Feasibility of acupuncture as an adjunct intervention for ovulatory disorder infertility: A systematic review and meta-analysis

Table 1 Search strategy for PubMed

Search	Terms
1	“Infertility” (MeSH Terms)
2	“Infertility” (Title/Abstract) OR “Infertile” (Title/Abstract) OR “Sterility” (Title/Abstract) OR “Sterile” (Title/Abstract)
3	1 OR 2
4	“Anovulation” (MeSH Terms)
5	“Ovulatory dysfunction” (Title/Abstract) OR “Anovulation” (Title/Abstract) OR “Anovulatory” (Title/Abstract) OR “Ovulatory disorders” (Title/Abstract) OR “Ovulation failure” (Title/Abstract) OR “Ovarian stimulation” (Title/Abstract) OR “Ovarian induction” (Title/Abstract)
6	4 OR 5
7	“Acupuncture” (MeSH Terms)
8	“Acupuncture” (Title/Abstract) OR “Acupuncture Therapy” (Title/Abstract) OR “Auricular Points” (Title/Abstract) OR “Ear acupuncture” (Title/Abstract) OR “Electroacupuncture” (Title/Abstract) OR “Electro-acupuncture” (Title/Abstract) OR “Meridians” (Title/Abstract) OR “Acupuncture Points” (Title/Abstract) OR “Acupressure” (Title/Abstract) OR “Auricular” (Title/Abstract) OR “Acusector” (Title/Abstract) OR “Needle” (Title/Abstract) OR “Fire Needle” (Title/Abstract) “Acupoint catgut embedding” (Title/Abstract) OR “Moxibustion” (Title/Abstract) OR “Scalp acupuncture points” (Title/Abstract) OR “Bleeding” (Title/Abstract) OR “Acupoint injection” (Title/Abstract) OR “Needle knife” (Title/Abstract)
9	7 OR 8
10	(“Randomized controlled trial” (Publication Type) OR “Controlled clinical trial” (Publication Type) OR “Randomized” (Title/Abstract) OR “Placebo” (Title/Abstract) OR “Clinical trials as topic” (MeSH Terms) OR “Randomly” (Title/Abstract) OR “Trial” (Title)) NOT “Animals” (MeSH Terms) NOT “Humans” (MeSH Terms)
11	3 AND 6 AND 9 AND 10

Table 2 The characteristics of included studies

Ref.	Sample size	Mean age in yr	Course of disease in yr	Intervention	Details of AT	Acupoint	Comparison	Duration	Outcomes
Su et al[17], 2022	T: 30, C: 30	T: 29.50 ± 2.50, C: 28.45 ± 2.50	NR	AT plus CC	Every other day, 5 consecutive times/starting on day 5 after the end of menstruation	RN4, RN6, Zigong, BL23, BL31, BL32, BL33, BL34, SP6	CC, 50 mg/tid, for 5 d, starting on day 5 after the end of menstruation	4 MC	1,4,5,7
Zhu and Xiang[18], 2022	T: 47, C: 51	T: 30 ± 3, C: 29 ± 3	T: 2.41 ± 1.37, C: 2.39 ± 1.42	AT plus CC	30 min, each day/until 1 wk before the next MC	RN4, Zigong, SP10, GV4, BL23, BL32, ST36, SP6, KI1, KI3, PC8	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1,4,5-7
Cui et al[19], 2022	T: 28, C: 28	T: 26.53 ± 3.11, C: 26.25 ± 3.01	T: 2.09 ± 0.29, C: 2.05 ± 0.27	AT plus CC	Starting on day 4 after the end of menstruation	BL31, BL32, BL33, BL34	CC, 50 mg/qd, for 5 d, starting on day 4 after the end of menstruation	3 MC	2,4-7
Li[20], 2015	T: 51, C: 51	T: 23.2 ± 0.5, C: 2.0 ± 0.6	T: 23.4 ± 0.6, C: 2.2 ± 0.9	AT	30 min, each day, for 10 d/starting on day 5 after the end of menstruation	RN3, RN4, RN8, ST36, Zigong, SP6	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1,3
Song et al[21], 2008	T: 60, C: 60	T: 28.60 ± 3.74, C: 28.30 ± 3.67	T: 3.75 ± 1.94, C: 3.69 ± 1.83	AT	30 min, each day, for 10 d/starting on day 5 after the end of menstruation	RN3, RN4, RN8, Zigong, ST36, SP6	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1-3
Zhang[22], 2019	T: 53, C: 53	T: 29 ± 4, C: 29 ± 4	T: 3.50 ± 0.43, C: 3.47 ± 0.41	AT plus CC	Starting on day 5 after the end of menstruation, every other day/until the next MC	BL23, GV4, RN3, RN4, ST25, ST29, SP6	CC, 50 mg/tid, for 5 d, starting on day 2-5 after the end of menstruation or day 6 of withdrawal bleeding	3 MC	1,2,4-6,8
Amina·and Yang[23], 2011	T: 66, C: 66	NR	NR	AT	30 min, each day, for 10 d/starting on day 5 after the end of menstruation	RN3, RN4, Zigong, ST36, SP6	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1-3
Zhong and Chen[24], 2017	T: 38, C: 38	T: 30.84 ± 1.64, C: 31.02 ± 1.56	T: 7.30 ± 1.27, C: 7.23 ± 1. 31	AT plus CC	30 min, each day, for 10 d/starting on day 5 after the end of menstruation	RN3, RN4, RN8, SP6, Zigong, ST36, LR3, KI3	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	2 MC	4-6,8
Yuan[25], 2022	T: 36, C: 36	T: 27.19 ± 2.58, C: 27.67 ± 2.74	T: 3.33 ± 1.88, C: 3.19 ± 1.26	AT	30 min, 6 times per week /starting on day 5 after the end of menstruation	RN4, RN5, BL20, BL23, SP6	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1,2,4-9
Zheng[26], 2019	T: 35, C: 35	T: 30.24 ± 3.05, C: 29.25 ± 3.53	T: 27.59 ± 12.20 m, C: 27.03 ± 11.34 m	AT plus CC	30 min, every other day/starting on day 5 after the end of menstruation	ST25, ST36, RN3, RN4, RN5, SP6, K13, BL20, BL23, LR03	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1-3,9
Zhu[27], 2017	T: 30, C: 30	T: 32.17 ± 3.23, C: 33.07 ± 3.13	T: 5.23 ± 3.21, C: 5.73 ± 2.10	AT plus CC	30 min, each day/starting on day 5 after the end of menstruation	ST25, ST28, ST36, SP6, RN7, RN9	CC, 50 mg/qd, for 3 d, starting on day 5 after the end of menstruation	3 MC	1,8,9
Su[28], 2016	T: 33, C: 33	T: 31.00 ± 4.57, C: 29.83 ± 4.99	NR	AT	20-30 min, once every 3 d/starting on day 5 after the end of menstruation	RN10, RN12, RN4, RN5, ST28, Zigong	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1-6,8,9
Liu[29], 2018	T: 26, C: 26	T: 32.1 ± 5.5,C: 31.5 ± 5.8	T: 3.4 ± 1.1, C: 3.2 ± 1.2	AT plus CC	30 min, each day, for 7 d/starting on day 5 after the end of menstruation	RN8, Zigong, RN4, RN3, SP6, ST36	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1,3
Wang[30], 2014	T: 50, C: 50	T: 28.70 ± 3.75, C: 28.40 ± 3.68	T: 3.76 ± 1.95, C: 3.70 ± 1.85	AT	30 min, each day, for 10 d/starting on day 6 after the end of menstruation	RN4, RN8, SP6, Zigong, RN3	CC, 50 mg/qd, for 5 d, starting on day 6 after the end of menstruation	3 MC	1-3
Danniyaer[31], 2023	T: 32, C: 32	T: 33.93 ± 3.59, C: 34.14 ± 3.51	T: 3.44 ± 1.12, C: 3.25 ± 1.17	AT plus CC	Starting on day 5 after the end of menstruation	RN4, RN3, Zigong, ST36	CC, 50 mg/qd, for 5 d, starting on day 5 after the end of menstruation	3 MC	1,2
Zhai[32], 2016	T: 30, C: 30	T: 28.26 ± 3.96, C: 28.45 ± 3.87	T: 3.37 ± 1.36, C: 3.52 ± 1.57	AT plus CC	20 min, each day, for 5 d/starting on day 5 after the end of menstruation	LI4, SP9, ST36, SP6	CC, 50 mg/qd, for 5 d, starting on 5 after the end of menstruation	3 MC	1-3,8,9
Wei et al[33], 2010	T: 93, C: 86	T: 33.0 ± 2.4, C: 31.0 ± 3.8	T: 7.0 ± 1.5, C: 7.0 ± 1.1	AT plus CC	40 min, every other day/starting on day 5 after the end of menstruation	RN4, Zigong, SP10, SP6, KI3, ST36, LI4, LR3	CC, 50 mg/qd, for 5 d, starting on 5 after the end of menstruation	3 MC	1,2,4-6,8,9
Zhou[34], 2019	T: 32, C: 32	T: 26.97 ± 3.85, C: 27.50 ± 2.58	T: 2.00 ± 1.58, C: 1.37 ± 0.81	AT plus CC	30 min, 3 times per week/starting on day 5 after the end of menstruation	RN4, RN3, Zigong, SP6	CC, 50 mg/qd, for 5 d, starting on 5 after the end of menstruation	3 MC	1,3,8,9
Zheng et al[35], 2007	T: 40, C: 40	T: 27.6 ± 7.6, C: 28.1 ± 7.4	T: 3.7 ± 4.1, C: 3.8 ± 4.1	AT	30 min, starting on day 5 after the end of menstruation	RN8, RN3, RN4, Zigong, ST36, SP6	CC, 50 mg/qd, for 5 d, starting on 5 after the end of menstruation	3 MC	1-3
Zhou et al[36], 2018	T: 30, C: 30	T: 29.3, C: 29.3	NR	AT	Each day, for 10 d/starting on day 5 after the end of menstruation	SP6, K17, BL23	CC, 50-100 mg/qd, for 5 d, starting on 5 after the end of menstruation	1 MC	1,3,8

¹Pregnancy rate; ²Ovulation rate; ³Miscarriage rate; ⁴Follicle-stimulating hormone; ⁵Luteinizing hormone; ⁶Estradiol; ⁷Progesterone; ⁸Thickness of endometrium; ⁹Adverse events. AT: Acupuncture; C: Control group; m: month; CC: Clomiphene citrate; MC: Menstrual cycles; NR: Not reported; T: Treatment group.

Table 3 Grade of evidence of outcomes of the included trials

Outcomes	Certainty assessment						Effect sizes	Certainty	Importance
	Number of trials (patients)	Risk of bias1	Inconsistency2	Indirectness3	Imprecision4	Publication bias5	RR or MD (95%CI)
AT plus CC vs CC
Pregnancy	10 (790)	Serious	No serious	No serious	No serious	Likelihood	RR 1.68 (1.45-1.95)	Moderate6	Critical
Ovulation	6 (1042)	Serious	No serious	No serious	No serious	Undetected	RR 1.34 (1.22-1.47)	Moderate6	Critical
Miscarriage rate	4 (102)	Serious	No serious	No serious	Serious	Undetected	RR 0.25 (0.09-0.65)	Low7	Critical
FSH	6 (572)	Serious	Serious	No serious	No serious	Undetected	MD -2.10 (-3.27 to -0.94)	Low7	Important
LH	6 (572)	Serious	Serious	No serious	No serious	Undetected	MD -6.94 (-9.89 to -4.00)	Low7	Important
E2	5 (515)	Serious	Serious	No serious	No serious	Undetected	MD 31.36 (21.83-40.88)	Low7	Important
P	3 (211)	Serious	Serious	No serious	Serious	Undetected	MD -1.66 (-2.98 to -0.34)	Very low8	Important
Thickness of endometrium	6 (538)	Serious	Serious	No serious	No serious	Undetected	MD 1.76 (0.71-2.81)	Low7	Important
AT vs CC
Pregnancy	8 (706)	Serious	No serious	No serious	No serious	Undetected	RR 1.52 (1.33-1.73)	Moderate	Important
Ovulation	6 (1151)	Serious	Serious	No serious	No serious	Undetected	RR 0.95 (0.87-1.04)	Low7	Important
Miscarriage rate	7 (376)	Serious	No serious	No serious	Serious	Undetected	RR 0.23 (0.13-1.04)	Low7	Important
FSH	2 (134)	Serious	Serious	No serious	Serious	Undetected	MD -0.55 (-0.86 to -0.24)	Very low8	Important
LH	2 (134)	Serious	Serious	No serious	Serious	Undetected	MD 3.27 (1.55-4.99)	Very low8	Important
E2	2 (134)	Serious	Serious	No serious	Serious	Undetected	MD 2.19 (1.10-3.28)	Very low8	Important
P	1 (72)	Serious	Undetected	No serious	Serious	Undetected	MD 3.02 (1.33-4.71)	Low7	Important
Thickness of endometrium	3 (194)	Serious	Serious	No serious	Serious	Undetected	MD 2.06 (1.23-2.89)	Very low8	Important

¹Risk of bias: Serious, study with unclear risk of bias.

²Inconsistency: Serious, I² > 50%.

³Indirectness: No indirectness of evidence was found in any study.

⁴Imprecision (based on sample size): Serious, n < 500 participants.

⁵Publication bias: Undetected due to the number of trials less than the recommended arbitrary minimum number of 10.

⁶Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

⁷Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

⁸Very low: We are very uncertain about the estimate. AT: Acupuncture; CC: Clomiphene citrate; CI: Confidence interval; E₂: Estradiol; FSH: Follicle-stimulating hormone; LH: Luteinizing hormone; MD: Mean difference; P: Progesterone; RR: Risk ratio.