Carolien M Boomsma1, Stephen D Keay, Nick S Macklon. 1. Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, Netherlands. 2Centre for Reproductive Medicine, UHCWNHS Trust, Coventry, UK. c.m.boomsma@umcutrecht.nl.
Abstract
BACKGROUND: In order to improve embryo implantation for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation. OBJECTIVES: To investigate whether the administration of glucocorticoids around the time of implantation improved clinical outcomes in subfertile women undergoing IVF or ICSI when compared to no glucocorticoid administration. SEARCH METHODS: The Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2011), MEDLINE (1966 to September 2011), EMBASE (1976 to September 2011), CINAHL (1982 to September 2011) and Science Direct (1966 to September 2011) were searched. Reference lists of relevant articles and relevant conference proceedings were handsearched. SELECTION CRITERIA: All randomised controlled trials (RCTs) addressing the research question were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of trials and extracted relevant data. MAIN RESULTS: Fourteen studies (involving 1879 couples) were included. Three studies reported live birth rate and these did not identify a significant difference after pooling the (preliminary) results (OR 1.21, 95% CI 0.67 to 2.19). With regard to pregnancy rates, there was also no evidence that glucocorticoids improved clinical outcome (13 RCTs; OR 1.16, 95% CI 0.94 to 1.44). However, a subgroup analysis of 650 women undergoing IVF (6 RCTs) revealed a significantly higher pregnancy rate for women using glucocorticoids (OR 1.50, 95% CI 1.05 to 2.13). There were no significant differences in adverse events, but these were poorly and inconsistently reported. AUTHORS' CONCLUSIONS: Overall, there was no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improved the clinical outcome. The use of glucocorticoids in a subgroup of women undergoing IVF (rather than ICSI) was associated with an improvement in pregnancy rates of borderline statistical significance and should be interpreted with care. These findings were limited to the routine use of glucocorticoids and cannot be extrapolated to women with autoantibodies, unexplained infertility or recurrent implantation failure. Further well designed randomised studies are required to elucidate the possible role of this therapy in well defined patient groups.
BACKGROUND: In order to improve embryo implantation for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation. OBJECTIVES: To investigate whether the administration of glucocorticoids around the time of implantation improved clinical outcomes in subfertile women undergoing IVF or ICSI when compared to no glucocorticoid administration. SEARCH METHODS: The Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2011), MEDLINE (1966 to September 2011), EMBASE (1976 to September 2011), CINAHL (1982 to September 2011) and Science Direct (1966 to September 2011) were searched. Reference lists of relevant articles and relevant conference proceedings were handsearched. SELECTION CRITERIA: All randomised controlled trials (RCTs) addressing the research question were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility and quality of trials and extracted relevant data. MAIN RESULTS: Fourteen studies (involving 1879 couples) were included. Three studies reported live birth rate and these did not identify a significant difference after pooling the (preliminary) results (OR 1.21, 95% CI 0.67 to 2.19). With regard to pregnancy rates, there was also no evidence that glucocorticoids improved clinical outcome (13 RCTs; OR 1.16, 95% CI 0.94 to 1.44). However, a subgroup analysis of 650 women undergoing IVF (6 RCTs) revealed a significantly higher pregnancy rate for women using glucocorticoids (OR 1.50, 95% CI 1.05 to 2.13). There were no significant differences in adverse events, but these were poorly and inconsistently reported. AUTHORS' CONCLUSIONS: Overall, there was no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improved the clinical outcome. The use of glucocorticoids in a subgroup of women undergoing IVF (rather than ICSI) was associated with an improvement in pregnancy rates of borderline statistical significance and should be interpreted with care. These findings were limited to the routine use of glucocorticoids and cannot be extrapolated to women with autoantibodies, unexplained infertility or recurrent implantation failure. Further well designed randomised studies are required to elucidate the possible role of this therapy in well defined patient groups.