ADJUSTED INDIRECT COMPARISON OF THE MEDICINES USING IN CONTROLLED OVARIAN STIMULATION FOR ASSISTED REPRODUCTIVE TECHNOLOGY

OBJECTIVES : to perform comparative effectiveness analysis of the three most common medicines for assisted reproductive technology (ART): follitropin-alpha + lutropin-alpha (A), menotropin (B), follitropin-alpha + menotropin (C) using in controlled ovarian stimulation (COS).

METHODS : systematic literature review in Cochrane library, Medline, Embase and clinicaltrials.gov was carried out on December 2019 – there was no direct trial between menotropin (B) and follitropin-alpha + menotropin (C) available, therefore adjusted indirect comparison (AIC) by Bucher`s method was performed. Only one post-marketing head-to-head clinical trial (CT) with retrospective efficacy data of the mentioned medicines was found (K.Buhler et al. 2012). Efficacy endpoint was the number of clinical pregnancies per initiated cycle. 219, 167 and 180 patients achieved clinical pregnancy in groups A, B and C respectively. CT showed statistically significant difference between group A vs. B (p = 0.007) and A vs. C. (p = 0.018). AIC was performed between B and C based on the Buhler`s trial outcomes using A as the common comparator. The odds ratio (OR) and risk ratio (RR) of clinical pregnancies per initiated cycle were chosen as the effect measure.

RESULTS : OR and RR for B-A comparison pair showed statistically significant difference: OR = 0,73 (0,59;0,91); RR = 0,76 (0,63;0,92). OR and RR for C-A comparison pair also showed statistically significant difference: OR = 0,80 (0,65;0,99); RR = 0,82 (0,68;0,99). AIC showed no significant difference between pair B-C since the CI cross one: OR = 0,92 (0,68;1,24); RR = 0,93 (0,71;1,21).

CONCLUSIONS : AIC showed the absence of a statistically significant difference in the efficacy between menotropin and follitropin-alpha + menotropin. Due to the limitations of indirect comparison methodology additional direct study are required.