Preconception depression reduces fertility: a couple-based prospective preconception cohort.

STUDY QUESTION: Is preconception depression associated with time to pregnancy (TTP) and infertility? SUMMARY ANSWER: Couples with preconception depression needed a longer time to become pregnant and exhibited an increased risk of infertility. WHAT IS KNOWN ALREADY: Preconception depression in women contributes to impaired fertility in clinical populations. However, evidence from the general population-especially based on couples-is relatively scant. STUDY DESIGN SIZE DURATION: A couple-based prospective preconception cohort study was performed in 16 premarital examination centers between April 2019 and June 2021. The final analysis included 16 521 couples who tried to conceive for ≤6 months at enrollment. Patients with infertility were defined as those with a TTP ≥12 months and those who conceived through ART. PARTICIPANTS/MATERIALS SETTING METHODS: Couples' depression was assessed using the Patient Health Questionnaire-9 at baseline. Reproductive outcomes were obtained via telephone at 6 and 12 months after enrollment. Fertility odds ratios (FORs) and infertility risk ratios (RRs) in different preconception depression groups were analyzed using the Cox proportional-hazard models and logistic regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 16 521 couples analyzed, 10 834 (65.6%) and 746 (4.5%) couples achieved pregnancy within the first 6 months and between the 6th and 12th months, respectively. The median (P25, P75) TTP was 3.0 (2.0, 6.0) months. The infertility rate was 13.01%. After adjusting for potential confounders, in the individual-specific analyses, we found that preconception depression in women was significantly related to reduced odds of fertility (FOR = 0.947, 95% CI: 0.908-0.988), and preconception depression in either men or women was associated with an increased risk of infertility (women: RR = 1.212, 95% CI: 1.076-1.366; men: RR = 1.214, 95% CI: 1.068-1.381); in the couple-based analyses, we found that-compared to couples where neither partner had depression-the couples where both partners had depression exhibited reduced fertility (adjusted FOR = 0.904, 95% CI: 0.838-0.975). The risk of infertility in the group where only the woman had depression and both partners had depression increased by 17.8% (RR = 1.178, 95% CI: 1.026-1.353) and 46.9% (RR = 1.469, 95% CI: 1.203-1.793), respectively. LIMITATIONS REASONS FOR CAUTION: Reporting and recall bias were unavoidable in this large epidemiological study. Some residual confounding factors-such as the use of anti-depressants and other medications, sexual habits, and prior depressive and anxiety symptoms-remain unaddressed. We used a cut-off score of 5 to define depression, which is lower than prior studies. Finally, we assessed depression only at baseline, therefore we could not detect effects of temporal changes in depression on fertility. WIDER IMPLICATIONS OF THE FINDINGS: This couple-based study indicated that preconception depression in individuals and couples negatively impacts couples' fertility. Early detection and intervention of depression to improve fertility should focus on both sexes. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the National Natural Science Foundation of China (No. 82273638) and the National Key Research and Development Program of China (No. 2018YFC1004201). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study.

BACKGROUND: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. METHODS: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20-49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). RESULTS: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. CONCLUSION: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.