Potential role of viral infections in miscarriage and insights into the underlying molecular mechanisms

Heydarifard, Zahra; Zadheidar, Sevrin; Yavarian, Jila; Malekshahi, Somayeh Shatizadeh; Kalantari, Shirin; Mokhtari‐Azad, Talat; Shafiei-Jandaghi, Nazanin Zahra

doi:10.1111/cga.12458

Cited by 10 publications

(8 citation statements)

References 136 publications

(164 reference statements)

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“…The literature is inconsistent in terms of reporting an association between pregnancy loss and HSV-2. A recently published review discussed the possible role of HSV-2 in miscarriage ( 26 ). A conclusion about this conflict could be crucial to further aid patients going through fertility treatment to avoid any possible pregnancy loss.…”

Section: Discussionmentioning

confidence: 99%

Herpes simplex virus type 2 seroprevalence and associated factors in fertility-treatment-seeking population: A cross-sectional survey in the United Arab Emirates

Abdo

Aslam²,

Suliansyah³

et al. 2022

Front. Public Health

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BackgroundHerpes simplex virus type 2 (HSV-2) is a common genitally-transmitted viral infection affecting more than 400 million individuals globally. In the United Arab Emirates (UAE), in specific at-risk population groups, the burden of HSV-2 has not been reported. This study investigated the prevalence of HSV-2 IgG antibodies in patients seeking fertility treatment and characterized patients with seropositivity to HSV-2 IgG antibodies.MethodologyA cross-sectional sample of patients seeking fertility treatment in a major fertility clinic in Abu Dhabi, UAE was surveyed from April to May 2021. Patients were consecutively invited to complete self-administered questionnaires and provide blood for HSV-2 testing. Information on sociodemographics, medical history, and infertility was collected. Serum specimens were screened using an enzyme-linked immunosorbent assay for HSV-2 IgG antibodies detection.ResultsTwo hundred and ninety-nine patients were surveyed and provided blood samples. The mean age of the patients was 35.9 ± 6.8 [mean ± standard deviation (SD)] years with 89.3% being women. Sixty-six percent were overweight or obese, 25.0% had at least one chronic comorbidity, and 19.6% reported ever-had genital infection. More than two-thirds (68.3%) of the patients were infertile for ≥ 6 months. Of the 42 infertile males, 69.0% had an abnormal semen analysis. HSV-2 IgG antibodies was detected in 12.4% of patients. The HSV-2 IgG seropositive patients had a higher mean age (39.5 vs. 35.4 years; p < 0.001) compared to seronegative patients. HSV-2 IgG antibodies seropositivity was more common in males (15.6%) than females (12.0%), in patients with secondary (14.1%) vs. primary (9.2%) infertility, or in males with abnormal (10.3%) vs. normal (7.7%) semen.ConclusionExposure to HSV-2 at any time in patients seeking fertility treatment in the UAE was found to be slightly common in more than one out of 10 patients. Tailored health campaigns on HSV-2 prevention are warranted.

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Section: Discussionmentioning

confidence: 99%

Herpes simplex virus type 2 seroprevalence and associated factors in fertility-treatment-seeking population: A cross-sectional survey in the United Arab Emirates

Abdo

Aslam²,

Suliansyah³

et al. 2022

Front. Public Health

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“…Possible suggestions include utero-placental dysfunction predisposing some women to adverse fetal outcomes including early pregnancy loss and stillbirth 36 . Infections can increase risk of early pregnancy loss and stillbirth, infecting the fetus via the placenta 37 with many infections asymptomatic. Fetal chromosomal abnormalities are the most common cause of early pregnancy loss in the first trimester, accounting for 50% of non-recurrent pregnancy losses 38 , 39 .…”

Section: Discussionmentioning

confidence: 99%

Bias in the association between advanced maternal age and stillbirth using left truncated data

Dunne

Tessema

Pereira

2022

Sci Rep

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Restriction to analysis of births that survive past a specified gestational age (typically 20 weeks gestation) leads to biased exposure-outcome associations. This bias occurs when the cause of restriction (early pregnancy loss) is influenced by both the exposure and unmeasured factors that also affect the outcome. The aim of this study is to estimate the magnitude of bias resulting from left truncated data in the association between advanced maternal age and stillbirth. We simulated data for the causal pathway under a collider-stratification mechanism. Simulation parameters were based on an observed birth cohort from Western Australia and a range of plausible values for the prevalence of early pregnancy loss, unmeasured factor U and the odds ratios for the selection effects. Selection effects included the effects of maternal age on early pregnancy loss, U on early pregnancy loss, and U on stillbirth. We compared the simulation scenarios to the observed birth cohort that was truncated to pregnancies that survived beyond 20 gestational weeks. We found evidence of marginal downward bias, which was most prominent for women aged 40 + years. Overall, we conclude that the magnitude of bias due to left truncation is minimal in the association between advanced maternal age and stillbirth.

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“…There are a number of potential explanations for how pandemic mitigation measures could plausibly contribute to a modest decreased risk of miscarriage. For example, certain infectious diseases are associated with an increased risk of miscarriage 26 , and a reduced number of social contacts (as a result of pandemic restrictions) may have led to fewer infections (not only COVID-19) among pregnant women. It is also possible that pandemic restriction measures resulted in less physical stress, which again could have reduced women’s risk of miscarriage, although the impact on work-related physical strain on the risk of miscarriage is likely to be modest 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Behavioural measures indicated that the strict lockdowns of Denmark and Norway resulted in more drastic behavioural changes than in Sweden 24 . We hypothesized that the pandemic mitigation measures could plausibly decrease the risk of fetal death, as pregnant women were likely to have less exposure to infections 25 , 26 .…”

mentioning

confidence: 99%

Fetal death after the introduction of COVID-19 mitigation measures in Sweden, Denmark and Norway: a registry-based study

Magnus

Oakley

Hansen

et al. 2022

Sci Rep

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It remains unclear whether the rate of fetal death has changed during the COVID-19 pandemic. We assessed the impact of COVID-19 mitigation measures on fetal death in Sweden (449,347 births), Denmark (290,857 pregnancies) and Norway (261,057 pregnancies) using robust population-based registry data. We used Cox regression to assess the impact of the implementation of pandemic mitigation measures on March 12th, 2020, on miscarriage (fetal loss before gestational week 22) and stillbirth (fetal loss after gestational week 22). A total of 11% of 551,914 pregnancies in Denmark and Norway ended in miscarriage, while the proportion of stillbirths among 937,174 births across the three countries was 0.3%. There was no difference in the risk of fetal death during the year following pandemic mitigation measures. For miscarriage, the combined hazard ratio (HR) for Norway and Denmark was 1.01 (95% CI 0.98, 1.03), and for stillbirth, the combined HR for all three countries was 0.99 (95% CI 0.89, 1.09). We observed a slightly decreased risk of miscarriage during the first 4 months, with an HR of 0.94 (95% CI 0.90, 0.99) after lockdown. In conclusion, the risk of fetal death did not change after the implementation of COVID-19 pandemic mitigation measures in the three Scandinavian countries.

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Potential role of viral infections in miscarriage and insights into the underlying molecular mechanisms

Cited by 10 publications

References 136 publications

Herpes simplex virus type 2 seroprevalence and associated factors in fertility-treatment-seeking population: A cross-sectional survey in the United Arab Emirates

Herpes simplex virus type 2 seroprevalence and associated factors in fertility-treatment-seeking population: A cross-sectional survey in the United Arab Emirates

Bias in the association between advanced maternal age and stillbirth using left truncated data

Fetal death after the introduction of COVID-19 mitigation measures in Sweden, Denmark and Norway: a registry-based study

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