Higher serum levels of IGF-1 is associated with a higher rate of pregnancy loss following frozen-thawed euploid embryo transfer cycles

Abstract

An elevated level of insulin growth factor (IGF-1) in rat uterine fluid has been shown to exert detrimental effects of embryo development possibly leading to an increase in pregnancy loss. Interestingly, the administration of somatostatin to rats undergoing superovulation reduced IGF-1 levels in uterine luminal fluid and thus reversed its deleterious effects on embryo development and increased the number of normal embryos. Therefore, we investigated whether serum levels of IGF-1 correlate with the incidence of pregnancy loss following IVF. Retrospective case-control study. A total of 238 consecutive natural frozen-thawed embryo transfer (FET) cycles with PGS-selected euploid blastocysts were reviewed. All patients who conceived were included. Serum levels of IGF-1 in the early follicular phase were compared between those who achieved live birth and those who had pregnancy loss. Pregnancy loss included biochemical pregnancy and spontaneous abortion. Serum IGF-1 levels were measured by ELISA assay. Values were expressed as mean ± SEM. t-test was used as appropriate. A total of 159 cycles that resulted in pregnancy following FET of euploid blastocyst(s) were included. The mean age was 36.2 ± 1.1 years, body mass index (BMI): 23.1 ± 1.2 kg/m2, gravidity: 1.7 ± 0.2, parity: 0.6 ± 0.3, and peak endometrial thickness: 8.8 ± 0.6 mm. 76.1% achieved live birth while 23.9% had pregnancy loss. Women who achieved live birth had a significantly lower serum IGF-1 levels compared to those who had pregnancy loss (14.3 ± 0.7 vs. 17.7 ± 1.2 ng/mL, respectively; P=0.03). There was no significant difference in women’s age, BMI, gravidity, parity, or endometrial thickness between the two groups. Serum IGF-1 levels are higher in women who have pregnancy loss compared to those who achieve live birth following natural FET cycle. Our findings are consistent with animal studies showing that elevated IGF-1 levels impair embryo development by down-regulating IGF-1 receptor and subsequently decreasing insulin-stimulated glucose uptake and triggering apoptosis. This may constitute a novel molecular explanation of pregnancy loss especially for that occurring with a euploid conceptus.