Integrating Acupuncture and Herbal Medicine into Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of East Asian Traditional Medicine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protocol and Registration
2.2. Search Strategy and Selection Criteria
2.3. Inclusion Criteria
- P (population): This is defined as infertile couples undergoing ART treatment (IVF and ICSI). ART refers to medical procedures and interventions that assist individuals or couples in achieving pregnancy, typically involving techniques such as IVF and ICSI.
- I (intervention): EATM therapies, including acupuncture (classic acupuncture, electro-acupuncture, laser acupuncture, and auricular acupuncture) and HM (herbal powders, pills, granules, decoctions, and ointments), were examined. The intervention protocols in ART cycles primarily focused on three aspects: duration, frequency, and timing. The duration ranged from 1 to 12 weeks. Acupuncture was administered once daily or every other day, while HM was taken two to three times per day. Interventions were implemented before and during IVF, as well as after embryo transfer (ET).
- C (comparison): Sham or placebo EATM therapies and conventional IVF/ICSI treatment (long protocol, GnRH antagonist protocol, Frozen ET protocol, IVF-ET microstimulation).
- O (outcome): A total of 4 outcome indices were analyzed in the meta-analysis (i.e., CPR, LBR, IR and AE). The CPR is defined as the presence of an intrauterine gestational sac. The LBR is defined as the ratio between the number of patients with live-born babies and the number of embryo transfers performed. The IR is defined as the percentage of embryos that were transferred that developed at least to the stage of fetal heart activity, as documented by pregnancy ultrasound. An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an EATM treatment.
- S (study design): Only English-language RCTs were included.
2.4. Definitions of Control, Sham, and Placebo Groups
- Control Group: Participants received standard ART treatments (e.g., IVF or ICSI) without any additional EATM intervention, providing a baseline for comparison.
- Sham Acupuncture Group: Used in six trials, sham acupuncture involved needling at nonacupuncture points (nonacupoints) or using noninvasive needles that did not penetrate the skin. This method mimicked the acupuncture procedure while minimizing specific therapeutic effects, serving as an active control to account for placebo responses.
- Placebo Group: In six HM trials, the placebo consisted of pills made from a mixture of starch and glucose, shaped to resemble real herbal medicine pills. This ensured blinding and allowed for an assessment of the specific effects of herbal medicine beyond psychological or expectancy-driven responses.
2.5. Exclusion Criteria
2.6. Data Extraction
2.7. Risk of Bias Assessment
- Studies rated low-risk (e.g., 7, 11, 33, 39, 41–44, 46–49, 52–55) showed robust randomization, effective blinding, and full outcome reporting.
- Studies showing some concerns (e.g., 9, 10, 12, 29–32, 36–38, 40, 45) typically reflected minor uncertainties that did not compromise study validity.
- High-risk studies (e.g., 50, 51, 56–60) had serious methodological issues such as inadequate randomization, a lack of blinding, or selective reporting.
2.8. Data Synthesis and Statistical Analysis
- 0–40%: no heterogeneity.
- 30–60%: moderate heterogeneity.
- 50–90%: substantial heterogeneity.
- 75–100%: considerable heterogeneity.
- 75–90% falls into both classifications, meaning it is at the higher end of substantial heterogeneity and the lower end of considerable heterogeneity.
- Sample size: Larger studies may yield more precise results than smaller trials.
- EATM intervention types: Distinguishing between acupuncture and HM allows us to isolate their unique effects. This is essential, as each intervention type may influence reproductive outcomes differently due to their distinct physiological mechanisms.
2.9. Publication Bias
2.10. Assessment of Evidence Quality
- Risk of Bias: Studies were downgraded if there were concerns about randomization, blinding, or selective reporting.
- Inconsistency: Evidence was downgraded if studies showed conflicting results across trials.
- Indirectness: Evidence was considered indirect if populations or interventions differed significantly from those relevant to the research question.
- Imprecision: Studies with wide confidence intervals or small sample sizes were downgraded.
- Publication Bias: We assessed whether smaller studies with negative results might not have been published, which could skew findings.
2.11. Impact on Study Findings
3. Results
3.1. Results of the Search
3.2. Characteristics of Included Studies
3.3. Risk of Bias
3.4. Outcomes
3.4.1. Primary Outcomes
3.4.2. Secondary Outcomes
3.4.3. Safety of Outcomes
3.4.4. Adherence
3.5. Subgroup Analyses
3.6. Sensitivity Analysis
- Acupuncture vs. Sham: The CPR showed a significant increase (RR = 1.218, 95% CI 1.019–1.455, p = 0.030), while the LBR did not show a significant improvement (RR = 1.152, 95% CI 0.892–1.488, p = 0.277), suggesting a moderate effect on clinical pregnancy but not on live birth rates.
- HM vs. Sham: The CPR was significantly higher in the HM group compared to placebo (RR = 1.211, 95% CI 1.071–1.370, p = 0.002), reinforcing the potential benefits of HM interventions.
- Acupuncture vs. Control: Both the CPR (RR = 1.416, 95% CI 1.231–1.629, p < 0.001) and LBR (RR = 1.465, 95% CI 1.163–1.846, p = 0.001) were significantly higher, indicating the positive effect of acupuncture when compared to a no-treatment control.
- HM vs. Control: No significant difference was observed in the CPR (RR = 1.101, 95% CI 0.646–1.876, p = 0.724), suggesting that HM did not outperform standard IVF treatment.
3.7. Publication Bias
3.8. Quality of Evidence by GRADE
3.9. Key Acupoints and Meridians
HM Intervention
4. Discussion
4.1. Summary of Main Results
4.2. EATM Mechanisms on Reproductive Outcomes
4.2.1. Acupuncture Mechanisms on ART Outcomes
4.2.2. HM Mechanisms on ART Outcomes
4.3. Strengths and Limitations
4.4. The Gaps in the Literature
4.5. Variability in Acupuncture and HM
- Different Acupuncture Techniques: Variations in types of acupuncture (e.g., body, electro-acupuncture, auricular), stimulation methods (manual vs. electrical), needle placement, and treatment duration introduce inconsistencies in administration, leading to variable outcomes across studies.
- Sham Acupuncture Impact: The range of sham techniques used affects control comparisons and complicates efficacy evaluation. Some sham methods may cause physiological responses, skewing results and making it difficult to assess the true effects of acupuncture.
- HM Diversity: The wide variety of herbal formulas (e.g., powders, pills, decoctions), dosages, and timing (before, during, or after IVF) complicates comparisons. These variations prevent clear conclusions about the efficacy of specific EATM interventions.
4.6. Practice and Future Research Implications
4.7. The Potential Policy Implications
- Standardization of EATM Treatments in ART: Policymakers should develop unified guidelines for the application of acupuncture and HM in ART. This includes standardizing treatment protocols to improve consistency, reproducibility, and clinical outcomes across settings.
- Practitioner Training and Certification: Establishing specialized training and certification programs for EATM practitioners working in ART settings can ensure safe, high-quality, and evidence-informed care.
- Insurance and Accessibility: Expanding insurance coverage to include evidence-based EATM therapies can improve accessibility and reduce financial barriers for patients seeking integrative ART support.
- Interdisciplinary Collaboration: Fostering collaboration between reproductive endocrinologists and EATM practitioners may promote comprehensive and patient-centered care, leading to better clinical outcomes and patient satisfaction.
4.8. Integration of EATM in Clinical Practice
- Preparation Phase (3 months before IVF)
- 2.
- Ovarian Stimulation to Egg Retrieval
- 3.
- Embryo Transfer (ET) Day
- 4.
- Post-Transfer to Beta-hCG Test
- 5.
- Post-Pregnancy Confirmation (up to 12 weeks)
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Outcomes | No. of Studies | No. of IG Patients | No. of CG Patients | RR (95% CI) | Study Heterogeneity | ||
---|---|---|---|---|---|---|---|
χ2 | df | I2 (%) | |||||
Primary outcomes | |||||||
Acupuncture vs. Sham+ No intervention | |||||||
Clinical pregnancy rate | 25 | 3565 | 3045 | 1.316 (1.171, 1.480) | 72.68 | 27 | 62.9% |
Live birth rate | 14 | 2517 | 2096 | 1.287 (1.081, 1.533) | 46.48 | 14 | 69.9% |
Herbal medicine vs. Sham+ No intervention | |||||||
Clinical pregnancy rate | 12 | 2142 | 2201 | 1.184 (1.017, 1.379) | 27.14 | 12 | 55.8% |
Live birth rate | 3 | 1407 | 1411 | 1.147 (1.010, 1.303) | 0.32 | 2 | 0.0% |
Secondary outcomes | |||||||
Acupuncture vs. Sham+ No intervention | |||||||
Implantation rate | 13 | 2302 | 1871 | 1.183 (1.028, 1.363) | 37.57 | 13 | 65.4% |
Adverse events * | 13 | 1064 | 1092 | 1.125 (0.926, 1.367) | 12.92 | 12 | 7.2% |
Herbal medicine vs. Sham+ No intervention | |||||||
Implantation rate | 5 | 1488 | 1547 | 1.106 (0.968, 1.264) | 4.65 | 4 | 14.0% |
Adverse events | 6 | 771 | 706 | 0.916 (0.726, 1.157) | 1.98 | 5 | 0.0% |
Factor | Outcome or Subgroup | No. of Studies | No. of Patients | RR (95% CI) | I2 | p Value |
---|---|---|---|---|---|---|
IG vs. CG CPR | ||||||
Type of CG | Sham Ac | 14 | 3730 | 1.218 (1.019, 1.455) | 69.7% | 0.030 |
No acupuncture | 14 | 2880 | 1.416 (1.231, 1.629) | 42.9% | 0.000 | |
Placebo HM | 8 | 3727 | 1.211 (1.071, 1.370) | 32.2% | 0.002 | |
No HM | 5 | 616 | 1.101 (0.646, 1.876) | 72.7% | 0.724 | |
LBR | ||||||
Type of CG | Sham Ac | 8 | 2743 | 1.152 (0.892, 1.488) | 74.4% | 0.277 |
No acupuncture | 7 | 1870 | 1.465 (1.163, 1.846) | 57.7% | 0.001 | |
Placebo HM+ No HM | 3 | 2818 | 1.147 (1.010, 1.303) | 0.0% | 0.035 | |
IR | ||||||
Type of CG | Sham Ac | 9 | 2317 | 1.192 (0.952, 1.493) | 72.3% | 0.125 |
No acupuncture | 5 | 1856 | 1.201 (1.031, 1.400) | 41.6% | 0.019 | |
Placebo HM+ No HM | 5 | 3035 | 1.106 (0.968, 1.264) | 14.0% | 0.137 | |
AE | ||||||
Type of CG | Sham Ac+ No acupuncture | 13 | 2156 | 1.125 (0.926, 1.367) | 7.2% | 0.236 |
Placebo HM+ No HM | 6 | 1477 | 0.916 (0.726, 1.157) | 0.0% | 0.463 |
Outcomes | No. of Studies | Sample Size | RR | Effects Model | 95% CI | I2 Value | Z Value | p Value |
---|---|---|---|---|---|---|---|---|
Vs. sham Ac/placebo HM | ||||||||
LBR (Ac) | 8 | 2743 | 1.152 | Random | 0.892, 1.488 | 74.4% | 1.09 | 0.277 |
CPR (Ac) | 14 | 3730 | 1.218 | Random | 1.019, 1.455 | 69.7% | 2.17 | 0.030 |
CPR (HM) | 8 | 3727 | 1.211 | Random | 1.071, 1.370 | 32.2% | 3.04 | 0.002 |
Vs. CG | ||||||||
LBR (Ac) | 7 | 1870 | 1.465 | Random | 1.163, 1.846 | 57.7% | 3.24 | 0.001 |
CPR (Ac) | 14 | 2880 | 1.416 | Random | 1.231, 1.629 | 42.9% | 4.88 | 0.000 |
CPR (HM) | 5 | 616 | 1.101 | Random | 0.646, 1.876 | 72.7% | 0.35 | 0.724 |
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Peng, X.; Wu, B.; Zhou, S.; Xu, Y.; Ogihara, A.; Nishimura, S.; Jin, Q.; Litscher, G. Integrating Acupuncture and Herbal Medicine into Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of East Asian Traditional Medicine. Healthcare 2025, 13, 1326. https://doi.org/10.3390/healthcare13111326
Peng X, Wu B, Zhou S, Xu Y, Ogihara A, Nishimura S, Jin Q, Litscher G. Integrating Acupuncture and Herbal Medicine into Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of East Asian Traditional Medicine. Healthcare. 2025; 13(11):1326. https://doi.org/10.3390/healthcare13111326
Chicago/Turabian StylePeng, Xiangping, Bo Wu, Siyu Zhou, Yinghan Xu, Atsushi Ogihara, Shoji Nishimura, Qun Jin, and Gerhard Litscher. 2025. "Integrating Acupuncture and Herbal Medicine into Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of East Asian Traditional Medicine" Healthcare 13, no. 11: 1326. https://doi.org/10.3390/healthcare13111326
APA StylePeng, X., Wu, B., Zhou, S., Xu, Y., Ogihara, A., Nishimura, S., Jin, Q., & Litscher, G. (2025). Integrating Acupuncture and Herbal Medicine into Assisted Reproductive Technology: A Systematic Review and Meta-Analysis of East Asian Traditional Medicine. Healthcare, 13(11), 1326. https://doi.org/10.3390/healthcare13111326