DOI: 10.6084/m9.figshare.31135580
title: Association between Gushen Antai recipe intervention and plasma cytokines during early pregnancy following IVF-ET: a cohort study

description: Gushen Antai recipe (GSAT), known herbal medicine, has long been used in China to treat early pregnancy loss. Several randomised controlled trials have demonstrated its efficacy in improving clinical pregnancy rates. This study aimed to elucidate the mechanism of GSAT in patients undergoing in vitro fertilisation–embryo transfer (IVF-ET). Patients undergoing IVF-ET were recruited on day 14 after embryo transfer. Participants either received GSAT alongside hormonal medication for 2 weeks (intervention group) or received hormonal treatment (control group). Plasma metabolites and inflammatory factors was analysed by gas chromatography-mass spectrometry and enzyme-linked immunosorbent assay, respectively. Faecal microbiota was assessed by 16S rRNA sequencing. GSAT was found to contain 56.44% flavonoids, primarily come from Scutellariae Radix, including baicalin, baicalein, wogonoside, wogonin, oroxylin A and Chrysin 6-C-glucoside 8-C-arabinoside. At the end of the fourth week after embryo transfer, plasma levels of interleukin (IL)-2 and tumour necrosis factor-α were significantly lower in the intervention group than in the control group, whereas the anti-inflammatory cytokine IL-10 were markedly higher (687.3 vs. 448.5 pg/mL, <i>p</i> &lt; 0.01). Moreover, the plasma IL-10 levels and proportion of four kinds of fatty acids (lauric acid, myristic acid, palmitic acid, linoleic acid) in plasma correlated with each other. These fatty acids were not directly detected in GSAT and may originate from biosynthesis by gut microbiota. The alteration of plasma cytokine levels (IL-10, TNF-α and IL-2) associated with GSAT intervention was linked to specific fatty acids produced by characteristic intestinal microbiota. These results provide insights into the mechanism underlying the role of the GSAT in improving clinical pregnancy rates. During pregnancy, the developing baby can sometimes be mistakenly identified as a foreign substance by the mother’s immune system, which may lead to rejection and miscarriage. To prevent this, the mother’s body naturally sends special peacekeeping cells to the womb and releases calming signals, like a substance called anti-inflammatory cytokines. Women who have experienced multiple miscarriages often have fewer of these peacekeeping cells and lower levels of these calming signals. Therefore, helping the body bring more of these cells to the womb and increasing calming signals are considered important ways to help prevent pregnancy loss. A herbal medicine known as Gushen Antai recipe appears to work in this manner. It has been used in China for a long time, and several clinical studies have shown that it can improve the chances of a successful pregnancy. However, exactly how it works has not been fully understood. This study found that when women took this herbal medicine for 2 weeks after embryo transfer, their blood showed higher levels of the calming cytokines and lower levels of inflammatory substances. This balancing effect is believed to be one of the ways Gushen Antai recipe helps support a healthy pregnancy.