1. Introduction
In most parts of the world, asthma is one of the most common chronic conditions among women of reproductive age [Citation1], and previous studies have suggested there might be a link between female asthma and a reduction in fertility [Citation2].
As up to 10% of children born in Western countries are conceived via assisted reproductive techniques or intrauterine insemination [Citation3], a negative impact of female asthma on fertility may have significant consequences not only at the individual level, but also for society.
2. Number of offspring in women with asthma
Several studies have investigated the number of offspring in atopic versus nonatopic women, and in general reported that atopic women have at least as many children as nonatopic women. In a study based on the Danish Twin Registry, Gade et al. [Citation4] addressed the impact of female asthma on fertility. Asthma was defined as an affirmative response to the question ‘Have you ever had asthma?’ No difference was found in number of offspring in women with asthma (n = 955) compared to those who did not report asthma (n = 14,011), 1.86 and 1.83, respectively. Furthermore, the study also revealed that women with asthma had their first child earlier in life (25.5 vs. 26.2 years; p = 0.001) compared to women without asthma.
Although the observed differences between asthmatic and non-asthmatic women are small, and may be of minor clinical significance, the available studies do not support the assumption that women with asthma conceive fewer biological children than non-asthmatic women throughout their reproductive lives.
3. Time to pregnancy in women with asthma
From the twin study described above, Gade et al. [Citation4] also studied a possible association between female asthma and prolonged time to pregnancy (TTP). Abnormal TTP was defined as an affirmative response to the question ‘Have you and your partner ever spent more than one year trying to become pregnant without pregnancy occurring within this year?’ Their study showed that TTP > 1 year was significantly more prevalent among women with asthma compared to non-asthmatic women (27% and 22%, respectively, p = 0.009), not least among women > 30 years of age (32% and 25%, respectively). Furthermore, they also reported that both untreated women with asthma and asthmatic women treated with inhaled corticosteroid had a higher prevalence of abnormal TTP compared to non-asthmatic women. However, women with asthma prescribed any asthma therapy tended to have a lower prevalence of abnormal TTP compared to untreated women with asthma (24% and 31%, respectively). In a further prospective study by the same group [Citation5], 245 women with unexplained infertility, including 81 women with current asthma, undergoing fertility treatment was followed. All enrolled women underwent clinical evaluation for asthma, including spirometry and bronchial challenge testing. Compared to non-asthmatic women, women with asthma had significantly prolonged TTP (32 and 56 months, respectively), which remained significant after adjusting for potential confounders, including BMI and smoking habits. Overall, females > 35 years of age were less likely to conceive than younger women, but no significant difference was found in TTP between treated and untreated women with asthma. The latter most likely caused by lack of power in the study.
TTP is prolonged in women with asthma, not least in women closer to the end of the reproductive period. Of even more clinical importance, based on the available evidence, it is likely that the reduction in fertility associated with asthma is less pronounced in women with treated asthma, as the reported association between TTP and prescribed treatment with inhaled corticosteroids is most likely only a marker of disease severity.
4. Reduction in fertility and fertility treatment
In a study from North America published more than 20 years ago focusing on women with ovulatory dysfunction as the cause of infertility, compared to women admitted to hospital for a life birth, Grodstein et al. [Citation6] reported that use of asthma medication for more than 6 months increased the risk of infertility, and, furthermore, the risk of ovulatory infertility was higher in women using beta2-agonists, whereas no significant increase was found in women treated with theofyllin. As described above, the study by Gade et al. [Citation5] revealed that among women with unexplained infertility, women with asthma were less likely to conceive than non-asthmatic women following fertility treatment, especially in women over 35 years of age with pregnancy rates were 26% and 57%, respectively, for asthmatic and non-asthmatic women. Overall, women not conceiving during the observation period were significantly older than those with successful fertility treatment (37 vs. 35 years of age).
Based on data from the Swedish Medical Birth Register, Källen et al. [Citation7] have previously reported that women using anti-asthma drugs during pregnancy were more likely to have experienced a period of subfertility compared to non-asthmatic controls, especially if they were on anti-asthma therapy in late pregnancy. However, women prescribed anti-asthma drugs were characterized by higher smoking rates and BMI, suggesting alternative mechanisms underlying the reduction in fertility than anti-asthma therapy. Furthermore, the observation related to the use of anti-asthma therapy late in pregnancy may be explained by an association between poor asthma control and a reduction in fertility.
In a study from Israel in a cohort comprising 139,168 deliveries, Sheiner et al. [Citation8] showed that women with asthma had more fertility treatment than non-asthmatic women (3.3% and 1.8%, respectively), and that maternal age was higher among women with asthma compared to the non-asthmatic women. So, although the prevalence of fertility treatment in this cohort was low compared to many other countries, this study supports the assumption that female asthma is associated with a reduction in fertility, and by that more need for fertility treatment.
5. Conclusions and perspectives
Female asthma is associated with a reduction in fertility, especially in women closer to the end of the reproductive period, and even with fertility treatment, they are less likely to conceive than their non-asthmatic counterparts. However, our knowledge of the underlying mechanisms is at present limited, although one may speculate that the association may be caused by the effects of systemic inflammation, also affecting the reproductive organs.
The observed differences in fertility between women with treated and untreated asthma suggests that optimizing asthma control, even in patients with more severe asthma, may have positive impact on fertility, and outcome of fertility treatment, in this large group of patients with coexistence of female asthma and infertility. Future studies of the association between female asthma and infertility should not only evaluate the importance of best possible asthma control for fertility in women within the full spectrum of disease severity, but should also address the effect of interventions aiming at reducing both airway and systemic inflammation, including with biologics, on fertility in women with more severe asthma.
Declaration of interest
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
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References
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