New guidance from ESHRE for maintaining safe fertility services during a dramatic spike in COVID-19 case numbers has realigned mitigation steps according to local levels of infection.

As countries throughout the world face up to a second wave of COVID-19 infections, ESHRE and others have upgraded safety guidelines for fertility clinics. ESHRE has reaffirmed its guidance from April on the reopening of clinics after lockdowns (phase 2 of the pandemic), but has now in this latest phase added two further measures as complementary to that April guidance: more testing in addition to the triage questionnaires; and greater information to patients on COVID-19 and its prevention before and during pregnancy.(1)

The new guidance also advises that mitigation measures should be in place depending on the level of infection in a region. Thus, a first core step in this latest guidance is to recognise the current epidemiological status of the pandemic and to assess its likely impact on internal resources (such as staff and equipment) and on patients. The second step is to plan mitigation measures according to that assessment to reduce those risks. A local notification rate of 20 to 60 cases per 100,000 population (moderate impact) might require no further measures than those already applied routinely. However, an area of major (60-120 cases per 100,000) or critical (>120 cases per 100,000) would require more intensive measures such as more routine testing of patients and staff, remote consultations, no accompanying persons, routine use of PPE, and even a freeze-all transfer policy. The measures relative to the case notification rate are set out in clear diagrammatic form in the ESHRE guidance.

The guidance was made public just a few days after the ESHRE COVID-19 working group published its review of resuming fertility services with mitigation measures after the initial flare of the pandemic.(2) The paper describes the measures needed to restart safe routine treatments in fertility clinics and the rationale behind their application. The review (published as an opinion) covers patient selection and informed consent, staff and patient triage and testing, the modification of ART services, treatment planning and a code of conduct. The code of conduct, as set out in ESHREs April guidance on the second phase of the pandemic, remains an important component of this latest guidance on the third phase.

The ASRM, though without the same infection spikes in the USA as seen in Europe, has also updated its COVID-19 recommendations to reaffirm the judicious delivery of reproductive care within a framework of careful preventive measures.(3) With COVID-19 case numbers still running high in the USA, the ASRM describes these measures as critical in managing this ongoing pandemic.

The worry for clinics back in Europe must be whether this second wave of infection becomes so critical in some countries that some centres might have to close once again. However, it now seems clear that the guidance on the resumption of routine treatments provided by ESHRE, the ASRM and other authorities has offered effective protocols for the safe provision of service. The paper from the ESHRE COVID-19 working group just published provides strong point-by-point evidence of that.(2) And it's on this basis that the UKs HFEA, for example, on 13 October reassuringly reported that with such professional guidelines in place a new national closure of fertility clinics should not be necessary. However, as ESHREs latest guidance notes, the HFEA also recognises that staff sickness or patient restrictions may yet force some clinics to close. Its likely that some countries may also requisition hospital beds for intensive care support.

Meanwhile, patients and staff may be further reassured by results from a case report from Spain in which two asymptomatic oocyte donors tested positive for SARS-CoV-2 infection before egg collection.(4) The eggs were subsequently donated for research for the presence of viral RNA. However, total RNA amplification from single cells of their vitrified-warmed oocytes failed to detect the presence of any viral RNA of SARS-CoV-2 in the cells. The authors thus concluded: Our report suggests that vertical transmission in these women may not occur through their oocytes during treatment, and that handling of this material in the clinical embryology laboratory may not constitute a hazard for healthcare professionals.

However, a meta-analysis just published in Nature Communications of 176 published cases of SARS-CoV-2 infections in neonates has found that the majority of them (around 70%) occurred postnatally, although vertical transmission may be possible in around 30% of the cases, either intrapartum or congenital.(6) Some 9% of these latter cases were actually confirmed as vertical infections. Just over half the infected neonates went on to develop COVID-19, while the rest were asymptomatic. One of the investigators, Daniele De Luca from the Antoine Beclere hospital in Paris, said that it was important for doctors to be aware that neonates can be born with the virus or contract it while in hospital. At the beginning of the pandemic, some argued that this would never touch babies, he reported. Its rare, but it does exist. Breastfeeding seemed not associated with SARS-CoV-2 infections, suggesting that viral transmission through the milk, if any, should be rare.

Further details on COVID-19 and pregnancy, including updates from ongoing registry studies, continue to be provided in detail by the UKs RCOG.(5)

1. See https://www.eshre.eu/covid19wg2. Gianaroli L, Ata B, Lundin K, et al. The calm after the storm: re-starting ART treatments safely in the wake of the COVID-19 pandemic. Hum Reprod 2020; doi.org/10.1093/humrep/deaa285.3. https://www.asrm.org/news-and-publications/news-and-research/?filterbycategoryid=214. Barragan M, Guilln JJ, Martin-Palomino N, et al. Undetectable viral RNA in oocytes from SARS-CoV-2 positive women. Hum Rep[rod 2020; doi.org/10.1093/humrep/deaa2845. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/coronavirus-pregnancy/6. Raschetti R, Vivanti AJ, Vauloup-Fellous C, et al. Synthesis and systematic review of reported neonatal SARS-CoV-2 infections. Nature Communications 2020; 11: 5164.

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ESHRE updates its fertility clinic guidance for second wave of infections - ESHRE