Table 2.

Summary of findings from intervention studies relevant to stress and human reproductive failure

Study type	Outcome	Intervention overview	Authors, year
Review: psychosocial interventions in pregnancy—25 independent evaluation studies	≥1 pregnancy outcome in any infertile group	More successful interventions were group format, lasted 6–12 weeks, >6 months follow up, emphasized strong educational and skills training, medical knowledge and acquisition of stress management and coping techniques. These were significantly more effective in producing positive change across a range of outcomes than counseling interventions emphasizing emotional expression or discussion of feelings related to infertility. Overall pregnancy rates were unlikely to be affected by psychosocial interventions. Note this review excluded ‘TLC’-type patient-centred care, as tested by Stray Pedersen and Stray Pedersen [92].	Boivin, 2003 [89]
Clinical guidelines and treatment evaluations: ‘tender loving care’ patient-centred routine clinical care	Pregnancy success after RSA	Women with unexplained recurrent first trimester miscarriage have an excellent pregnancy outcome without pharmacological intervention offered supportive care alone in a dedicated miscarriage clinic.	RCOG-UK [90]
		Supportive care in early pregnancy conferred a significant beneficial effect on the outcome of the pregnancy (79% success for women <40 years <6 misc. offered supportive care).	Clifford et al., 1997 [91]
		Couples receiving antenatal counseling and psychological support in a clinical setting had 86% pregnancy success, compared to 33% in controls given no antenatal care.	Stray Pedersen and Stray Pedersen, 1984 [92]
Cochrane review: bed rest interventions to prevent miscarriage (two studies, total 84 women)	Miscarriage	There was no statistically significant difference in the risk of miscarriage in the bed rest group versus the no bed rest group (placebo or other treatment) (relative risk (RR) 1.54, 95% confidence interval (CI) 0.92 to 2.58).	Aleman et al., 2005 [93]
Cochrane Review: Any uterine muscle relaxing drugs compared with placebo or no drugs (One trial, 170 women)	Miscarriage, stillbirth, maternal death	There was a lower risk of intrauterine death associated with the use of a beta-agonist (relative risk [RR] = 0.25, 95% confidence interval [CI] = 0.12 to 0.51).	Lede and Duley, 2005 [94]
Cochrane review: vitamin supplementation to prevent miscarriage (17 trials, 37,353 pregnancies)	Pregnancy failure	No difference seen between women taking any vitamins compared with no-supplementation controls for total fetal loss (relative risk [RR] = 1.05 (95%CI = 0.95–1.15), early or late miscarriage (RR = 1.08, 95%CI = 0.95–1.24) or stillbirth (RR = 0.85, 95%CI = 0.63–1.14) and most other primary outcomes, using fixed-effect models. However, women taking vitamin supplements may be less likely to develop pre-eclampsia and more likely to have a multiple pregnancy.	Rumbold et al., 2005 [97]
Cochrane review: aerobic exercise during pregnancy (11 trials, 472 women)	Maternal fitness and pregnancy maintenance	Regular aerobic exercise during pregnancy appears to improve physical fitness, but the evidence is insufficient to infer important risks or benefits for the mother or baby. The trials were small, not high methodologic quality.	Kramer and Macdonald, 2003 [96]
Cochrane review: dydrogesterone effects on cytokine production in lymphocytes from women with recurrent miscarriage; controlled prospective maternity hospital study	Inhibition of Th1 cytokines in lymphocytes	Dydrogesterone significantly inhibited the production of the Th1 cytokines IFN-gamma (P = 0.0001) and TNF-alpha (P = 0.005) and induced an increase in the levels of the Th2 cytokines IL-4 (P = 0.03) and IL-6 (P = 0.017) resulting in a substantial shift in the ratio of Th1/Th2 cytokines. Dydrogesterone effect blocked by mifepristone a progesterone-receptor antagonist, indicating dydrogesterone acts via the progesterone receptor. Dydrogesterone induced the production of PIBF.	Raghupathy et al., 2005 [64]
Cochrane review: dydrogesterone in threatened abortion; prospective open clinical study	Pregnancy outcome after dydrogesterone treatment for vaginal bleeding ≤13 weeks	The continuing pregnancy success rate was significantly (P = 0.037) higher in women treated with dydrogesterone (95.9%) compared with women who received conservative treatment (86.3%). The odds ratio of the success rate between dydrogesterone treatment and non-treatment was 3.773 (95%CI = 1.009–14.108).	Omar et al., 2005 [65]