Background <p>Jinfeng pills (JFP), a well-known traditional Chinese medicine (TCM) consisted of 9 herbs, benefit <i>Qi</i>, nourish the blood, effectively regulate the menstrual cycle, promote ovulation and improve endometrial thickness and blood flow. Previous studies have shown that JFP has certain effect on premature ovarian insufficiency (POI). In this prospective cohort study, the effect and mechanisms of JFP on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in poor ovarian response(POR) was investigated.</p> Methods <p>Patients diagnosed with POR based on the Bologna criteria were prospectively randomized into two groups: the JFP group and the POR group. Young patients with normal ovarian reserve were included in the Control (Con) group. The live birth rate (LBR), levels of estradiol (E<sub>2</sub>), progesterone, total testosterone (TT), and insulin-like growth factor-1 (IGF-1) in the follicular fluid (FF) and outcomes of IVF-ET were compared. Network pharmacology, combined with transcriptomics and proteomics, was used to identify core targets and signaling pathways. Molecular docking was performed to evaluate the interactions between the core components of JFP and the identified targets.</p> Results <p>Compared with the Con group, the POR group presented significantly lower levels of E<sub>2</sub> [1302.00 (985.50, 1464.50) ng/mL vs. 2561.00 (2190.50, 3084.00) ng/mL] and TT [2.41 (1.45, 3.15) ng/mL vs. 5.12 (4.00, 6.79) ng/mL] in FF (<i>P</i> &lt; 0.017). These levels were greater in the JFP group [E<sub>2</sub>: 2450.00 (1603.00, 2842.00) ng/mL; TT: 2.85 (2.08, 4.55) ng/mL] than in the POR group (<i>P</i> &lt; 0.017). IGF-1 levels in FF [79.60 (64.00, 88.50) ng/mL vs. 87.90 (78.80, 112.00) ng/mL], the implantation rate, and the LBR per treatment were significantly lower in the POR group than in the Con group (<i>P</i> &lt; 0.017), while there was no significant difference compared with those in the JFP group (<i>P</i> &gt; 0.05). The birth weight and height of the infants did not differ significantly among the three groups (<i>P</i> &gt; 0.05). Transcriptomic and proteomic analyses revealed seven core genes (<i>ALPL</i>,<i> HPSE</i>,<i> KRT1</i>,<i> LDLR</i>,<i> METTL7B</i>,<i> TGFBI</i>, and <i>TMOD1</i>) and one key pathway (glycosaminoglycan degradation). Molecular docking confirmed strong binding activity between the core components of JFP and these genes.</p> Conclusion <p>JFP enhances the ovarian levels of steroid hormones in poor ovarian responders undergoing IVF-ET. The therapeutic effects of JFP may involve the regulation of <i>ALPL</i>,<i> HPSE</i>,<i> KRT1</i>,<i> LDLR</i>,<i> METTL7B</i>,<i> TGFBI</i>,<i> TMOD1</i>, and the glycosaminoglycan degradation pathway.</p>

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Multi-omics analysis reveals the effects of Jinfeng pills on the outcomes of IVF-ET in patients with poor ovarian response: a randomized controlled trial

  • Xumei Kong,
  • Qianwen Luo,
  • Tianhong Huang,
  • Furui Chen,
  • Yanan Zhang,
  • Dongsheng Xiong,
  • Yu Qiu,
  • Wei Lai,
  • Xiaoyan Yan,
  • Fangyi Long,
  • Yan Gong

摘要

Background

Jinfeng pills (JFP), a well-known traditional Chinese medicine (TCM) consisted of 9 herbs, benefit Qi, nourish the blood, effectively regulate the menstrual cycle, promote ovulation and improve endometrial thickness and blood flow. Previous studies have shown that JFP has certain effect on premature ovarian insufficiency (POI). In this prospective cohort study, the effect and mechanisms of JFP on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in poor ovarian response(POR) was investigated.

Methods

Patients diagnosed with POR based on the Bologna criteria were prospectively randomized into two groups: the JFP group and the POR group. Young patients with normal ovarian reserve were included in the Control (Con) group. The live birth rate (LBR), levels of estradiol (E2), progesterone, total testosterone (TT), and insulin-like growth factor-1 (IGF-1) in the follicular fluid (FF) and outcomes of IVF-ET were compared. Network pharmacology, combined with transcriptomics and proteomics, was used to identify core targets and signaling pathways. Molecular docking was performed to evaluate the interactions between the core components of JFP and the identified targets.

Results

Compared with the Con group, the POR group presented significantly lower levels of E2 [1302.00 (985.50, 1464.50) ng/mL vs. 2561.00 (2190.50, 3084.00) ng/mL] and TT [2.41 (1.45, 3.15) ng/mL vs. 5.12 (4.00, 6.79) ng/mL] in FF (P < 0.017). These levels were greater in the JFP group [E2: 2450.00 (1603.00, 2842.00) ng/mL; TT: 2.85 (2.08, 4.55) ng/mL] than in the POR group (P < 0.017). IGF-1 levels in FF [79.60 (64.00, 88.50) ng/mL vs. 87.90 (78.80, 112.00) ng/mL], the implantation rate, and the LBR per treatment were significantly lower in the POR group than in the Con group (P < 0.017), while there was no significant difference compared with those in the JFP group (P > 0.05). The birth weight and height of the infants did not differ significantly among the three groups (P > 0.05). Transcriptomic and proteomic analyses revealed seven core genes (ALPL, HPSE, KRT1, LDLR, METTL7B, TGFBI, and TMOD1) and one key pathway (glycosaminoglycan degradation). Molecular docking confirmed strong binding activity between the core components of JFP and these genes.

Conclusion

JFP enhances the ovarian levels of steroid hormones in poor ovarian responders undergoing IVF-ET. The therapeutic effects of JFP may involve the regulation of ALPL, HPSE, KRT1, LDLR, METTL7B, TGFBI, TMOD1, and the glycosaminoglycan degradation pathway.