Erzhi Tiangui Granules Improve In Vitro Fertilization Outcomes in Infertile Women with Advanced Age

Abstract

Background. The fertility of females with advanced age declines with aging. Therefore, for medical and social reasons, it is important to establish mechanisms to protect and improve the fertility of such populations. With widespread use of traditional Chinese medicine (TCM) in in vitro fertilization (IVF), studies have evaluated their impact on improving the fertility of females with advanced age. In this study, we performed proteomic analysis of follicular fluid to reveal mechanisms of the Erzhi Tiangui (EZTG) granule (Chinese herbs for replenishing vital essence to tonify the kidney) in improving the outcomes of IVF in infertile women with advanced age. Methods. This was a randomized, double-blind, and placebo-controlled trial in which 100 patients with advanced age were divided into the EZTG group and the placebo group by the random number table plus envelope method. Both groups were subjected to controlled ovarian stimulation with a GnRH antagonist regimen. Differences between the two groups were evaluated, including the TCM syndrome score after treatment, gonadotrophin (Gn) days and Gn doses, the number of retrieved oocytes, 2 pronucleus (PN) fertilization, 2PN cleavage, and high-quality embryos. Differentially expressed proteins were identified using the LC-MS/MS method, and their functions were determined through bioinformatics analyses. Results. The number of high-quality embryos in the placebo group was significantly lower than that in the EZTG group (2.88 ± 1.85 vs. 4.13 ± 2.83, $p=0.011$ ). Eleven differentially expressed proteins were identified between the two groups. Four proteins were highly expressed, whereas seven were suppressed in the control group, compared to the EZTG group. The overall trend suggested that the apoptotic effect in the follicular fluid of the EZTG group was downregulated. Conclusion. Treatment with the EZTG granule can improve embryo quality in IVF of advanced age females with both kidney Qi and Yin deficiency syndromes. The mechanism is attributed to downregulation of apoptotic-effector protein expressions in the follicular fluid. This trial is registered with ChiCTR1900025139.