients. These checks a re simple and cheap

enough to apply, justifying their use on large crowds, although

they are likely to miss the mildly symptomatic and asymptom-

atic patients [17]. Temperature checks can also be ‘deceived’.

In the fertility clinic setting, the bene fit of temperature

checks has not been established. Some of the guidelines refer

to them as optional, while others do not even consider them

(Table 1). CFAS suggests that temperature checks may be of

limited value if patients have been previously symptom-

triaged. Moreover, there is an element of risk exposure for

the individual assigned to perform temperature checks.

Obviously, this risk needs to be balanced against the risk of

a larger team of staff being exposed to a febrile COVID-19

patient that has been allowed to enter the clinic.

Deriving best local practice

There is very limited knowledge on the safety and effective-

ness of viral screening measures within the reproductive med-

icine setting. Unsurprisingly, currently published screening

pathways rely heavily on expert opinion and are subject to

change with time. In the absence of reliable research evidence,

clinics must therefore aim to internally monitor the ongoing

risk associated with their COVID-19 policies. Prospectively

auditing COVID-19 outcomes is paramount, as this will instil

confidence in the clinic’s policies and inform future restriction

or relaxation of the screening protocols.

Along the same lines, clinics may wish to apply more,

rather than fewer, risk assessment measures at the restart

(e.g. collect more triage self-assessments or perform routine

and repeated viral detection tests, if available). This is not only

because i t is pre sumed safer (until proven otherwise); the

auditing process is also likely to be more informative with a

wealth of data collected along the way.

Conclusion

Current guidance on COVID-19 screening during fertility

treatment supports a triage approach, with emphasis on regu-

lar self-assessments that are complemented by viral testing.

Nonetheless, there are significant differences in the proposed

pathways for delivering the screening, which will hopefully

ameliorate with accumulated experience and research in the

fertility setting.

Currently, there is a scientific argument in support of more

liberal use of viral testing for improving detection of

asymptomatic or mildly symptomatic fertility patients. On

the other hand, a negative test result on symptomatic individ-

uals should not be over-relied upon for allowing the treatment

to proceed. In these cases, a low threshold for cancellation

may still need to be maintained. These points need to be cov-

ered by future updates of the guidance.

In the absence of concrete research evidence, prospective

auditing of COVID-19-related screening measures and out-

comes is essential, in order to ascertain the effectiveness of

locally enforced policies and to inform needful amends to

future practice.

Compliance with ethical standards

Conflict of interest The author declares that he has no conflict of

interest.

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