Programmed Cycle FET Lowers Early Pregnancy PAPP-A and IGF-1 Levels, Indicating Altered Placental Function

Frozen embryo transfer (FET) is a common fertility treatment, but the choice of endometrial preparation protocol can impact pregnancy outcomes. Specifically, programmed cycle (PC) FET, which uses exogenous hormones to prepare the uterus, has been linked to increased risks of preeclampsia and other placenta-related complications. This suggests that PC-FET may alter early placental development and function. Pregnancy-associated plasma protein-A (PAPP-A) and insulin-like growth factor-1 (IGF-1) are crucial biochemical markers of early placental health, with reduced levels often associated with adverse pregnancy outcomes like preeclampsia. Understanding how different FET protocols affect these markers could illuminate the underlying pathways contributing to the distinct risk profiles of PC-FET.

This secondary analysis utilized stored biobank samples from a randomized controlled trial investigating hormone concentrations in FET treatments. The study included women aged 18-40 years with a BMI ≤35 kg/m2 undergoing frozen-thawed autologous blastocyst transfer. Ovulatory women were randomized to either modified natural cycle (mNC) FET or programmed cycle (PC) FET, while anovulatory women were randomized to gonadotrophin-stimulated cycle (gSC) FET or PC-FET. The main analysis focused on n=116 women with ongoing pregnancies, with additional IGF-1 analyses performed on n=193 ovulatory women with available samples. Blood samples were collected at 7 timepoints throughout treatment, including gestational ages 4+2, 6+0, 8+0, and 9+6 weeks, for biochemical analyses of PAPP-A and IGF-1 concentrations.

The study revealed significant differences in early pregnancy biomarker concentrations based on the FET protocol. Maternal concentrations of PAPP-A and IGF-1 were consistently lower in women undergoing programmed cycle (PC) FET compared to other methods. This effect was observed distinctly across different patient populations:

Maternal concentrations of PAPP-A and IGF-1 were significantly lower in programmed cycle (PC) FET compared to modified natural cycle (mNC) FET among ovulatory women. Similarly, in anovulatory women, PAPP-A and IGF-1 concentrations were significantly lower following PC-FET when compared to gonadotrophin-stimulated cycle (gSC) FET. These findings suggest that the specific hormonal environment created by PC-FET may lead to altered early placental function, as indicated by these critical biochemical markers. While the abstract confirms statistical significance, specific numerical reductions or p-values for these differences were not provided.