Diminished ovarian reserve (DOR), manifested as lower fertility due to poor oocyte quality, is a prevalent condition experienced by more than 26% of young patients recently (1, 2). Although the etiology of DOR is currently unclear, an increasing quantity of evidence demonstrated various conditions contributed to the process of DOR, such as higher age (3), natural history (4), surgery (5, 6), chemotherapy (7), as well as lifestyle behaviors, including frequent binge drinking and smoking (8, 9). Furthermore, the accepted definition of DOR is not uniform globally owing to the changing lab testing options and complex interpretation for ovarian reserve tests, but the popular clinical diagnosis for DOR involved follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and antral follicle count (AFC) (10, 11).

At present, the treatment regimen for DOR is based on whether the patient has fertility needs, menstrual dysfunction, and the symptoms of estrogen deficiency. For example, ovulation induction assisted reproductive technology (ART) and coenzyme Q10 were adopted for those with infertility (12–14). And pharmacotherapies such as hormonal contraceptives, estrogen, and progesterone were usually used to restore the menstrual cycle regularity. However, these may account for adverse risks like ovarian hyperstimulation syndrome, venous thromboembolism, stroke, and breast cancer (15, 16). Owing to these side effects, an increasing number of patients with DOR have sought complementary and alternative medicine based on growing clinical evidence, such as acupuncture, to improve treatment outcomes (17, 18).

Acupuncture, a nonpharmacological intervention, has been widely introduced in the reproductive disorders field with supportive scientific evidence (19). Leading organizations in the field, such as the Chinese Reproductive Medicine Group, recommend acupuncture for strengthening ovarian reserve (20). Recently, randomized controlled trials (RCTs) on acupuncture for DOR have been increasing, but these clinical studies have usually had small sample sizes, and therefore the findings have been inconsistent (21). Hence, we conducted a systematic review and meta-analysis of the existing evidence with critical evaluation to inform clinical practice. The investigation’s specific objective was as follows: Is acupuncture effective in regulating sex hormones level and increasing AFC in patients with DOR?

This study was conducted following the preferred reporting program of the systematic review and meta-analysis (PRISMA) (22), and was registered on PROSPERO (registration number: CRD42023402336).

Acupuncture, as a novel therapy for DOR (38), has been proven to involve diverse cellular functions and mechanisms. Zhang et al. (39) found that electro-acupuncture could increase primordial follicle counts, E₂ and AMH levels, while decreasing FSH and LH levels by targeting the PI3K/AKT/mTOR signaling pathway. Another study indicated that acupuncture could inhibit bta-miR-7857-3p_R-1, mdo-miR-26b-5p_R+1_1ss10TC, and rno-miR-92b-3p expression in ovarian tissues and improve ovarian function via relieving DOR-mediated oxidative stress (18). Besides, some investigations also found acupuncture could reduce granulosa cell autophagy by weakening the expression of LncMEG3 and regulating the PI3K/AKT/mTOR pathway (40). The findings were consistent with Wang et al. (41). Interestingly enough, electro-acupuncture could alter the intestinal microbiota and block the accumulation of Fe²⁺, thereby increasing mature follicles as well as improving the sex hormones level in premature ovarian failure mice (42). Moreover, a clinical trial published recently demonstrated that electro-acupuncture might improve embryonic development and oocyte quality by regulating IRS-1/PI3K/GLUT4 pathway in ovarian granulosa cells (43). Similarly, Kim et al. (44) revealed that acupuncture combined with in vitro fertilization (IVF) therapy remarkably enhanced the number of retrieved mature oocytes, regardless of controlled ovarian hyperstimulation cycles, compared with the IVF therapy alone in women aged > 37 years.

To the best of our knowledge, this is the first meta-analysis to evaluate the clinical efficacy of acupuncture for DOR. In this study, we included 13 RCTs involving 787 patients to investigate the association of acupuncture therapy with DOR. Evidence was found that the use of acupuncture was correlated with decreased FSH levels, FSH/LH ratio, and increased AFC and AMH levels. According to our results, the LH and E₂ levels could not be statistically significantly improved with acupuncture intervention. Moreover, to provide more convincing evidence and explore the potential factors that may affect the clinical efficacy of acupuncture, a subgroup analysis based on the different types of intervention was conducted. The results indicated manual acupuncture was superior in reducing FSH levels, FSH/LH ratio, and increasing AMH levels and AFC when compared with electro-acupuncture treatment. Furthermore, a notable association was also seen when acupuncture was combined with traditional Chinese medicine therapy for improving FSH levels, FSH/LH ratio, and AFC. Besides, a high dose of acupuncture (≥10 acupoints) was more conducive to ameliorating FSH levels, FSH/LH ratio, and AFC than a low dose of acupuncture (<10 acupoints). Nevertheless, our subgroup analysis included a limited number of RCTs. For example, only one study was included when estimating the correlation of AMH levels with different types of intervention (electro-acupuncture, acupuncture plus Western medicine, and high dose of acupuncture), and it produced no convincing results. This revealed that our result might be more probably on account of insufficient statistical power rather than due to a lack of clinical efficacy from acupuncture.

While this meta-analysis results, from a clinical perspective, support the treatment with acupuncture in patients with DOR, it should be considered that these findings were derived from 13 RCTs with high heterogeneity. To minimize heterogeneity, we performed subgroup analysis based on six different types of intervention, but the heterogeneity was stable. The underlying factors contributed to severe heterogeneity were as followings: first, all included studies were single-center trials; thus, the adjunctive regimen with acupuncture varied considerably among studies. For instance, although the adjunctive regimens were traditional Chinese medicine, herb types and doses within each study were various. Second, acupuncture acupoints and examination technology adopted by included studies were not uniform, which likely contributed to heterogeneity as well. Furthermore, pregnancy outcomes are one of the major concerns for reproductive-aged women with DOR, but only one study (36) reported this. Therefore, we failed to explore the correlation of acupuncture with pregnancy outcomes, which might be an inherent deficiency of our meta-analysis. Besides, the 13 RCTs were from China, which usually incorporates poor descriptions of their methodologies, such as only two studies included reported blinding. Nevertheless, nonblinded pragmatic trials which emphasize extrapolation and practical applicability in real-world situations, in recent years, have been recommended to acquire clinically connected outcomes over treatment efficacy (45). This suggestion is especially qualified for estimating flexible and complicated interventions, such as acupuncture (46). To guarantee the quality of source RCTs, we adopted more stringent inclusion criteria, and a substantial endeavor was made to perform an extensive literature search. Consequently, we can only present a weak proposal to access acupuncture therapy as part of comprehensive DOR management. However, further investigations including larger and higher-quality RCTs are warranted to reinforce or refute the current evidence.

These findings suggest that acupuncture, as a nonpharmacological intervention, has excellent clinical potential for patients with DOR in decreasing FSH levels and FSH/LH ratio, along with increasing AMH levels and AFC. Acupuncture may be recommended for the treatment of DOR. However, our findings should be cautiously adopted due to the high heterogeneity. Therefore, more high-quality studies conducted in diverse regions worldwide are necessary to verify the efficacy of acupuncture for patients diagnosed with DOR.

The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding author.

Study design: GYL, LWX. Data collections: GYL, SRC, CC. Data analysis: GYL, CC, XYL. Writing the manuscript: GYL. Revising the manuscript: LWX. All authors read and approved the final version of manuscript.