Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relevance to clinical outcomes from in vitro fertilization (Study 5).

In this fifth study examining the relevance of the insulin-like growth factor (IGF) profiles, namely serum IGF-1 levels, its main binding protein, serum IGFBP-3 levels and the IGF ratio (IGFBP-3/IGF-1), we have examined clinical outcomes with respect to the quartile ranges of each parameter measured in 1633 IVF-naïve women. The outcomes were derived from 1035 of these women who initiated 1747 IVF cycles. Of the three parameters, only IGF-1 levels proved relevant to the clinical outcomes. In particular, this study confirmed our earlier report that IGF-1 levels decline across the quartiles with the woman’s advancing age and the proportion of women with IGF-1 levels in the highest quartile comprised the younger, whilst those women ≥40 years were mostly in the lowest quartile (p<0.0001). IVF cycle cancellations were not different across the quartiles but at oocyte pick-up (OPU) there were significantly more oocytes from the highest IGF-1 quartile (10.4 oocytes) compared to the lowest (8.9 oocytes; p<0.01). Furthermore, the proportion of oocytes shown to be at the mature MII stage were also significantly higher (p=0.01). Consequently, the oocyte utilization rate was significantly greater from those women with the highest IGF-1 levels generating 5.3 embryos vs 4.3 embryos for the lowest quartile. However, the utilization rate of those embryos generated were similar across the IGF-1 quartiles and there were similar rates of “freeze-all embryos”, albeit more women had increased monitoring for ovarian hyperstimulation risk, related to the higher egg numbers in the highest IGF-1 quartile. The most striking clinical outcomes were that of the pregnancy productivity rate (including fresh and frozen embryo transfers from a single OPU) which was greatest in the highest IGF-1 quartile (61.5% vs 48.2% per OPU across all ages p<0.0002). Miscarriage rates were not different but live birth productivity rates were significantly greatest for the highest IGF-1 quartile (49% vs 33% per OPU across all ages; p<0.0002). We conclude that a preliminary measurement of the IGF-1 level can help to define the poor-prognosis female prior to IVF treatment and on whom adjuvant studies can be focused.