Antral Follicle Priming Before Intracytoplasmic Sperm Injection in Previously Diagnosed Low Responders: A Randomized Controlled Trial (FOLLPRIM).

Abstract

A low response to controlled ovarian hyperstimulation implies a reduced number of embryos and impaired pregnancy rate. Follicular priming with steroids before controlled ovarian hyperstimulation has been suggested to improve the subsequent ovarian response. The purpose of this study was to determine the best follicular priming protocol in low responders and to investigate the intrafollicular mechanisms triggered by steroid hormone priming. This was a single-center, randomized, parallel, open-label, controlled trial, in two phases. The setting was a university-based in vitro fertilization unit. Potential low responders (n = 99) underwent a first intracytoplasmic sperm injection cycle. Confirmed low responders (n = 66) were randomized to different priming protocols before a new intracytoplasmic sperm injection. Randomized patients underwent one of the following priming strategies: transdermal testosterone (20 μg/kg/d), transdermal estradiol (200 μg/d), or combined estrogens and oral contraceptive pills (30 μg of ethinyl estradiol plus 150 μg of desogestrel administered during the luteal phase of two consecutive cycles) and 4 mg/d of estradiol valerate during the follicular phase between them. Metaphase II (MII) oocytes were retrieved. Gene expression levels in the granulosa cells of steroidogenesis enzymes and FSH, LH, and androgen receptors were measured. The number of retrieved MII oocytes did not differ between the interventional groups (testosterone, 2.2 ± 2.0; estrogen, 2.7 ± 1.7; and combined estrogens and oral contraceptive pills, 2.0 ± 1.3; not significant). Compared with those in nonprimed cycles, estradiol pretreatment yielded more MII oocytes (primed, 2.7 ± 1.7; nonprimed, 1.6 ± 1.2; P = .029) although the clinical pregnancy rate was higher in patients treated with testosterone (P = .003). Testosterone pretreatment increased androgen receptor expression (P = .028) compared with that for the previous cycle without priming. The results of the present trial do not support the superiority of one priming strategy over the others.