A randomized controlled trial has demonstrated that manual acupuncture significantly improves embryo quality, two-pronuclei (2PN) fertilization rates, and cumulative pregnancy outcomes in women aged 35 to 42 undergoing in vitro fertilization (IVF). Conducted at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, the study also revealed key metabolic pathway changes in follicular fluid after acupuncture, highlighting retinol, glycine-serine-threonine, and glycerophospholipid metabolism as biological mechanisms of efficacy [1].
The trial included 60 women with kidney qi deficiency syndrome, evenly randomized into a treatment group receiving acupuncture and a sham control group using noninvasive Streitberger placebo needles at identical points. All participants underwent identical ovarian stimulation protocols using the GnRH-a luteal-phase long protocol. [1].
Acupuncture performed three times per week until hCG injection. The protocol used sterile disposable Hwato-brand needles (0.30 × 40 mm and 0.30 × 75 mm), inserted 10 to 30 mm deep at the following points: Zhongwan (CV12), Guanyuan (CV4), Baihui (GV20), Yintang, Taixi (KD3), Shenshu (BL23), Sanyinjiao (SP6), Taichong (LV3), Tianshu (ST25), Dahe (KD12), Zigong (EX-CA1), Ciliao (BL32), and Zhongzhu (TB3). Needles were manually manipulated to elicit deqi, then retained for 30 minutes. Reinforcement techniques were repeated every 10 minutes to maintain stimulation. Communication during treatment was minimized to reduce nonspecific effects [1].
The control group received sham treatment with the Streitberger placebo needle, which mimics insertion visually but does not penetrate the skin. Sham points matched the treatment group, and superficial “pretend” stimulation was mimicked every 10 minutes. Both groups received identical IVF medication protocols [1].
Clinical outcomes favored the acupuncture group. The 2PN fertilization rate was significantly higher in the acupuncture group at 61.9% (172/278) versus 46.4% (103/222) in controls (p = .001). High-quality embryo rate also improved: 61.5% (91/148) versus 44.2% (38/86), p = .010. Most notably, the cumulative pregnancy rate per egg retrieval cycle reached 50.0% (14/28) in the acupuncture group compared to 18.2% (4/22) in controls (p = .042) [1].
To investigate biological mechanisms, researchers collected follicular fluid on oocyte retrieval day and analyzed it using UHPLC–MS (ultra-high-performance liquid chromatography–mass spectrometry). Metabolomic analysis showed statistically significant shifts in 28 metabolites between the groups, with changes clustered into three primary pathways: retinol metabolism, glycine-serine-threonine metabolism, and glycerophospholipid metabolism [1].
In the retinol metabolism pathway, retinol and its oxidized metabolite 4-oxo-retinoic acid were downregulated in the acupuncture group, while retinyl palmitate—a storage and transport form of vitamin A—was upregulated. These changes indicate enhanced regulation of vitamin A metabolism, possibly improving oocyte maturation and reducing teratogenic risks associated with unbalanced retinoid signaling [1].
Glycine, serine, and threonine metabolism was also altered. In the acupuncture group, glycine and pyruvic acid levels decreased, while guanidinoacetic acid increased. This shift suggests restored enzyme activity in amino acid conversion, aligning with previous data showing excess glycine and threonine correlates with poor embryo development and chromosomal anomalies in older IVF patients. L-cysteine, a critical antioxidant, was better regulated in the acupuncture group, potentially improving oocyte oxidative stability [1].
Within the glycerophospholipid metabolism pathway, the acupuncture group exhibited decreased levels of lysophosphatidylcholine (LysoPC 16:1) and increased levels of sn-glycero-3-phosphocholine. This pattern reflects restored phospholipid homeostasis, supporting membrane integrity and cellular signaling essential for oocyte competence. The regulation of these pathways may underlie the improved embryo quality observed [1].
The study also measured kidney qi deficiency symptom scores. Patients receiving acupuncture showed a significant decrease in symptoms over the stimulation period, with an average score improvement of 5.63 ± 2.16, compared to −0.10 ± 1.06 in controls (p < .001), suggesting not only reproductive but systemic effects consistent with TCM (traditional Chinese medicine) diagnostics [1].
Researchers used SPSS 22.0 for statistical analysis and performed principal component analysis (PCA) and partial least squares–discriminant analysis (PLS–DA) to confirm that metabolomic shifts were group-specific. Visual heatmaps and VIP scores confirmed metabolite differences with high confidence. After acupuncture, PLS–DA plots of treated participants showed clustering closer to younger control patients than to untreated elderly controls, indicating biochemical reversion toward a more youthful follicular profile [1].
Limitations of the study include small sample size and cost-limited metabolomic testing. Though pregnancy and embryo quality improved, the trial was not powered to assess live birth or neonatal outcomes. Future multicenter RCTs with long-term follow-up and inclusion of hormonal assays and uterine blood flow imaging are warranted [1].
In conclusion, this single-blind, sham-controlled RCT provides compelling clinical and biochemical evidence that manual acupuncture—applied with precise needling technique, correct gauge and depth, and repeated deqi stimulation—improves IVF fertilization and embryo development outcomes. The observed metabolic changes in follicular fluid support a mechanistic model where acupuncture enhances oocyte microenvironment through regulation of vitamin A derivatives, amino acids, and phospholipids. These findings validate acupuncture as a targeted adjunctive therapy in age-related infertility [1].
Source:
1. Qingchang Xia, Lingyu Yu, Jingyan Song, and Zhengao Sun, “The Role of Acupuncture in Women with Advanced Reproductive Age Undergoing In Vitro Fertilization–Embryo Transfer: A Randomized Controlled Trial and Follicular Fluid Metabolomics Study,” Medicine 102, no. 36 (2023): e34768.
