Sleep and sleep disturbances are increasingly recognized as determinants of women's health and well-being, particularly in the context of the menstrual cycle, pregnancy, and menopause. At present, however, little is known about whether fertility is affected by sleep quantity and quality. That is, to what degree, and by what mechanisms, do sleep and/or its disturbances affect fertility? The purpose of this review is to synthesize what is known about sleep disturbances in relation to reproductive capacity. A model is provided, whereby stress, sleep dysregulation, and circadian misalignment are delineated for their potential relevance to infertility. Ultimately, if it is the case that sleep disturbance is associated with infertility, new avenues for clinical intervention may be possible.
Introduction
The relationship between sleep and fertility is largely unknown. This paucity of research is surprising, given that sleep is such a critical component to one's physical and emotional health and well-being. Among both women and men, it is well established that sleep disorders, particularly insomnia, contribute to, or are associated with, myriad health conditions, including cardiovascular disease, hypertension, glucose dysregulation, depression, and anxiety disorders. Specific to women, sleep disturbances coincide with premenstrual dysphoria, pregnancy, postpartum depression, and the menopausal transition [1]. While there appears to be a relationship between sleep disturbance and reproductive health, little is known about which form of sleep disturbance is related to reproductive capacity and which specific aspects of reproductive capacity are particularly affected. With respect to sleep disturbance, the relevant domains could include sleep fragmentation, sleep continuity disturbance, short or long sleep duration, circadian dysrhythmia, and/or hypoxia. With respect to reproductive capacity, the relevant domains could include problems with fertility, conception, implantation, gestation, delivery, and/or neonatal health. Finally, it is possible that the relationship between these domains is reciprocal in nature, such that sleep disturbances and their associated sequelae may not only ensue from, but also interfere with, reproductive processes.
To date, the majority of evidence for the association between sleep disturbance and diminished reproductive capacity has been within the area of shift work [2], [3], [4], [5], [6]. In general, adverse reproductive health outcomes were observed (e.g., menstrual irregularities, dysmenorrhea, increased time to, and reduced rates for, conception, increased miscarriages, lower birth weights) and were taken to implicate the negative effects of circadian misalignment, and/or the sleep disturbance that coincides with shift work. There is a more limited literature with respect to sleep disordered breathing and infertility. Polycystic ovary syndrome (PCOS) is known to reduce reproductive potential and is believed to be one of the most common causes of female infertility. Two key studies demonstrate the association between sleep disordered breathing and PCOS. One seminal study showed that premenopausal women with PCOS were 30 times more likely to suffer from sleep disordered breathing (SDB) than controls [7]. Another key study similarly showed obstructive sleep apnea (OSA) was prevalent in 44% of obese women with PCOS, compared to 6% of age- and weight-matched reproductively normal women [8]. OSA is believed to contribute to the metabolic abnormalities (insulin resistance and decreased glucose tolerance) in women with PCOS [9]. Therefore, it is possible that OSA contributes to one form of female factor infertility. Finally, with respect to sleep continuity disturbance, only two studies have evaluated the direct association between sleep continuity disturbance and infertility. First, Pal et al. found that sleep disturbance, assessed using the single item query “do you experience disturbed sleep?”, occurred in 34% of infertile women [10]. In addition, women with diminished ovarian reserve were found to be 30 times more likely to have disturbed sleep, while controlling for race, body mass index (BMI), and vasomotor symptoms. Second, Lin and colleagues [11] found that greater than 35% of women receiving intrauterine insemination reported disturbances in their sleep. While these studies are among the first to examine sleep disturbance in relation to successful pregnancy outcomes and in populations of infertile women, sleep disturbance was assessed globally (i.e., is phrased in such a way to be all-inclusive and non-specific with respect to individual sleep disorders). Further, the direction of the findings suggests that the observed sleep disturbance is a consequence of infertility. The purpose of the present paper is to examine the reciprocal proposition, that sleep disturbance may adversely affect fertility.
In order to lay the foundation for the possibility that sleep disturbance contributes to infertility, several domains of information are provided. First, the prevalence and significance of infertility are highlighted. Second, three proposed pathways by which sleep disturbance could contribute to infertility are presented. Theoretical and empirical support for each is reviewed. Third, clinical relevance and implications, not only for extending sleep medicine practices to this population, but also for addressing infertility from a behavioral sleep medicine perspective, are discussed.
Section snippets
Definition and prevalence
Infertility is defined as “the failure to achieve a successful pregnancy after 12 mo or more of appropriate, timed unprotected intercourse or therapeutic donor insemination. Earlier evaluation and treatment may be justified based on medical history and physical findings and is warranted after 6 mo for women over age 35 y” [12]. An estimated 72.4 million women worldwide currently encounter infertility, with approximately 6.1 million having difficulty becoming pregnant or carrying a pregnancy to
How might sleep affect fertility?
Provided here is both a) a synthesis of literature that relates sleep and/or sleep disturbance to reproductive indices and b) a framework encompassing the pathways by which sleep disturbance can interfere with fertility (see Fig. 2). There are at least three possible pathways by which sleep disturbance may be related to infertility: 1) the hypothalamic-pituitary-adrenal (HPA) activation that precipitates sleep disturbance may also interfere with reproduction; 2) altered sleep duration and/or
Clinical and research implications
Insomnia disorder disproportionately affects women compared to men. Reproductive transitions (menstrual, pregnancy, menopause) are thought to precipitate sleep continuity disturbance, hence heightening women's risk for sleep problems throughout their lifespan. Traditional ways of thinking are that the endocrinology, mood dysregulation, and/or lifestyle changes that accompany reproductive transitions present a vulnerability to insomnia. It is posited here that the converse may also be true.
Conflict of interest
None.
Practice point
1)
Targeted treatment for sleep dysregulation (e.g., sleep continuity disturbance, abnormal sleep duration and/or sleep disordered breathing), or circadian misalignment may contribute to enhanced reproductive capacity, and barring this, will certainly enhance quality of life for individuals struggling with infertility.
2)
It is possible that stress affects fertility and that chronic insomnia, to the extent that it produces stress responses, also affects fertility. Thus, targeted
Acknowledgments
First, we would like to acknowledge Caterina Mosti and Diana D'Argenio for their work on literature searches. Second, we like to thank Dr. Mary Spiers for her feedback on an earlier draft of this manuscript. Third, we would like to thank the reviewers for their considerate and comprehensive feedback. This manuscript is immeasurably better because of their thoughtful review. Finally, we would like to thank Mahendra De Silva, Ph.D for helping to inspire this idea so many years ago.
To investigate the real-world effectiveness and safety of lemborexan for treating comorbid insomnia associated with other psychiatric disorders, and whether lemborexant helps reduce the dose of benzodiazepines (BZs).
This retrospective observational study was conducted on outpatients and inpatients treated by physicians of Juntendo University Hospital Mental Clinic between April 2020 and December 2021.
Data of 649 patients who were treated with lemborexant were eventually enrolled. About 64.5% of patients were classified as the responder group. Response rates of ≥60% were recorded for most psychiatric disorders. Upon administration of lemborexant, diazepam-equivalent dose of BZs had been significantly reduced in participants (3.7 ± 8.2 vs. 2.9 ± 7.9, p < 0.001). The results of logistic regression analysis showed that outpatient (odds ratios: 2.310; 95% confidence interval [CI]: 1.32–4.05), shorter duration of BZ use (<1 year) (odds ratios: 1.512; 95% CI: 1.02–2.25), no adverse events (odds ratios: 10.369; 95% CI: 6.13–17.54), larger reduction of diazepam-equivalent dose of BZs upon introducing lemborexant prescription (odds ratios: 1.150; 95% CI: 1.04–1.27), and suvorexant was the replacement drug (odds ratios: 2.983; 95% CI: 1.44–6.19), which were significant predictors of good response.
Although this is a retrospective and observational study with many limitations, our study results suggest that lemborexant is effective and safe.
Postpartum depression (PPD) is associated with various adverse health outcomes among mothers and babies. Meta-synthesis can improve our understanding of postpartum women's experiences. However, the meta-analysis of PPD among Chinese women is limited. Therefore, a meta-analysis was conducted to evaluate the prevalence of PPD among Chinese women and if and how traditional culture may exacerbate PPD. Qualitative studies on the experiences of Chinese women with PPD were searched from database establishment until May 2022 in ten databases. The meta-ethnography reporting guidelines and framework was applied to the writing and reporting of this review. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42022323388). 2321 studies were retrieved, and 11 studies qualified for the meta-synthesis. The final five themes extracted and re-conceptualized from these studies were as follows: the gap between expectation and reality, conflicts with family, physical and mental frustrations, critical needs for coping with changes, and measures against PPD. Chinese women with PPD frequently feel vulnerable physically, mentally, or both after childbirth and often have conflicts with their families due to the influence of traditional Chinese culture. Family relationships and social support often are factors preventing women from seeking help.
To analyse the dietary habits, alcohol consumption, healthy eating index and student performance of a sample of students at a Spanish university to determine if their intake of nutrients reach optimal levels for fertility.
Descriptive cross-sectional study of female university students in Madrid, data were collected in Nutrition classes. Participants were 470 women nursing studying at a private university in Madrid, non-random sample was used. An AUDIT test was conducted to determine alcohol consumption. Habits and dietary assessment with a three-day record using DIAL® program to know main nutrients intake. Quantitative variables appeared as mean ± standard deviation, adjusted for all pairwise comparisons using the Bonferroni correction Statistical analysis was performed using SPSS 25®.
The majority of the Spanish university women of reproductive age participating in the study did not have the recommended intake of some macro and micronutrients carbohydrates, vitamins D and B9, Mg, Fe, and I.
This study opens further lines of research. It is necessary to carry out qualitative research into students’ self-perception and their dietary and sleeping habits. Addressing ways to improve food access, dietary quality, and healthy lifestyle, should be focused on future intervention programs and policies for college students.
To evaluate the associations between preconception sleep characteristics and shift work with fecundability and live birth.
Secondary analysis of the Effects of Aspirin in Gestation and Reproduction study, a preconception cohort.
Four US academic medical centers.
Women aged 18–40 with a history of 1–2 pregnancy losses who were attempting to conceive again.
Not applicable.
We evaluated baseline, self-reported sleep duration, sleep midpoint, social jetlag, and shift work among 1,228 women who were observed for ≤6 cycles of pregnancy attempts to ascertain fecundability. We ascertained live birth at the end of follow up via chart abstraction. We estimated fecundability odds ratios (FORs) using discrete, Cox proportional hazards models and risk ratios (RRs) for live birth using log-Poisson models.
Sleep duration ≥9 vs. 7 to <8 hours (FOR: 0.81, 95% confidence interval [CI], 0.61; 1.08), later sleep midpoints (3rd tertile vs. 2nd tertile: FOR: 0.85; 95% CI, 0.69, 1.04) and social jetlag (continuous per hour; FOR: 0.93, 95% CI: 0.86, 1.00) were not associated with reduced fecundability. In sensitivity analyses, excluding shift workers, sleep duration ≥9 vs. 7 to <8 hours (FOR: 0.62; 95% CI, 0.42; 0.93) was associated with low fecundability. Night shift work was not associated with fecundability (vs. non-night shift work FOR: 1.17, 95% CI, 0.96; 1.42). Preconception sleep was not associated with live birth.
Overall, there does not appear to be a strong association between sleep characteristics, fecundability, and live birth. Although these findings may suggest weak and imprecise associations with some sleep characteristics, our findings should be evaluated in larger cohorts of women with extremes of sleep characteristics.
Duración y horario del sueño y trabajo por turnos en el periodo preconcepción y su asociación con la fecundabilidad y tasa de nacido vivo en mujeres con historia de aborto de repetición.
Evaluar las asociaciones entre características del sueño y del trabajo por turnos en el periodo preconcepción con la fecundabilidad y la tasa de nacido vivo.
Análisis secundario del estudio Effects of Aspirin in Gestation and Reproduction, una cohorte preconcepción.
Cuatro centros académicos en EEUU.
Mujeres de entre 18 y 40 años de edad con historia de 1 ó 2 abortos intentando volver a concebir.
No aplicable.
Evaluamos parámetros basales auto-reportados de duración del sueño, punto medio del sueño, jetlag social, y trabajo por turnos entre 1.228 mujeres que fueron observadas durante hasta 6 ciclos de intento de embarazo para determinar la fecundabilidad. Determinamos la tasa de nacido vivo al final del seguimiento mediante extracción de la historia clínica. Estimamos ratios de probabilidad de fecundabilidad (FORs) utilizando modelos discretos de riesgo proporcional de Cox y ratios de riesgo (RR) para nacido vivo empleando modelos log-Poisson.
Duración del sueño ≥ 9 vs 7 a < 8 horas (FOR: 0,81, intervalo de confianza 95% [CI], 0,61; 1,08), punto medio del sueño tardío (3er tercil vs 2do tercil: FOR: 0,85; IC95%, 0,69, 1,04) y jetlag social (continuo por hora; FOR: 0,93, CI95%: 0,86, 1,00) no se asociaron con menor fecundabilidad. En análisis de sensibilidad, excluyendo a las trabajdoras por turnos, la duración del sueño ≥ 9 vs 7 a < 8 horas (FOR: 0,62, IC95%, 0,42; 0,93) se asoció con baja fecundabilidad. Trabajar el turno de noche no se asoció con la fecundabilidad (vs trabajar otro turno FOR FOR: 1,17, IC95%, 0,96; 1,42). El sueño preconcepción no se asoció con la tasa de nacido vivo.
En general, no parece haber una fuerte asociación entre características del sueño, fecundabilidad y tasa de nacido vido. Aunque estos hallazgos puedan sugerir asociaciones débiles e imprecisas con algunas características de sueño, nuestros hallazgos deben ser evaluados en cohortes más amplias de mujeres con características de sueño extremas.