We found that infertile women reported significantly higher stress and psychological distress levels than fertile women, similar to findings from previous studies [1, 3]. This confirms that infertility is associated with high psychosocial strain and infertile women experience higher levels of stress and psychological distress compared to fertile women.
However, we found no significant difference in serum AMH levels between the two groups, which is contrary to previous studies comparing serum AMH among infertile and fertile women, in which authors reported a significantly lower serum AMH level among infertile women [18, 19]. The contradiction between our findings and that of other studies may be due to the inclusion of women with polycystic ovary syndrome (PCOS)—which is associated with significantly higher levels of serum AMH—in our study, contrary to previous studies. However, we found no significant difference in serum AMH levels between the two groups after the exclusion of women with PCOS from the infertile group and controlling for age, BMI, stress, and psychological distress. Furthermore, given the heterogeneous nature of infertility, a measure of ovarian function is not an exclusive marker of fertility. Therefore, findings may vary based on underlying factors responsible for infertility in the women in each study population.
Also, we found no significant correlation between stress and serum AMH level among infertile and fertile women. This is similar to findings by Vitek et al. in which psychosocial stress was not demonstrated to have any relationship with AFC or AMH among women with unexplained infertility [21]. Conversely, Dong et al. found a significant negative correlation between salivary amylase as a marker of psychological stress and serum AMH among Chinese women with unexplained infertility [20]. Contrary to previous findings, Kudesia et al. reported a positive correlation between chronic stress—measured with Wheaton’s Chronic Stress Scale—and serum AMH in pre-menopausal women [22].
The contradictions could be because of the difference in the marker of psychological stress used and the overall sensitivity of perceived stress scale-10 used in our study to the biological response to stress. Since some of the theories surrounding the influence of psychological stress borders on the eventual influence the biological response to stress can have on human reproduction [11], a biomarker of this process will most likely be a more sensitive measure of an effect. Although perceived stress scale is a valid and reliable measure of stress [24, 25], it may not translate in all situations to the biological response or vulnerability to stress which could influence a significant change in serum AMH levels in these women.
We found no significant correlation between psychological distress—measured by the Kessler psychological distress scale-10—and serum AMH in infertile and fertile women. This finding is similar to those of Vitek et al. in which psychological distress—measured by the Patient Health Questionnaire (PHQ)—did not demonstrate any significant relationship with serum AMH or AFC [21]. Perhaps, the nonspecific and subjective nature of the instruments used affects their sensitivity to the biological distress that affects serum AMH levels.
We found that with an increase in age, there was a corresponding reduction in serum AMH among infertile and fertile women. This is similar to findings by other studies and lends credence to the use of serum AMH as a marker of ovarian ageing [26, 27]. However, infertile women showed almost twice the reduction in serum AMH with age, when compared to fertile women in this study population, suggesting that ovarian ageing is accelerated in women with infertility. Contrary to findings from previous studies, the rate of decrease in serum AMH with age remained constant in both groups despite controlling for stress and psychological distress, which suggests that the acceleration in ovarian ageing in infertile women was not dependent on these psychological variables [12, 13]. However, the rate of reduction in serum AMH with age was 0.7% less following the exclusion of women with PCOS from the infertile group. This suggests that the inclusion of young women with PCOS with higher serum AMH levels contributed partly to the accelerated decrease in serum AMH with age in the infertile group. Also, previous studies reported that women with PCOS have an accelerated decrease in serum AMH with age compared to non-PCOS controls [28, 29].
There was a positive relationship between BMI and AMH in the infertile group, while none was found in the fertile group. This contradicts the findings by previous studies in southwest Nigeria, in which Okunola et al. found no relationship between BMI and random serum AMH in infertile and fertile women, while Oke and colleagues reported no significant relationship between BMI and day 3 AMH in all study participants [18, 30]. Outside Nigeria, Freeman et al. reported a negative relationship between BMI and serum AMH in Caucasians and African-American women of late reproductive age, while Moy et al. in a multi-ethnic study among infertile women also found a negative correlation between BMI and serum AMH levels in Caucasians, although no relationship was demonstrated in African-American, Hispanic, or Asian women [31, 32]. Dólleman et al., however, demonstrated no relationship between levels of BMI and serum AMH in a large population study of premenopausal women [33].
However, following the exclusion of women with PCOS in the infertile group, we found no significant relationship between BMI and serum AMH, suggesting that the significant positive relationship demonstrated in the infertile group was due to the inclusion of anovulatory women with PCOS in the infertile group of this study, which is often associated with high BMI and high serum AMH levels [34].
Strength and limitations
The case-control design of our study gave room for comparison and sub-analysis to further understand the effect of stress and psychological distress on serum AMH levels in infertile and fertile women, independently. This further removed the influence of infertility as a confounder, since stress, psychological distress, and abnormalities of serum AMH have all been found to be independently associated with infertility.
However, this study is not without its limitations. In determining the effect of stress and psychological distress on serum AMH, self-administered scales—which measured the perception of stress and psychological distress over a month—used are highly subjective and could be biased by the language barrier, concentration, and environment of the participants during the process of completing the questionnaires, although there is evidence that perceived-stress scale scores correlate with the biological response to stress [25]. The inclusion of a more objective measure of the biological response and vulnerability to stress would have increased the reliability of stress measurement and broadened the scope of the study.