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

Alicia Marzal Escriva, Cesar Diaz-Garcia, Mercedes Monterde, José María Rubio, Antonio Pellicer

Low response to controlled ovarian stimulation (COH) implies a reduced number of embryos and impaired pregnancy rate. Follicular priming with steroids prior to COH has been suggested to improve the subsequent ovarian response. To determine the best follicular priming protocol in low responders and to investigate the intrafollicular mechanisms triggered by steroid-hormone priming. Single center, randomized, parallel, open-label, controlled trial, in two phases. University-based IVF Unit. Potential low responders (n=99) underwent a first ICSI cycle. Confirmed low responders (n=66) were randomized to different priming protocols prior to a new ICSI. Randomized patients underwent one of the following priming strategies: transdermal testosterone (T:20 μ g/kg/day), transdermal estradiol (E:200 μ g/day) or combined oral contraceptive pills (EOCP:30 μ g of ethinyl-estradiol plus 150 μ g of desogestrel administered during the luteal phase of two consecutive cycles) and 4 mg/day of estradiol valerate during the follicular phase between them. Metaphase II (MII) oocytes retrieved. Gene expression in granulosa cells of steroidogenesis enzymes and the following receptors: FSH, LH and androgen. The number of retrieved MII didn't differ between interventional groups (T:2.2±2.0; E:2.7±1.7; EOCP:2.0±1.3; n.s). When compared to non-primed cycles, estradiol pretreatment yielded more MII oocytes (Primed:2.7±1.7; Non-primed:1.6±1.2; p=0.029) although clinical pregnancy rate was higher in patients treated with testosterone (p=0.003). Testosterone pre-treatment increased androgen receptor expression (p=0.028) when compared to the previous cycle without priming. the results of the present trial do not support the superiority of one priming strategy over the others.