In this study, we performed a pioneering comparative analysis of fertility rates between women of childbearing age with Crohn's disease and the general female population in China. The results indicated that the overall fertility rate of female with Crohn's disease was significantly lower than that of the general female population, at approximately 82% of the latter (43.41 vs. 52.80 live births per 1,000 person-years, AFRR 0.82, 95% CI [0.75–0.90], p < 0.001). Notably, in the 20–24 and 25–29 age groups, the fertility rates of female Crohn's disease were significantly lower post-disease onset compared to pre-disease onset. Undergoing bowel surgery and having perianal disease further reduced fertility rates. These findings provide crucial information for gastroenterologists and obstetricians in guiding fertility decisions for female with Crohn's disease.
Previous epidemiological studies conducted in Europe have indicated that female with Crohn's disease have lower fertility rates compared to those without inflammatory bowel disease, which is consistent with our findings[9, 13]. A study found that female with Crohn's disease had an average live birth rate of 1.2 per female, compared to 1.9 per female in the general population. The study also observed that fertility rates were lower post-diagnosis compared to pre-diagnosis, which is consistent with our results[13].However, it did not account for follow-up duration or the impact of bowel surgery and perianal disease on fertility rates. Our study found that fertility rates of female with Crohn's disease in the 20–24 and 25–29 age groups dropped to 19% and 36% of their pre-disease onset levels, respectively. This decline in fertility rates is likely due to the peak incidence of Crohn's disease occurring within these age groups[14, 15]. Severe symptoms such as abdominal pain, diarrhea, and fever can significantly impact psychological well-being and sexual behavior, thereby reducing the likelihood of conception. Patients in this stage often prioritize disease management over family planning, leading to interruptions or delays in their pregnancy plans. Additionally, insufficient knowledge about the disease and pregnancy, coupled with concerns about adverse outcomes and genetic risks, can further discourage attempts to conceive. However, during this peak fertility period, most patients who have yet developed the disease likely possess relatively healthy reproductive capabilities and higher fertility intentions, and many have already had children. This contributes to significant difference in fertility rates pre and post disease onset. Nevertheless, as patients age, the fertility rate gap between pre-disease and post-disease onset is gradually narrowed. Female over 30 who have not yet developed the disease typically have already had children during the peak fertility period of 20–29 years old, ant their fertility rates naturally decline with age post-30. In contrast, female over 30 who have developed the disease have accumulated more experience in disease management and pregnancy knowledge, and they benefit from stronger social and family support networks. Following a period of disease remission, these patients, mindful of the natural decline in fertility with age, begin to reconsider their reproductive plans. This result in an increase in fertility rates for female aged 30–34. However, due to age-related factors, fertility rates naturally decline again post-35. This trend has also been observed in epidemiological studies conducted in Europe[16]. Although China enforced strict fertility policies until 2016, fertility rates over the past 20 years have been higher than those in most European countries. Interestingly, fertility rates among Chinese female with Crohn's disease appear lower than those reported in European studies. This discrepancy may be attributed to a lack of disease self-management and knowledge, particularly concerning reproductive health, leading to excessive concerns about fertility and pregnancy. Therefore, more rigorous epidemiological research is needed to analyze fertility rate differences and influencing factors between countries and regions.
A study conducted in Europe on fertility rates of patients with inflammatory bowel disease found that compared to the general population, the fertility rates of Crohn's disease patients who did not undergo bowel surgery decreased by 5% while those who underwent surgery experienced a 16% decrease[15]. These findings were consistent with our results, which show that the fertility rates of patients both pre and post bowel surgery were significantly lower than those of the general population, at 85% and 58% respectively. Our study indicates that fertility rates were already significantly reduced pre bowel surgery, likely due to the average age of bowel surgery for Chinese Crohn's disease patients being 31.83 ± 7.64 years old, with many experiencing decreased fertility pre bowel surgery. We further compared fertility rates pre and post bowel surgery and found a significant decline post bowel surgery (31.44 live births per 1,000 person-years, 95% CI [21.06–92.49] vs. 49.92 live births per 1,000 person-years, 95% CI [45.35–54.91]; AFRR 0.63, 95% CI [0.45–0.89], p = 0.008). Bowel surgery is a common treatment for Crohn's disease, particularly when medication proves ineffective or complications such as bowel obstruction, fistulas, or abscesses arise. Several factors may contribute to the decline in fertility following bowel surgery. Firstly, bowel surgery, especially when involving the pelvis, can lead to anatomical changes that disrupt the normal function of the fallopian tubes, thereby reducing the likelihood of conception. Secondly, bowel surgery can result in adhesions in the abdomen and pelvis, which can obstruct the fallopian tubes or damage other reproductive organs, impairing fertility. Additionally, bowel surgery, particularly ostomy surgery, can cause psychological and social stress, which may affect sexual activity and the desire to conceive. In summary, our study indicates that bowel surgery may negatively impact fertility among Chinese women with Crohn's disease. Therefore, surgical indications should be strictly managed, and patients should receive appropriate psychological support to mitigate stress and avoid unnecessary damage to reproductive organs.
In our study, the fertility rates of Crohn’s disease patients without perianal disease did not significantly differ from those of the general population. However, patients with perianal disease exhibited significantly lower fertility rates compared to the general population (25.05 live births per 1,000 person-years, 95% CI [18.94–40.97] vs. 52.80 live births per 1,000 person-years, 95% CI [52.72–52.97]; AFRR 0.47, 95% CI [0.43–0.52], p < 0.001). Previous studies have indicated that perianal disease in Crohn's patients may reduce the frequency of sexual activity, likely due to decreased libido and pain during intercourse caused by the condition[17, 18]. Consequently, perianal disease may lower fertility rates by negatively impacting quality of life and sexual activity. However, a study from Europe indicates that perianal disease dose not further reduce fertility rates in Crohn's patients[9, 19]. This may be because the negative impact of perianal disease on fertility rates primarily from its effect on sexual quality of life, rather than directly impairing reproductive capability. In Europe, effective disease management, advanced medical resources, and comprehensive psychosocial support can mitigate the negative effects of perianal disease on fertility rates. Therefore, in China, it is essential to strengthen the comprehensive management and support systems for perianal disease, including psychological support and improvements in sexual quality of life, to help patients maintain normal fertility. In our study, when comparing fertility rates across different age groups of patients with and without perianal disease, we observed that the most significant decline occurred in the 20–24 and 25–29 age groups. However, fertility rates gradually recovering after age 30. We estimate that several factors contribute to this phenomenon. The 20–24 and 25–29 age groups represent the peak fertility period for women. However, the pain, discomfort, and psychological stress associated with perianal disease can severely impact the quality and frequency of sexual activity, significantly reducing fertility rates[20, 21]. After age 30, the fertility rates of patients without perianal disease naturally decline. In contrast, patients with perianal disease, concerned about age-related infertility, may actively pursue pregnancy during periods of disease remission. Additionally, these patients may adopt more sophisticated disease management strategies. Consequently, the fertility rate gap between the two groups of Crohn's disease patients narrows after age 30.
In this study, we conducted an in-depth analysis of the impact of Crohn's disease on female fertility. Patients were primarily selected through disease coding, with diagnoses further confirmed through comprehensive information from the HIS, including medical history, imaging, endoscopy, and pathology data, to minimize diagnostic errors. This is the first study focusing on fertility in Chinese female with Crohn's disease, analyzing the impact of disease onset, bowel surgery, and perianal disease on fertility. These findings provide a solid theoretical basis for fertility planning in these patients. Despite many significant findings, this study has certain limitations. Due to the lack of relevant information in the control group, we were unable to adjust for confounding factors such as smoking, economic status, and cultural background. Future research should incorporate more detailed information, to further validate the fertility impairment in female Crohn's disease patients and provide more targeted guidance for these patients.