Prophylactic antibiotics for preventing pelvic inflammatory disease after embryo transfer in patients with endometriosis: A single-center retrospective cohort study

Prophylactic antibiotics for preventing pelvic inflammatory disease after embryo transfer in patients with endometriosis: A single-center retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prophylactic antibiotics for preventing pelvic inflammatory disease after embryo transfer in patients with endometriosis: A single-center retrospective cohort study Maho Furukawa, Masashi Takamura, Osamu Wada-Hiraike, Yusuke Sasabuchi, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8750076/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Objective To evaluate the efficacy of prophylactic antibiotic regimens in preventing pelvic inflammatory disease (PID) after embryo transfer (ET) among patients with endometriosis, a risk factor of PID. Material and methods This retrospective cohort study used patient data from a single institution from January 2009 to June 2018. Cycles involving fresh ET, two-step ET, and from patients who used steroids or immunosuppressants were excluded. The primary outcome was the incidence of PID within one month after ET, which was compared between groups that received different antibiotic regimens (no antibiotics, oral antibiotics only, and oral plus vaginal antibiotics). The secondary outcomes were clinical pregnancy and live birth to evaluate the safety of the antibiotics. Fisher’s exact test and multivariable logistic regression were used for statistical analysis. Results A total of 357 eligible ET cycles were identified. PID occurred after ET in 5/143 (3.5%) cycles with no antibiotics, 2/90 (2.2%) cycles with oral antibiotics, and 0/124 (0%) cycles with combined antibiotics. Although multivariable adjustment could not be performed because of the small number of events, no significant differences were observed among the three groups (Fisher’s exact test, P = 0.081). Regarding the safety of the antibiotics, there were no significant differences among the three groups in either clinical pregnancy or live birth after adjustment. Conclusions Prophylactic antibiotics had no significant effect on preventing PID after ET in patients with endometriosis. Although not statistically significant, the absence of PID cases after combined oral and vaginal antibiotics suggests potential benefits, warranting further investigation. Embryo transfer Endometriosis Intravaginal antibiotic therapy Pelvic inflammatory disease Prophylactic antibiotics Figures Figure 1 1. Introduction The use of artificial reproductive technologies (ART) is becoming increasingly more common in Japan [ 1 ], and this can be attributed to a growing interest and awareness in ART and/or delayed childbearing [ 2 – 4 ]. Embryo transfer (ET) is a critical step in ART, but in rare cases, it can cause pelvic inflammatory disease (PID) [ 5 , 6 ]. Prolonged hospitalization and surgical treatment may be required in such patients, and this can result in severe reproductive consequences [ 6 ]. Therefore, preventing PID is of great importance among patients undergoing ET. Endometriosis is a common gynecological disease characterized by the presence of endometrial-like tissue outside the uterus, affecting 5%–10% of reproductive-age women [ 7 , 8 ] and 25%–40% of women with infertility [ 9 , 10 ]. Additionally, endometriosis is also a significant risk factor for the development and exacerbation of PID [ 11 , 12 ]. There is a scarcity of information about preventing PID after ET. Some studies have examined the effectiveness of prophylactic antibiotics in reducing bacterial contamination of the catheter and increasing the clinical pregnancy rate [ 13 , 14 ]. Although prophylactic antibiotics decreased catheter bacterial contamination, this did not increase the clinical pregnancy rate [ 13 ], and thus, routine antibiotic prophylaxis was not recommended for all ETs. However, these studies excluded patients with a high risk for PID (i.e., previous PID or endometriosis) and did not focus on PID as an outcome. The use of prophylactic antibiotics for PID in these patients should be considered, but this has not been established. Our institution, the University of Tokyo Hospital, has an outpatient department specializing in endometriosis that caters to many women with endometriosis who desire pregnancy and need ART. Since 2011, our institution has followed a policy of starting oral antibiotics (cefcapene pivoxil hydrochloride hydrate 100 mg 3 times daily for 4 days from the day before ET) for the prevention of PID after ET in patients with endometrioma or adenomyosis. Adenomyosis is a common gynecological disease characterized by endometrial-like tissue within the myometrium [ 15 ], which is often accompanied by endometriosis [ 16 ]. Endometriosis and adenomyosis are believed to represent different phenotypes of a single disease [ 17 ], and severe cases of PID have been reported among women with adenomyosis [ 18 ]. Therefore, our institution also considers adenomyosis as a risk factor for PID, and thus, the same policy is followed for patients with adenomyosis. Cefcapene pivoxil hydrochloride hydrate is used due to its broad-spectrum coverage for common organisms that cause PID [ 19 ]. Since 2012, the same policy has been followed for patients with a history of previous surgery for endometriosis, including those with no evident lesions at the time of ET. However, we still encountered a severe recurrent case of PID despite starting oral antibiotic prophylaxis. Accordingly, in 2015, an intravaginal antibiotic (metronidazole 250 mg once daily starting from the day ET was scheduled until the day before ET) was added to this prophylactic regimen to reduce contamination through the catheter during ET. This retrospective study investigated the effectiveness of prophylactic antibiotics in preventing PID after ET among patients with endometriosis. 2. Materials and Methods 2.1. Data Source This retrospective cohort study extracted patients’ clinical information from the medical records at the University of Tokyo Hospital from January 2009 to June 2018. This hospital is a tertiary medical institution that performs approximately 260 ET cycles (80 fresh ET cycles and 180 frozen ET cycles) annually. 2.2. Participants This study included patients diagnosed with endometriosis (including both pathological and clinical diagnoses) prior to undergoing ET. The clinical diagnosis of endometriosis included subtypes of ovarian endometriosis (endometrioma), deep infiltrating endometriosis mostly detected at the pouch of Douglas, and/or adenomyosis, which were diagnosed via pelvic internal examination, transabdominal or transvaginal ultrasound, and/or magnetic resonance imaging. Patients with previous endometriotic lesions that had already been removed were also included. The following cases were excluded: (i) fresh ET, since we could not distinguish PID caused by oocyte retrieval (i.e., all included cases were frozen ET), (ii) two-step ET (usually day 3 and day 5), since this has double the chance of infection, and (iii) ET cycles from patients who were receiving steroids or immunosuppressants. The eligible patients were divided into three groups based on the prophylactic regimen: (i) no antibiotics before/after ET, (ii) oral antibiotics group (i.e., oral cefcapene pivoxil hydrochloride hydrate 100 mg 3 times daily for 4 days from the day before ET), and (iii) combined antibiotics group (i.e., oral cefcapene pivoxil hydrochloride hydrate 100 mg 3 times daily for 4 days from the day before ET, plus vaginal metronidazole 250 once daily starting from the day ET was scheduled until the day before ET). 2.3. Outcome The primary outcome was the diagnosis of PID within one month after ET. PID was diagnosed based on the presence of lower abdominal pain or uterine/adnexal tenderness, plus either fever (≥ 38.0°C), increased white blood cell or C-reactive protein count, or an abscess seen on transvaginal ultrasound [ 20 ]. All patients were followed up at the outpatient clinic at least once within one month after ET. To evaluate the safety of the antibiotics, the secondary outcomes included clinical pregnancy (i.e., the presence of one or more gestational sacs within the uterus) and live birth. 2.4. Variables The following variables were evaluated: year of frozen ET performed, maternal age at frozen ET, previous parity, endometrial preparation protocols (i.e., natural cycle, hormone replacement cycle, or mild ovarian stimulation cycle with administration of human menopausal gonadotropin and human chorionic gonadotropin), presence of ovarian endometrioma or adenomyosis at the time of frozen ET, and previous history of surgery for endometrioma or adenomyosis. 2.5. Statistical Analysis Continuous and categorical variables are presented as mean ± standard deviation (SD) and n (%), respectively. A one-way analysis of variance was used to compare continuous baseline characteristics (e.g., age), while Fisher’s exact test was used to compare categorical characteristics (e.g., the presence/absence of endometrioma at frozen ET). Fisher’s exact test and multivariable logistic regression were used to evaluate the association between each group and the outcomes. For multivariable analyses, we adjusted the following baseline characteristics: maternal age at frozen ET, previous parity, endometrial preparation protocols, and presence of ovarian endometrioma or adenomyosis at the time of frozen ET. All statistical analyses were conducted using the STATA/SE version 18.0 software (STATA, College Station, TX). 2.6. Ethics This study was approved by the Research Ethics Committee of the Faculty of Medicine of the University of Tokyo (the University of Tokyo IRB number is 3128-6) and was performed in accordance with the Declaration of Helsinki. 3. Results We collected data from 564 ET cycles in patients with endometriosis at the University of Tokyo Hospital from January 2009 to June 2018. After excluding 207 cases as per the exclusion criteria, 357 frozen ET cycles were eligible for analysis. These included 143 frozen ET cycles with no antibiotics, 90 frozen ET cycles with oral antibiotics, and 124 frozen ET cycles with combined antibiotics. The flowchart of the included ET cycles is shown in Fig. 1 . Table 1 illustrates the changes in antibiotic use over the study period for patients with endometriosis treated at our hospital. Oral antibiotics have been used since 2011, while combined antibiotics were used starting in 2015, reflecting the changes in clinical guidelines at our department. Table 1 Temporal changes in antibiotic use during the study period. Regimen Year 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Total No antibiotics, n 28 16 11 22 22 12 9 12 10 1 143 % 100 100 68.8 84.6 75.9 23.5 22.5 20.7 15.4 3.6 40.1 Oral antibiotics only, n 0 0 5 4 7 39 10 10 10 5 90 % 0 0 31.3 15.4 24.1 76.5 25 17.2 15.4 17.9 25.2 Combined oral plus vaginal antibiotics, n 0 0 0 0 0 0 21 36 45 22 124 % 0 0 0 0 0 0 52.5 62.1 69.2 78.6 34.7 Table 2 presents the baseline characteristics of the three groups. There were significant differences across the three groups in terms of endometrial preparation, presence of endometrioma at the time of frozen ET, and previous history of surgery for endometriosis. Table 2 Characteristics of patients who underwent frozen embryo transfer. No antibiotics Oral antibiotics only Combined oral plus vaginal antibiotics p-value (n = 143) (n = 90) (n = 124) Age, mean (SD) 37.1 3.9 37.3 4.5 37.1 4.7 0.90 Parity 0.12 0, n (%) 123 86 85 94 109 88 1, n (%) 20 14 5 5.6 15 12 Protocols for endometrial preparation < 0.001 Natural cycle, n (%) 37 26 22 24 5 4.0 Hormone replacement cycle, n (%) 104 73 68 76 115 93 Ovarian stimulation cycle, n (%) 2 1.4 0 0.0 4 3.2 Presence of endometrioma at FET, n (%) 24 17 30 33 27 22 0.014 Adenomyosis, including post-adenomyomectomy, n (%) 44 31 36 40 41 33 0.34 Previous surgical history for endometriosis, n (%) 94 66 50 56 62 50 0.030 Previous surgical history for endometrioma, n (%) 91 64 44 49 56 45 0.006 Previous surgical history for adenomyosis, n (%) (adenomyomectomy) 3 2.1 8 8.9 10 8.1 0.032 All categories have p-values to compare the three groups. SD, standard deviation; FET, frozen embryo transfer Table 3 shows the occurrence of PID and pregnancy outcomes after frozen ET in each group. PID occurred after ET in 5/143 (3.5%) cycles with no antibiotics, 2/90 (2.2%) cycles with oral antibiotics, and 0/124 (0%) cycles with combined antibiotics. Among the PID cases, one case with no antibiotics was a recurrent PID case. Inpatient management was required in 4 of 5 cases (80.0%) with no antibiotics and in all cases with oral antibiotics, whereas surgery was not required in any case. Ovarian endometrioma at the ET was observed in 1 of 5 cases (20.0%) with no antibiotics and in 1 of 2 cases (50.0%) with oral antibiotics. Although no cases of PID occurred in the combined antibiotics group, there was no statistically significant difference in the occurrence of PID among the three groups (Fisher’s exact test, p = 0.081). Multivariable logistic regression analysis could not be performed because of the small number of events. Table 3 The occurrence of PID and pregnancy outcomes after frozen embryo transfer according to antibiotic regimen. No antibiotics n = 143 Oral antibiotics only n = 90 Combined oral plus vaginal antibiotics n = 124 p-value PID 5 (3.6%) 2 (2.2%) 0 (0.0%) 0.081 Clinical pregnancy 30 (21.0%) 14 (15.6%) 25 (20.2%) 0.59 Live birth 19 (13.3%) 11 (12.2%) 14 (11.3%) 0.88 PID, pelvic inflammatory disease Table 4 presents the results of the logistic regression analyses for clinical pregnancy and live birth. After adjusting for baseline characteristics, the type of prophylactic regimen had no significant association with clinical pregnancy (adjusted odds ratio [OR] and 95% confidence interval [CI]; oral antibiotics vs. no antibiotics, 0.65 [0.32–1.32]; combined antibiotics vs. no antibiotics, 0.98 [0.53–1.83]) and with live birth (adjusted OR and 95% CI: oral antibiotics vs. no antibiotics, 0.90 [0.40–2.07]; combined antibiotics vs. no antibiotics, 0.92 [0.42–2.01]). Table 4 Adjusted odds ratios to determine the association of each antibiotic regimen with clinical pregnancy and live birth. Outcome Adjusted values OR (95% CI) a p-value OR (95% CI) b p-value Clinical pregnancy 0.65 (0.32–1.32) 0.23 0.98 (0.53–1.83) 0.96 Live birth 0.90 (0.40–2.07) 0.81 0.92 (0.42–2.01) 0.84 Adjusted by age at frozen embryo transfer, parity, endometrial preparation protocols, presence or absence of endometriosis, and presence or absence of adenomyosis. a Adjusted OR of oral antibiotics vs. no antibiotics b Adjusted OR of combined antibiotics vs. no antibiotics OR, odds ratio; 95% CI, 95% confidence interval. 4. Discussion 4.1. Principal Findings This retrospective study investigated whether prophylactic antibiotics can effectively prevent PID after frozen ET among patients with endometriosis. No cases of PID were noted among patients taking oral plus vaginal antibiotic prophylaxis. However, no statistically significant differences were detected among the three groups, likely due to the small sample size. Furthermore, the use of prophylactic antibiotics, regardless of purely oral or combined regimens, did not suggest any significant impact on clinical pregnancy or live birth. The policy changes regarding the use of prophylactic antibiotics for patients with endometriosis likely affected the number of patients in each group, resulting in the observed differences in patient characteristics and backgrounds (e.g., the presence of endometrioma at frozen ET and previous surgery for endometriosis). These variations in the endometrial preparation protocol were influenced by the medical care system in our facility. To eliminate the potential confounding effects of oocyte retrieval, only frozen ET cases were analyzed in this study. Since fresh ET is assumed to carry a similar infection risk as frozen ET, the same prophylactic antibiotic protocol is applied for both procedures at our facility. Therefore, we believe that our findings can be applied to all ET procedures. 4.2. Results in the Context of What is Known Two previous studies have discussed the necessity of prophylactic antibiotics at ET [ 14 , 21 ]. Both of these studies cited the randomized controlled trial of Brook, which recommended against the routine use of antibiotics at ET, because the pregnancy rates did not improve despite having decreased ET catheter contamination rates [ 13 ]. However, that study did not consider the incidence of PID and excluded patients with a high risk of PID (e.g., those with a history of pelvic infections or endometriosis). Since our gynecological team has an outpatient department specializing in endometriosis, we encounter many patients with endometriosis, some of whom wish to conceive. This allows us to focus on this high-risk group and assess the relationship between prophylactic antibiotic use and PID in this specific population. In agreement with these previous studies, our findings suggest that routine prophylactic antibiotic use during ET may not be necessary, even for patients with endometriosis, which is a known risk factor for PID. 4.3. Clinical and Research Implications The lack of impact of antibiotic use on the incidence of PID could be attributed to several factors. First, even if the ET procedure is a critical step in ART [ 22 ], its degree of invasiveness may not be sufficient to cause infection. PID is generally thought to result from an ascending infection that originates from the lower genital tract [ 23 ]. In theory, techniques for endometrial cytology and endometrial histology, similar to ET, can also cause PID through an ascending infection, but only a few reports have described this. Even during saline infusion sonography or hysteroscopy, which involves injecting fluid into the uterus, routine antibiotic prophylaxis is not recommended, although individual risk of PID should be considered [ 21 ]. Second, removing excess mucus before ET may be sufficient for preventing PID after ET [ 22 ]. This is a common practice that is also routinely followed for all patients at our hospital. Third, the choice of antibiotic regimen may have been inappropriate. Cefcapene pivoxil hydrochloride hydrate belongs to the class of oral third-generation cephalosporins, which provide a broad spectrum of coverage [ 19 ] and are frequently utilized in Japan [ 24 ]. However, these drugs have poor oral bioavailability [ 19 , 25 ], which may limit their ability to achieve therapeutic concentrations at the target site, potentially reducing their effectiveness despite having adequate antimicrobial coverage. Vaginal drug administration is a route of drug delivery that is easy to use and enables targeted regional therapeutic administration [ 26 ]. Moreover, metronidazole can cover organisms that are not covered by (or resistant to) cephalosporins [ 27 , 28 ]. Previous reports have described the superiority of cephalosporins plus metronidazole compared to cephalosporins alone in preventing surgical site infection [ 29 ]. Thus, the use of intravenous or oral metronidazole in combination with other drugs has been recommended for the treatment of PID [ 30 ]. Additionally, metronidazole vaginal tablets are also known to be effective in treating bacterial vaginosis and preventing surgical site infection [ 31 , 32 ]. Although the doses differed, previous reports claim that vaginal administration of metronidazole had the same efficacy as oral administration [ 31 ]. In this study, the absence of PID cases after using combined antibiotics did not reach statistical significance, probably due to the rare incidence of PID after ET [ 6 ] and the small sample size. Nevertheless, the outcomes in this study, especially alongside previous reports, suggest the potential protective effect of combination therapy with vaginal metronidazole plus cephalosporins, warranting further investigation. 4.4. Strengths and Limitations The strength of this study was that it was the first to investigate the efficacy of prophylactic antibiotics, specifically combination therapy with oral plus vaginal antibiotics, for preventing PID during ET among patients with endometriosis, a known risk factor for PID. However, several limitations must be considered. First, this was a single-institution study, thereby limiting the generalizability of our findings. This can be addressed by conducting a multicenter study using a large database, such as health insurance claims data. Since ET procedures have been covered by insurance in Japan since April 2022, future research could use this data to enable a broader analysis. Second, this study failed to consider the difficulty of each ET procedure. Some patients would complete ET after a single catheter insertion, whereas others might require several insertions depending on the orientation of the uterus and the narrowing of the cervix. Third, we could not fully adjust for baseline characteristics, especially for the primary outcome. Additionally, each method was used during different periods, and unmeasured differences between periods may have affected the outcomes. Fourth, we were unable to collect data regarding previous PID or active sexually transmitted infections at the time of ET (e.g., Chlamydia trachomatis or Neisseria gonorrhoeae ) for all patients. Regarding the history of previous PID, only 1 of 7 patients with PID in our cohort had a previous PID that required surgical drainage. Regarding sexually transmitted infections, Chlamydia trachomatis and Neisseria gonorrhoeae are well-known major causes of PID [ 23 , 33 ], and patients are routinely screened for these infections prior to ART as part of the work-up for infertility. Since any positive cases were treated accordingly, we assumed that there was no active infection at the time of ET. Fifth, our institution initially used oral antibiotics alone as prophylaxis; vaginal antibiotics were added to the regimen later on. Therefore, the effect of vaginal antibiotics alone was not examined. Lastly, the long-term side effects (other than pregnancy and childbirth) associated with the use of these antibiotics also remain unknown. 4.5. Conclusions No significant association was found between different prophylactic antibiotic regimens and the incidence of PID after ET among patients with endometriosis. Our findings do not support the routine use of prophylactic antibiotics for all ETs, but there was a notable absence of PID cases after a combined antibiotic regimen (oral cefcapene pivoxil hydrochloride hydrate and vaginal metronidazole). Despite not reaching statistical significance, this finding suggests the potential benefit of combined oral plus vaginal antibiotics in preventing PID, thereby warranting further investigation. Abbreviations Artificial reproductive technologies, ART Embryo transfer, ET Pelvic inflammatory disease, PID Declarations Ethics approval and consent to participate This study was approved by the Institutional Review Board of the University of Tokyo Hospital (the University of Tokyo IRB number is 3128-6). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to the risk of compromising individual privacy given the single-center nature of the study, but are available from the corresponding author on reasonable request. Competing interests The authors have no conflicts of interest relevant to this article. Funding No funding was received for this study. Authors' contributions MF: Conceptualization, Data curation, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review and editing. 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Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 21 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviewers agreed at journal 10 Mar, 2026 Reviewers agreed at journal 06 Mar, 2026 Reviewers invited by journal 05 Mar, 2026 Editor invited by journal 02 Feb, 2026 Editor assigned by journal 01 Feb, 2026 Submission checks completed at journal 01 Feb, 2026 First submitted to journal 31 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8750076","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":603371588,"identity":"2bed5089-fdaa-48f3-ae6d-619158093965","order_by":0,"name":"Maho Furukawa","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Maho","middleName":"","lastName":"Furukawa","suffix":""},{"id":603371591,"identity":"6db5b530-2dba-4dc8-b4d7-310d3b84de79","order_by":1,"name":"Masashi Takamura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIiWNgGAWjYHACZgaGCgYGNjj/AIjgwaOBDaTlDJCG6yFKC2MbA5I1Bwi4Snd+82ODn/Pq5Pnkm59u+MGwTY7vAPPDDwwyd3BqMTvGZpzYu+2wYRsbm9nNHobbxpIH2IwlGHie4dHCYHyAd9sBxjY2BrMbvP9uJ244wGAG9MthPFrYPx/8O6fOvo2N/dvNPwy36zccYP9GQAuPcTJvA3NiGxuP2W0ehtsJBgd4CNmSU2wsc+xwchtbTtltGYbbhjMP8xRLJODzy+HjmyXf1NTZzm8+vu3mG4bb8nzH2zd++NiDO8SwAGDUMiT2HCBFCxj8IF3LKBgFo2AUDFsAAOzjVZeJL1YXAAAAAElFTkSuQmCC","orcid":"","institution":"The University of Tokyo","correspondingAuthor":true,"prefix":"","firstName":"Masashi","middleName":"","lastName":"Takamura","suffix":""},{"id":603371593,"identity":"ac0bc278-745d-424e-a748-a45e3f76e53d","order_by":2,"name":"Osamu Wada-Hiraike","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Osamu","middleName":"","lastName":"Wada-Hiraike","suffix":""},{"id":603371596,"identity":"eea3bc47-43e9-4103-a288-48951d5bfc5f","order_by":3,"name":"Yusuke Sasabuchi","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"","lastName":"Sasabuchi","suffix":""},{"id":603371598,"identity":"6ac3c4cf-a6c4-4512-b277-f1c66fdd06c4","order_by":4,"name":"Masao Nakabayashi","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Masao","middleName":"","lastName":"Nakabayashi","suffix":""},{"id":603371599,"identity":"5291d8b6-df4f-4c94-8ae8-73d263094a2d","order_by":5,"name":"Hiroshi Koike","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Koike","suffix":""},{"id":603371600,"identity":"942fb8e2-e361-4f82-a13f-4be9a04c57a8","order_by":6,"name":"Mariko Miyashita","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Mariko","middleName":"","lastName":"Miyashita","suffix":""},{"id":603371603,"identity":"76a5f119-3294-46cc-bb24-845f6994b01c","order_by":7,"name":"Hirofumi Haraguchi","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Hirofumi","middleName":"","lastName":"Haraguchi","suffix":""},{"id":603371605,"identity":"ed218fef-f86a-4ff9-8e8b-3bc8324f7e16","order_by":8,"name":"Miyuki Harada","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Miyuki","middleName":"","lastName":"Harada","suffix":""},{"id":603371607,"identity":"60f7ca89-04be-4b1a-b426-366453a23b74","order_by":9,"name":"Yasushi Hitota","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Yasushi","middleName":"","lastName":"Hitota","suffix":""}],"badges":[],"createdAt":"2026-01-31 13:08:51","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8750076/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8750076/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104374842,"identity":"0ba3f7f7-6e52-4226-99be-3c3215803669","added_by":"auto","created_at":"2026-03-11 06:11:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":81875,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the included embryo transfer cycles.\u003c/p\u003e\n\u003cp\u003eThe initial review included 564 embryo transfer (ET) cycles in patients with endometriosis from January 2009 to June 2018. Among these, 207 cycles were excluded based on the following criteria: fresh ET cycles (n = 180), two-step ET cycles (n = 16), and patients using steroids or immunosuppressants (n = 11). The remaining 357 ET cycles were grouped based on the prophylactic antibiotic regimen (no antibiotics, oral antibiotics only, and combined oral plus vaginal antibiotics).\u003c/p\u003e","description":"","filename":"Onlinefloatimage.png","url":"https://assets-eu.researchsquare.com/files/rs-8750076/v1/28ded3da519c88e499797cc3.png"},{"id":104374873,"identity":"a50304df-f7e6-4c27-a2b0-d067e719a5ef","added_by":"auto","created_at":"2026-03-11 06:11:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":969970,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8750076/v1/0a1bcc16-fac8-4aca-9bb9-949e1f581ab5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prophylactic antibiotics for preventing pelvic inflammatory disease after embryo transfer in patients with endometriosis: A single-center retrospective cohort study","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe use of artificial reproductive technologies (ART) is becoming increasingly more common in Japan [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and this can be attributed to a growing interest and awareness in ART and/or delayed childbearing [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Embryo transfer (ET) is a critical step in ART, but in rare cases, it can cause pelvic inflammatory disease (PID) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Prolonged hospitalization and surgical treatment may be required in such patients, and this can result in severe reproductive consequences [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, preventing PID is of great importance among patients undergoing ET.\u003c/p\u003e \u003cp\u003eEndometriosis is a common gynecological disease characterized by the presence of endometrial-like tissue outside the uterus, affecting 5%\u0026ndash;10% of reproductive-age women [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and 25%\u0026ndash;40% of women with infertility [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Additionally, endometriosis is also a significant risk factor for the development and exacerbation of PID [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is a scarcity of information about preventing PID after ET. Some studies have examined the effectiveness of prophylactic antibiotics in reducing bacterial contamination of the catheter and increasing the clinical pregnancy rate [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Although prophylactic antibiotics decreased catheter bacterial contamination, this did not increase the clinical pregnancy rate [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and thus, routine antibiotic prophylaxis was not recommended for all ETs. However, these studies excluded patients with a high risk for PID (i.e., previous PID or endometriosis) and did not focus on PID as an outcome. The use of prophylactic antibiotics for PID in these patients should be considered, but this has not been established.\u003c/p\u003e \u003cp\u003eOur institution, the University of Tokyo Hospital, has an outpatient department specializing in endometriosis that caters to many women with endometriosis who desire pregnancy and need ART. Since 2011, our institution has followed a policy of starting oral antibiotics (cefcapene pivoxil hydrochloride hydrate 100 mg 3 times daily for 4 days from the day before ET) for the prevention of PID after ET in patients with endometrioma or adenomyosis.\u003c/p\u003e \u003cp\u003eAdenomyosis is a common gynecological disease characterized by endometrial-like tissue within the myometrium [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], which is often accompanied by endometriosis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Endometriosis and adenomyosis are believed to represent different phenotypes of a single disease [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], and severe cases of PID have been reported among women with adenomyosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Therefore, our institution also considers adenomyosis as a risk factor for PID, and thus, the same policy is followed for patients with adenomyosis. Cefcapene pivoxil hydrochloride hydrate is used due to its broad-spectrum coverage for common organisms that cause PID [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Since 2012, the same policy has been followed for patients with a history of previous surgery for endometriosis, including those with no evident lesions at the time of ET. However, we still encountered a severe recurrent case of PID despite starting oral antibiotic prophylaxis. Accordingly, in 2015, an intravaginal antibiotic (metronidazole 250 mg once daily starting from the day ET was scheduled until the day before ET) was added to this prophylactic regimen to reduce contamination through the catheter during ET.\u003c/p\u003e \u003cp\u003eThis retrospective study investigated the effectiveness of prophylactic antibiotics in preventing PID after ET among patients with endometriosis.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Data Source\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study extracted patients\u0026rsquo; clinical information from the medical records at the University of Tokyo Hospital from January 2009 to June 2018. This hospital is a tertiary medical institution that performs approximately 260 ET cycles (80 fresh ET cycles and 180 frozen ET cycles) annually.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Participants\u003c/h2\u003e \u003cp\u003eThis study included patients diagnosed with endometriosis (including both pathological and clinical diagnoses) prior to undergoing ET. The clinical diagnosis of endometriosis included subtypes of ovarian endometriosis (endometrioma), deep infiltrating endometriosis mostly detected at the pouch of Douglas, and/or adenomyosis, which were diagnosed via pelvic internal examination, transabdominal or transvaginal ultrasound, and/or magnetic resonance imaging. Patients with previous endometriotic lesions that had already been removed were also included. The following cases were excluded: (i) fresh ET, since we could not distinguish PID caused by oocyte retrieval (i.e., all included cases were frozen ET), (ii) two-step ET (usually day 3 and day 5), since this has double the chance of infection, and (iii) ET cycles from patients who were receiving steroids or immunosuppressants.\u003c/p\u003e \u003cp\u003eThe eligible patients were divided into three groups based on the prophylactic regimen: (i) no antibiotics before/after ET, (ii) oral antibiotics group (i.e., oral cefcapene pivoxil hydrochloride hydrate 100 mg 3 times daily for 4 days from the day before ET), and (iii) combined antibiotics group (i.e., oral cefcapene pivoxil hydrochloride hydrate 100 mg 3 times daily for 4 days from the day before ET, plus vaginal metronidazole 250 once daily starting from the day ET was scheduled until the day before ET).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Outcome\u003c/h2\u003e \u003cp\u003eThe primary outcome was the diagnosis of PID within one month after ET. PID was diagnosed based on the presence of lower abdominal pain or uterine/adnexal tenderness, plus either fever (\u0026ge;\u0026thinsp;38.0\u0026deg;C), increased white blood cell or C-reactive protein count, or an abscess seen on transvaginal ultrasound [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. All patients were followed up at the outpatient clinic at least once within one month after ET.\u003c/p\u003e \u003cp\u003eTo evaluate the safety of the antibiotics, the secondary outcomes included clinical pregnancy (i.e., the presence of one or more gestational sacs within the uterus) and live birth.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Variables\u003c/h2\u003e \u003cp\u003eThe following variables were evaluated: year of frozen ET performed, maternal age at frozen ET, previous parity, endometrial preparation protocols (i.e., natural cycle, hormone replacement cycle, or mild ovarian stimulation cycle with administration of human menopausal gonadotropin and human chorionic gonadotropin), presence of ovarian endometrioma or adenomyosis at the time of frozen ET, and previous history of surgery for endometrioma or adenomyosis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical Analysis\u003c/h2\u003e \u003cp\u003eContinuous and categorical variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and n (%), respectively. A one-way analysis of variance was used to compare continuous baseline characteristics (e.g., age), while Fisher\u0026rsquo;s exact test was used to compare categorical characteristics (e.g., the presence/absence of endometrioma at frozen ET). Fisher\u0026rsquo;s exact test and multivariable logistic regression were used to evaluate the association between each group and the outcomes. For multivariable analyses, we adjusted the following baseline characteristics: maternal age at frozen ET, previous parity, endometrial preparation protocols, and presence of ovarian endometrioma or adenomyosis at the time of frozen ET. All statistical analyses were conducted using the STATA/SE version 18.0 software (STATA, College Station, TX).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6. Ethics\u003c/h2\u003e \u003cp\u003eThis study was approved by the Research Ethics Committee of the Faculty of Medicine of the University of Tokyo (the University of Tokyo IRB number is 3128-6) and was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eWe collected data from 564 ET cycles in patients with endometriosis at the University of Tokyo Hospital from January 2009 to June 2018. After excluding 207 cases as per the exclusion criteria, 357 frozen ET cycles were eligible for analysis. These included 143 frozen ET cycles with no antibiotics, 90 frozen ET cycles with oral antibiotics, and 124 frozen ET cycles with combined antibiotics. The flowchart of the included ET cycles is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the changes in antibiotic use over the study period for patients with endometriosis treated at our hospital. Oral antibiotics have been used since 2011, while combined antibiotics were used starting in 2015, reflecting the changes in clinical guidelines at our department.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTemporal changes in antibiotic use during the study period.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eRegimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"10\" nameend=\"c11\" namest=\"c2\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2012\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2016\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo antibiotics, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e84.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e40.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral antibiotics only, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e76.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e15.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e17.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e25.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombined oral plus vaginal antibiotics, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e52.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e62.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e69.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e78.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e34.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the baseline characteristics of the three groups. There were significant differences across the three groups in terms of endometrial preparation, presence of endometrioma at the time of frozen ET, and previous history of surgery for endometriosis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of patients who underwent frozen embryo transfer.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eNo antibiotics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eOral antibiotics only\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eCombined oral plus vaginal antibiotics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;143)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;90)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProtocols for endometrial preparation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNatural cycle, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHormone replacement cycle, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvarian stimulation cycle, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of endometrioma at FET, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenomyosis, including post-adenomyomectomy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious surgical history for endometriosis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious surgical history for endometrioma, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious surgical history for adenomyosis, n (%) \u003c/p\u003e \u003cp\u003e(adenomyomectomy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eAll categories have p-values to compare the three groups.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eSD, standard deviation; FET, frozen embryo transfer\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the occurrence of PID and pregnancy outcomes after frozen ET in each group. PID occurred after ET in 5/143 (3.5%) cycles with no antibiotics, 2/90 (2.2%) cycles with oral antibiotics, and 0/124 (0%) cycles with combined antibiotics. Among the PID cases, one case with no antibiotics was a recurrent PID case. Inpatient management was required in 4 of 5 cases (80.0%) with no antibiotics and in all cases with oral antibiotics, whereas surgery was not required in any case. Ovarian endometrioma at the ET was observed in 1 of 5 cases (20.0%) with no antibiotics and in 1 of 2 cases (50.0%) with oral antibiotics. Although no cases of PID occurred in the combined antibiotics group, there was no statistically significant difference in the occurrence of PID among the three groups (Fisher\u0026rsquo;s exact test, p\u0026thinsp;=\u0026thinsp;0.081). Multivariable logistic regression analysis could not be performed because of the small number of events.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe occurrence of PID and pregnancy outcomes after frozen embryo transfer according to antibiotic regimen.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo antibiotics\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;143\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOral antibiotics only\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;90\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCombined oral plus vaginal antibiotics\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;124\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePID\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25 (20.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (13.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14 (11.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePID, pelvic inflammatory disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e presents the results of the logistic regression analyses for clinical pregnancy and live birth. After adjusting for baseline characteristics, the type of prophylactic regimen had no significant association with clinical pregnancy (adjusted odds ratio [OR] and 95% confidence interval [CI]; oral antibiotics vs. no antibiotics, 0.65 [0.32\u0026ndash;1.32]; combined antibiotics vs. no antibiotics, 0.98 [0.53\u0026ndash;1.83]) and with live birth (adjusted OR and 95% CI: oral antibiotics vs. no antibiotics, 0.90 [0.40\u0026ndash;2.07]; combined antibiotics vs. no antibiotics, 0.92 [0.42\u0026ndash;2.01]).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAdjusted odds ratios to determine the association of each antibiotic regimen with clinical pregnancy and live birth.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eAdjusted values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (95% CI) \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.65 (0.32\u0026ndash;1.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.98 (0.53\u0026ndash;1.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLive birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.90 (0.40\u0026ndash;2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.92 (0.42\u0026ndash;2.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAdjusted by age at frozen embryo transfer, parity, endometrial preparation protocols, presence or absence of endometriosis, and presence or absence of adenomyosis.\u003c/p\u003e \u003cp\u003e \u003csup\u003ea\u003c/sup\u003e Adjusted OR of oral antibiotics vs. no antibiotics\u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e Adjusted OR of combined antibiotics vs. no antibiotics\u003c/p\u003e \u003cp\u003eOR, odds ratio; 95% CI, 95% confidence interval.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e4.1. Principal Findings\u003c/h2\u003e \u003cp\u003eThis retrospective study investigated whether prophylactic antibiotics can effectively prevent PID after frozen ET among patients with endometriosis. No cases of PID were noted among patients taking oral plus vaginal antibiotic prophylaxis. However, no statistically significant differences were detected among the three groups, likely due to the small sample size. Furthermore, the use of prophylactic antibiotics, regardless of purely oral or combined regimens, did not suggest any significant impact on clinical pregnancy or live birth.\u003c/p\u003e \u003cp\u003eThe policy changes regarding the use of prophylactic antibiotics for patients with endometriosis likely affected the number of patients in each group, resulting in the observed differences in patient characteristics and backgrounds (e.g., the presence of endometrioma at frozen ET and previous surgery for endometriosis). These variations in the endometrial preparation protocol were influenced by the medical care system in our facility.\u003c/p\u003e \u003cp\u003eTo eliminate the potential confounding effects of oocyte retrieval, only frozen ET cases were analyzed in this study. Since fresh ET is assumed to carry a similar infection risk as frozen ET, the same prophylactic antibiotic protocol is applied for both procedures at our facility. Therefore, we believe that our findings can be applied to all ET procedures.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e4.2. Results in the Context of What is Known\u003c/h2\u003e \u003cp\u003eTwo previous studies have discussed the necessity of prophylactic antibiotics at ET [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Both of these studies cited the randomized controlled trial of Brook, which recommended against the routine use of antibiotics at ET, because the pregnancy rates did not improve despite having decreased ET catheter contamination rates [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. However, that study did not consider the incidence of PID and excluded patients with a high risk of PID (e.g., those with a history of pelvic infections or endometriosis). Since our gynecological team has an outpatient department specializing in endometriosis, we encounter many patients with endometriosis, some of whom wish to conceive. This allows us to focus on this high-risk group and assess the relationship between prophylactic antibiotic use and PID in this specific population. In agreement with these previous studies, our findings suggest that routine prophylactic antibiotic use during ET may not be necessary, even for patients with endometriosis, which is a known risk factor for PID.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4.3. Clinical and Research Implications\u003c/h2\u003e \u003cp\u003eThe lack of impact of antibiotic use on the incidence of PID could be attributed to several factors. First, even if the ET procedure is a critical step in ART [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], its degree of invasiveness may not be sufficient to cause infection. PID is generally thought to result from an ascending infection that originates from the lower genital tract [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In theory, techniques for endometrial cytology and endometrial histology, similar to ET, can also cause PID through an ascending infection, but only a few reports have described this. Even during saline infusion sonography or hysteroscopy, which involves injecting fluid into the uterus, routine antibiotic prophylaxis is not recommended, although individual risk of PID should be considered [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Second, removing excess mucus before ET may be sufficient for preventing PID after ET [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This is a common practice that is also routinely followed for all patients at our hospital. Third, the choice of antibiotic regimen may have been inappropriate. Cefcapene pivoxil hydrochloride hydrate belongs to the class of oral third-generation cephalosporins, which provide a broad spectrum of coverage [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and are frequently utilized in Japan [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, these drugs have poor oral bioavailability [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], which may limit their ability to achieve therapeutic concentrations at the target site, potentially reducing their effectiveness despite having adequate antimicrobial coverage. Vaginal drug administration is a route of drug delivery that is easy to use and enables targeted regional therapeutic administration [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Moreover, metronidazole can cover organisms that are not covered by (or resistant to) cephalosporins [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Previous reports have described the superiority of cephalosporins plus metronidazole compared to cephalosporins alone in preventing surgical site infection [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Thus, the use of intravenous or oral metronidazole in combination with other drugs has been recommended for the treatment of PID [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Additionally, metronidazole vaginal tablets are also known to be effective in treating bacterial vaginosis and preventing surgical site infection [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Although the doses differed, previous reports claim that vaginal administration of metronidazole had the same efficacy as oral administration [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In this study, the absence of PID cases after using combined antibiotics did not reach statistical significance, probably due to the rare incidence of PID after ET [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and the small sample size. Nevertheless, the outcomes in this study, especially alongside previous reports, suggest the potential protective effect of combination therapy with vaginal metronidazole plus cephalosporins, warranting further investigation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.4. Strengths and Limitations\u003c/h2\u003e \u003cp\u003eThe strength of this study was that it was the first to investigate the efficacy of prophylactic antibiotics, specifically combination therapy with oral plus vaginal antibiotics, for preventing PID during ET among patients with endometriosis, a known risk factor for PID. However, several limitations must be considered. First, this was a single-institution study, thereby limiting the generalizability of our findings. This can be addressed by conducting a multicenter study using a large database, such as health insurance claims data. Since ET procedures have been covered by insurance in Japan since April 2022, future research could use this data to enable a broader analysis. Second, this study failed to consider the difficulty of each ET procedure. Some patients would complete ET after a single catheter insertion, whereas others might require several insertions depending on the orientation of the uterus and the narrowing of the cervix. Third, we could not fully adjust for baseline characteristics, especially for the primary outcome. Additionally, each method was used during different periods, and unmeasured differences between periods may have affected the outcomes. Fourth, we were unable to collect data regarding previous PID or active sexually transmitted infections at the time of ET (e.g., \u003cem\u003eChlamydia trachomatis\u003c/em\u003e or \u003cem\u003eNeisseria gonorrhoeae\u003c/em\u003e) for all patients. Regarding the history of previous PID, only 1 of 7 patients with PID in our cohort had a previous PID that required surgical drainage. Regarding sexually transmitted infections, \u003cem\u003eChlamydia trachomatis\u003c/em\u003e and \u003cem\u003eNeisseria gonorrhoeae\u003c/em\u003e are well-known major causes of PID [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], and patients are routinely screened for these infections prior to ART as part of the work-up for infertility. Since any positive cases were treated accordingly, we assumed that there was no active infection at the time of ET. Fifth, our institution initially used oral antibiotics alone as prophylaxis; vaginal antibiotics were added to the regimen later on. Therefore, the effect of vaginal antibiotics alone was not examined. Lastly, the long-term side effects (other than pregnancy and childbirth) associated with the use of these antibiotics also remain unknown.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.5. Conclusions\u003c/h2\u003e \u003cp\u003eNo significant association was found between different prophylactic antibiotic regimens and the incidence of PID after ET among patients with endometriosis. Our findings do not support the routine use of prophylactic antibiotics for all ETs, but there was a notable absence of PID cases after a combined antibiotic regimen (oral cefcapene pivoxil hydrochloride hydrate and vaginal metronidazole). Despite not reaching statistical significance, this finding suggests the potential benefit of combined oral plus vaginal antibiotics in preventing PID, thereby warranting further investigation.\u003c/p\u003e \u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eArtificial reproductive technologies, ART\u003c/p\u003e\n\u003cp\u003eEmbryo transfer, ET\u003c/p\u003e\n\u003cp\u003ePelvic inflammatory disease, PID\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Review Board of the University of Tokyo Hospital (the University of Tokyo IRB number is 3128-6). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to the risk of compromising individual privacy given the single-center nature of the study, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest relevant to this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMF: Conceptualization, Data curation, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review and editing. MT: Conceptualization, Data curation, Supervision, Writing – review and editing. OWH: Conceptualization, Supervision, Writing – review and editing. YS: Conceptualization, Methodology, Supervision, Writing – review and editing. MN, HK, MM, and HH: Conceptualization, Data curation, Writing – review and editing. MH and YH: Conceptualization, Supervision, Writing – review and editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Enago for the English language editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eIshihara O, Jwa SC, Kuwahara A, Katagiri Y, Kuwabara Y, Hamatani T, et al. Assisted reproductive technology in Japan: a summary report for 2018 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology. Reprod Med Biol. 2021;20:3\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarada S, Yamada M, Shirasawa H, Jwa SC, Kuroda K, Harada M, et al. Fact-finding survey on assisted reproductive technology in Japan. J Obstet Gynaecol Res. 2023;49:2593\u0026ndash;601.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrejka T, Jones GW, Sardon JP. East Asian childbearing patterns and policy developments. Popul Dev Rev. 2010;36:579\u0026ndash;606.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIijima S, Yokoyama K. Socioeconomic factors and policies regarding declining birth rates in Japan. Nihon Eiseigaku Zasshi. 2018;73:305\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConte Mart\u0026iacute;n MP, Navarro Mart\u0026iacute;n R, Narv\u0026aacute;ez Salazar M, Gim\u0026eacute;nez Molina C, Navarro Sierra J, Benito Vielba M. Report of two cases of pelvic inflammatory disease complicating transcervical frozen embryo transfer. Clin Exp Obstetr Gynecol. 2023;50:20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFriedler S, Ben-Shachar I, Abramov Y, Schenker JG, Lewin A. Ruptured tubo-ovarian abscess complicating transcervical cryopreserved embryo transfer. Fertil Steril. 1996;65:1065\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiudice LC. Clinical practice. Endometriosis. N Engl J Med. 2010;362:2389\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397:839\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D'Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil Steril. 2009;92:68\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and evidence-based treatments. Ann NY Acad Sci. 2008;1127(1):92\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElizur SE, Lebovitz O, Weintraub AY, Eisenberg VH, Seidman DS, Goldenberg M, et al. Pelvic inflammatory disease in women with endometriosis is more severe than in those without. Aust NZ J Obstet Gynaecol. 2014;54:162\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClarizia R, Capezzuoli T, Ceccarello M, Zorzi C, Stepniewska A, Roviglione G, et al. Inflammation calls for more: severe pelvic inflammatory disease with or without endometriosis. Outcomes on 311 laparoscopically treated women. J Gynecol Obstet Hum Reprod. 2021;50:101811.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrook N, Khalaf Y, Coomarasamy A, Edgeworth J, Braude P. A randomized controlled trial of prophylactic antibiotics (co-amoxiclav) prior to embryo transfer. Hum Reprod. 2006;21:2911\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmeratunga D, Yazdani A, Kroon B. Antibiotics prior to or at the time of embryo transfer in ART. Cochrane Database Syst Rev. 2023;11:CD008995.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBulun SE, Yildiz S, Adli M, Chakravarti D, Parker JB, Milad M, et al. Endometriosis and adenomyosis: shared pathophysiology. Fertil Steril. 2023;119:746\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKishi Y, Suginami H, Kuramori R, Yabuta M, Suginami R, Taniguchi F. Four subtypes of adenomyosis assessed by magnetic resonance imaging and their specification. Am J Obstet Gynecol. 2012;207:e1141\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaruyama S, Imanaka S, Nagayasu M, Kimura M, Kobayashi H. Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease? Eur J Obstet Gynecol Reprod Biol. 2020;253:191\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePushpalatha K, Kalra R, Singh B, Devalla A. Rare complication of adenomyosis: acute purulent peritonitis and septicaemia in a young nulligravida. BMJ Case Rep. 2021;14:e238374.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArumugham VB, Gujarathi R, Cascella M. Third-Generation Cephalosporins. StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Jan-.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawaguchi R, Matsumoto K, Ishikawa T, Ishitani K, Okagaki R, Ogawa M, et al. Guideline for gynecological practice in Japan: Japan society of obstetrics and gynecology and Japan association of obstetricians and gynecologists 2020 edition. J Obstet Gynaecol Res. 2021;47:5\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePereira N, Hutchinson AP, Lekovich JP, Hobeika E, Elias RT. antibiotic prophylaxis for gynecologic procedures prior to and during the utilization of assisted reproductive technologies: a systematic review. J Pathog. 2016;2016:4698314.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrauer AA, Schattman G. Embryo transfer. Methods Mol Biol. 2014;1154:541\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreydanus DE, Bacopoulou F. Acute pelvic inflammatory disease: a narrative review. Pediatr Med. 2019;2:36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuraki Y, Yagi T, Tsuji Y, Nishimura N, Tanabe M, Niwa T, et al. Japanese antimicrobial consumption surveillance: first report on oral and parenteral antimicrobial consumption in Japan (2009\u0026ndash;2013). J Glob Antimicrob Resist. 2016;7:19\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGilbert DNCH, Saag MS, Pavia AT, Boucher HW. The Sanford Guide to Antimicrobial Therapy. Sperryville (VA): Antimicrobial Therapy Inc.; 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlexander NJ, Baker E, Kaptein M, Karck U, Miller L, Zampaglione E. Why consider vaginal drug administration? Fertil Steril. 2004;82:1\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSnydman DR, Jacobus NV, McDermott LA, Golan Y, Goldstein EJ, Harrell L, et al. Update on resistance of Bacteroides fragilis group and related species with special attention to carbapenems 2006\u0026ndash;2009. Anaerobe. 2011;17:147\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAldridge KE, Sanders CV. Susceptibility trending of blood isolates of the Bacteroides fragilis group over a 12-year period to clindamycin, ampicillin-sulbactam, cefoxitin, imipenem, and metronidazole. Anaerobe. 2002;8:301\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTill SR, Morgan DM, Bazzi AA, Pearlman MD, Abdelsattar Z, Campbell DA, et al. Reducing surgical site infections after hysterectomy: metronidazole plus cefazolin compared with cephalosporin alone. Am J Obstet Gynecol. 2017;217:e1871\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorkowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021;70:1\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBistoletti P, Fredricsson B, Hagstr\u0026ouml;m B, Nord CE. Comparison of oral and vaginal metronidazole therapy for nonspecific bacterial vaginosis. Gynecol Obstet Invest. 1986;21:144\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkamura A, Isono W, Tsuchiya A, Honda M, Saito A, Tsuchiya H, et al. Preventive effect of metronidazole vaginal tablets on vaginal bacteria-related postoperative complications with total laparoscopic hysterectomy. J Med Case Rep. 2023;17:47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJenkins SM, Vadakekut ES. Pelvic Inflammatory Disease. StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. Jan-.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Embryo transfer, Endometriosis, Intravaginal antibiotic therapy, Pelvic inflammatory disease, Prophylactic antibiotics","lastPublishedDoi":"10.21203/rs.3.rs-8750076/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8750076/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo evaluate the efficacy of prophylactic antibiotic regimens in preventing pelvic inflammatory disease (PID) after embryo transfer (ET) among patients with endometriosis, a risk factor of PID.\u003c/p\u003e\u003ch2\u003eMaterial and methods\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study used patient data from a single institution from January 2009 to June 2018. Cycles involving fresh ET, two-step ET, and from patients who used steroids or immunosuppressants were excluded. The primary outcome was the incidence of PID within one month after ET, which was compared between groups that received different antibiotic regimens (no antibiotics, oral antibiotics only, and oral plus vaginal antibiotics). The secondary outcomes were clinical pregnancy and live birth to evaluate the safety of the antibiotics. Fisher\u0026rsquo;s exact test and multivariable logistic regression were used for statistical analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 357 eligible ET cycles were identified. PID occurred after ET in 5/143 (3.5%) cycles with no antibiotics, 2/90 (2.2%) cycles with oral antibiotics, and 0/124 (0%) cycles with combined antibiotics. Although multivariable adjustment could not be performed because of the small number of events, no significant differences were observed among the three groups (Fisher\u0026rsquo;s exact test, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.081). Regarding the safety of the antibiotics, there were no significant differences among the three groups in either clinical pregnancy or live birth after adjustment.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eProphylactic antibiotics had no significant effect on preventing PID after ET in patients with endometriosis. Although not statistically significant, the absence of PID cases after combined oral and vaginal antibiotics suggests potential benefits, warranting further investigation.\u003c/p\u003e","manuscriptTitle":"Prophylactic antibiotics for preventing pelvic inflammatory disease after embryo transfer in patients with endometriosis: A single-center retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-11 06:10:11","doi":"10.21203/rs.3.rs-8750076/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-03-21T05:33:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"296194700437536114871452676741069441462","date":"2026-03-14T02:07:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"123553082363689496716640732839722250421","date":"2026-03-10T11:48:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331832074646270538196160853871648336205","date":"2026-03-06T14:44:59+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-05T09:41:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-02T11:56:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-02T01:07:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-02T01:06:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2026-01-31T12:51:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"86ba9894-f9b3-4746-aebd-da0f6fc18da6","owner":[],"postedDate":"March 11th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-11T06:10:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-11 06:10:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8750076","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8750076","identity":"rs-8750076","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}