| خلاصه مقاله | Study question: Association between follicular fluid (FF) levels of adrenomedullin 2 (ADM2), vascular endothelial growth factor (VEGF) and its soluble receptors with ICSI outcome.
Summary answer: The FF ADM2 could be a potential predictive marker for ovarian non-responders with cutoff value of 348.55 (pg/ml).
What is known already: ADM2 and VEGF are involved in ovarian function especially angiogenesis, follicular development, and ovulation. VEGF action could be antagonized by its soluble receptors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), via decreasing its free form, thereby decreasing angiogenesis. It has been reported that sFlt-1 and sVEGFR-2 have low expression in post-selected follicles (POF) compared with preselected follicles (PRF). However, after dominant follicle selection, sVEGFR-2 expression increases while sFlt-1 expression reduces along with the days of cycle.
Study design, size, and duration: Ninety non-smoker women aged from 20-40 years with fallopian tube obstruction, idiopathic infertility and male factor infertility (varicocele and oligospermia) were enrolled in this study. The long GnRH agonist–recombinant FSH protocol was used for all patients and a single FF aspiration without blood was done. All patients were treated with ICSI and were categorized as non-, poor-, normo- and high-responders according to the retrieved oocytes number.
Participants/materials, setting, methods: The fertilization rates were determined by dividing the number of fertilized oocytes with the number of mature oocytes and the clinical pregnancy was evaluated by existence of the intrauterine gestational sac via transvaginal ultrasound. Implantation rate was defined as the quantity of visible sacs per number of transferred embryos. FF ADM2, VEGF, sFlt-1 and sVEGFR-2 levels were determined by ELISA kits and the VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios were also calculated.
Main results and the role of chance: In the present study, for first time existence of ADM2 in FF was reported; its mean level was 62.2±66.86 pg/ml. Also, it was found that age of the patients was significantly correlated with ADM2 (r=0.268, p=0.049). ADM2 level was positively correlated with VEGF and sVEGFR-2 levels (r=0.586, p=0.001 and r=0.482, p=0.001, respectively). Our results showed that the levels of ADM2 in FF were significantly higher in ovarian non-responders in comparison to patients with poor- normo- and high- ovarian responses (p<0.05). Also, the FF levels of VEGF, and sVEGFR-2 were significantly higher in the non-responders than in poor-responder patients (p<0.05). We found no significant association between FF levels of ADM2, VEGF and sVEGFR-2 with clinically pregnant. Based on receiver operating characteristic (ROC) analyses, cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with sensitivity and specificity of 67.7 % (CI, 67.21–68.25%) and 94.6% (CI, 94.11–95.08%), respectively.
Limitations, reasons for caution: It is a preliminary report covering exist-ence of ADM2 in FF and further studies are required to clarify mode of action of ADM2 in ovarian angiogenesis. The number of subjects was almost low and there may have been other confounding factors that we were unable to account for.
Wider implications of the findings: We found higher FF levels of ADM2 in non-responder women and proposed ADM2 as a potential predictive marker for non-responders. Besides, positive correlations of ADM2 with VEGF and sVEGFR-2 were obtained, what could be considered as an important clue regarding the roles of ADM2 in ovarian angiogenesis.
Trial registration number:Not applicable |