Abstract
BackgroundDuring the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Based on the theory of traditional Chinese medicine, Bushen Huoxue recipe (BSHXR) has been indicated to facilitate embryo implantation.MethodsThe COH model (Kunming breed) was induced by injecting mice with pregnant mare serum gonadotrophin (0.4 IU/g) and human chorionic gonadotropin (1 IU/g), followed by treatment with BSHXR at three different concentrations (5.7, 11.4, and 22.8 g/kg), Bushen recipe (BSR) (5.7 g/kg), and Huoxue recipe (HXR) (5.7 g/kg). After successful mating, the pregnancy rate and implantation sites were examined on embryo day 8 (ED8), and the weight ratio of endometrium was calculated on ED4 midnight. Serum estrogen, progesterone, and endometrial PGE2 levels were measured using enzyme-linked immunosorbent assay. The endometrial microvasculature was evaluated using CD31 immunostaining. The protein and mRNA levels of the angiogenic factors in the endometrium were evaluated using western blot, immunohistochemistry, and polymerase chain reaction.ResultsIn the COH group, the pregnancy rate and implantation sites were significantly decreased, and abnormal serum hormone levels and impaired endometrial vascular development were observed. After BSHXR treatment, the supraphysiological serum progesterone level in COH mice was restored to normalcy. Moreover, the abnormal expression of the endometrial pro-angiogenic factors, including HIF1α, COX2-PGE2 pathway, and the down-stream factors, namely, MMP2, MMP9, TIMP2, and FGF2 after subjecting mice to COH was significantly improved after BSHXR treatment.ConclusionBSHXR could improve embryo implantation by regulating hormonal balance and modulating endometrial angiogenesis in mice, without inducing any side effects in normal pregnancy.
Highlights
During the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity
Bushen Huoxue recipe (BSHXR) improved embryo implantation and endometrial development First, we evaluated the efficacy of BSHXR in mice that were subjected to COH
The pregnancy outcome in the control + BSHXR group was comparable to that in the control group, demonstrating the safety of BSHXR administration during pregnancy. Apart from these findings, we further found that BSHXR could increase the expression of angiogenesis factors, such as HIF1α, Cyclooxygenase 2 (COX2), prostaglandin E 2 (PGE2), EP2 receptor, MMP2, MMP9, and fibroblast growth factor 2 (FGF2), and inhibit TIMP2 in the endometrium, all of which could participate in the vascular development during early pregnancy
Summary
During the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Upon adhering to the luminal epithelium, the trophectoderm starts to invade on ED4 midnight and is buried into the endometrium on the evening of ED5, which indicates the completion of implantation [7] All of these steps are critically governed by steroid hormones [8]. Accumulating evidence reveals that high levels or a rapid elevation in the levels of estrogen, progesterone, or human chorionic gonadotropin (HCG) could be associated with suboptimal and asynchronous endometrial development, resulting in implantation failure [9]
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