Stress and Recurrent Miscarriage

This thesis investigated the role of stress in RM using both psychometric and biochemical measures. The majority of previous studies on the impact of stress on RM only addressed the psychological aspect without concurrent biochemical stress measurements. In this thesis the stress status in women with RM was evaluated by using a validated questionnaire package and biochemical measurements of stress markers including cortisol, natural killer cells and prolactin.

The first part of this thesis compared the psychological stress status in a cohort of women with unexplained RM with that of fertile health women. The results showed that women with RM had higher levels of psychological stress than fertile women. RM women with higher perceived stress and being less optimistic appeared to have an increased likelihood of live birth. Based on the findings in the present study we speculate that stress coping strategies adopted by individuals may have a prognostic value on subsequent pregnancy outcomes more than stress levels in women with RM.

The next part of this thesis investigated the biochemical stress markers including natural killer cells, cortisol and prolactin in the same cohort of women with unexplained RM. The increases in pNK CDdim cells were found to be associated with a higher risk of a subsequent miscarriage in women with RM, suggesting a prognostic value of measuring pNK subset of CDdim cells in RM. In addition, no correlation between the measurements of pNK cells and those of uNK cells was found in women with RM, suggesting that pNK measurements do not reflect uNK measurements in RM.

Next, we conducted a study to investigate the relationship between prolactin and RM. We found that within normal physiological range low plasma prolactin concentrations were associated with an increased risk of a subsequent miscarriage in women with RM. No significant difference in the measurements of endometrial prolactin receptor was found between women with RM and fertile women. There was also no association between the expression of endometrial prolactin receptor and subsequent pregnancy outcomes in women with RM.

The following part of this thesis examined the activation of the hypothalamo-pituitary-adrenal (HPA) axis in response to stress in women with RM with cortisol measurements. No non-suppression of cortisol following Dexamethasone Suppression Test (DST) was found in women with RM. There was also no association between cortisol measurements and pregnancy outcomes in women with RM. Based on the findings in this study we speculate that chronic stress of RM has no effect on feedback dysregulation of the HPA axis.

The final part of this thesis correlated the results of various stress measurements. High levels of fertility stress were associated with a decrease in the numbers of pNK CDbright cells. High basal salivary cortisol concentrations were associated with an increase in uNK cell measurements. The results of serum cortisol suppression following DST had an inverse correlation with the values of pNK CDdim cells whereas the results of salivary cortisol suppression following DST had a positive association with uNK cell measurements. The exact physiological mechanism of this observation is not known.

In summary, the studies presented in this thesis showed that stress was associated with RM. There was some evidence that stress affected subsequent pregnancy outcomes in women with RM.