Effects of Physical Activity and Fitness, Cardiovascular- and Psychosocial Health on Medically Assisted Reproduction

Infertility affects approximately 8-12% of couples of reproductive age worldwide and represents a major medical and psychosocial burden. Medically assisted reproduction (MAR), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), is widely used to address infertility, with more than 12,000 ART cycles performed annually in Switzerland. Despite advances in reproductive medicine, cumulative live birth rates following MAR remain moderate, highlighting the need to better understand modifiable factors that may influence treatment success.

Emerging evidence suggests that general health-related factors-such as physical activity, cardiorespiratory fitness, cardiovascular health, stress, psychosocial well-being, sleep quality, and cognitive function-may play an important role in fertility and MAR outcomes. While moderate physical activity has been associated with improved clinical pregnancy and live birth rates in some studies, the current literature is inconsistent, with conflicting findings regarding the optimal level of activity. Similarly, obesity and cardiovascular risk factors are known to negatively affect fertility and ART outcomes, potentially through mechanisms such as systemic inflammation, insulin resistance, and impaired ovarian responsiveness. Retinal microvascular markers have emerged as early indicators of cardiovascular risk and may provide additional insights into pregnancy-related complications.

Psychological stress, depression, poor sleep quality, and altered psychosocial health are prevalent among women experiencing infertility and may adversely affect reproductive physiology and treatment outcomes. Cognitive and psychosocial factors may further influence fertility indirectly through behavioral, hormonal, and lifestyle pathways. However, these domains are rarely assessed in an integrated and longitudinal manner in women undergoing MAR.

The primary objective of this exploratory, prospective, longitudinal observational study is to examine the association between physical activity and clinical pregnancy rate following MAR in biological women experiencing infertility. Secondary objectives include assessing the relationship of cardiorespiratory fitness, body mass index, blood pressure, retinal microvascular health, psychosocial health, perceived stress, sleep quality, and cognitive function with clinical pregnancy outcomes. Additional objectives are to evaluate short-term changes in physical activity, stress, psychosocial health, sleep, and cognition during hormonal stimulation, as well as changes in retinal microvascular health after completion of the first trimester in cases of pregnancy.

Inclusion criteria

• Voluntary written informed consent of the participant has been obtained prior to any screening procedures
• Age 18-43
• Planning to undergo MAR (eg, IUI, IVF, ICSI) - Physically able to cycle for cardiopulmonary exercise testing (CPET)

Exclusion criteria

• Any reduction in general state of health preventing from performing hormonal stimulation for MAR
• Absolute and relative contraindications for cardiopulmonary exercise testing (CPET) - No pregnancy at initial screening - Current illicit drug abuse including daily marijuana and CBD consumption (alcohol ≤2 drinks per day allowed)
• Any kind of severe chronic disease (e.g. severe heart failure, active cancer disease)
• Severe renal impairment (e.g. estimated glomerular filtration rate <30 ml/min/m2)
• Known liver cirrhosis or other severe liver impairment
• Uncontrolled dysthyroidism
• Uncontrolled hypertension
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, etc.