Among all women who reported regular exercise compared with those who did not, there was a 20% lower likelihood of successful live birth (OR 0.8, CI 0.7–1.0; P=.07), but this was not statistically significant. Regularly exercising women also had an increased risk of implantation failure (OR 1.3, CI 1.0–1.6; P=.04) (Table 3). Analysis of hours, months, and years of exercise as continuous variables did not reveal a linear relation between the amount of exercise and the success of IVF outcomes. Additionally, no significant linear association was identified by the use of a “lifetime exercise” variable, multiplying hours of exercise per week times 52 weeks times the number of reported years of exercise.
When compared with women who do not regularly exercise, women who exercised 4 or more hours per week for 1–9 years (exercise duration category 2) were 40% less likely to have a successful live birth after the first cycle of IVF (Table 3). These women were almost three times more likely to have a cycle cancellation (OR 2.8, CI 1.5–5.3) and twice as likely to experience implantation failure (OR 2.0, CI 1.4–3.1) or pregnancy loss (OR 2.0, CI 1.2–3.4) than women who did not report regular exercise. There was no difference in the rate of failed fertilization when comparing the women in exercise duration category 2 to women who did not exercise. The remaining exercise duration categories were not significantly different from the nonexercisers with respect to IVF outcomes. These results remained statistically significant after adjusting for FSH levels (data not shown).
For all analyses, the effect of BMI was closely analyzed. When patients were stratified by BMI using the World Health Organization BMI Categories for underweight (BMI<18.5), normal (BMI 18.5–24.9), overweight (BMI 25.0–29.9) and obese (BMI>30.0), no differences in the association between exercise and the IVF outcomes were noted (data not shown). Analysis by infertility diagnosis (ovulatory, male factor, tubal factor, uterine or cervical anomalies, endometriosis, and unexplained infertility) did not reveal any relation, confounding, or effect modification between infertility diagnosis and the effects of exercise on IVF outcomes (data not shown).
Further analyses examined the effect of the type of exercise on IVF outcomes. Three different groups were created based on the type of exercise women reported most frequently: “walking,” “cardiovascular,” or “other.” There were statistically significant differences in age, gravity, parity, BMI, and use of alcohol and tobacco between the women in these groups (data not shown); confounders were adjusted for in all analyses.
Compared with those who do not exercise regularly, the likelihood of successful live birth for walkers in general was not different (OR 0.9, CI 0.7–1.2), whereas the likelihood of successful live birth for those undertaking cardiovascular exercise was 30% lower (OR 0.7, CI 0.6–0.9). However, among the exercise duration categories discussed in Table 1, focusing on category 2 (≥4 hours per week for 1–9 years) and category 3 (1–3 hours per week for 10–30 years) we observed exercise type specific associations (Table 4). Among the women who walked, those who had done so for 4 hours or more per week for 1–9 years (exercise duration category 2) were 50% less likely to have a successful live birth compared with women who did not regularly exercise. This was similar to the risk of IVF failure observed for exercisers overall in exercise duration category 2. Walking for 1–3 hours per week for 10–30 years (exercise duration category 3) was not associated with any change in the IVF outcomes.
Interestingly, the most detrimental effect was observed in cardiovascular exercisers, who had a 30% lower chance of successful pregnancy after their first cycle of IVF (OR 0.7, CI 0.6–0.9) than women who did not exercise. Among women who participated in cardiovascular exercise, exercise duration category 2 (≥4 hours per week for 1–9 years) was consistently associated with a significant decrease in IVF success. When compared with women who did not exercise, there was a 50% reduction in live births (OR 0.5, CI 0.3–0.8), with more than a five-fold increase in cycle cancellation (OR 5.1, CI 2.3–11.5) and an approximately a 2.5-fold increase in failed implantation (OR 2.6, CI 1.5–4.6) and pregnancy loss (OR 2.4, CI 1.1–4.9) (Table 4). These remained statistically significant after adjusting for FSH. Among the cardiovascular exercisers in exercise duration category 3 (1–3 hours per week for 10–30 years) there was less likelihood of a successful live birth (OR 0.6, CI 0.4–1.0, P=.04); however, this association was weaker than that seen in exercise duration category 2. This detrimental effect of cardiovascular exercise on IVF outcomes was not seen in exercise duration categories 1 and 4. The greatest effect was seen in moderate exercisers.
In this prospective study of women undergoing their first cycle of IVF, we observed a complex relation among exercise duration, exercise type, and IVF outcomes. Overall, exercise seems to be associated with reduced success after the first cycle of IVF. More specifically, exercising 4 hours or more per week for 1–9 years is associated with a decreased chance of a successful live birth. Cardiovascular exercise may have a more detrimental effect than walking.
Reproductive dysfunction associated with exercise seems to be related to alterations of the hypothalamic-pituitary axis. In some situations, such as intense exercise and decreased body mass, exercise can lead to anovulation and infertility.10 On the other hand, in overweight patients with ovulatory dysfunction, exercise can lead to increased ovulation and improved fertility.2,5,6
There are several mechanisms by which exercise can lead to reproductive dysfunction. In women who participate in intense physical activities emphasizing leanness, suppression of pulsatile gonadotropin releasing hormone from the hypothalamus results in a hypoestrogenic state.10–13 Sports that emphasize strength over leanness can be associated with menstrual irregularities,10 mildly elevated luteinizing hormone levels, and mild hyperandrogenism rather than hypoestrogenism.10,14,15 Intense exercisers have decreased levels of leptin, triiodothyronine (T3), and insulin.10,12,16,17 Overall, the incidence of luteal phase defects, oligomenorrhea, anovulation, and subsequent infertility are significantly higher in athletes than nonathletes10; however, the mechanisms of the dysfunction may vary according to type of exercise.
Although IVF attempts to manipulate the hypothalamic-pituitary-ovarian axis, many other factors in the hormonal milieu can be influenced by exercise and may affect the success of the IVF cycle, as mentioned above. These factors may not be recognized, addressed or negated during an IVF cycle, and thus may still have an effect on overall IVF success.
We observed that in general, exercise could negatively affect the first cycle of IVF. However, there was no linear relation between the number of hours per week of exercise, number of years of exercise or lifetime exercise and IVF outcomes. When exercise duration categories were created, the negative effect of exercise (a statistically and clinically significant decrease in successful live births) is seen predominantly in women who reported exercising for 4 or more hours per week for 1–9 years (exercise duration category 2). The decrease in successful live births seen in exercise duration category 2 is supported by the increase in multiple points of failure: cycle cancellation, failed implantation, and pregnancy loss compared with women who did not exercise. Fertilization, which occurs in vitro in an artificial, standardized environment, is not affected by the exercise pattern of the women, suggesting that the detrimental effect on IVF outcomes is related to alterations in the woman’s hormonal milieu or uterine environment.
Women in exercise duration category 2 were consistently noted to have poorer IVF outcomes. This finding persisted in women who reported either walking or cardiovascular as their primary exercise, although the effect was stronger in the cardiovascular group. It is possible that women in this category exercise long enough to alter their endogenous hormonal environment and affect the outcome of their first cycle of IVF.
In general, women in exercise duration category 1 (1–3 hours of exercise per week for 1–9 years) or exercise duration category 3 (1–3 hours of exercise per week for 10–30 years) did not have less successful IVF outcomes than women who do not exercise. One possible explanation is that women who exercise for such a short duration each week may not change their hormonal environment enough to affect the outcome of their first IVF cycle. The women in exercise duration category 4 (≥4 hours per week for 10–30 years) did not demonstrate any differences in their IVF outcomes when compared with women who do not exercise. It is possible that the women who exercised at this intensity for more than 10 years have achieved an equilibrium or created a different hormonal environment from those women who exercise for the same number of hours per week for less than 10 years. Our results were unexpected. Although we cannot explain the pathophysiology of these findings with the information obtained in out study, we provide one possible explanation above.
Cardiovascular exercise in general was correlated with a statistically significant decrease in IVF success, whereas walking was not. This implies that walking may not be an intense enough exercise to alter the environment to affect the IVF outcomes negatively.
There is increased risk for ovulatory infertility in both underweight patients (BMI<20) and overweight patients (BMI>24).2,3 Among overweight patients with ovulatory dysfunction, exercise can lead to increased ovulation and improved fertility.2,5,6 However, we did not observe any difference in the relation between exercise and IVF outcomes among the different BMI groups.
There are several limitations of this study. Patients completed the survey and reported their exercise history before the start of the IVF cycle. Although there may be inaccuracies in the self-reporting of exercise, any differential bias should be negated, given that the patients had not yet undergone IVF and thus did not know their outcome. Because of the prospective nature of the data collection before the IVF cycle, recall bias is eliminated. The self-reported exercise inaccuracies should not be different in those patients with successful IVF outcomes and those with unsuccessful cycle outcomes; the exercise information was gathered before knowledge of the cycle outcome. Furthermore, we have information only about general exercise patterns before starting the first cycle of IVF. Patients reported exercise patterns over years (hours per week and years they have been exercising); the exact exercise pattern, types of exercise performed, and intensity of exercise most likely. Furthermore, patients may have altered their exercise patterns when they started trying to conceive, before their referral for IVF. We did not have information about exercise patterns during the IVF cycle which could also affect outcomes.
In general, the type, intensity, frequency, and duration of exercise are difficult to quantify. Although patients did report average hours of exercise per week, we do not have information about the length, intensity, or frequency of each individual exercise session. For example, 4 hours of reported exercise per week could be two 2-hour sessions or eight half-hour sessions. Thus, the effect of such differences could not be studied. When creating exercise variables, we attempted to report standardized metabolic equivalents, but without more specific information on intensity of the physical activity, this could not be done with accuracy. In creation of the general exercise type categories (ie, “walking,” cardiovascular,” and “other”) we initially attempted to follow the Centers for Disease Control and Prevention and American College of Sports Medicine categorization of physical activity. However, these systems are based on metabolic equivalents that could not be accurately defined with the survey information obtained. When trying to examine very specific exercise categories separately (such as stretching and strengthening exercises) the numbers were too small to yield any meaningful results. This led to the development of the final exercise type categories presented, with the lumping of “cardiovascular” and “other” activities.
The survey completion rate was 65%. Typically 70% is the desired completion rate in epidemiologic studies. Given the stress than most couples are under by the time they reach IVF, we feel that this is an excellent response rate.
Last, exercise is a lifestyle factor with associated behaviors that may be potential confounders. The analysis in this study was designed to address some of these factors by adjusting for BMI and use of alcohol, caffeine, and tobacco. However, there are certainly other confounders that we could not identify or account for, such as diet and level of job stress.
Despite these limitations, this large, prospective study demonstrates that certain types of exercise patterns may affect the success of IVF. Although exercise has many known health benefits, it does not seem to contribute to successful IVF outcomes. However, our findings are not strong enough to encourage women to abandon exercise and embrace a sedentary lifestyle. Future studies are needed to clarify the relation between exercise and IVF outcomes. As with all studies, these findings should be replicated before making any definitive clinical recommendations.
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© 2006 The American College of Obstetricians and Gynecologists
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