| Abstract: | Study question: Whether oxidative/nitrative stress biomarkers increased the risk of recurrent pregnancy loss (RPL)? Summary answer: Patients with higher oxidative/nitrative stress biomarkers of 8-NO2Gua and HNE-MA had an increased risk of recurrent pregnancy loss compared with controls. What is known already: In reproductive medicine, recurrent pregnancy loss (RPL) is a major problem including the most unknown and lack of evidence-based diagnostics and therapies. Certain oxidative stress markers play an important role in the progress of some diseases. In one study, subsequent increases in 8-OHdG levels in the RPL group indicated extensive DNA damage and the lipid peroxidation products dramatically increased before an abortion occurred. Large unknowns of other indicators of oxidative stress, such as markers of lipid peroxidation (8-isoPF 2a, HNE-MA, and MDA), and DNA damage (8-NO2Gua), are studied for their impacts on RPL. Study design, size, duration: We used an established case-control study, the Taiwan Recurrent Pregnancy Loss and Environmental Study (TRIPLES), which included 514 reproductive age (20-50) women (including 397 cases and 117 controls) from obstetric clinics at National Cheng Kung University Hospital in southern Taiwan from 2013 to 2022. Participants/materials, setting, methods: The physicians diagnosed two or more consecutive miscarriages before 20 weeks of pregnancy as RPL cases. They excluded uterine anomalies, maternal diseases, chromosomal abnormalities, polycystic ovarian syndrome (PCOS), premature ovarian failure, and endometriosis. As a control group, we included married women, who delivered at least one child without artificial reproduction, underwent laparotomy for other clinical reasons, and did not suffer from the above-mentioned gynecological diseases. Main results and the role of chance: Recurrent pregnancy loss (RPL) groups were older (mean¼35.13) and had more time to prepare for pregnancy (mean¼10.66 months). Their marital status mainly was married, their household income exceeded around 33,000 USD, and they consumed coffee habits. The median oxidative/nitrative stress biomarkers of 8-NO2Gua and HNE-MA in the case group were significantly higher than those in the control group (6.15 and 30.12 vs. 3.77 and 21.54 ug/L, p<0.001), indicating that the oxidative stress biomarkers of 8-NO2Gua and HNE-MA could be an essential effect factor in RPL. By categorizing the data by tertile of oxidative/nitrative stress biomarkers, we found that the RPL risk was 3.19 times higher in the third tertile of log 8-NO2Gua than in the first tertile (OR: 3.19, 95% CI: 1.66–6.10) and that the RPL risk in log HNE-MA was higher in the third tertile (OR: 2.05, 95% CI: 1.12–3.74). After adjustment for age, time to pregnancy (months), and coffee drinking habits, the RPL risk in the third tertile of log 8-NO2Gua was 2.01 times significantly higher than that in the first tertile (AOR: 2.01, 95% CI: 1.00–4.04). Limitations, reasons for caution: Limitation of a case-control study. The oxidative stress biomarkers 8-NO2Gua and HNE-MA were significantly higher in the RPL groups, however, the causes of oxidative stress (like multiple environmental exposures, etc.) remain more studies to elucidate. Wider implications of the findings: We provided evidence for oxidative/ nitrative stress biomarkers in RPL patients, which implies the reduction of oxidative/nitrative stress may improve the progress of RPL. As important information for preventive medicine, more studies are needed to understand the adverse outcome pathway of oxidative/nitrative stress in RPL. |
