A joint statement from ESHRE, ASRM and IFFS in explaining their support for resumed fertility treatment reaffirms a need for data collection to monitor the effects of COVID-19 infection in pregnancy.
Three of the world's leading organisations in reproductive medicine - ESHRE, ASRM and IFFS - have issued a joint statement explaining their support for a resumption of routine fertility treatment during this coronavirus pandemic.(1) Describing the continuation of care as 'important' for personal well-being and national fertility rates, the three societies are now behind a 'gradual and judicial' return to a full programme of treatments.
In early March, as the coronavirus infection curve climbed steeply, both ESHRE and ASRM advised - controversially to some - the closure of fertility clinics. The initial precautionary explanation from both societies was the unknown effect of COVID-19 on pregnancy, but within a few weeks this reasoning had moved on to include the consolidation of healthcare resources. However, by 23 April ESHRE in its updated guidance recognised 'a need to restart the provision of ART treatments' and set out a detailed scheme of staff and patient triage to prevent infection. By 11 May ASRM too had reaffirmed its support of resumed treatments, with recommendations for schemes of risk assessment and risk mitigation, emergency planning, and effective use of limited resources.
Now, the joint statement from ESHRE, ASRM and IFFS, issued on 29 May, provides a rationale for those positions and a ten-point list of recommendations during this resumption.
However, the statement also makes clear that knowledge on the effect of the virus on reproductive cells, pregnancy and newborns remains limited, and that the three societies are committed to collecting data on pregnancy and birth during the pandemic. One example cited is the ASPIRE (Assessing the Safety of Pregnancy In the CoRonavirus PandEmic) study organised by the University of California San Francisco to monitor the effects of COVID-19 during pregnancy (spontaneous or ART) in US hospitals, particularly during the first trimester.(2) ESHRE too has put in place a survey among its members to collect data and monitor pregnancy in COVID-19 positive women.
There have now been several studies monitoring such pregnancies, some dating back to the early stages of the pandemic in China, but few are population-based. For example, a small review of nine pregnant women positive for COVID-19 admitted to a Wuhan hospital in January concluded that their clinical characteristics were comparable to non-pregnant cases, with no evidence of intrauterine transmission.(3) That reassuring finding has been echoed in several later reviews and guidance statements, the latest of which (from WHO on 27 May) reports no known difference between the clinical manifestations of COVID-19 infection in pregnant and non-pregnant women.(4)
Later, a systematic review of 108 COVID-19-confirmed pregnancies in studies and case reports (most from China) published up to 1 April found that most mothers were discharged after delivery 'without any major complications', although severe virus-associated morbidity was reported in some.(5) The cases had commonly presented with a fever at admission (68%) and persistent, dry cough (34%). There were, however, isolated cases of maternal and perinatal complications, with a high rate (91%) of cesarean delivery. Only one of 75 newborns tested positive for COVID-19. 'From these findings,' the authors wrote, 'we cannot exclude that the fetus and newborn baby might show a response, often sub‐clinical, to the mother’s infection and, thus, vertical maternal‐fetal transmission cannot be ruled out.'(6) More recently still, a case report posted on 5 May to the preprint server medRxiv.com described the 'for the first time, SARS-CoV-2 invasion of the placenta' in a second trimester pregnancy, highlighting, say the authors, 'the potential for severe morbidity among pregnant women with Covid-19'.(7)
While studies are now ongoing to plot the characteristics and course of COVID-19 infection in pregnancy, the largest cohort study would appear to be from the UK's Obstetric Surveillance System, which in its latest report provides data on 427 COVID-19-confirmed pregnancies admitted to all 194 obstetrics units in the UK (up to 14 April).(8) This study, originally posted to medRxiv.com but now published, estimated an incidence of hospitalisation with confirmed COVID-19 in pregnancy of 4.9 per 1000, with a median gestation at symptom onset of 34 weeks. Minority ethnicity, older maternal age, overweight and pre-existing comorbidities were all associated with infection during pregnancy. Indeed, more than half these admissions (56%) were from black or other ethnic minority groups. About one in 10 of those admitted required respiratory support, and 12% were delivered preterm solely because of maternal respiratory compromise. Of the 243 women who had given birth, 74% did so at term, 59% by cesarean section, although the majority of these were for indications other than COVID-19. Most women, however, 'had good outcomes'.
The authors also describe neonatal outcomes as 'largely reassuring', although 2% of infants did have evidence of viral RNA on a sample taken within 12 hours of birth, 'which suggests that vertical transmission may be occurring', say the authors. This, they add, remains one of many 'unanswered questions', and emphasises the need - as ESHRE, ASRM and IFFS propose - for ongoing data collection. So far, conclude the authors, 'these data suggest that the majority of women do not have severe illness and that transmission of infection to infants of infected mothers may occur but is uncommon'.
And this was a similar conclusion to that made after a study of 215 pregnant women at a single New York hospital; 29 of the 33 patients who were positive for SARS-CoV-2 at admission had no symptoms at presentation.(9) With asymptomatic and mild infection the most apparent presentation, effects on obstetric and neonatal complications will need time and data to clarify - and comparison with populations of non-infected pregnancies. Such efforts will also need wholesale commitments, and the collective determination of three leading societies will now add great weight to those efforts.
1. See https://www.eshre.eu/Press-Room/ESHRE-News#COVID19Joint
2. See https://aspire.ucsf.edu
3. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020; 395: p809-815. doi: https://doi.org/10.1016/S0140-6736(20)30360-3
4. See https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected
5. Zaigham M, Andersson O. Maternal and perinatal outcomes with COVID‐19: A systematic review of 108 pregnancies. Acta Obstet Gynecol Scand 2020; doi: 10.1111/aogs.13867
6. Zeng L, Xia S, Yuan W, et al. Neonatal early‐onset infection with SARS‐CoV‐2 in 33 neonates born to mothers with COVID‐19 in Wuhan, China. JAMA Pediatr 2020.
7. Hosier H, Farhadian S, Morotti R, et al. SARS-CoV-2 infection of the placenta. https://www.medrxiv.org/content/10.1101/2020.04.30.20083907v3
8. Knight M, Bunch K, Vousden N, et al. Characteristics and outcomes of pregnant women hospitalised with confirmed SARS-CoV-2 infection in the UK: a national cohort study using the UK Obstetric Surveillance System (UKOSS). BMJ 2020; 369: m2107 doi.org/10.1136 bmj.m2107
9. Sutton D, Fuchs K, D'Alton M, Goffman D. Universal screening for SARS-CoV-2 in women admitted for delivery. N Engl J Med 2020; 382: 2163-2164. doi: 10.1056/NEJMc2009316