IGF-1 and IGFBP-3 serum concentrations in patients undergoing programmed frozen-thawed embryo transfer of euploid PGT-A embryos

Abstract

IGF-1 has been shown to induce embryonic development in vitro, but at high concentrations exhibits toxic effects by decreasing embryonic glucose uptake. IGFBP-3 binds IGF-1, modulating its bioavailability and is essential to its function. Prior reports have associated elevated follicular phase IGF-1 with pregnancy loss in frozen-thawed embryo transfer in natural cycles (n-FET), but an association in programmed (p-FET) cycles or in the luteal phase has not been analyzed. We sought to determine whether serum levels of IGF-1 and IGFBP-3 correlate with the outcome of p-FET cycles. Retrospective cohort study. Patients who underwent p-FET of single, good quality (Grade ≥2BB), PGT-normal embryos were included in the study. GnRH-agonist suppression was started in the preceding luteal phase, overlapped with estradiol patches, and stopped with the start of progesterone. Serum samples were collected on cycle day 2 (CD2), the day of progesterone start (CDP4), and cycle days 28 (CD28) and 30 (CD30). Embryo transfer occurred on the 7th day of P4 administration. Serum levels of IGF-1 and IGFBP-3 were compared between those who did not achieve pregnancy, those who had a live birth, and those who had a pregnancy loss. Serum IGF-1 and IGFBP-3 levels were measured by chemiluminescent immunoassays using the Immulite 2000 XPi. Statistical analysis was performed using Chi-square and Fisher’s exact test. P<0.05 was deemed statistically significant. A total of 102 patients who underwent p-FET of single euploid embryos over 2 years were analyzed. The mean age at retrieval was 35.7 ± 4.1 years, BMI 24.2 ± 4.8 kg/m2, gravity 1.8 ± 1.6, parity 0.4 ± 0.6 and peak endometrial thickness 9.7 ± 2.0 mm. 76.5% of patients were pregnant and 78.2% of those had a live birth. Among women who conceived, those who had a subsequent pregnancy loss had significantly higher serum IGF-1 levels on CDP4 and CD28 compared to those who achieved live birth when analyzing patients whose serum IGF-1 levels were above the mean value of IGF-1 level on CDP4 (136 ng/ml, p= 0.044) and CD28 (138 ng/ml, p=0.007), and between patients with CD28 IGF-1 levels one standard deviation above the mean (≥160 ng/ml, p=0.007). There was no significant difference in the serum levels of IGFBP-3 in any of the treatment cycle days.Tabled 1p-FET, Deliveredp-FET, Pregnancy losspIGF-1 CDP4 (≥ mean value)63.6%33%0.044IGF-1 CD 28(≥ mean value)58%14%0.044IGF-1 CD28 (≥ 160 ng/ml)70.8%14%0.007 Open table in a new tab In p-FET cycles with transfer of a single, euploid, high quality embryo, IGF-1 serum levels on day of progesterone start and CD28 are significantly higher in patients who subsequently had a pregnancy loss compared to those who had a live birth. This is in contrast to the findings of prior studies in n-FET.