Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders: a systematic review and meta-analysis.

STUDY QUESTION: Does a luteal estradiol (LE) stimulation protocol improve outcomes in poor responders to IVF?

SUMMARY ANSWER: LE priming is associated with decreased cycle cancellation and increased chance of clinical pregnancy in poor responders

WHAT IS KNOWN ALREADY: Poor responders to IVF are one of the most challenging patient populations to treat. Many standard protocols currently exist for stimulating these patients but all have failed to improve outcomes.

STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis including eight published studies comparing assisted reproduction technology (ART) outcomes in poor responders exposed to controlled ovarian hyperstimulation with and without LE priming. A search of the databases MEDLINE, EMBASE and PUBMED was carried out for studies in the English language published up to January 2012.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies evaluating women defined as poor responders to ART were evaluated. These studies were identified following a systematic review of the literature and data were analyzed using the DerSimonian-Laird random effects model. The main outcomes of interest were cycle cancellation rate and clinical pregnancy. Although the definition of clinical pregnancy varied between studies, the principal definition included fetal cardiac activity as assessed by transvaginal ultrasonography after 5 weeks of gestation.

MAIN RESULTS AND THE ROLE OF CHANCE: A total of 2249 publications were identified from the initial search, and the bibliographies, abstracts and other sources yielded 11 more. After excluding duplications, 1227 studies remained and 8 ultimately met the inclusion criteria. Compared with women undergoing non-LE primed protocols (n = 621), women exposed to LE priming (n = 468) had a lower risk of cycle cancellation [relative risk (RR): 0.60, 95% confidence interval (CI): 0.45-0.78] and an improved chance of clinical pregnancy (RR: 1.33, 95% CI: 1.02-1.72). There was no significant improvement in the number of mature oocytes obtained or number of zygotes obtained per cycle.

LIMITATIONS, REASONS FOR CAUTION: These findings are limited by the body of literature currently available. As the poor responder lacks a concrete definition, there is some heterogeneity to these results, which merits caution when applying our findings to individual patients. Furthermore, the increased clinical pregnancy rate demonstrated when using the LE protocol may be principally related to the decreased cycle cancellation rate.

WIDER IMPLICATIONS OF THE FINDINGS: The LE protocol may be of some utility in the poor responder to IVF and may increase clinical pregnancy rates in this population by improving stimulation and thereby decreasing cycle cancellation.

STUDY FUNDING/COMPETING INTERESTS: NIH K12 HD063086 (ESJ, MGT), NIH T32 HD0040135-11 (KAR), F32 HD040135-10 NIH (KRO), 5K12HD000849-25 (PTJ). No competing interests.