Disturbed sleep characteristics found to impair oocyte quality in cohort study

Published 22 March 2022

A large cohort study of more than 1200 women having IVF in China has found that ‘unhealthy sleep characteristics’ do indeed have some adverse effect on outcome by reducing the number of oocytes retrieved and their ability to fertilise.

Few could argue that the relationship between sleep and reproductive function has not been industriously studied. A meta-analysis reporting last year found 33 eligible studies from an opening total of more than 1200.(1) Topics covered were male and female infertility (sperm parameters, ovarian function), and IVF treatment. However, despite the volume of studies, no firm conclusions were drawn other than that ‘sleep may be an original and innovative parameter to consider in the reproduction field’ – and that there’s more yet to be done to understand how sleep may be ‘a useful modifiable target’ in infertility management.

Now, a large prospective cohort study analysing the sleep patterns of 1276 women having IVF in China indeed suggests that ‘unhealthy sleep characteristics’ - short nocturnal sleep, inadequate sleep time, poor sleep quality and having trouble falling asleep – may inhibit the quantity of oocytes and their potential for maturity and fertilisation.(2) Specifically, women who slept less than seven hours a night and reported trouble falling asleep had fewer IVF oocytes retrieved (-11.5%) and of lower quality than those sleeping seven-to-eight hours (the reference duration). Additionally, those who reported poor sleep quality had a 20% lower fertilisation rate than the women who reported good sleep quality. And women with trouble falling asleep on more than three occasions a week had fewer MII oocytes and embryos available than those with no trouble falling asleep.

However, analysis did curiously find that women who slept from nine-to-ten hours per night had a lower chance of clinical pregnancy than those within the reference duration of sleep, reflected in an adjusted odds ratio of 0.65. Moreover, the strong positive associations between sleep duration and fertilisation rate, number of oocytes retrieved and good quality embryos, and pregnancy rate was only evident in women over 30 years or those with poor reported sleep quality – thus suggesting that an effect of nocturnal sleep duration on implantation and clinical pregnancy is modified by age. But unlike some other studies, this analysis did not find any adverse effect of shift work on implantation and pregnancy rate.

This, however, was a complicated study in which sleep patterns were self-reported and with multiple covariates integrated into the analytical model (age, BMI, smoke exposure, alcohol consumption, stimulation protocol, infertility diagnosis, and FSH and AMH levels at day 3). The analysis began with baseline assessment of subjects at enrolment which was followed-up at oocyte retrieval with questions about lifestyle and sleep (based on the Pittsburg Sleep Quality Index). The sleep quality (and quantity) self-reports thus covered the period of ovarian stimulation and were later correlated with IVF outcomes taken from medical records (from a first IVF/ICSI cycle). These included the number of retrieved oocytes, mature oocytes (MII), fertilised oocytes, good quality embryos on day 3, implantation, biochemical pregnancy and clinical pregnancy.

The complexity of the study means that definitive conclusions are hard to draw, but the authors seem confident that ‘short sleep duration and disorders were associated with impaired oocyte quantity and quality’. However, they concede that the underlying mechanisms are poorly understood, but note that the ‘dysregulation of clock genes . . . may cause diminished ovarian reserve, abnormal reproductive hormone sensitivity of theca cells, disturbed DNA repair and eventual reduction in oocyte quality’. They also note that a disrupted circadian rhythm can reduce levels of melatonin in follicular fluid and trigger oxidative stress damage to oocytes. Melatonin is available in some jurisdictions as a prescription treatment for short-term insomnia, and elsewhere over-the-counter as a hopeful fix for jet lag.

Interestingly, ‘season’ was one of many covariates included in the study model, with the timing of egg collection allocated to spring, summer, autumn or winter. While the majority of retrievals (48%) took place in the summer, there are no details of seasonality-affected results. However, a recent retrospective study analysing more than 3000 frozen transfers with oocyte retrievals performed in a single US centre between 2012 and 2017 found that patients with egg collections carried out in summer months had a 45% greater chance of clinical pregnancy (OR 1.45) and 42% of live birth than those with retrieval dates in winter.(3) However, there was no association between the date of embryo transfer and treatment outcome, suggesting to the authors ‘that any seasonality effects on in vitro fertilization success are related to ovarian function and not uterine receptivity’.

1. Caetano G, Bozinovic I, Dupont C, et al. Impact of sleep on female and male reproductive functions: a
systematic review. Fertil Steril 2021; 115: 715-730.
2. Yao Q-Y, Yuan X-Q, Liu C, et al. Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study. Hum Reprod 2022;
3. Correia KFB, Farland LV, Missmer SA, Racowski C. Fertil Steril 2022; 117: 539-547.

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