Consequences of female night shift work for fertility, assisted conception and fetal development

Abstract

It is estimated that 1 in 7 women in paid employment in Australia are working at night, on either permanent or rotating shift rosters. Night shift work can disrupt circadian rhythms, contributing to cardiometabolic disturbance, psychosocial stress, and could potentially affect human reproductive health. This thesis investigated whether female night shift workers were more likely to require fertility treatment to achieve a first birth and whether this reflected specific reproductive health problems. The thesis then examined whether this combination of patient and treatment factors contributed to adverse perinatal outcomes, specifically congenital urogenital anomalies, in the first births of night shift workers when compared to non-shift workers. An initial step entailed a review of the literature concerning night shift work and female fertility, miscarriage and perinatal outcomes, resulting in a published manuscript focusing on fertility (including time to pregnancy, menstrual irregularity and endometriosis) and miscarriage. This manuscript represents a multidisciplinary project in which a complex literature is critiqued and summarised. It also provided an overview of current clinical guidance and policies in place internationally. Australian research on shift work has been constrained by the absence of a tool to assess this exposure on a large scale. Accordingly, a shift work job-exposure matrix specific to occupations in Australia was developed using established methods. The job-exposure matrix was applied to a large population-based cohort of births produced via linkage of routine perinatal registries with fertility clinic data. These included the South Australian Perinatal Statistics Collection, the South Australian Birth Defects Register and data from the two clinics registered to provide fertility treatment in South Australia between 1986–2002. This allowed identification of primiparous women with probable exposure to light at night during night shift work, forming the basis for two subsequent studies of reproductive function and treatment outcomes. One study considered the use of fertility treatment among night shift workers. The analysis indicated that a higher proportion of women in occupations likely to involve night shift conceived their first birth with fertility treatment, compared to their unexposed counterparts in paid employment (OR = 1.25, 95% CI 1.09–1.43). However, this was attenuated when adjusted for age (OR = 1.10, 95% CI 0.95–1.26). Among those who accessed treatment, night shift workers were more likely to be diagnosed with menstrual irregularity (OR = 1.42, 95% CI 1.05–1.91) and endometriosis (OR = 1.34, 95% CI 1.00–1.80). A second study examined the associations of night shift work, subfertility and fertility treatment with urogenital anomalies occurring in first births. This outcome was pre-specified based on plausible mechanisms linking circadian rhythms to perturbed maternal endocrinology and subsequent fetal exposures in utero. Results indicated that singleton births to primiparous night shift workers, conceived using fertility treatment, were more likely to have a urogenital anomaly, compared to those of non-shift workers who conceived using fertility treatment (OR = 1.80, 95% CI 0.94–3.46). The effect was greater among multiple births (OR = 2.94, 95% CI 1.26-6.85). This finding was not related to differences in the type of fertility treatment received by night shift workers compared to other women who did not work night shift. The outcome was also specific to fertility treatment, and did not extend to naturally conceived singleton or multiple births to night shift workers in the general population, for which there was no significant association. Further analysis indicated an ordering of risk, whereby the greatest risk of urogenital anomalies occurred among births that were jointly exposed to maternal night shift work and fertility treatment (OR for singletons = 2.11, 95% CI 1.17–3.79), an additive interaction. This thesis represents the first research to investigate the use of fertility treatment among female night shift workers and whether this contributes to congenital anomalies in offspring. The finding that night shift workers were more likely to conceive their first birth using fertility treatment is potentially a consequence of a higher prevalence of menstrual irregularities and endometriosis. Alternatively it may reflect psychosocial effects of night shift work, or a combination of these factors, on women’s age of first childbearing. A subgroup of women who undertake night shift work may be most susceptible to the effects of circadian disruption on their fertility, either directly or through exacerbation of underlying fertility problems, which contribute to adverse outcomes for offspring conceived using fertility treatment. Future research concerning night shift work, infertility, and recourse to fertility treatment would benefit from inclusion of all women who undergo fertility treatment, regardless of whether a birth was achieved. Despite this limitation, the depth and breadth of information in this large population-based cohort has enabled the first steps towards identifying requirements for fertility treatment by night shift workers and demonstrated a combined impact of patient and treatment factors on fetal development.