Abstract

Abstract Study question Does follicular fluid insulin like growth factor level (IGF-1) in poor responders (PR) differ from normoresponders? Is there a correlation between IGF-1 and IVF outcomes? Summary answer Follicular IGF-1 levels are decreased in poor-responders A positive correlation exists between IGF-1 and number of metaphase II (MII) oocytes, fertilized oocytes and transferred embryos What is known already IGFs are mainly synthesized in liver with growth hormone stimulation. IGF-1 component in follicular fluid has been reported to play a crucial role in follicular and embryonic development. In addition to previously reported positive correlation between follicular IGF-I levels and number of high quality embryos, a significant decrease in IGF-1 levels with PR and advanced maternal age has also been reported. GH supplementation in poor responders undergoing IVF has been suggested to improve IVF outcomes. A recent Cochrane analysis reported that GH slightly increases the number of oocytes retrieved and there is an uncertain effect on live birth rates (LBR). Study design, size, duration Study was designed prospectively. A power analysis, of 91% determined a need for 186 patients. Therefore 186 women undergoing IVF between October 2019 and December 2020 were included. 72 (%38,7) patients were assigned to PRs group according to Bologna criteria (BC) and 114 patients (%61.3) were recruited as controls. Antagonist protocol was used for controlled ovarian hyperstimulation. hCG was administered for ovulation trigger. Participants/materials, setting, methods Following the ovarian hyperstimulation follicular fluid samples were collected during oocyte retrieval. When the total desired number of patients was reached, frozen and preserved follicle fluids were thawed at room temperature. IGF-1 levels in samples were measured using hIGF-1 ELISA kit (BT®, China). Follicular IGF-1 levels in PRs were compared to normoresponders and correlation between IGF-1 levels and AMH levels, number of retrieved oocytes, MII and fertilized oocytes, transferred embriyos and LBR were evaluated. Main results and the role of chance Mean IGF-1 levels of normoresponders and Bologna subgroups (B1, B2, B3, B4) were 13.79±14.50 ng/ml vs 5.75±1.86, 5.47±2.83, 5.96±2.16 and 5.03±1.85 ng/ml respectively (p < 0.001). There was no statistically significant difference in clinical pregnancy (CP) per transfer and LBR per transfer between normoresponders and PRs (CPR/ET: 55.1% vs 43.7%, p:0.375; 26.5% vs 12.5% , p: 0.257). In the ROC analysis for the prediction of collection of fewer than 4 oocytes at retrieval (according to BC definition of PR), statistically determined IGF-1 value was 7.02 with a sensitivity of 83% and a specificity of 38.6%. Patients with an IGF-1 value below 7.02 had a higher risk of having an oocyte number less than 4According to the results of Spearman's correlation analysis, IGF-1 levels were negatively correlated with age and number of previous failed cycles (r:-0.250, p:0,001; r:-0.153, p:0,039 respectively). IGF-1 levels were positively correlated with AMH levels, oocyte, MII oocyte, fertilized oocyte numbers and number of transferred embriyos (r: 0.221, p: 0.007; r: 0.283, p < 0.001; r: 0.293, p < 0.001; r: 0.282, p < 0.001; r: 0.194, p: 0.008 respectively). There was a positive correlation between IGF-1 levels and cycle cancellation rates (r: 0.637, p < 0,001). There was no correlation between IGF-1 levels and LBR (p:0.118). Limitations, reasons for caution Small number of patients was the main limitation of study.Results were not interpreted as LBR in all cases, as 21% (n:24) of the cases had still ongoing pregnancies Wider implications of the findings Detecting lower follicular levels of IGF-1 which plays a crucial role in GH activity may highligt the effect of GH supplementation in poor responders undergoing IVF in terms of improved outcomes. However, there is need for more solid data to employ GH in IVF treatment modalities of poor-responders. Trial registration number not applicable

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