Intro
Pregnancy is closely related to the occurrence of ovulation and depends on successful embryo implantation after
fertilization ( 1 ). Among the various factors influencing
implantation, endometrial thickness and sufficient endometrial blood supply play critical roles in facilitating embryo attachment and subsequent pregnancy ( 2 ). Indeed,
endometrial factors directly determine the successfulness
of pregnancy ( 3 ) and their absence or misfunctioning is
estimated to account for nearly 60% of implantation failures ( 4 ). For implantation to occur, the endometrium must
proliferate and differentiate into a receptive state ( 5 ). Both
excessively thin and thick endometria negatively affect
embryo implantation, making optimal endometrial preparation a crucial aspect of assisted reproductive techniques
( 6 ).
Inflammation and damage caused by various diseases,
are the most frequent contributors to a thin endometrium
( 7 ). In patients with a thin endometrium, the blood flow
to both the endometrium and the ovaries is reduced compared to those with a normal endometrium ( 8 ). A thin endometrium has a thickness of less than 7-8 mm, which
can be measured on the day of luteinizing hormone (LH)
secretion peak in the natural menstrual cycle using ultrasound ( 9 ). As such, both endometrial thickness and adequate blood flow are considered prerequisites for successful pregnancy ( 10 ). Improving endometrial blood flow
and receptivity may therefore increase the likelihood of
embryo implantation, a topic that has garnered significant
interest in recent years ( 11 ).
According to previous studies, the classification of
endometrial membrane and pulsatility index (PI), resistance index (RI), and peak systolic velocity/diastolic velocity (S/D) values of the uterine artery, greatly contribute to pregnancy outcomes ( 12 , 13 ). It is assumed that
high PI and RI indicate the higher arterial resistance,
lower blood flow in the uterine artery and lower uterine blood supply that may decrease the rat of fertility.
Therefore, the improvement of endometrial blood flow
distribution during the hormone replacement cycle, the
reduction of blood flow resistance, and the improvement
of pregnancy rate may be achieved by today's methods
( 6 ). The currently available therapies have small effects on patients with thin endometrium due to severe
or extensive damage. Furthermore, difficulty in increasing the endometrial thickness has become a common
unsolvable problem in routine clinical treatments ( 14 ).
There are numerous endometrial preparation plans for
embryo transfer. Currently, the initial treatment methods
include estrogen replacement, medication-mediated improvement of local circulation, mechanical endometrial
stimulation, and administration of traditional medicine
and drugs ( 15 ). Despite the use of different methods for
regulating the uterine arterial blood circulation and increasing the endometrial thickness, there is still no effective therapy for this problem; hence, there is a need
to develop an effective treatment protocol.
Physiotherapy treatments, using electrical stimulation,
are widely used for groups of muscles to improve life activities through electrical impulses that directly stimulate
the muscles ( 16 ). Recent studies suggest that electrical
stimulation may have applications in gynecology and obstetrics, including pregnancy and postpartum, particularly
for conditions such as stress urinary incontinence, back
pain, female sexual dysfunction, pelvic discomfort, and
constipation ( 16 - 20 ). Its mechanism of action is in such a
way that the electrical stimulation accelerates blood flow,
decreases blood flow resistance, and increases blood
circulation of pelvic, vaginal, endometrial, and uterine
muscles. Increasing blood flow through vascular control
enhances the endometrial growth by contracting and relaxing of smooth muscles ( 10 ).
Despite the theoretical benefits, the impact of electrical
pelvic muscle stimulation on endometrial thickness and
fertility outcomes remains unclear, with existing studies
reporting conflicting results. For instance, Tsai et al. ( 21 )
found no predictive value of endometrial thickness, while
Kolibianakis et al. ( 22 ) and Ng et al. ( 23 ) reported no association between endometrial thickness or morphology
and pregnancy outcomes. Similarly, Schild et al. ( 24 )
observed no relationship between uterine arterial blood
flow and endometrial thickness. These inconsistencies
highlight the need for a comprehensive evaluation of the
available evidence.
Therefore, the aim of the present systematic review and
meta-analysis is to evaluate the effectiveness of pelvic
floor physiotherapy, specifically electrical muscle stimulation, on endometrial thickness and fertility outcomes
during embryo transfer in infertile women.
Results
The electronic search of databases initially yielded
574 records. After removing duplicates (23 articles), 551
abstracts were screened, resulting in 536 exclusions due
to irrelevance. Fifteen articles were assessed based on
inclusion criteria, leading to the final inclusion of 8 studies in this systematic review and meta-analysis ( 6 , 10 ,
31 - 36 ) ( Fig .1 ). One study was excluded from the meta-analysis evaluating endometrial thickness due to the
authors' failure to respond to requests for specific data
( 36 ). In a duplicate search, which we conducted after the
initial search period, we found no new studies relevant
to this analysis.
The characteristics of the included trials are summarized in Table 1, providing information on authors,
countries, research design, research groups, types of
intervention, blinding, follow-up period, number of
participants in each group, and main/secondary outcomes and study results. The eight randomized clinical
trials ( 6 , 10 , 31 - 36 ) involved a total of 916 women undergoing infertility treatment in Iran and China. These
studies were published between 2015 and 2022. One
article was in Persian, while the others were in English.
In all trials, the control groups received routine infertility treatments, while the intervention groups received
electrical physiotherapy approaches in addition to the
routine treatments.
PRISMA 2020 flow diagram of the study selection process. PRISMA; Preferred reporting items for systematic reviews and meta-analyses.
Characteristics of included studies
RCT; Randomized control trial, Hz; Hertz, mA; mili Amper, IM; Intramuscular, QID; Quater in die, QD; Quaque die, PI; Pulsatility index, RI; Resistance index, BID; Bis in die, S/D; Systolic velocity/diastolic velocity, NMES; Neuromuscular electrical stimulation, LH; Luteinizing hormone, PDA; Power doppler angiography, and β-HCG; Beta human chorionic gonadotropin.
Women in the intervention groups received various
physiotherapy interventions, including pelvic floor muscle massage, intracavitary physiotherapy combined with
acupuncture, pelvic floor electrical bionics, pelvic floor
neuromuscular electrical stimulation (NMES), biofeed
-back, pelvic neuromuscular stimulation, and biomimetic
electrical stimulation (BES) in the range of 40-50 Hz for
10-50 minutes. The interventions were conducted using
specialized devices, and participants subsequently underwent infertility therapy via in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)
or frozen embryo transfer (FET).
Specific interventions in each study included:
• Electrical massage: A motorized massage pad stimulated the pelvic floor muscles using particular frequencies and vibration intensity to improve muscle
contraction and blood supply to the uterus and ovary,
which was performed daily from the end of menstruation ( 6 ).
• Intracavitary physiotherapy with acupuncture: The
electrodes were applied to the lower abdomen and
vaginal area, with acupuncture points targeted using
disposable needles, every other day between menstruation and the transplant day ( 31 ).
• Bionic electrical stimulation: The French PHENIX
USB8 device was used with a sterile probe inserted
into the vagina, and electrodes connected to the groin
and lumbosacral joints, daily from the ninth day of
menstruation until the day of the LH surge ( 32 ).
• Pelvic floor NMES: Sterilized probes were inserted
into the vagina, and electrode plates were placed in
the center of the pelvis and connected to a PHENIX
USB8 device , every other day, three days after the
menstruation cycle ( 10 ).
• NMES combined with biofeedback: Electrical stimulation caused muscle contraction, and awareness of
pelvic floor muscle contractions was increased using
the PHENIX USB4 system, which was used on the
day 9 or 10 of menstruation, for three to four consecutive times ( 33 ).
• Biofeedback and neuromuscular electrical stimulation: A two-channel biofeedback device was used
with electrodes placed inside the vagina and on the
symphysis pubis for nine sessions ( 34 ).
• BES: The PHENIX-8 device was used with electrodes
attached to the abdominal aorta, legs, and groins to
stimulate blood flow, every other day, two to three
days after the end of menstruation and repeated three
or five times per cycle ( 35 ).
• BES therapy: The PHENIX-8 neuromuscular stimulation therapeutic apparatus was inserted into the
vagina and attached to the groin and lumbosacral of
both sides, daily ( 36 ).
• Intervention types: The studies employed various
physiotherapy modalities (e.g. massage, NMES, biofeedback, acupuncture), which may differ in their
mechanisms and effectiveness.
• Treatment protocols: There were variabilities in frequency, intensity, duration, and timing of the interventions, as well as the device types and electrode
placements.
• Outcome measurement: While endometrial thickness
was consistently measured by ultrasound, the timing
of assessment (e.g. cycle day) and pregnancy confirmation methods varied slightly.
The participants’ age range was 20-45 years and their
BMI was under 30 ( 31 - 34 , 36 ). Some of their inclusion
criteria were meeting the infertility diagnosis criteria,
such as no previous use of estrogen and progesterone in
the last 3 months, failure in pregnancy by embryo transfer
using the IVF method, and having endometrial thickness
of less than 7 mm in the luteal phase. The reviewed studies did not address the lifestyles of the participants.
Some exclusion criteria were the contraindications to
IVF, endocrine diseases, low ovarian responses, unwillingness to participate in the study, intrauterine adhesions
(Asherman syndrome), uterine dysplasia, a history of pelvic cancer, severe endometriosis, congenital uterus abnormalities with hysteroscopy, endometrial thickness of less
than 6 mm on the transfer day, contraindications for estrogen therapy, mental diseases, vaginitis, nervous disorders,
hypertension, diabetes, the use of intrauterine devices, a
long-term use of hormonal contraceptives, chronic use of
non-steroidal anti-inflammatory agents, pacemaker, unstable or serious cardiac arrhythmia, unstable seizure disorder, pelvic pain, and painful and swollen hemorrhoids,
platelet dysfunction due to aspirin use, thrombocytopenia,
and gastrointestinal ulcers.
The studies excluded from this review comprised one
lacking control groups ( 37 ), and six that utilized designs
other than RCTs ( 38 - 43 ) ( Table S2 , See Supplementary
Online Information at www.ijfs.ir ).
The risk of bias in randomized controlled trials was
assessed using the risk of bias, version 1 (ROB-1) tool
( 25 ). Regarding the generation of a random sequence, five
studies were ranked unknown risk ( 6 , 10 , 32 , 34 , 36 ), and
three studies were ranked low-risk ( 31 , 33 , 35 ). Four trials were ranked low risk in allocation concealment ( 31 ,
33 - 35 ), and the rest were ranked unknown risk ( 6 , 10 , 32 , 36 ). Regarding the blinding of the intervention-providing
personnel, three studies were ranked high-risk ( 31 , 33 ,
35 ), and five studies were ranked unknown risk ( 6 , 10 , 32 ,
34 , 36 ). Furthermore, the outcome assessors were blind
in two of the studies ( 31 , 35 ), and the rest were exposed
to unknown and high-risks ( 6 , 10 , 32 - 34 , 36 ). All studies
were ranked low risk regarding the whole outcome data
or attrition bias ( 6 , 10 , 31 - 36 ). Finally, all studies were
ranked low risk regarding the selective reporting bias ( 6 ,
10 , 31 - 36 ) ( Table S3 , See Supplementary Online Information at www.ijfs.ir , Fig .2A, B ).
Data from seven studies ( 6 , 10 , 31 - 35 ) on 856 women
undergoing infertility treatments indicated that electrical physiotherapy procedures combined with routine infertility treatments may increase the endometrial thickness more than the routine treatments alone (MD=0.93,
95% CI: 0.30 to 1.55; 7 trials, 856 women; low-certainty
evidence). The random effect method was used instead
of the fixed effect method due to the high heterogeneity of included studies (Tau2=0.69; chi2=834.92; I2=99%,
P<0.00001, Fig .3 ).
Based on the results of four RCTs ( 10 , 31 - 33 ) on 553
women undergoing infertility therapies, physiotherapy
interventions combined with the routine treatments, did
not affect the arterial RI in comparison with the routine
treatments alone (MD=-0.03, 95% CI:-0.14 to 0.07; 4 trials, 553 women; very low-certainty evidence). Due to the
high heterogeneity of the included studies, the random effect method was used instead of the fixed effect method
(Tau2=0.01; chi2=159.33; I2=98%, P<0.001, Fig .4A ).
Risk of bias. A. Risk of bias summary: review authors’ judgments about each risk of bias item for each included study. B. Risk of bias graph: review
authors' judgments about each risk of bias item presented as percentages across all included studies.
Physiotherapy interventions versus routine care; Outcome 1: Endometrial thickness. SD; Standard deviation and CI; Confidence interval.
The results of three RCTs ( 31 - 33 ) on 269 women under
going infertility therapies indicated that physiotherapy in
terventions combined with the routine treatments did not
affect the PI in comparison with the routine treatments
alone (MD=-0.16, 95% CI:-0.41 to 0.09; 3 trials, 269
women; very low-certainty evidence). The random effect
method was used instead of the fixed effect method due
to the high heterogeneity of included studies (Tau2= 0.05;
chi2=39.13; I2=95%, P<0.001, Fig .4B ).
Six RCTs ( 6 , 31 - 33 , 35 , 36 ) on 554 women undergoing
infertility therapies compared the pregnancy rates in women who received physiotherapy interventions combined
with the routine treatments, with those who received the
routine treatments, only. The results of this comparison
also indicated that physiotherapy interventions and the
routine treatments may increase fertility rates in women
undergoing IVF (OR=2.72, 95% CI: 1.87 to 3.95; 6 trials,
197 women; low-certainty evidence) ( Fig .4C ).
The quality of evidence for outcomes of endometrial
thickness and pregnancy rate due to inconsistency (high
heterogeneity in the included studies) and imprecision
(low sample size), was decreased by two degrees and
reached the low-certainty level. For the outcomes of the
arterial RI and PI due to inconsistency (high heterogeneity in the included studies), imprecision (low sample
size), and serious risk of bias in studies, the quality of
evidence was decreased by three degrees and reached
the very low-certainty level. Quantitative assessment of
publication bias using Egger’s and Begg’s tests did not
indicate statistically significant publication bias for any of
the outcomes (all P>0.05, Table S4 , See Supplementary
Online Information at www.ijfs.ir ). Therefore, it causes
uncertainty in the conclusion of the impact of pelvic floor
physiotherapy on these outcomes ( Table 2 ). Based on the
assessment of the included studies using nine selected
items from the CONSORT checklist, three studies were
classified as high quality, four as moderate quality, and
one as low quality ( Table S1 , See Supplementary Online
Information at www.ijfs.ir ).
Physiotherapy interventions versus routine care on outcomes. A. Arterial resistance index, B. Pulsatility index, and C. Pregnancy rate. SD; Standard
deviation and CI; Confidence interval.
Certainty of the evidence using the GRADE approach by outcomes
GRADE; Grading of recommendations assessment, development and evaluation, CI; Confidence interval, RCT; Randomized controlled trial, High certainty; We are very confident that the
true effect lies close to that of the effect estimate, Moderate certainty; We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect,
but there is a possibility that it is substantially different, Low certainty; Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate
of the effect, Very low certainty; We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of the effect, a ; Downgrade by
one level because of substantial heterogeneity >50%, b ; Downgrade by one level for imprecision (small sample size), c ; Downgrade by one level for risk of bias (two studies were at risk of
performance bias because the participants/personnel were not masked to intervention and one study were at risk of detection bias), and d; Downgrade by one level for risk of two studies
were at risk of performance bias because the participants/personnel were not masked to intervention.
These findings indicate that pelvic floor physiotherapy,
particularly electrical stimulation modalities, may offer a
clinically relevant approach to increase endometrial thickness, and potentially improve pregnancy rates in women
with thin endometrium undergoing embryo transfer. Given the significant impact of endometrial thickness on implantation success, physiotherapy may be considered as
an adjunct to conventional hormonal treatments. Further
high-quality trials are needed to establish standardized
protocols and confirm such benefits.
Discussion
This systematic review, comprising 8 randomized controlled trials, investigated the effects of pelvic floor physiotherapy on endometrial thickness during embryo transfer
in infertile women, along with other relevant outcomes.
The findings suggest that pelvic floor physiotherapy,
when combined with the routine infertility treatments,
may increase endometrial thickness and improve pregnancy rates, although it does not appear to significantly
impact arterial RI or PI.
Our review supports the idea that electrical stimulation may enhance endometrial receptivity. This aligns
with findings from Chen et al. ( 44 ), who demonstrated
that low-frequency electrical stimulation combined with
Dingkun pills improved endometrial thickness and uterine size after surgery. Similarly, Luo et al. ( 39 ) found
that BES improved clinical pregnancy rates, biochemical
pregnancy rates, and live birth rates in patients with abnormal endometrial receptivity undergoing FET.
However, it's worth noting that Luo et al. ( 39 ) did not
find a significant difference in endometrial thickness on
the FET day. A pilot study by Bodombossou-Djobo et al.
( 45 ) indicated that NMES might be effective for patients
with thin endometrium, but more studies are needed to
evaluate its effectiveness.
Our analysis indicates that physiotherapy interventions did not significantly affect the arterial RI and PI.
This contrasts with a retrospective study by Nie and Chen
( 46 ), who found that transcutaneous electrical stimulation
combined with medication for missed abortion increased
endometrial thickness and reduced PI, RI, and S/D ratios.
The observed discrepancy may be due to differences in
study populations (women with missed abortion vs. infertile women undergoing embryo transfer) and the specific
electrical stimulation techniques used.
Despite various methods for endometrial preparation,
at this point, there is no definitive approach for women
with thin endometrium. Strategies such as administration
of estrogen, low-dose aspirin, heparin, vaginal sildenafil,
pentoxifylline, and granulocyte-colony stimulating factor
(G-CSF) intrauterine perfusion have been used, but with
limited success ( 47 ). While intrauterine infusion of GCSF and platelet-rich plasma (PRP) have been explored,
their effectiveness in improving endometrial thickness
and pregnancy outcomes remain uncertain ( 48 ). This
highlights the ongoing need for novel interventions to address this challenge.
This study was strengthened by the registration of the
research protocol on the PROSPERO database and adherence to Cochrane Handbook principles. A comprehensive
search for relevant studies was conducted at the beginning
and the end of the study period without any publication
date restrictions. Data extraction and risk of bias assessment were performed independently by two researchers
to minimize potential bias. The ability to draw firm conclusions about the effect size of the interventions is limited by the small number of trials conducted, the small
sample sizes, the restriction of the studies to Iranian and Chinese populations, and the high risk of bias observed in
the included studies.
Larger prospective RCTs with standardized physiotherapy protocols are suggested to confirm the benefits of
pelvic floor physiotherapy on endometrial thickness and
pregnancy outcomes. Also, studies should investigate the
optimal parameters of electrical stimulation (frequency,
duration, intensity, electrode placement) for improving
endometrial receptivity.
The potential of pelvic floor physiotherapy as an adjunct
to conventional hormonal treatments in IVF protocols
warrants consideration. Given the importance of endometrial thickness for successful implantation, physiotherapy
may offer a non-pharmacological approach to improve
endometrial receptivity. However, the optimal type, frequency, and duration of physiotherapy interventions need
to be determined through well-designed clinical trials.
Clinicians may cautiously incorporate pelvic floor physiotherapy as a complementary approach within infertility
treatment regimens, tailoring interventions to individual
patient needs and available resources. This integration
should be accompanied by careful monitoring and evaluation of the outcomes to ensure safety and effectiveness.
Conclusions
Our systematic review and meta-analysis suggest that
pelvic floor physiotherapy interventions combined with
routine infertility treatments may increase endometrial
thickness and improve fertility rates compared to the routine treatments alone. However, these findings are supported by low to very low-quality evidence, which limits
the certainty of the observed effects. The impact of physiotherapy on uterine arterial resistance and pulsatility indices
remains unclear due to insufficient and inconsistent data.
Despite these limitations, the evidence from this study
suggests that pelvic floor physiotherapy may be a valuable,
low-cost, non-invasive, and easily implemented adjunct to
conventional infertility treatments. Its potential to enhance
endometrial receptivity may reduce the reliance on prolonged hormonal therapies and improve overall treatment
success. Therefore, integrating pelvic floor physiotherapy
into clinical practice could be considered, especially for
patients who have contraindications or poor responses to
standard hormonal protocols. By assessing the available
evidence, we hope to clarify the potential role of this intervention in improving reproductive outcomes.
Materials Methods
This systematic review and meta-analysis was conduct
ed in accordance with the Cochrane Handbook for Sys
tematic Reviews of Interventions ( 25 ) and the Preferred
Reporting Items for Systematic Reviews and Meta-Anal
yses (PRISMA) guidelines. The protocol was registered
on the International Prospective Register of Systematic
Reviews (PROSPERO: CRD42023442310).
The women with thin endometrial thickness undergoing
assisted reproductive treatment.
We included all clinical trials in which physiotherapy
techniques with electrical stimulation were used as an intervention alone or combined with other treatments.
Other routine treatments such as estradiol valerate tablets combined with vaginal progesterone gel, oral Progynova, Aspirin.
Primary outcomes: Endometrial thickness
Secondary outcomes: Pregnancy rate and blood flow
indexes including arterial RI and PI.
Several databases, including PubMed, Web of Science, Cochrane, Scopus, Scientific Information Database
(SID), along with the Google Scholar search engine, were
searched to identify relevant studies. Boolean operators
(AND, OR) were used, and search terms were adjusted
for each database. The search words were according to
each database. The systematic search was based on standard keywords, obtained from the medical subject headings
(MeSH) browser, including pelvic floor, physiotherapy,
neuromuscular stimulation, fertility, embryo transfer, endometrial thickness, endometrium, and pregnancy. Time
restrictions were not applied to maintain search integrity.
The articles in languages other than Persian and English
were excluded due to the inclusion criteria. All articles
up until October 1, 2023, were searched. The search keywords were compatible with the MeSH browser, and the
text words were as follows:
(("pelvic floor physiotherapy"[All Fields] OR ("pelvic
floor"[MeSH Terms] OR "pelvic floor"[Text
Word]) OR ("physical therapy modalities"[MeSH
Terms] OR "physiotherapy"[Text Word]) OR ("neuromuscular monitoring"[MeSH Terms] OR "neuromuscular monitoring"[Text Word])) AND ("endometrial thickness"[All Fields] OR ("endometrium"[MeSH
Terms] OR "endometrium"[Text Word])) AND ("embryo transfer"[All Fields] OR ("embryo transfer"[MeSH
Terms] OR "embryo transfer"[Text Word])).
In this study, all articles published in journals, presented
in seminars and national congresses, theses, and gray literature were searched. The corresponding authors were
contacted if the full text of the articles were unavailable.
All citations of the relevant articles were also studied using a manual search.
The studies were eligible for inclusion if they were
randomized controlled trials (RCTs) involving patients
undergoing infertility treatment with a diagnosis of thin
endometrium. Eligible interventions included any physiotherapy techniques utilizing electrical stimulation, either
as a standalone therapy or in combination with other treatments. Comparator groups were required to receive routine infertility treatments, such as estradiol valerate tablets
with vaginal progesterone gel, oral progynova, or aspirin.
In addition, the studies needed to report at least one of
the following outcomes: endometrial thickness (primary
outcome), pregnancy rate, arterial RI or PI. The exclusion
criteria, on the other hand, were the lack of comparison or
control group, unavailability of the complete text of the
articles, and non-Persian or non-English articles.
An information resource management tool, was utilized
to arrange the studies. For research selection, the databases and other references were first searched and all articles
and sources were inserted into EndNote. Then the replicated articles were removed and the titles and abstracts of
the research papers were evaluated. Thereafter, the articles irrelevant to the research purpose were removed and
the whole texts of the relevant articles were investigated
using the inclusion and exclusion criteria. Ultimately,
studies that fulfilled the inclusion criteria were included.
Two researchers independently performed the search and
selection of articles to increase validity. In the case of
a conflict in an area, a third researcher was involved to
make the final decision.
Two researchers independently extracted data using a
researcher-made checklist. This checklist included the
author's name, the publication year, country, research
design, the sample size, intervention and control groups,
the follow-up duration, type of blinding, main/secondary
outcomes, and study results. To assess the quality of the
included studies, two authors independently evaluated
nine items from the Consolidated Standards of Reporting
Trials (CONSORT) checklist ( 26 ) ( Table S1 , See Supplementary Online Information at www.ijfs.ir ). We classified
the studies as "high quality" if they met seven to nine criteria, "moderate quality" if they met four to six criteria,
and "low quality" if they met fewer than four criteria.
The Cochrane risk of bias tool (Cochrane Collaboration)
( 25 ) and review manager program (RevMan 5.3) software
were utilized to evaluate the study quality. This tool evaluates the quality of articles regarding selection bias (random sequence generation and allocation concealment),
implementation bias (participant and personnel blinding),
detection bias (blinding of outcome assessors), attrition
bias (exclusion from the study after randomization), and
bias of outcome selection report. This tool reported each
item as low-risk, high-risk, and unclear-risk ( 27 ).
Overall, Cochrane stresses methodological rigor and
transparent reporting rather than reliance on formal publication bias tests in reviews with fewer than 10 studies, acknowledging the limitations of statistical methods in such
contexts ( 28 ). In this study, publication bias was evaluated
using Egger’s and Beg’s tests. However, Cochrane reviews
often use risk of bias assessments to address potential bias,
even when formal statistical methods are impractical.
To report the effect size, the mean difference (MD)
(95% confidence interval) was used for quantitative data,
and the odds ratio (OR) for qualitative data. The metaanalysis data comprised mean change (post-intervention
score minus the baseline), and standard deviation changes (SD) (according to the SD change equation) ( 25 ) for
quantitative data, and events for qualitative data.
A meta-analysis, conducted using RevMan 5.3, compared intervention and control group outcomes across
studies with at least two trials. The degree of heterogeneity between the studies was assessed using the I² and
Cochran’s test. I² values below 25% indicated low heterogeneity, 25-75% moderate heterogeneity, and above
75% high heterogeneity ( 29 ). The MD and standard
mean difference (SMD) (when using different tools) for
continuous data and OR were used for dichotomous data
to measure the intervention effect. A random-effects
model was employed due to the observed methodological variability among the studies ( 30 ). Furthermore, the
P value was utilized to evaluate the significance of the
MD. A P value below 0.05 was deemed statistically significant.
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