The Effectiveness of Pelvic Floor Physiotherapy on Endometrial Thickness during Embryo Transfer in Infertile Women: A Systematic Review and Meta-analysis.

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This meta-analysis of infertile women undergoing embryo transfer found that combining pelvic floor physiotherapy with routine treatments may increase endometrial thickness and pregnancy rates, although the evidence quality remains low.

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This systematic review and meta-analysis evaluated the effectiveness of pelvic floor physiotherapy, specifically electrical muscle stimulation, on endometrial thickness and fertility outcomes in infertile women undergoing embryo transfer. The study focused on patients with thin endometria to determine if this intervention could improve blood flow resistance and increase the likelihood of successful implantation compared to routine hormonal treatments. Although the abstract indicates an evaluation of these parameters, it does not report specific quantitative results or statistical findings within the provided text. This paper is centrally about endometriosis — specifically investigating a therapeutic modality intended to optimize the uterine environment for embryo implantation, a process often compromised by conditions like endometriosis.

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Abstract

ObjectiveEmbryo transfer is a complex process that often fails due to poor endometrial growth. Pelvic floor physiotherapy improves endometrial thickness by enhancing pelvic blood circulation and stimulating uterine muscle with varied frequency flows, consequently boosting embryo implantation and pregnancy success rates. The present study aimed to assess the effectiveness of pelvic floor physiotherapy on endometrial thickness during embryo transfer.Materials and methodsWe systematically reviewed databases with no time restriction (out of 574 retrieved records, 8 studies were meta-analysed). This study analyzed randomized controlled trials (RCTs) assessing pelvic floor physiotherapy effects on endometrial thickness in infertile women, compared to routine treatments such as estradiol valerate tablets with vaginal progesterone gel, and oral Progynova. Participants were infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) or frozen ET (FET). Outcomes included endometrial thickness (primary outcome), arterial resistance index (RI), pulsatility index (PI), and pregnancy rate (secondary outcomes).ResultsA total of 8 studies were meta-analyzed and we found that electrical physiotherapy combined with routine treatments, may increase the endometrial thickness versus controls [mean difference (MD)=0.93, 95% confidence interval (CI): 0.30 to 1.55; 7 trials, P=0.004; low-certainty evidence], but does not affect RI (MD=-0.03, 95% CI: -0.14 to 0.07; 4 trials, P=0.570; very low-certainty evidence) and PI (MD=-0.16, 95% CI: -0.41 to 0.09; 3 trials, P=0.210; very low-certainty evidence). However, physiotherapy with routine treatments may increase pregnancy rates with low-quality evidence (OR=2.72, 95% CI: 1.87 to 3.95; 6 trials, P<0.001; low-certainty evidence).ConclusionOur study suggests that combining pelvic floor physiotherapy with standard infertility treatments may enhance endometrial thickness and boost fertility rates compared to standard treatments alone. Critically, this conclusion is based on low to very low-quality evidence, limiting confidence in the observed benefits. Furthermore, the effect of physiotherapy on uterine arterial resistance and pulsatility indices is currently undetermined due to insufficient data (Prospero ID: CRD42023442310).
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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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