key: cord-1048522-6btnbyus
authors: Kyriacou, C.; Cooper, N.; Robinson, E.; Parker, N.; Barcroft, J.; Kundu, S.; Letchworth, P.; Sur, S.; Gould, D.; Stalder, C.; Bourne, T.
title: Ultrasound characteristics, serum biochemistry and outcome of ectopic pregnancies presenting during COVID‐19 pandemic
date: 2021-12-01
journal: Ultrasound Obstet Gynecol
DOI: 10.1002/uog.24793
sha: 13d248666b20705e405e9dd8c535fffd6340ee99
doc_id: 1048522
cord_uid: 6btnbyus

OBJECTIVE: To describe and compare the characteristics of ectopic pregnancies (EPs) in the year prior to vs during the coronavirus disease 2019 (COVID‐19) pandemic. METHODS: This was a retrospective analysis of women diagnosed with an EP on transvaginal sonography conducted at a center in London, UK, providing early‐pregnancy assessment, between 1 January 2019 and 31 December 2020. Women were identified via the Astraia ultrasound reporting system using coded and non‐coded outcomes of EP or pregnancy outside the uterine cavity. Data related to predefined outcomes were collected using Astraia and Cerner electronic reporting systems. Main outcome measures included clinical, ultrasound and biochemical features of EP, in addition to reported complications and management. RESULTS: There were 22 683 consultations over the 2‐year period. Following consultation, a similar number and proportion of EPs were diagnosed in 2019 (141/12 657 (1%)) and 2020 (134/10 026 (1%)). Both cohorts were comparable in age, ethnicity, weight and method of conception. Gestational age at the first transvaginal sonography scan and at diagnosis were similar, and no difference in location, size or morphology of EP was found between the two cohorts. Serum human chorionic gonadotropin (hCG) levels at the time of EP diagnosis were higher in 2020 than in 2019 (1005 IU/L vs 665 IU/L; P = 0.03). The proportions of women according to type of final EP management were similar, but the rate of failed first‐line management was higher during vs before the pandemic (16% vs 6%; P = 0.01). The rates of blood detected in the pelvis (hemoperitoneum) on ultrasound (23% vs 26%; P = 0.58) and of ruptured EP confirmed surgically (9% vs 3%; P = 0.07) were similar in 2019 vs 2020. CONCLUSIONS: No difference was observed in the location, size, morphology or gestational age at the first ultrasound examination or at diagnosis of EP between women diagnosed before vs during the COVID‐19 pandemic. Complication rates and final management strategy were also unchanged. However, hCG levels and the failure rate of first‐line conservative management measures were higher during the pandemic. Our findings suggest that women continued to access appropriate care for EP during the COVID‐19 pandemic, with no evidence of diagnostic delay or an increase in adverse outcome in our population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) a global pandemic in March 2020, having both direct and indirect impacts on UK healthcare provision. Emergency department attendance was reduced by 25% in the first week following government-imposed lockdown 1, 2 . The British Medical Association estimated that there were 1.32-1.50 million fewer elective hospital admissions in April, May and June 2020, with planned services in May 2020 operating at 31% of the preceding 2018-2019 average 2, 3 .

Both the Royal College of Obstetricians and Gynaecologists (RCOG) and the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) developed guidelines that aimed to rationalize early pregnancy and gynecological ultrasound service provision during the COVID-19 pandemic. Both advised that a scan should be carried out within 24 h for women with risk factors or symptoms associated with ectopic pregnancy (EP) [4] [5] [6] . In the event of an EP diagnosis, conservative management strategies were encouraged to minimize exposure to hospitals 4 . Surgery was recommended when no other management option was feasible 4, 7 . For all patients, a policy of telephone triage was introduced in the UK before women were able to access a hospital for the assessment of early-pregnancy problems.

There are concerns that a fear of attending hospital due to the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may have led women to delay accessing care for early pregnancy and acute gynecological problems. Findings from Italy and Israel suggest higher rates of surgery, ruptured EP and blood loss in women with EP during vs before the COVID-19 pandemic [8] [9] [10] . In New York, USA, 83% of women with EP presenting to an emergency department during the first wave of the pandemic were hemodynamically unstable, requiring urgent surgical intervention, compared with 23.5% in the previous year 11 . From an obstetric perspective, delayed presentation to the emergency department and subsequent increase in the number of emergency interventions secondary to the pandemic have been described 12 .

We aimed to describe and compare the characteristics of EPs presenting to an early-pregnancy assessment center in Inner London, UK, during vs before the COVID-19 pandemic.

This retrospective observational cohort study was performed at a dual center providing early-pregnancy and acute gynecological services in Northwest London, UK. All cases of EP for this study were identified on transvaginal sonography (TVS).

Relevant case records were identified via a search of the Astraia™ (Astraia Software GmbH, Ismaning, Germany) database over a 2-year period from 1 January 2019 to 31 December 2020, encompassing the time period prior to and during the COVID-19 pandemic, when the structure of our service was adapted according to national and international recommendations 4-6 . Search terms included a coded or non-coded diagnosis of EP or pregnancy outside the uterine cavity. Heterotopic pregnancies were included. Pregnancies were dated according to the last menstrual period or embryo transfer date.

Electronic case records were reviewed, and information related to predefined outcome measures was recorded as part of this retrospective analysis. The manuscript was written in accordance with the STROBE cohort study statement. The evaluated time period prior to the COVID-19 pandemic was between January 2019 and December 2019, and the time period during the COVID-19 pandemic was between January 2020 and December 2020.

In addition to delaying non-essential appointments, reducing follow-up appointments and reducing surgical management of miscarriage and EP, telephone triage was performed to rationalize service provision, in accordance with RCOG and ISUOG COVID-19 guidelines 4-6 . Measures were in place from January 2020 onwards, with the most stringent implementation between April 2020 and September 2020.

Month of diagnosis, age, ethnicity, weight, mode of conception, gestational age at first TVS scan and at diagnosis, obstetric history, morphological and biochemical features of EP, admission and management were recorded.

Continuous data were assessed for normality using the D'Agostino-Pearson normality test. If data were distributed normally, a two-tailed t-test was performed, assuming both populations had similar SD. Normally distributed data are presented as mean with 95% CI. If data were not distributed normally, a two-tailed Mann-Whitney U-test was performed to compare ranks. Data with non-normal distribution are presented as median and interquartile range (IQR). Given the nature of the dataset and the study question, data were not paired.

Categorical data were analyzed using Fisher's exact test when comparing one or two variables and using chi-square test when comparing more than two variables. These data are presented as n (%). Statistical analysis was carried out using GraphPad Prism v8.2.1 (GraphPad Software, San Diego, CA, USA). A P-value < 0.05 indicated statistical significance.

Ethical approval and written consent were not required, as this study involved retrospective review of case notes. As such, it was performed as a local clinical audit, as it was designed to produce information to inform on whether delivery of care was affected by the COVID-19 pandemic. Audit approval was obtained, local registration number GRM_071.

There were 21% fewer early-pregnancy and acute gynecological consultations during the COVID-19 pandemic compared to the previous year, with 12 657 consultations in 2019 compared to 10 026 in 2020 (Table 1 ). All consultations were face-to-face. The ratio of new (52%) to follow-up (48%) consultations was the same in both years (P = 0.88), with a lower proportion of blood tests performed in 2019 (2222 (18%)) vs 2020 (2184 (22%)) (P < 0.0001). There was no difference between 2019 and 2020 in the rates of miscarriage (18% vs 20%), pregnancy of unknown location (PUL) (7% vs 7%) or EP (1% vs 1%) observed in the unit (P = 0.38).

A total of 275 EPs were diagnosed in the 2-year period, including 141 (51%) cases in 2019 and 134 (49%) cases in 2020 (Table S1 ). Thirteen (9%) EP patients did not complete follow-up in 2019, and nine (7%) did not complete follow-up in 2020 (Table 1) .

Women with EP diagnosed prior to and during the pandemic were comparable in age (mean (95% CI), (7) Data are given as n (%) or n/N (%), unless indicated otherwise. P-values were calculated using: *Fisher's exact test; or †chi-square test. PUL, pregnancy of unknown location. Table 2 ). Method of conception was similar in 2019 vs 2020, with 126 (89%) vs 118 (88%) women conceiving naturally and 15 (11%) vs 16 (12%) women having assisted conception (P = 0.85). The majority of EP cases in both 2019 (89 (63%)) and 2020 (78 (58%)) were diagnosed on the first TVS examination, with the remainder having been classified initially as PUL in both groups (52 (37%) vs 56 (42%); P = 0.46).

Thirteen (9%) patients in 2019 had a history of EP compared with 14 (10%) cases in 2020 (P = 0.84), with the majority having undergone surgical management ( Table 3 (Table 3 and Figure 1a ,b). Both in 2019 and in 2020, most women had tubal EP (90% vs 93%; P = 0.67) ( Table 3) , with non-tubal cases including cornual, interstitial, myometrial, ovarian, cervical and Cesarean scar pregnancies. Figure 2 ). This difference in median (IQR) serum hCG levels between 2019 and 2020 was also observed when comparing only cases with tubal EP (603 (182-2216) vs 952 (411-2544) IU/L; P = 0.03) ( Table 3) . 0.03 ¶ Data are given as n (%), n/N (%), n or median (interquartile range). *Gestational age (GA) data at transvaginal sonography (TVS) were missing for 12 cases in 2019 and eight cases in 2020. †EP diameter data were missing in two cases in 2019 and five cases in 2020. ‡Human chorionic gonadotropin (hCG) level data were missing in two cases in 2019 and five cases in 2020. P-values were calculated using: §Fisher's exact test; ¶Mann-Whitney U-test; or **chi-square test. GS, gestational sac; YS, yolk sac. Year

Year

Year Year 

Similar proportions of EPs were admitted for secondary care during vs before the COVID-19 pandemic (58% vs 63%; P = 0.46). There were significant differences between 2019 and 2020 when comparing the planned treatment strategy, with conservative management planned in 74 (52%) vs 85 (63%) cases and surgery planned in 66 (47%) vs 46 (34%) cases (P = 0.049) ( Table 4) . However, the final type of EP management was similar prior to and during the pandemic, with the majority of patients undergoing surgical intervention (52% in 2019 and 49% in 2020; P = 0.49) ( Table 4 ). Prior to the pandemic, 28% of EPs were managed expectantly, whilst 20% were managed medically with methotrexate. These rates were similar to those during the pandemic (P = 0.49), with 24% of EPs managed expectantly and 25% managed medically. Median hCG levels at the time of EP diagnosis in patients who were treated successfully using conservative measures were similar in 2019 and 2020 (expectant management: 219.0 vs 312.0 IU/L; P = 0.32, medical management: 815.5 vs 847.5 IU/L; P = 0.54) ( Table 4 ).

More women required further treatment following failure of first-line management in 2020 compared with 2019 (16% vs 6%; P = 0.01). Median hCG levels at the time of EP diagnosis in women undergoing surgical intervention were lower in 2019 than in 2020 (1571.0 vs 2664.0 IU/L; P = 0.01). The rate of ruptured EP confirmed surgically was similar between 2019 and 2020 (9% vs 3%; P = 0.07) ( Table 4 ). 

In 2020, 60% of women admitted for secondary care underwent SARS-CoV-2 polymerase chain reaction testing and obtained a negative result, while 40% were not tested (Table S2) . Most women (88%) were not self-isolating at the time of admission; the remainder were admitted elsewhere or had missing details regarding self-isolation. No cases that were managed as outpatients or admitted locally experienced management delay due to the pandemic.

We found no difference in the mode of conception, gestational age at the first TVS examination and at diagnosis, location, size and morphology on ultrasound of EPs diagnosed in the year before vs during the COVID-19 pandemic. The rates of pregnancy complications and secondary-care admissions and the proportion of patients managed conservatively and surgically were also similar between the two cohorts. Among patients who underwent surgical management, the levels of serum hCG at diagnosis were higher during the pandemic compared to the year before the pandemic. Although the proportions of patients undergoing each management strategy were similar between the two years, we observed a reduction in the success of conservative management strategies during the COVID-19 pandemic. No woman with EP managed as an outpatient or admitted locally experienced management delay due to the pandemic. Although there were fewer patient visits in 2020 than in 2019, the number of new and follow-up face-to-face consultations, loss to follow-up and rates of early-pregnancy complications were similar.

The main strength of this study is the relatively large number of women with EP included, allowing appropriate detailed comparison of multiple outcome measures. The inclusion of patients from an Inner London center ensured that the cohort studied was diverse and the findings were more likely to be generalizable to a wider population. The identification of cases by electronic means reduced the possibility of any EP case not being included in the final analysis. This is reflected by the fact that, for many outcome measures, few data were missing.

The key weakness of the study was its retrospective nature, as the true impact of the COVID-19 pandemic may not be captured completely in the electronic notes. Another limitation is that this was a descriptive study.

We expected to find that women with EP presented later and with a higher rate of pregnancy complications, such as ruptured EP, during the pandemic. However, this hypothesis is not supported by the findings of this study. Our findings are also in contrast to those of the currently available literature on the impact of the COVID-19 pandemic on EP diagnosis and management, in which it has been suggested that hesitancy amongst patients in accessing healthcare resources led to an increase in the rates of surgery, ruptured EP, blood loss and hemodynamic instability [8] [9] [10] [11] [12] [13] .

For women attending early-pregnancy assessment, a recent report suggested a 25% increase in the proportion of those with a diagnosis of miscarriage during the COVID-19 pandemic. This may reflect effective triage, with priority being given to those with complications 14 . Although virtual clinics were not implemented, telephone triage rationalized service provision, reducing patient visits during the pandemic. As all women with heavy bleeding or abdominal or pelvic pain were invited for prompt review, similar proportions of miscarriage, PUL and EP were reported 4 . However, even with rationalization measures in place, women were keen to avoid hospital settings 1-6 due to the risk of contracting SARS-CoV-2 infection.

In the UK, the average ratio of new to follow-up consultations in an early pregnancy unit has been reported 15 to be 1.88:1. Our prepandemic ratio of 1.1:1 reflects the greater number of follow-up consultations associated with having several second-opinion referrals, conservative miscarriage and EP management and use of a two-visit mathematical model for PUL. Perhaps, most relevant is our unit policy of allowing relatively liberal access to follow-up for patients, as we believe this may help ameliorate some of the known psychological sequelae of early-pregnancy complications [16] [17] [18] [19] [20] [21] [22] .

During the pandemic, although we reduced the number of visits in 2020, a considerable number of low-risk women would have had follow-up under normal circumstances. As higher-risk patients continued to attend, our new-to-follow-up consultations ratio remained relatively unchanged compared to that before the pandemic.

The detection rates of EP on the first TVS scan in this study were lower than those reported in the literature 23 . This is likely due to variation in staffing, scanning protocols and sonographer expertise within our training unit. Reductions in staffing due to shielding during the pandemic is likely to explain why the initial detection rate was slightly lower in 2020.

Although we found no difference in the ultrasound features of EP in women diagnosed during the pandemic compared to those diagnosed in the preceding year, serum hCG levels were higher in the former group. Single measurements of serum hCG are generally unhelpful when evaluating PUL, but higher levels are associated with an increased risk of failure of conservative management strategies 24 . This is reflected by the higher failure rate of first-line management strategies during the pandemic observed in this study and may suggest that the current use of serum hCG levels as a marker of likely success of conservative management has some merit.

The rapid changes in guidance for the management of early pregnancy complications as a result of the COVID-19 pandemic encouraged our increased use of conservative management. However, adopting more liberal inclusion criteria appears to have been associated with an increase in the failure rate of first-line management [4] [5] [6] in 2020. Although the proportions of patients according to the final management type were similar between those diagnosed before and during the pandemic, conservative management was recommended initially to more women in 2020 than in 2019. As conservative management failed in some of these women, a similar proportion underwent surgery as a final treatment in both years.

We found that the overall number and proportion of EPs diagnosed following assisted conception were similar in both years studied. However, when assessing the data more closely, there were no EP cases following fertility treatment in April, May or June 2020. This is consistent with the British Fertility Society guidance at that time 25 , which advised ceasing assisted conception services from mid-March to mid-May 2020. Similar overall numbers of EP cases following assisted conception in both years probably reflects fertility services increasing their capacity in order to deal with the backlog of cases once they reopened.

Our observations suggest that the guidance implemented to rationalize early-pregnancy care reduced attendances, with no evidence of women with EP being unable to access care in a timely and safe way. Although conservative management was encouraged, in our unit, this was associated with an increase in failure of this approach. Whilst our findings suggest that early-pregnancy care can be rationalized in the event of a healthcare emergency, such as the COVID-19 pandemic, this does not necessarily mean that the cancelled visits were unnecessary. Whilst rationing appointments was not associated with physical harm, it is important to acknowledge the psychological impact of early-pregnancy complications and the support and reassurance many women feel when attending consultation with what may appear to be relatively minor problems.

The following supporting information may be found in the online version of this article:

Breakdown of ectopic pregnancy diagnosis by year and month, with associated statistical tests and missing data documentation Table S2 SARS-CoV-2 testing, self-isolation at the time of admission and delays in ectopic pregnancy management during the COVID-19 pandemic

Implications for the future of Obstetrics and Gynaecology following the COVID-19 pandemic: a commentary

Covid-19: A&E visits in England fall by 25% in week after lockdown

The hidden impact of COVID-19 on patient care in the NHS in England

Guidance for rationalising early pregnancy services in the evolving coronavirus (COVID-19) pandemic. Information for healthcare professionals

ISUOG Consensus Statement on rationalization of early-pregnancy care and provision of ultrasonography in context of SARS-CoV-2

ISUOG Consensus Statement on rationalization of gynecological ultrasound services in context of SARS-CoV-2

Expectant care versus surgical treatment for miscarriage

Increased rate of ruptured ectopic pregnancy in COVID-19 pandemic: analysis from the North of Italy

Increase rate of ruptured tubal ectopic pregnancy during the COVID-19 pandemic

Delayed presentation of ectopic pregnancy during the COVID-19 pandemic: A retrospective study of a collateral effect

Change in ectopic pregnancy presentations during the Covid-19 pandemic

Changes in the obstetrical emergency department profile during the COVID-19 pandemic

Study of impact of COVID-19 infection on ectopic pregnancy in a tertiary care center

Increased first-trimester miscarriage during the COVID-19 pandemic

Variations in the organisation of and outcomes from Early Pregnancy Assessment Units: the VESPA mixed-methods study

Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta-analysis

Triaging women with pregnancy of unknown location using two-step protocol including M6 model: clinical implementation study

External validation of models to predict the outcome of pregnancies of unknown location: a multicentre cohort study

Post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy: a prospective cohort study

The psychological impact of early pregnancy loss

Posttraumatic stress, anxiety and depression following miscarriage and ectopic pregnancy: a multicenter, prospective, cohort study

Differences in post-traumatic stress, anxiety and depression following miscarriage or ectopic pregnancy between women and their partners: multicenter prospective cohort study

The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy

Diagnostic accuracy of varying discriminatory zones for the prediction of ectopic pregnancy in women with a pregnancy of unknown location

British Fertility Society (BFS) U.K. best practice guidelines for reintroduction of routine fertility treatments during the COVID-19 pandemic

We acknowledge all the staff working in early pregnancy at Imperial College Healthcare NHS Trust, London, UK, with particular thanks to our specialist nurse sonographers, Maeve Tuomey and Lorraine Howell.C.K. is supported by Imperial Health Charity based at Imperial College Healthcare NHS Trust, London, UK, grant number RFPrD1920/116. T.B. is supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Center based at Imperial College Healthcare NHS Trust and Imperial College London, UK, grant number IS-BRC-1215-20013. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.