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Associations of parental age, socioeconomic status, antral follicle count with assisted reproductive technology treatment outcomes

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Abstract
Introduction: Infertility is recognized as a global public health priority, and Assisted Reproductive Technology (ART) serves as an effective treatment for this issue. It is unclear whether advanced parental age, low socio-economic status (SES), and antral follicle count (AFC) are significantly and independently associated with adverse ART outcomes. There is little known about their interaction effects with an unhealthy lifestyle on adverse ART outcomes. This PhD study investigated the associations of parental age, SES and AFC with implantation failure (IF), miscarriage and preterm birth (PB) using ART treatment. Methods: The Anhui Maternal Child Health Cohort Study (AMCHS) was conducted to explore risk factors for IF, miscarriage and PB. The studied population were those infertile couples who received ART treatment at the First Affiliated Hospital of Anhui Medical University, located in Anhui Province, China during the period of 1st May 2017 to 31st December 2020. The AMCHS consecutively recruited 1910 couples for IF analysis, 1082 remained for miscarriage analysis and 1035 couples for PB analysis. Implantation failure was defined as the inability to detect serum β-HCG levels ranging from 0 to 25 IU/L on the 14th day after embryo transfer surgery, followed by the absence of fetal sac on the 30th day after the embryo transfer surgery. Miscarriage was defined as detecting serum β-HCG between ≥ 25 IU/L on day 14 after embryo transfer surgery but failed to detect fetal cardiac activity through ultrasound prior to 22 complete weeks of gestation. Preterm is defined as babies born alive before 37 weeks of pregnancy are completed. Multivariable logistic regression models were used for data analysis, and the interaction effects were tested. Results: The mean age of the female participants was 30.9 years (SD 4.3), ranging from 20 to 47 years, while the mean age of the male participants was 32.3 years (SD 5.1), with a range of 23 to 57 years. A linear association was found between maternal age and both IF (multiple adjusted odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.09) and miscarriage (OR 1.11, CI 1.02-1.20), though no significant association was observed for preterm birth (PB) (OR 1.05, CI 0.97-1.12). Analysis across age groups (20-<25, 25-<30, 30-<35, 35-<40, and 40-47 years) also revealed significant associations with IF and miscarriage, but not with PB. There was no observed linear association between paternal age and adverse ART outcomes. ORs for ART outcomes across paternal age groups (22-<25, 25-<30, and 30-<35 years) were not significantly different. Compared to all paternal age groups of 22-<35 years, the multiple adjusted OR (excluding maternal age) for IF was 1.39 (CI 1.08-1.80) for ages 35-<40 years, 1.74 (CI 1.12-2.71) for ages 40-<45, and 3.05 (CI 1.62-5.75) for ages 45-57. After adjusting for maternal age, these ORs were reduced to 1.16 (CI 0.87-1.54), 1.23 (CI 0.75-2.03), and 2.01 (CI 1.01-4.03), respectively, with a significant increased risk still present for paternal age ≥45 years. No significant associations were found between advanced paternal age and either miscarriage or PB. There were significant associations between educational levels and ART outcomes; compared to those with a university first degree or above, women who had an educational level of high school/secondary technical school had increased the risk of IF (multiple adjusted OR1.35, 95% CI:1.02-1.80), but reduced the risk of PB (0.43, 0.22-0.83). Other measurements of SES (occupational class, family income and urban-rurality) were not associated with the ART outcomes, except for that woman employed as civil servants increased the risk of PB compared to those as service personnel (multiple adjusted OR: 1.82, 95% CI: 1.06-3.11). AFC was significantly associated with IF (compared to AFC at 11-15, multiple adjusted OR was 1.49 (1.10-2.03) at AFC 6-10, and 1.73 (1.20-2.50) at AFC <=5, but not significant OR at AFC >15 (1.24, 0.94-1.62). AFC was not associated with miscarriage and PB. The interaction analysis indicated a significant interaction between advanced maternal age and paternal age on IF (multiple adjusted OR: 2.59, 95% CI:1.17-5.71). Passive smoking has interaction effect with younger maternal age (≤35 years) on PB (3.31, 1.09-10.01). Advanced maternal age interacted with low AFC on PB (3.69, 1.03-13.21). In male participants, paternal age was interacted with smoking on miscarriage; smoking significantly increased the risk of miscarriage in the younger paternal age group of 22-30 (2.49, 1.04-5.94), while it decreased the risk in the older paternal age group of 35-52 years (0.15, 0.05-0.41). Advanced paternal age had an interaction effect with male alcohol consumption on IF (2.40, 1.44-4.01). Furthermore, a significant interaction effect was observed between males’ alcohol consumption and AFC <=5 on the risk of IF (2.50, 1.09-5.71). Conclusion: Advanced maternal age, advanced paternal age, lower educational levels and fewer AFC increase the risk of IF. Advanced maternal age increases the risk of miscarriage. Women employed as service personnel have a decreased risk of PB. The impacts of advanced parental age, lower SES, low AFC, and interaction effects with exposure to smoking and alcohol drinking should be taken into consideration clinically. Patients should be counselled by combining the effect of individual characteristics when evaluating their risk factors during ART treatment to improve the ART outcomes.
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Yin, J. (2025) Associations of parental age, socioeconomic status, antral follicle count with assisted reproductive technology treatment outcomes. University of Wolverhampton.
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en
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A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy.
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