Recurrent implantation failure (RIF) — defined as the absence of clinical pregnancy after at least three transfers of good-quality embryos or the transfer of ten or more high-quality embryos without success — constitutes one of the most frustrating challenges in reproductive medicine. It is estimated that about two thirds of failures are related to reduced endometrial receptivity, a factor that remains partially refractory to conventional pharmacologic interventions. A meta-analysis published in Medicine(Baltimore), bringing together 15 randomized clinical trials with 1,029 patients, presents the most comprehensive evidence to date on the impact of acupuncture and moxibustion in this population.
DIMENSIONS OF THE META-ANALYSIS
Primary Results: Pregnancy and Live Births
The primary results of the meta-analysis revealed statistically significant and clinically expressive benefits of acupuncture and moxibustion on the two most relevant reproductive outcomes: clinical pregnancy rate and live birth rate.
For clinical pregnancy rate, analyzed in 12 studies with 887 patients (445 in the treatment group, 442 in the control), the relative risk was 1.84 (95% CI: 1.53-2.20; p < 0.05), with null heterogeneity (I² = 0.0%; p = 0.98). For the live birth rate, evaluated in 3 studies with 242 patients (122 treatment, 120 control), the relative risk reached 2.39 (95% CI: 1.59-3.58; p < 0.05), also without heterogeneity (I² = 0.0%; p = 0.75). In clinical terms, this means that women treated with acupuncture and moxibustion had 2.4 times greater probability of having a live birth compared with isolated hormonal treatment.
This finding is preliminary — it is based on only 3 trials conducted in China, with aggregate sample of 242 patients. Independent studies in Western populations are needed before incorporating this result into clinical guidelines.
Endometrial Parameters: Thickness and Morphology
In addition to reproductive outcomes, the meta-analysis evaluated endometrial parameters that reflect uterine receptivity. Endometrial thickness — one of the most widely used echographic markers to evaluate the implantation window — presented a mean increase of 1.37 mm in the acupuncture group (95% CI: 0.95-1.80; 12 studies, 879 patients). Although heterogeneity was high (I² = 86%), reflecting variations in protocols and treatment durations between studies, the effect remained consistently favorable to the intervention in all sensitivity analyses.
Endometrial morphology — echographically classified as type A (trilaminar), type B (intermediate), or type C (homogeneous) — was also significantly benefited: the proportion of patients with type A pattern (considered the most favorable for implantation) was 67% higher in the acupuncture-treated group (RR = 1.67; 95% CI: 1.30-2.14; I² = 0%).
Subgroup Analysis: Which Protocol is Most Effective?
One of the most valuable contributions of this meta-analysis is the subgroup analysis, which allows identification of the protocols with the greatest impact on outcomes. The results revealed significant differences according to the type of intervention, duration of treatment, and method of acupoint selection — information that directly guides clinical decision-making.
ENDOMETRIAL THICKNESS BY TYPE OF PROTOCOL
Acupoint Selection: Staged Approach by Cycle Phase
The subgroup analysis by acupoint selection method revealed that the staged approach — in which acupoints are selected according to the patient’s menstrual cycle phase — produced the greatest gains in endometrial thickness (MD = 2.41 mm; I² = 0%). This strategy adapts the acupuncture protocol to physiologic hormonal fluctuations, selecting different points in the follicular, peri-ovulatory, and luteal phases.
For serum estradiol levels, the most effective combination was the three-cycle protocol with staged acupoint selection: SMD = 4.42 (95% CI: 3.75-5.09; p < 0.001) — a large-magnitude effect. Other selection methods — such as the root/branch meridian theory and ordinary point selection — produced positive results, but of inferior magnitude.
Methodologic Quality and Limitations
The risk-of-bias assessment by the RoB-2 instrument classified 11 of the 15 studies as low risk and 4 as presenting partial concerns — mainly related to vague descriptions of randomization and inadequate analysis of allocation concealment. The Egger test for publication bias was significant for the clinical pregnancy rate (p = 0.010), but the trim-and-fill analysis confirmed that the results remained robust after correction (p < 0.001 before and after). For endometrial thickness, the Egger test did not detect publication bias (p = 0.721).
The limitations acknowledged by the authors include: all 15 studies were conducted in China, which may limit generalization of the results; literature in languages beyond Chinese and English was not included; small samples in some subgroup analyses; and high heterogeneity in endometrial thickness outcomes (I² = 86%) and serum estradiol (I² = 98%), whose source was not completely elucidated by the subgroup analyses.
Frequently Asked Questions
RIF is defined as the absence of clinical pregnancy after at least three transfers of good-quality embryos in in vitro fertilization cycles, or after the cumulative transfer of ten or more high-quality embryos. It is one of the most challenging situations in reproductive medicine, as embryologic factors have already been optimized and the residual cause is generally related to endometrial receptivity.
In this meta-analysis, the live birth rate was 2.39 times higher in the group that received acupuncture and moxibustion compared with isolated conventional hormonal treatment (95% CI: 1.59-3.58). This means that, for patients with recurrent implantation failure, the addition of acupuncture to the protocol more than doubled the probability of having a live birth.
The combination of electroacupuncture with warming acupuncture (moxa), applied over three menstrual cycles with staged acupoint selection by reproductive cycle phase, produced the greatest gains in endometrial thickness (+2.41 mm) and in serum estradiol levels.
The data suggest starting acupuncture at least three menstrual cycles before the planned embryo transfer. The subgroup analysis demonstrated a clear dose-response effect: 3-cycle treatments produced the greatest benefits in endometrial thickness (+1.62 mm) versus 1 cycle (+1.01 mm).
In the 15 studies analyzed (1,029 patients), no serious adverse events related to acupuncture or moxibustion were reported. The favorable safety profile — without medication interactions with ovarian stimulation protocols — makes acupuncture a viable complementary option in the context of assisted reproduction.
Founded in 1989 by physicians trained at the University of São Paulo (USP) and specialized in China, CEIMEC is a Brazilian national reference in the teaching and practice of medical acupuncture. With more than 3,000 physicians trained over 35 years, it collaborates with HC-FMUSP and is recognized by the Brazilian Medical College of Acupuncture (CMBA/AMB).
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