Documente Academic
Documente Profesional
Documente Cultură
www.asiaandro.com; www.ajandrology.com
Open Access
ORIGINAL ARTICLE
The aim of this review is to evaluate the effectiveness and safety of acupuncture for poor semen quality in infertile men. We searched
for relevant trials registered up to May 2013 in 14 databases. We selected randomized controlled trials(RCTs) that compared
acupuncture, with or without additional treatment, against placebo, sham, no treatment, or the same additional treatment. Two
reviewers independently performed the study selection, data extraction, risk of bias and reporting quality appraisal. Risk of bias
and reporting quality were appraised by the Cochrane risk of bias tool, the consolidated standards of reporting trials and Standards
for Reporting Interventions in Clinical Trials of Acupuncture. The outcomes were sperm motility, sperm concentration, pregnancy
rate, and adverse events. Pregnancy was defined as a positive pregnancy test. Four RCTs met the eligibility criteria. Acupuncture
increased the percentage of sperm with rapid progression(mean difference6.35, 95% confidence interval(CI): 4.388.32,
P<0.00001) and sperm concentration(mean difference6.42, 95% CI: 4.917.92, P<0.00001), but these two outcomes were
substantially heterogeneous among the studies(I2=72% and 58%, respectively). No differences in pregnancy rate were found
between acupuncture and control groups(odds ratio 1.60, 95% CI: 0.703.69, P=0.27, I2=0%). No participants experienced
adverse events. The current evidence showing that acupuncture might improve poor semen quality is insufficient because of the
small number of studies, inadequacy of procedures and/or insufficient information for semen analysis, high levels of heterogeneity,
high risk of bias, and poor quality of reporting. Further large, welldesigned RCTs are required.
Asian Journal of Andrology(2014) 16,884891; doi: 10.4103/1008-682X.129130; published online: 27 June 2014
Figure1: Study selection flow chart. NRCT: non-randomized controlled trial; QES: quasi-experimental study; RCT: randomized controlled trial.
The diagnostic criterion for pregnancy was a positive pregnancy All of the RCTs either improperly reported or did not report items
test. None of the studies documented the pregnancy rate using this such as specific objectives and hypothesis, clearly defined outcome
criterion. Although two trials14,15 reported the pregnancy rate of couples measures, methods of random allocation concealment, the precision
with male factor infertility, the diagnostic criterion for pregnancy was of each outcome, ancillary analysis, and generalizability. The detailed
not clearly documented. We attempted to contact the authors of the two results are presented in Supplement 2.
trials to determine which diagnostic criterion for pregnancy they had One study13 mentioned that it had been conducted in accordance
used. The author of one study14 only replied that the diagnostic criterion with STRICTA, but it did not report the rationale for treatment,
for pregnancy was a positive pregnancy test. All of the included trials needle type, practitioners training duration, or practitioners years
reported that none of the participants experienced adverse events. of clinical experience. Three RCTs12,14,15 were evaluated as having
equal reporting quality based on STRICTA. They had good reporting
Risk of bias
quality in 11 subitems(style of acupuncture, rationale for treatment,
Among the four RCTs, three12,14,15 adopted poor randomization
acupuncture response elicited, type of needle stimulation, needle
procedures with an allocation concealment method based on hospital
retention time, number of treatment sessions, frequency of treatment,
visitation order, while only one13 described adequate methods of
cointerventions, intended effect of control intervention, precise
random sequence generation and allocation concealment. One trial13
description of control intervention, and sources that justified the
blinded patients and outcome assessors. The other three trials12,14,15 did
choice of control). The detailed results are presented in Supplement 3.
not report any information on blinding. Although all the trials reported
how many participants dropped out or withdrew, three trials12,14,15 were Effects of interventions
estimated to have a high risk of bias because they did not include any
Sperm motility
information on whether dropouts or withdrawals occurred before or
The percentages of gradeA and gradeA+B motile sperm were pooled
after randomization. Risk of bias from selective outcome reporting or
because these outcomes were used to diagnose asthenozoospermia.17,18
from other sources was unclear in all of the included trials(Figure2).
Three trials1315 measured the percentage of gradeA sperm motility, and
Reporting quality the other trial12 measured the percentage of gradeA+B sperm motility.
Even though the CONSORT statement and STRICTA recommendations Overall, the pooled data indicated considerable heterogeneity(2=122.19,
were updated in 2010, the 2001 versions were used to assess reporting P<0.00001, I2=98.0%), so subgroup analysis was conducted. The pooled
quality because all four trials were conducted before 2010. Based on data for the percentage of gradeA sperm motility showed large differences
the CONSORT statement, all the RCTs described the eligibility criteria, between acupuncture and control groups(mean difference 6.35, 95% CI:
sequence generation, adverse events, and a general interpretation of 4.388.32, P<0.00001), but the results across the trials were substantially
the results. Three RCTs1214 documented the statistical methods used heterogeneous(2=7.09, P=0.03, I2=72%). Subgroup analysis was not
to compare outcomes between groups. Two RCTs14,15 presented the performed for the percentage of gradeA+B sperm motility because it
baseline demographic and clinical characteristics of the participants. was only evaluated in one trial(Figure3).
Figure3: Forest plot for comparison: acupuncture with/without additional treatment versus placebo or same additional treatment. Outcome: sperm motility.
Figure 4: Forest plot for comparison: acupuncture with/without additional treatment versus placebo or same additional treatment. Outcome: sperm concentration.
Figure5: Forest plot for comparison: acupuncture with/without additional treatment versus placebo or same additional treatment. Outcome: pregnancy rate.
study13 might be underestimated, while the differences in the other herbs compared with herbs alone, while another study13 evaluated the
three studies 12,14,15 might be overestimated. Second, inadequate effects of acupuncture compared with placebo acupuncture. Third,
procedures and/or insufficient information for semen analysis could different target populations among infertile men could have resulted
affect outcomes. The WHO states that two semen samples should be in heterogeneity. Two RCTs14,15 recruited oligozoospermia and/or
collected after a minimum of 2days to a maximum of 7days of sexual asthenozoospermia patients, whereas one study13 recruited only severe
abstinence and that the interval between the two collections should oligozoospermia patients. Finally, inconsistency regarding the risk of
range from 7days to 3weeks to ensure reliable results.17,29 Although bias and reporting quality could have led to heterogeneity. Two14,15 of
semen samples were collected after a sufficient period of abstinence the three studies were identical in all items related to the risk of bias.
in the three RCTs, semen sample collection was only conducted The other study13 and the above two studies14,15 were identical in only
once before and once after treatment.12,14,15 Although the remaining two items related to the risk of bias. Asimilar tendency was observed
RCT13 collected two samples at every assessment, the shortest interval in our assessment of reporting quality. Two studies14,15 had similar
between semen collections was 1month, and there was no report of results for each item on STRICTA and CONSORT, but the other study13
whether semen collections were conducted after abstinence. These differed from the above two studies in more than 50% of the items.
inadequate procedures and the insufficient information provided The pooled result for pregnancy rate of couples with male
for semen analysis made it difficult to validate these results. Finally, infertility showed no significant difference between the treatment and
high risk of bias and poor reporting quality could cause inconsistent control groups. However, we could not conclude that acupuncture in
effects. Three RCTs12,14,15 used inadequate methods for sequence infertile men has no effect on the pregnancy rate from this result. The
generation and allocation concealment, which could have caused herbal cointervention could have contributed to the nonsignificant
selection bias. In addition, most items in CONSORT and STRICTA differences in pregnancy outcomes. Two studies14,15 used the Wuzi
were not described in the three studies.12,14,15 This means that the Yanzong herb mixture, which is often administered to improve
studies might not have been conducted according to a predefined semen quality in traditional Chinese medicine, as a cointervention
plan; therefore, outcomes could have been biased. Furthermore, it in the treatment and control groups. This medication might have
is known that there can be an inherent tendency for the treatment enhanced semen quality in both groups and thus resulted in the lack
group to show more positive results than its control group in a study of a difference in pregnancy rate. Insufficient treatment sessions and
with poor reporting quality.30 short duration of the intervention could also have caused the lack of
Substantial heterogeneity among the three included studies1315, significant difference between the groups. Acupuncture in two included
which reported the percentage of sperm with rapid progression and studies14,15 was performed only 20times over27days, whereas other
sperm concentration, is another factor that makes it difficult to draw therapies to improve semen quality and spontaneous pregnancy,
definite conclusions. Feature differences among the three studies including clomiphene citrate and antioxidants, were taken daily for
could have led to substantial heterogeneity. First, different treatment 56days to 6months.3134 Therefore, the treatment period might have
protocols might have induced heterogeneity. The participants in two been too short to significantly enhance the pregnancy rate of couples.
RCTs14,15 received two different acupuncture regimens. After receiving Other factors associated with spontaneous pregnancy might also
one regimen daily for 10days, the participants had a rest for 7days, have led to the nonsignificant pregnancy results. Age of the spouse
and then another regimen was also applied daily for 10days(Table2). and duration of infertility are associated with pregnancy rate.35,36
The participants in another study13 received one acupuncture regimen The proportion of sperm with normal morphology is also strongly
twice a week for 6weeks without a resting period. Second, differences associated with time to pregnancy.37 Two included studies14,15 did not
in the objectives among the studies might have caused heterogeneity. report any information on these factors and hence there could have
Two RCTs14,15 evaluated the combined effects of acupuncture and been an imbalance in these factors between groups.
2009, (2) Severe acupuncture before treatment, (Grade A, total sperm motility,
nd
Germany13 oligoasthenozoospermia 2 : Less than 3months GradeB, but no effect on sperm
before treatment, Grade C, concentration was
3rd : Less than 2months Grade from A found after acupuncture
after treatment, to C, Grade D) compared with placebo
4th : Less than 3months acupuncture
after treatment
Liu 2011b, (1) T: 60, C: 60; (1) EA; (1) Yuzi tang, three 1st : Before treatment, Seminal plasma The Yuzi tang combined
Acupuncture for poor semen quality
China12 (2) Asthenozoospermia (2) Yuzi tang, three times a day 2nd : After treatment (Grade from A neutral alpha1, 4 with electroacupuncture
times a day to B) glycosidase level, can also increase the
Seminal plasma motility of sperm
zinc level*
No.: number; T: treatment group; C: control group; EA: electroacupuncture; MA: manual acupuncture; o: the study which measured this outcome; x: the study which did not measured this outcome
Table2: Summary of the acupuncture points and techniques used in the randomized controls trials
Author, year Style of Treatment acupuncture points Reasoning Details of needling
acupuncture for treatment
Wang etal., EA (A) CV6, CV4, CV3, KI3(nr), ST36(nr) TCM theory All participants alternately received(A) and(B) daily for 10days. After the
200814 (B) GV4, BL23(nr), BL32(nr), needles were inserted, the practitioner evoked the Deqi sensation using
SP6(nr) the tonifying method. After the Deqi sensation had been evoked, an
electrostimulator was connected to the acupuncture points. The frequency
was 1426 Hz with an irregular wave. The intensity of the current was enough
for patients to feel tolerable pain, numbness, or tingling. Electrostimulation
lasted 30min. Aweek later, the same treatment was continued for 10days
Shi, 200915 MA (A) CV6, CV4, CV3, KI3(nr), ST36(nr) TCM theory All participants alternately received(A) and(B) daily for 10days. After the
(B) GV4, BL23(nr), BL32(nr), needles were inserted, the practitioner evoked the Deqi sensation using the
SP6(nr) tonifying method. The needles were left in 30min. Aweek later, the same
treatment was continued for 10days
Dieterle MA ST29(bi), ST36(bi), SP6(bi), Past Acupuncture needles(0.30 mm3.0 mm) were inserted to a depth of 1530
etal., SP10(bi), KI3(bi), LR3(bi), research mm. They were rotated manually to evoke the Deqi sensation. A10min later,
200913 BL23(bi), BL32(bi), CV4, GV20 all needles were manipulated again for the Deqi sensation
Liu etal., EA (A) GV20, CV6, CV4, KI3(nr), TCM theory All participants alternately received(A) and(B) every other day for three
201112 ST36(nr), SP6(nr) months. After the needles were inserted, an electrostimulator was connected
(B) BL23(nr), BL24(nr), GV4, to the acupuncture points. The frequency was 1426 Hz with an irregular
SP9(nr), KI7(nr) wave. The intensity of the current was enough for patients to feel tolerable
pain, numbness, or tingling. Electrostimulation lasted 30min
EA: electroacupunture; MA: manual acupuncture; bi: bilateral; un: unilateral; nr: not reported whether acupuncture is unilateral or bilateral; TCM: traditional Chinese medicine
All the studies reported no adverse events, but it is uncertain whether Supplementary Information is linked to the online version of the paper on
acupuncture is a safe treatment for poor semen quality. To reduce the Asian Journal of Andrology website.
publication bias, Ioannidis and Lau38 recommend that authors describe
the information on patients who withdrew because of adverse effects. REFERENCES
1 NgEH, SoWS, GaoJ, WongYY, HoPC. The role of acupuncture in the management
One included study13 mentioned that five patients in the total population of subfertility. Fertil Steril 2008; 90:113.
discontinued the intervention because of a lack of time. However, the 2 HirshA. Male subfertility. BMJ 2003; 327:66972.
other three studies12,14,15 did not describe why participants withdrew or 3 TremellenK. Oxidative stress and male infertilityA clinical perspective. Hum
Reprod Update 2008; 14:24358.
discontinued during the study. Therefore, there is a possibility of missing
4 JungwirthA, DiemerT, DohleGR, GiwercmanA, KopaZ, et al. Guidelines on Male
data on adverse events. Future clinical trials are required to understand Infertility. Arnhem: European Association of Urology; 2013. p.40.
why and when participants withdraw or discontinue. 5 RossC, MorrissA, KhairyM, KhalafY, BraudeP, etal. Asystematic review of
the effect of oral antioxidants on male infertility. Reprod Biomed Online 2010;
CONCLUSIONS 20:71123.
6 ShowellMG, BrownJ, YazdaniA, StankiewiczMT, HartRJ. Antioxidants for male
This review suggests that current evidence regarding whether subfertility. Cochrane Database Syst Rev 2011; (1): CD007411.
acupuncture in infertile men improves sperm motility, sperm 7 OldereidNB, RuiH, PurvisK. Male partners in infertile couples. Personal attitudes
concentration, and the pregnancy rate of couples is insufficient. The and contact with the Norwegian health service. Scand J Soc Med 1990; 18:20711.
poor quality of the evidence is attributable to the small number of 8 MoherD, HopewellS, SchulzKF, MontoriV, Gtzsche PC, etal. CONSORT 2010
explanation and elaboration: updated guidelines for reporting parallel group
studies, inadequate procedures and/or insufficient information for randomised trials. BMJ 2010; 340: c869.
semen analysis, high risk of bias, methodological heterogeneity, and 9 MacPhersonH, AltmanDG, HammerschlagR, YoupingL, TaixiangW, etal. Revised
poor reporting quality. Largescale RCTs with elaborate designs are STandards for Reporting Interventions in Clinical Trials of Acupuncture(STRICTA):
Extending the CONSORT statement. JEvid Based Med 2010; 3:14055.
needed to rigorously test the effectiveness and safety of acupuncture on
10 LunX. Effects of electroacupuncture on nitric oxide and trace elements in patient
semen quality. Appropriate target populations and sufficient treatment of male immune infertility. Zhongguo Zhen Jiu 2004; 24:8546.
periods should also be considered in future studies. 11 LiuL, Yue ZX, FuW, HouQ, HeX. Effect of YuZi tang combined with electric
acupuncture on seminal plasma zinc in patients with weak sperm. JMod Clin Med
AUTHOR CONTRIBUTIONS 2011; 37:2512.
12 LiuL, YueZX, FuW, ZhangLJ, HeX. The effect of Traditional Chinese Drug combined
UMJ and JYJ planned and designed the study, searched for articles from with electric acupuncture on seminal plasma neutral alpha1, 4 glycosidase enzymes
the databases, selected relevant studies, extracted the data, analyzed in patients with male infertility due to weak sperm. Chin J Fam Plann Gynecotokology
the data, and drafted the manuscript. SL and JML made substantial 2011; 3:324.
contributions to the study design. SL arbitrated contradictory 13 DieterleS, LiC, GrebR, BartzschF, HatzmannW, etal. Aprospective randomized
placebocontrolled study of the effect of acupuncture in infertile patients with severe
assessments. SL helped to draft the manuscript. SL and OK participated oligoasthenozoospermia. Fertil Steril 2009; 92:13403.
in the critical revision of the manuscript. OK had the final responsibility 14 WangZQ, HuangYQ, LiangB. Clinical observation on electroacupuncture and
for the submission decision for publication. All of the authors read and Chinese drug for treatment of oligospermia and asthenospermia of the male infertility
patient. Zhongguo Zhen Jiu 2008; 28:8057.
approved the final manuscript.
15 ShiXF. Effects of acupuncture and traditional Chinese medicinal for oligozoospermia and/
or asthenozoospermia in male infertility(Chinese). China Mod Med 2009; 16:1156.
COMPETING INTERESTS 16 LeungAY, ParkJ, SchulteisG, DuannJR, YakshT. The electrophysiology of de qi
The authors declare that they have no conflict of interest. sensations. JAltern Complement Med 2006; 12:74350.
17 World Health Organization. WHO Laboratory Manual for the Examination and
ACKNOWLEDGMENTS Processing of Human Semen. 4thed. Cambridge: Cambridge University Press;
1999. p.4, 10.
This study was supported by the New Donguibogam Compilation Project
18 World Health Organization. WHO Laboratory Manual for the Examination and
for the expansion of Korean Medical Knowledge(No. K13380) of the Korea Processing of Human Semen. 5 thed. Geneva: World Health Organization;
Institute of Oriental Medicine. 2010. p.10, 226.
19 PeiJ, StrehlerE, NossU, AbtM, PiomboniP, etal. Quantitative evaluation of 31 Zvaczki Z, Szllsi J, KissSA, Koloszr S, FejesI, etal. Magnesiumorotate
spermatozoa ultrastructure after acupuncture treatment for idiopathic male infertility. supplementation for idiopathic infertile male patients: a randomized,
Fertil Steril 2005; 84:1417. placebocontrolled clinical pilot study. Magnes Res 2003; 16:1316.
20 GurfinkelE, CedenhoAP, YamamuraY, SrougiM. Effects of acupuncture and moxa 32 RolfC, CooperTG, YeungCH, NieschlagE. Antioxidant treatment of patients with
treatment in patients with semen abnormalities. Asian J Androl 2003; 5:3458. asthenozoospermia or moderate oligoasthenozoospermia with highdose vitamin C
21 SitermanS, EltesF, WolfsonV, ZabludovskyN, BartoovB. Effect of acupuncture on and vitamin E: a randomized, placebocontrolled, doubleblind study. Hum Reprod
sperm parameters of males suffering from subfertility related to low sperm quality. 1999; 14:102833.
Arch Androl 1997; 39:15561. 33 BalerciaG, BuldreghiniE, VigniniA, TianoL, PaggiF, etal. Coenzyme Q10
22 SitermanS, EltesF, WolfsonV, LedermanH, BartoovB. Does acupuncture treatment treatment in infertile men with idiopathic asthenozoospermia: a placebocontrolled,
affect sperm density in males with very low sperm count? A pilot study. Andrologia doubleblind randomized trial. Fertil Steril 2009; 91:178592.
2000; 32:319. 34 GhanemH, ShaeerO, ElSeginiA. Combination clomiphene citrate and antioxidant
23 SitermanS, EltesF, SchechterL, MaimonY, LedermanH, etal. Success of therapy for idiopathic male infertility: a randomized controlled trial. Fertil Steril
acupuncture treatment in patients with initially low sperm output is associated with 2010; 93:22325.
a decrease in scrotal skin temperature. Asian J Androl 2009; 11:2008. 35 HunaultCC, HabbemaJD, EijkemansMJ, CollinsJA, EversJL, etal. Two new prediction
24 ZhangM, HuangG, LuF, PaulusWE, SterzikK. Influence of acupuncture on rules for spontaneous pregnancy leading to live birth among subfertile couples, based
idiopathic male infertility in assisted reproductive technology. JHuazhong Univ Sci on the synthesis of three previous models. Hum Reprod 2004; 19:201926.
Technolog Med Sci 2002; 22:22830. 36 SripadaS, TownendJ, CampbellD, MurdochL, MathersE, etal. Relationship
25 EnblomA, JohnssonA, HammarM, Onelv E, SteineckG, etal. Acupuncture between semen parameters and spontaneous pregnancy. Fertil Steril 2010;
compared with placebo acupuncture in radiotherapyinduced nauseaA randomized 94:62430.
controlled study. Ann Oncol 2012; 23:135361. 37 SlamaR, EustacheF, DucotB, JensenTK, Jrgensen N, etal. Time to pregnancy
26 SchneiderA, WeilandC, EnckP, JoosS, StreitbergerK, etal. Neuroendocrinological and semen parameters: a crosssectional study among fertile couples from four
effects of acupuncture treatment in patients with irritable bowel syndrome. European cities. Hum Reprod 2002; 17:50315.
Complement Ther Med 2007; 15:25563. 38 IoannidisJP, LauJ. Improving safety reporting from randomised trials. Drug Saf
27 KongJ, KaptchukTJ, PolichG, KirschI, VangelM, etal. Expectancy and treatment 2002; 25:7784.
interactions: a dissociation between acupuncture analgesia and expectancy evoked
placebo analgesia. Neuroimage 2009; 45:9409.
28 ColagiuriB, SmithCA. Asystematic review of the effect of expectancy on
treatment responses to acupuncture. Evid Based Complement Alternat Med 2012; How to cite this article: Jerng UM, Jo JY, Lee S, Lee JM,
2012:857804. Kwon O. The effectiveness and safety of acupuncture for
29 LeushuisE, van der SteegJW, SteuresP, ReppingS, BossuytPM, etal. poor semen quality in infertile males: a systematic review
Reproducibility and reliability of repeated semen analyses in male partners of and meta-analysis. Asian J Androl 27 June 2014.
subfertile couples. Fertil Steril 2010; 94:26315. doi: 10.4103/1008-682X.129130. [Epub ahead of print]
30 CliffordTJ, BarrowmanNJ, MoherD. Funding source, trial outcome and reporting
quality: are they related? Results of a pilot study. BMC Health Serv Res 2002; 2:18.