COVID-19: Impact on pregnancy outcomes and fertility
As of 16 June 2020, over 8 million people worldwide had been infected with coronavirus disease 2019 (COVID-19), including pregnant women. Dr Louis Chan, Specialist in Obstetrics & Gynaecology in private practice in Hong Kong, discusses the impact of COVID-19 on pregnancy outcomes and fertility, as well as the results of surveys showing low acceptance of gamete donation in Hong Kong.
Pregnancy and perinatal outcomes in women with COVID-19
Obstetric and perinatal outcomes were not favourable in pregnant women with severe acute respiratory syndrome (SARS), with one case series reporting a 25 percent mortality rate, 57 percent spontaneous miscarriage rate, and higher risks of intrauterine growth retardation and preterm delivery. [Am J Obstet Gynecol 2004;191:292-297] Similarly, outcomes of pregnant women infected with Middle East respiratory syndrome coronavirus (MERS-CoV) were also poor, with a mortality rate of 25 percent and mechanical ventilation rate of 41 percent. [Am J Obstet Gynecol 2020;222:521-531] Such poor outcomes could be attributed to physiological changes in pregnancy. Increases in oestrogen and progesterone levels in pregnancy cause thickening of upper respiratory tract mucosa, leading to mild congestion and oedema. The enlarged uterus also causes diaphragm elevation and limits lung expansion.
In contrast, data published so far suggest a much better prognosis in pregnant women with COVID-19 compared with SARS or MERS. In a systematic scoping review that included 385 pregnant women with COVID-19, disease severity was mild in 95.6 percent, severe in 3.6 percent, and critical in only 0.8 percent of cases, with one case of maternal death. [Int J Gynaecol Obstet 2020, doi: 10.1002/ijgo.13182] Another case series from the UK reported five deaths out of 427 pregnant women admitted for COVID-19; three of the deaths were a direct result of COVID-19 complications. [BMJ 2020, doi: 10.1136/bmj.m2107]
Similar to non-pregnant patients with COVID-19, cough and fever were the major symptoms. (Table) Of these 385 cases, 109 presented in the first or second trimester. Three women had spontaneous miscarriage, suggesting that miscarriage risk is not particularly high in women with COVID-19. [Int J Gynaecol Obstet 2020, doi: 10.1002/ijgo.13182]
Among 256 newborns (248 singletons and four twins), 15.2 percent were delivered preterm. The Caesarean section rate was 69.4 percent. There were two cases of stillbirth from mothers in critical condition and one case of neonatal death due to prematurity. [Int J Gynaecol Obstet 2020, doi: 10.1002/ijgo.13182]
Obstetricians should be aware that a pre-eclampsia (PE)-like syndrome may develop in pregnant women with severe pneumonia. In a prospective observational study of 42 pregnant women with COVID-19, six had elevated liver enzymes, proteinuria and hypertension. However, PE was ruled out in five of the women after assessment by uterine artery pulsatility index, placental growth factor and soluble fms-like tyrosine kinase-1 levels. Two women remained pregnant after recovery from pneumonia, with spontaneous resolution of all PE-like signs and symptoms. These data suggest that the PE-like clinical features are a consequence of COVID-19 infection. [BJOG 2020, doi: 10.1111/1471-0528.16339]
Vertical transmission of SARS-CoV-2 to newborns?
In the above systematic scoping review, four of the 256 newborns from COVID-19–infected mothers tested positive for the infection on real-time polymerase chain reaction (RT-PCR) assay after delivery. However, it is difficult to delineate whether the infection was vertically transmitted or acquired during or after delivery. [Int J Gynaecol Obstet 2020, doi: 10.1002/ijgo.13182]
Of note, three of the four newborns also tested positive for immunoglobulin M (IgM). While IgG can cross the placenta and reach the foetus, IgM is usually not transferred from the mother to the foetus due to its large macromolecular structure. The presence of IgM in the three newborns may be a consequence of placental damage caused by the infection, leading to placental transfer of IgM. However, one cannot exclude the possibilities of the virus crossing the placenta and the foetus producing IgM in response to the infection. [JAMA 2020;323:1848-1849]
In the UK series, 12 newborns (5 percent) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, with six of the newborns testing positive within 12 hours of delivery. Given the short time from delivery to testing, the authors raised concern of the possibility of mother-to-infant vertical transmission. However, with no information on whether the newborns were isolated from their mother after delivery or whether skin-to-skin contact was permitted, it is difficult to delineate how these newborns acquired the virus. [BMJ 2020, doi: 10.1136/bmj.m2107]
While all samples of cord blood (n=30), amniotic fluid (n=23), placenta (n=12) and breast milk (n=26) from the above 385 infected mothers tested negative for SARS-CoV-2, a more recent study of 11 placental or membrane swabs from 32 infected pregnant women showed positive PCR results in one placental swab and two membrane swabs. Therefore, the possibility of vertical transmission of SARS-CoV-2 cannot be ruled out. [Int J Gynaecol Obstet 2020, doi: 10.1002/ijgo.13182; Am J Obstet Gynecol MFM 2020, doi: 10.1016/j.ajogmf.2020.100133]
COVID-19 screening in pregnant women
Radiographic imaging is an essential part of assessment for suspected COVID-19 cases. Pregnant women are often concerned about the effect of radiation on the developing foetus. High-dose radiation (>610 mGy) is associated with foetal growth restriction, microcephaly and intellectual disability. However, the radiation dose to the foetus is only about 0.0005–0.01 mGy if a pregnant woman undergoes a chest X-ray, and only about 0.01–0.66 mGy with chest CT, which should serve to reassure expectant mothers in need of screening. [Review Ultrasound Obstet Gynecol 2020, doi: 10.1002/uog.22088]
Many pregnant women with COVID-19 are asymptomatic. In one study, 19.9 percent of women admitted to a labour ward screened positive for COVID-19, but 66 percent of the positive women had no symptoms. [Am J Obstet Gynecol 2020, doi: 10.1016/j.ajog.2020.04.024] In another report, 32.6 percent of pregnant women with test-confirmed COVID-19 were asymptomatic. [Am J Obstet Gynecol MFM 2020, doi: 10.1016/j.ajogmf.2020.100118]
In areas with large number of COVID-19 cases, screening of pregnant women before delivery should be considered for precautions to be taken to prevent transmission from asymptomatic mothers to newborns.
Impact of COVID-19 on male fertility
SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) receptors to gain entry into human cells, and ACE2 is expressed in the testis, ovary and endometrium. Despite early reports suggesting that semen from infected men is virus free, a recent study found SARS-CoV-2 in semen of 15.8 percent of men with confirmed COVID-19. Notably, SARS-CoV-2 was detected in semen of 26.7 percent of men at an acute stage of infection vs 8.7 percent in those who were recovering. [JAMA Netw Open 2020, doi: 10.1001/jamanetworkopen.2020.8292] These results suggest a possibility of SARS-CoV-2 transmission via sexual intercourse.
In another study, researchers examined the testes of 12 men who died from COVID-19 and found seminiferous tubular injury as well as a reduction in Leydig cells. These results suggest that SARS-CoV-2 can cause significant damage to the testes. [European Urology Focus 2020, doi: 10.1016/j.euf.2020.05.009]
Sperm quality appears to be impaired in COVID-19–infected individuals compared with controls. In a study that compared semen parameters in patients with mild or moderate COVID-19 vs controls, total sperm number and total motile sperm number were 19 times and 42 times lower, respectively, in patients with moderate COVID-19 vs controls. In patients with mild disease, semen parameters were comparable vs controls. The authors concluded that while testicular and epididymal function appeared unaffected in patients with mild infection, there was indeed an adverse effect in patients with moderate COVID-19. [Fertil Steril 2020, doi: 10.1016/j.fertnstert.2020.05.028]
At present, the effect of SARS-CoV-2 on oocytes, the uterus or endometrium is unknown.