Does stress lower IVF success rates?

Stress may have an impact on IVF success, such as pregnancy rates. In this post we’ll look at what stress is, how it’s measured, and its impact on pregnancy outcomes after IVF, specifically stress measured before IVF starts, during the egg retrieval and during the embryo transfer. We’ll also look at how stress can be alleviated to potentially improve outcomes.

Note that this article mainly consists of studies from Zanettoullis et al. (2024), who did a review to examine how acute and chronic stress impact IVF success at different stages of the IVF process. Over time I’ll add more to this article that may not be included in the review.

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What is stress and how might it lower IVF success rates?

There are different types of stress, but it’s essentially how your body reacts to a threat or challenge.

For example, if you spot a bear approaching, your body prepares itself by initiating the “fight or flight” response, or the acute stress response. Here, your body releases hormones that work to produce a burst of energy so you can fight or run (flight).

The fight or flight response causes the body’s blood pressure and heart rate to increase to supply more blood to the muscles to respond more quickly. Muscles use sugars to produce the energy they need to contract and work, so some hormones act to increase the availability of these sugars.

You don’t need to see a bear approaching in order for the fight or flight response to be activated. Financial problems, marriage, or even IVF could trigger feelings of stress!

Acute stress usually resolves itself shortly after the stressful situation ends, but people with chronic stress can feel stressed for long periods of time. The long-term impact of an increased heart rate and stress hormone production could be damaging to the body.

Chronic stress can lead to anxiety, depression or obesity and and can also have a negative effect on the body’s cardiovascular, endocrine, immune and nervous system (Khan 2017). Chronic stress could affect the hypothalamic-pituitary-gonadal (HPG) axis which might contribute to infertility (reviewed by Vigil et al. 2022).

Note that some studies presented below might use depression or anxiety as a measure for chronic stress.

Tests used to evaluate stress during IVF

There are different ways to evaluate stress, including questionnaires, hormone levels and physiological responses.

Below is a list of questionnaires used to measure stress. Some of these questionnaires measure acute or chronic stress, depression or anxiety.

• Spielberger State-Trait Anxiety Inventory (STAI; the STAI-state measures acute stress and the STAI-T measures chronic stress)
• Perceived Stress Scale (PSS)
• Infertility Self-Efficacy Scale (ISES)
• Positive and Negative Affect Scale (PANAS)
• Bipolar Profile of Moods States (POMS)
• Visual Analogue Scale (VAS)
• Lubin’s Depression 200 Adjective Check List (DACL)
• General Health Questionnaire (GHQ28)
• Self Rating Depression Scale (SDS)
• Center for Epidemiologic Study of Depression Scale (CESD)
• Hospital Anxiety and Depression Scale (HADS)
• Perceived Stress Scale-10 (PSS-10)

Hormones can also be used to measure stress:

• Cortisol is considered to be the primary stress hormone and helps the body get energy by increasing the availability of sugars.
• Norepinephrine (aka noradrenaline) is a fight-or-flight hormone produced in response to stress or danger that helps mobilize the body and brain for action.
• Prolactin is best known for its role in lactation, but it can be increased in response to stress.
• There’s other stress hormones, but they weren’t addressed in Zanettoullis et al. (2024) so I won’t mention them.

Additionally, physiological responses, like heart rate or blood pressure can be used to measure stress.

Does stress before starting IVF influence success rates?

Some studies looked at how stress before IVF impacts success rates. Note that the pre-treatment stage wasn’t included in the Zanettoullis et al. (2024) review, so there may be more studies that address this stage that I’m not covering.

Peng et al. (2021)

• 450 women were evaluated for stress before IVF using questionnaires (SAS, CESD)
• There was no difference in stress scores and pregnancy outcomes.
• This suggests that pre-treatment stress isn’t associated with pregnancy outcomes after IVF.

Maroufizadeh et al. (2019)

• 142 women were evaluated for stress before IVF using questionnaires (HADS, PSS).
• There were no differences in stress scores and pregnancy outcomes.

Does stress during the egg retrieval influence success rates?

Some studies looked at how stress impacts success during the egg retrieval. Here, both chronic and acute stress are mentioned. Acute stress refers to stress experienced because of the egg retrieval, and isn’t long lasting. Chronic stress is long lasting and may be related to a mood disorder, like anxiety or depression.

Turner et al. (2013)

• 36 women were evaluated for acute/chronic stress the day before the egg retrieval using questionnaires (STAI-S, STAI-T, ISES, PSS).
• Those with lower acute/chronic stress scores and higher ISES scores were more likely to become pregnant. High ISES scores indicate more positive emotions.

Klonoff-Cohen et al. (2001)

• 151 women were evaluated for stress at the initial visit (pre-treatment) and at the time of egg retrieval using questionnaires (PANAS and POMS).
• Increased chronic stress was associated with decreased numbers of eggs retrieved.
• There were no differences in acute stress scores and pregnancy outcomes.

An et al. (2013)

• 264 women were evaluated for stress using questionnaires at egg retrieval (STAI-S and C-BDI-II) and stress hormones (norepinephrine and cortisol).
• Increased acute stress at egg retrieval (STAI-S) showed a lower pregnancy/live birth rate.
• There were increases in stress hormones during ovarian stimulation, and women with lower levels during the egg retrieval were more likely to have success.

Merari et al. (1992)

• 113 couples were evaluated for stress using questionnaires (DACL, STAI) and stress hormones at different time points, including during the egg retrieval.
• Based on the questionnaires, there were differences in anxiety levels on the egg retrieval day in women who became pregnant.
• Cortisol levels weren’t related to pregnancy outcomes, although prolactin levels increased during the retrieval. There were higher levels of prolactin in women who weren’t successful.

Facchinetti et al. (1997)

• 49 women had their blood pressure and heart rate taken before, during, and after their egg retrieval.
• Patients with a positive pregnancy had a lower percent increase in both blood pressure and heart rate than those with a negative pregnancy.
• Acute/chronic stress wasn’t specified in this study.

Miller et al. (2019)

• 72 patients had salivary and follicular cortisol levels measured before egg retrieval, along with questionnaires (STAI, VAS).
• Stress was higher at the time of egg retrieval by both salivary cortisol and questionnaires, but this had no impact on reproductive outcomes. This study concluded that acute stress at egg retrieval had no impact.
• Higher follicular cortisol was associated with improved fertilization.

Purewal et al. (2018) performed a meta-analysis and combined the results of 11 studies, which involved measuring anxiety/depression by questionnaire mainly during the egg retrieval stage:

• Depression and anxiety scores from questionnaires were lower in patients who became pregnant.
• When anxiety/depression levels before treatment (baseline) changed during treatment, there was no difference in outcomes.

Overall, Zanettoullis et al. (2024) (who reviewed the above studies) concluded that both chronic and acute stress during the egg retrieval can have an impact on outcomes.

Does stress during the embryo transfer influence success rates?

Some studies looked at how stress impacts success during the embryo transfer. Here, both chronic and acute stress are mentioned. Acute stress refers to stress experienced because of the egg retrieval, and isn’t long lasting. Chronic stress is long lasting and may be related to a mood disorder, like anxiety or depression.

Merari et al. (1992)

• 113 couples had a stress test (DACL, STAI) and hormone levels tested at different time points, including just before the embryo transfer. There was no difference in patients who conceived or didn’t.

Taguchi et al. (2015)

• 114 women were evaluated for stress before embryo transfer by measuring hormone levels (salivary cortisol and alpha-amylase) and after transfer using a questionnaire (GHQ28, SDS).
• There were no differences in hormone levels or questionnaire responses in those who became pregnant or didn’t.

Miller et al. (2019)

• 72 patients had salivary and follicular cortisol levels measured before egg retrieval, along with STAI and VAS tests.
• On the embryo transfer day, cortisol levels dropped 29% and the Stress Scale score dropped 12%. This suggests that acute stress is present during IVF, and fluctuates between procedures.
• Pregnancy outcomes weren’t tied to stress by cortisol levels or questionnaire responses.

Overall, Zanettoullis et al. (2024) (who reviewed the above studies) concluded that stress during the embryo transfer stage doesn’t have an impact on pregnancy outcomes.

How to overcome stress to improve IVF success rates?

Zanettoullis et al. (2024) share several studies that show a benefit of supplements as it relates to stress, although this in a very general way and may not be specific for improving IVF outcomes:

• Inositol may be beneficial for patients with depression (Concerto et al. 2023).
• Omega-3 fatty acids like DHA may improve cortisol levels in response to stress (ter Horst et al. 2018).
• B vitamins including folic acid may improve anxiety symptoms (Field et al. 2022).
• Melatonin might contribute to stress reduction (Eryilmaz et al. 2011).

In addition, psychological interventions might help in reducing stress. These could include counselling, stress management, coaching, interviews, mind/body programs, or cognitive behavioral therapy.

• In their review, Chow et al. (2016) found that psychological interventions were effective improving psychological outcomes and pregnancy rates, and that these interventions should be incorporated into routine practice.
• In their meta-analysis, Frederiksen et al. (2015) found that psychological interventions could reduce anxiety and improve pregnancy rates.

Conclusions

Stress, either acute or chronic, might have an impact on IVF outcomes like number of eggs retrieved or pregnancy rates. This seems to be more relevant during the egg retrieval stage compared to the embryo transfer stage, as noted by Zanettoullis et al. (2024).

This data is based off of questionnaires, stress hormone levels or heart rate/blood pressure measurements, with a heavy emphasis on questionnaires. Overall there doesn’t seem to be a consistent approach to measure stress:

• Some measure a baseline stress level, while others don’t.
• There’s a large number of questionnaires, some of which measure stress, anxiety or depression. I’m not sure if they’re all equal in their ability to measure stress, or if they can be compared to one another.
• Different hormones can be measured from different bodily fluids, along with different physiological responses like heart rate or blood pressure.
• Different physiological responses can be measured.

In my opinion, there needs to be more consistency in how these studies are done before drawing conclusions. I also didn’t notice any randomized controlled trials (RCTs), so more effort should be made to design better studies that are higher quality.

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.

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