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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">ETM</journal-id>
<journal-title-group>
<journal-title>Experimental and Therapeutic Medicine</journal-title>
</journal-title-group>
<issn pub-type="ppub">1792-0981</issn>
<issn pub-type="epub">1792-1015</issn>
<publisher>
<publisher-name>D.A. Spandidos</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">ETM-28-1-12572</article-id>
<article-id pub-id-type="doi">10.3892/etm.2024.12572</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Effect of previous caesarean section on reproductive and pregnancy outcomes after assisted reproductive technology: A systematic review and meta‑analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Cao</surname><given-names>Dan</given-names></name>
<xref rid="af1-ETM-28-1-12572" ref-type="aff">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Chen</surname><given-names>Lifen</given-names></name>
<xref rid="af2-ETM-28-1-12572" ref-type="aff">2</xref>
<xref rid="c1-ETM-28-1-12572" ref-type="corresp"/>
</contrib>
</contrib-group>
<aff id="af1-ETM-28-1-12572"><label>1</label>Department of Gynaecology, Huzhou Maternity and Child Care Hospital, Huzhou, Zhejiang 313000, P.R. China</aff>
<aff id="af2-ETM-28-1-12572"><label>2</label>Reproductive Center, Huzhou Maternity and Child Care Hospital, Huzhou, Zhejiang 313000, P.R. China</aff>
<author-notes>
<corresp id="c1-ETM-28-1-12572"><italic>Correspondence to:</italic> Dr Lifen Chen, Reproductive Center, Huzhou Maternity and Child Care Hospital, 2 East Street, Huzhou, Zhejiang 313000, P.R. China <email>chenlifenabc123@163.com drlxd@sina.com </email></corresp>
</author-notes>
<pub-date pub-type="collection">
<month>07</month>
<year>2024</year></pub-date>
<pub-date pub-type="epub">
<day>15</day>
<month>05</month>
<year>2024</year></pub-date>
<volume>28</volume>
<issue>1</issue>
<elocation-id>284</elocation-id>
<history>
<date date-type="received">
<day>15</day>
<month>11</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>17</day>
<month>04</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright: &#x00A9; 2024 Cao and Chen.</copyright-statement>
<copyright-year>2024</copyright-year>
<license license-type="open-access">
<license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">Creative Commons Attribution-NonCommercial-NoDerivs License</ext-link>, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.</license-p></license>
</permissions>
<abstract>
<p>Pregnancies following previous caesarean section (CS) are associated with higher incidence of infections, postpartum haemorrhage and obstetric complications. The present study aimed to explore the effect of previous CS on reproductive, maternal and neonatal outcomes in women who underwent assisted reproductive techniques (ART). A systematic review and meta-analysis were conducted to assess reproductive and pregnancy outcomes following ART in women with and without a previous CS. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. Eligible language articles written in English, published up to October 2023, were identified in Medline, Google Scholar and Science Direct databases. The quality of the included studies was assessed using the Newcastle Ottawa Scale. A total of 19 articles, reporting on 13 different outcomes met the inclusion criteria. It was revealed that women with previous CS had 9&#x0025; lower clinical pregnancy rates, 13&#x0025; lower live birth rates, 11&#x0025; lower implantation rates and 28&#x0025; lower multiple pregnancy rates compared with women who had prior natural vaginal deliveries. Additionally, previous CS was associated with an 8-fold higher risk of difficult embryo transfers. No significant differences were noted in ectopic pregnancy rates, miscarriage rates or biochemical pregnancy rates. The present systematic review and meta-analysis demonstrated that previous CS is associated with decreased prospects of clinical pregnancy, live birth and successful embryo implantation during ART. The findings of the present study underscored the need to counsel women with prior CS regarding its potential impact on ART outcomes.</p>
</abstract>
<kwd-group>
<kwd>caesarean section</kwd>
<kwd>assisted reproductive techniques</kwd>
<kwd>vaginal delivery</kwd>
<kwd>pregnancy outcomes</kwd>
<kwd>reproductive outcomes</kwd>
</kwd-group>
<funding-group>
<funding-statement><bold>Funding:</bold> No funding was received.</funding-statement>
</funding-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<title>Introduction</title>
<p>The rates of caesarean section (CS) have increased globally from 7&#x0025; in 1990 to 21&#x0025; in 2023(<xref rid="b1-ETM-28-1-12572" ref-type="bibr">1</xref>), and are particularly high in developing countries (30-35&#x0025;) (<xref rid="b2-ETM-28-1-12572 b3-ETM-28-1-12572 b4-ETM-28-1-12572" ref-type="bibr">2-4</xref>). Numerous studies have revealed that previous CS is associated with an increased risk of infections and postpartum haemorrhage, as well as an increased incidence of obstetric complications, such as abnormal placentation and risk of uterine rupture, in subsequent pregnancies (<xref rid="b5-ETM-28-1-12572" ref-type="bibr">5</xref>). Additionally, 42-58&#x0025; of women who underwent CS reported post-caesarean scar defects (PCSD), such as isthmocele (an iatrogenic defect in the myometrium at the site of a previous caesarean scar due to defective tissue healing) (<xref rid="b6-ETM-28-1-12572" ref-type="bibr">6</xref>). While the incidence of PCSD is 61&#x0025; in women who have had one previous CS, it reaches 100&#x0025; in women who have had at least three CS (<xref rid="b5-ETM-28-1-12572" ref-type="bibr">5</xref>,<xref rid="b7-ETM-28-1-12572" ref-type="bibr">7</xref>).</p>
<p>Correlation between previous CS, fertility and other pregnancy outcomes is still not clear. While a previous study reported reduced fertility and live birth rates subsequent to previous CS (<xref rid="b8-ETM-28-1-12572" ref-type="bibr">8</xref>), another study claimed that previous CS has only marginal impact on future fertility and that clinical and societal factors, leading to higher CS rates, may have a greater impact on reproductive health than CS itself (<xref rid="b9-ETM-28-1-12572" ref-type="bibr">9</xref>). Since the use of assisted reproductive technology (ART) continues to rise globally (<xref rid="b10-ETM-28-1-12572" ref-type="bibr">10</xref>), there is an increasing need to understand the implications of previous CS for maternal and fetal health. A previous study suggested that previous CS is correlated with lower subsequent clinical pregnancy rates (CPR) and longer time to conceive compared with natural vaginal delivery (NVD) (<xref rid="b11-ETM-28-1-12572" ref-type="bibr">11</xref>). However, the true impact of previous CS on subsequent pregnancies remains unclear. The latest meta-analysis exploring the same research topic by Zhao <italic>et al</italic> (<xref rid="b12-ETM-28-1-12572" ref-type="bibr">12</xref>) (2021), included just seven studies and lacks a comprehensive analysis of maternal and neonatal outcomes. Thus, in the present systematic review and meta-analysis the effects of previous CS compared with normal vaginal delivery (NVD) were analysed with regard to the following: i) The reproductive outcomes such as live birth rate (LBR), biochemical pregnancy rate (BPR), clinical pregnancy rates (CPR), implantation rate (IR) and ectopic pregnancy rate (EPR); ii) pregnancy outcomes including preterm birth rate (PBR), still birth rate (SBR), miscarriage rate (MR), birth defects (BD), birth weight (BW) and multiple pregnancy rate (MPR); and iii) other outcomes such as endometrial thickness (EMT) and difficult transfer rate (DTR).</p>
<p>The present systematic review and meta-analysis aimed to summarize and analyse data of all reproductive, pregnancy and perinatal outcomes in women who underwent ART treatment after previous CS.</p>
</sec>
<sec sec-type="Patients|methods">
<title>Patients and methods</title>
<p><italic>Protocol registration and methodology</italic>. The present study was registered at PROSPERO (an international database of systematic review protocols; no. CRD42023468689). The latest (2020) &#x2018;Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)&#x2019; framework was used to report the findings of the present study (<xref rid="b13-ETM-28-1-12572" ref-type="bibr">13</xref>). Ethical approval was not obtained, since only information that was freely available across various databases was utilized.</p>
<p><italic>Inclusion criteria.</italic> Studies that included the following were selected: i) Studies reporting on pregnant women who underwent ART; ii) studies reporting on women with previous CS and ART; iii) studies reporting on women with previous NVD and ART; iv) studies reporting various reproductive, pregnancy and neonatal outcomes; and v) analytical studies including cross sectional, prospective and retrospective observational, as well as case control studies.</p>
<p><italic>Exclusion criteria.</italic> Studies with the following characteristics were excluded: i) Studies without a control group of patients who underwent vaginal birth; and ii) studies without follow-up records, with inadequate data, not peer-reviewed, and grey literature (policy reports, newsletters and working papers). In addition, only articles published in the English language across Medline (<ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://pubmed.ncbi.nlm.nih.gov">https://pubmed.ncbi.nlm.nih.gov</ext-link>), Google Scholar (<ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://scholar.google.com">https://scholar.google.com</ext-link>) and Science Direct (<ext-link ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="https://www.sciencedirect.com">https://www.sciencedirect.com</ext-link>) databases, from inception until October 2023 were included.</p>
<p><italic>Search strategy.</italic> Medical Subject Heading terms such as: &#x2018;Previous C section&#x2019; OR &#x2018;Previous Caesarean section&#x2019; AND &#x2018;Previous Vaginal delivery&#x2019; AND &#x2018;<italic>In vitro</italic> fertilisation&#x2019; OR &#x2018;Assisted reproductive techniques&#x2019; OR &#x2018;Embryo transfer&#x2019; AND &#x2018;Observational studies&#x2019; OR &#x2018;Cohort studies&#x2019; OR &#x2018;Prospective studies&#x2019; were utilized to search in the three aforementioned databases. No geographical limitations were considered. Additionally, studies that were missed by computerised searches were examined by searching the reference lists of all qualifying articles and were included if found eligible. Two primary investigators (DC and LC) independently conducted the search and assessed the quality of individual studies. All cases of disagreements were resolved by consensus. The detailed search strategy is presented in <xref rid="SD15-ETM-28-1-12572" ref-type="supplementary-material">Table SI</xref>.</p>
<p><italic>Outcome parameters and operational definitions.</italic> The primary outcomes of interest were: Reproductive outcomes such as CPR, defined as the presence of an intrauterine gestational sac through ultrasound confirmation; LBR, defined as the birth of a live fetus 24 weeks after conception; EPR, defined as the presence of an extrauterine gestational sac through ultrasound confirmation; MR, defined as pregnancy loss before 12 weeks of gestation; BPR, defined as an elevated serum level of &#x03B2;-human chorionic gonadotropin &#x005B;&#x003E;5 IU/l&#x005D; after 14 days; SBR, defined as the delivery of a fetus with no signs of viability/after 28 weeks; and IR. Secondary outcomes of interest were: PBR, defined as the delivery of a live fetus before 37 completed weeks; as well as EMT, BW, MPR, DTR and BD.</p>
<p><italic>Data extraction and management.</italic> Relevant information such as the details of the authors, study design, duration, sample size, geographical location, inclusion criteria, embryo transfer type and relevant primary and secondary outcomes were extracted and entered in the data documentation sheet.</p>
<p><italic>Statistical analysis.</italic> The extracted data were analysed using Stata 14.2 (StataCorp LLC). Each data entry was double-checked by the investigators. The effect across studies was pooled for binary outcomes through the inverse variance method using risk ratios (RR) with a 95&#x0025; confidence interval (CI), and continuous outcomes as a mean difference with a 95&#x0025; CI. In case of missing data, efforts were made to contact the author for necessary information, such as data pertaining to the study period, mean age distribution of cases and controls and other information necessary for assessing the quality of the studies. In all cases where it was not possible to obtain the necessary data, it was considered not reported. Pooled effect sizes were graphically represented as forest plots and publication bias was graphically represented as funnel plots and was statistically tested using Egger&#x0027;s test (<xref rid="b14-ETM-28-1-12572" ref-type="bibr">14</xref>). P&#x003C;0.05 was considered to indicate a statistically significant difference.</p>
<p><italic>Assessment of heterogeneity.</italic> The I<sup>2</sup> statistic and the Chi-square heterogeneity test were used to examine the between-study variability. Three levels of heterogeneity were identified: Mild (I<sup>2</sup>&#x003C;25&#x0025;), moderate (I<sup>2</sup>=25-75&#x0025;) and considerable (I<sup>2</sup>&#x003E;75&#x0025;).</p>
<p><italic>Quality of the included studies.</italic> Quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS) (<xref rid="b15-ETM-28-1-12572" ref-type="bibr">15</xref>). The scale assesses the quality of studies using three criteria: Ascertainment of outcome, selection and comparability of the study groups. A study may receive a maximum of one star for each numbered item in the selection and outcome categories. For comparability, a maximum of two stars may be assigned. Thus, the maximum NOS score is nine.</p>
</sec>
<sec sec-type="Results">
<title>Results</title>
<p><italic>Study selection.</italic> A total of 4,263 articles were identified by the literature search across the databases. Of these, 3,168 were removed as duplicates. Another 817 articles were excluded after screening the title and abstract. From the remaining 278 studies, 104 free full text articles were retrieved. Finally, a total of 19 articles that met eligibility criteria, were selected for the present systematic review and meta-analysis (<xref rid="b16-ETM-28-1-12572 b17-ETM-28-1-12572 b18-ETM-28-1-12572 b19-ETM-28-1-12572 b20-ETM-28-1-12572 b21-ETM-28-1-12572 b22-ETM-28-1-12572 b23-ETM-28-1-12572 b24-ETM-28-1-12572 b25-ETM-28-1-12572 b26-ETM-28-1-12572 b27-ETM-28-1-12572 b28-ETM-28-1-12572 b29-ETM-28-1-12572 b30-ETM-28-1-12572 b31-ETM-28-1-12572 b32-ETM-28-1-12572 b33-ETM-28-1-12572 b34-ETM-28-1-12572" ref-type="bibr">16-34</xref>). In total, 18 studies reported on the LBR (<xref rid="b16-ETM-28-1-12572 b17-ETM-28-1-12572 b18-ETM-28-1-12572 b19-ETM-28-1-12572 b20-ETM-28-1-12572 b21-ETM-28-1-12572 b22-ETM-28-1-12572 b23-ETM-28-1-12572 b24-ETM-28-1-12572 b25-ETM-28-1-12572 b26-ETM-28-1-12572 b27-ETM-28-1-12572 b28-ETM-28-1-12572 b29-ETM-28-1-12572 b30-ETM-28-1-12572 b31-ETM-28-1-12572 b32-ETM-28-1-12572 b33-ETM-28-1-12572" ref-type="bibr">16-33</xref>), 17 reported on the CPR (<xref rid="b16-ETM-28-1-12572 b17-ETM-28-1-12572 b18-ETM-28-1-12572 b19-ETM-28-1-12572 b20-ETM-28-1-12572 b21-ETM-28-1-12572 b22-ETM-28-1-12572 b23-ETM-28-1-12572 b24-ETM-28-1-12572 b25-ETM-28-1-12572 b26-ETM-28-1-12572 b27-ETM-28-1-12572 b28-ETM-28-1-12572 b29-ETM-28-1-12572 b30-ETM-28-1-12572 b31-ETM-28-1-12572 b32-ETM-28-1-12572" ref-type="bibr">16-32</xref>), 17 on the MR (<xref rid="b16-ETM-28-1-12572 b17-ETM-28-1-12572 b18-ETM-28-1-12572 b19-ETM-28-1-12572 b20-ETM-28-1-12572 b21-ETM-28-1-12572 b22-ETM-28-1-12572 b23-ETM-28-1-12572 b24-ETM-28-1-12572 b25-ETM-28-1-12572 b26-ETM-28-1-12572 b27-ETM-28-1-12572 b28-ETM-28-1-12572 b29-ETM-28-1-12572" ref-type="bibr">16-29</xref>,<xref rid="b31-ETM-28-1-12572 b32-ETM-28-1-12572 b33-ETM-28-1-12572" ref-type="bibr">31-33</xref>), 16 on the EPR (<xref rid="b16-ETM-28-1-12572 b17-ETM-28-1-12572 b18-ETM-28-1-12572 b19-ETM-28-1-12572 b20-ETM-28-1-12572 b21-ETM-28-1-12572 b22-ETM-28-1-12572 b23-ETM-28-1-12572 b24-ETM-28-1-12572 b25-ETM-28-1-12572 b26-ETM-28-1-12572 b27-ETM-28-1-12572 b28-ETM-28-1-12572 b29-ETM-28-1-12572" ref-type="bibr">16-29</xref>,<xref rid="b31-ETM-28-1-12572" ref-type="bibr">31</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>), 13 on the BPR (<xref rid="b16-ETM-28-1-12572 b17-ETM-28-1-12572 b18-ETM-28-1-12572 b19-ETM-28-1-12572 b20-ETM-28-1-12572 b21-ETM-28-1-12572" ref-type="bibr">16-21</xref>,<xref rid="b23-ETM-28-1-12572 b24-ETM-28-1-12572 b25-ETM-28-1-12572" ref-type="bibr">23-25</xref>,<xref rid="b27-ETM-28-1-12572" ref-type="bibr">27</xref>,<xref rid="b29-ETM-28-1-12572" ref-type="bibr">29</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>,<xref rid="b33-ETM-28-1-12572" ref-type="bibr">33</xref>), nine on the PBR (<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b22-ETM-28-1-12572" ref-type="bibr">22</xref>,<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>,<xref rid="b25-ETM-28-1-12572" ref-type="bibr">25</xref>,<xref rid="b28-ETM-28-1-12572" ref-type="bibr">28</xref>,<xref rid="b29-ETM-28-1-12572" ref-type="bibr">29</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>,<xref rid="b34-ETM-28-1-12572" ref-type="bibr">34</xref>), eight studies on the EMT (<xref rid="b16-ETM-28-1-12572" ref-type="bibr">16</xref>,<xref rid="b17-ETM-28-1-12572" ref-type="bibr">17</xref>,<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b22-ETM-28-1-12572" ref-type="bibr">22</xref>,<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>,<xref rid="b30-ETM-28-1-12572" ref-type="bibr">30</xref>,<xref rid="b33-ETM-28-1-12572" ref-type="bibr">33</xref>), seven each on the MPR (<xref rid="b16-ETM-28-1-12572" ref-type="bibr">16</xref>,<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b23-ETM-28-1-12572" ref-type="bibr">23</xref>,<xref rid="b25-ETM-28-1-12572" ref-type="bibr">25</xref>,<xref rid="b28-ETM-28-1-12572" ref-type="bibr">28</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>), SPR (<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b22-ETM-28-1-12572" ref-type="bibr">22</xref>,<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>,<xref rid="b26-ETM-28-1-12572" ref-type="bibr">26</xref>,<xref rid="b29-ETM-28-1-12572" ref-type="bibr">29</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>) and IR (<xref rid="b16-ETM-28-1-12572" ref-type="bibr">16</xref>,<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>,<xref rid="b27-ETM-28-1-12572" ref-type="bibr">27</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>,<xref rid="b33-ETM-28-1-12572" ref-type="bibr">33</xref>), five on the BW (<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>,<xref rid="b31-ETM-28-1-12572" ref-type="bibr">31</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>), three on the DTR (<xref rid="b17-ETM-28-1-12572" ref-type="bibr">17</xref>,<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>,<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>) and two on the BD (<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>,<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>) respectively. The PRISMA 2020 flow diagram is explained in <xref rid="f1-ETM-28-1-12572" ref-type="fig">Fig. 1</xref>.</p>
<p><italic>Characteristics of the included studies.</italic> General characteristics of the included studies are detailed in <xref rid="tI-ETM-28-1-12572" ref-type="table">Table I</xref>. Of the 19 studies included, 11 were from China, two were from the Netherlands and the USA, and one study each from Turkey, Canada, Germany and UAE. All studies reported results in English. The sample size of the included studies ranged between 150 to 9,124. Most (17/19) studies were retrospective cohort studies, one was a prospective cohort study and one was a retrospective case control study.</p>
<p><italic>Excluded studies</italic>. Of the 104 full-text articles extracted, 93 studies were excluded during secondary screening. Specifically, 31 were excluded as they had mixed study participants groups, 47 did not report the outcome clearly and 15 were published in languages other than English.</p>
<p><italic>Reproductive outcomes across the study groups.</italic> A total of 17 studies (n=29,400; CS=13,252 and NVD=16,148) reported on the CPR. It was observed that women with previous CS had a 9&#x0025; lower CPR compared with women who had previous NVD (pooled RR of 0.91, 95&#x0025; CI: 0.87-0.96, with high heterogeneity I<sup>2</sup>=67.2; P&#x003C;0.001) (<xref rid="f2-ETM-28-1-12572" ref-type="fig">Fig. 2</xref>). Furthermore, 18 studies (n=29,925; CS=13,452 and NVD=16,473) reported on the LBR. It was observed that women with previous CS had a 13&#x0025; lower LBR compared with women who had previous NVD (pooled RR of 0.87, 95&#x0025; CI: 0.82-0.93, with high heterogeneity I<sup>2</sup>=62.8; P&#x003C;0.001) (<xref rid="f3-ETM-28-1-12572" ref-type="fig">Fig. 3</xref>). Next, seven studies (n=21,439; CS=9,299 and NVD=12,140) reported on the IR. Women with previous CS had an 11&#x0025; lower IR compared with women with previous NVD (pooled RR of 0.89, 95&#x0025; CI: 0.81-0.99, with high heterogeneity I<sup>2</sup>=76.1; P&#x003C;0.001) (<xref rid="SD1-ETM-28-1-12572" ref-type="supplementary-material">Fig. S1</xref>). However, there was no significant difference in the EPR (pooled RR of 1.15, 95&#x0025; CI: 0.87-1.51, with no heterogeneity I<sup>2</sup>=0; P=0.850) (<xref rid="SD2-ETM-28-1-12572" ref-type="supplementary-material">Fig. S2</xref>) and BPR (pooled RR of 0.95, 95&#x0025; CI: 0.84-1.07, with high heterogeneity I<sup>2</sup>=94.2; P&#x003C;0.001) (<xref rid="SD3-ETM-28-1-12572" ref-type="supplementary-material">Fig. S3</xref>). Publication bias was assessed only for four of the reproductive outcomes (BPR, CPR, EPR and LBR) that were reported by &#x003E;10 studies. No publication bias was reported for outcomes such as CPR (Egger coefficient, 0.42; P=0.63) (<xref rid="SD4-ETM-28-1-12572" ref-type="supplementary-material">Fig. S4</xref>), LBR (Egger coefficient, 1.03; P=0.20) (<xref rid="SD5-ETM-28-1-12572" ref-type="supplementary-material">Fig. S5</xref>), BPR (Egger coefficient, -1.0; P=0.66) (<xref rid="SD6-ETM-28-1-12572" ref-type="supplementary-material">Fig. S6</xref>) and EPR (Egger coefficient, 0.41; P=0.30) (<xref rid="SD7-ETM-28-1-12572" ref-type="supplementary-material">Fig. S7</xref>).</p>
<p><italic>Secondary pregnancy outcomes across the study groups.</italic> A total of seven studies (n=11,002; CS=5,310 and NVD=5,692) reported on the MPR. Women with previous CS had a 28&#x0025; lower MPR compared with women who had previous NVD (pooled RR of 0.72, 95&#x0025; CI: 0.53-0.96, with high heterogeneity I<sup>2</sup>=81.0; P&#x003C;0.001) (<xref rid="f4-ETM-28-1-12572" ref-type="fig">Fig. 4</xref>). Furthermore, eight studies (n=6,111; CS=2,629 and NVD=3,482) reported on the EMT. Women with previous CS had -0.14 lower EMT compared with women who had previous NVD (pooled WMD of -0.14, 95&#x0025; CI: -0.26 to -0.01, with no heterogeneity I<sup>2</sup>=0&#x0025;; P=0.745) (<xref rid="SD8-ETM-28-1-12572" ref-type="supplementary-material">Fig. S8</xref>). DTRs were reported by three studies that showed that women with previous CS had an 8-fold higher DTR compared with women with NVD (pooled RR of 8.02, 95&#x0025; CI: 4.54-14.16, with no heterogeneity I<sup>2</sup>=0&#x0025;; P=0.600) (<xref rid="SD9-ETM-28-1-12572" ref-type="supplementary-material">Fig. S9</xref>). However, no significant difference was detected in terms of the PBR (pooled RR of 1.08, 95&#x0025; CI: 0.82-1.42, with high heterogeneity I<sup>2</sup>=79.3&#x0025;; P&#x003C;0.001) (<xref rid="SD10-ETM-28-1-12572" ref-type="supplementary-material">Fig. S10</xref>), MR (pooled RR of 1.08, 95&#x0025; CI: 0.96-1.20, with moderate heterogeneity I<sup>2</sup>=32.2; P=0.098) (<xref rid="SD11-ETM-28-1-12572" ref-type="supplementary-material">Fig. S11</xref>), SBR (pooled RR of 0.82, 95&#x0025; CI: 0.31-2.21, with low heterogeneity I<sup>2</sup>=11.1; P=0.342) (<xref rid="SD12-ETM-28-1-12572" ref-type="supplementary-material">Fig. S12</xref>), BW (pooled WMD of 17.41, 95&#x0025; CI: -74 to 108.8, with moderate heterogeneity I<sup>2</sup>=59.4; P=0.043) (<xref rid="SD13-ETM-28-1-12572" ref-type="supplementary-material">Fig. S13</xref>) and BD (pooled RR of 1.72, 95&#x0025; CI: 0.49-5.97, with no heterogeneity I<sup>2</sup>=0&#x0025;; P=0.440) (<xref rid="SD14-ETM-28-1-12572" ref-type="supplementary-material">Fig. S14</xref>). Publication bias was assessed only for the MR, among the secondary pregnancy outcomes, as it had &#x003E;10 studies reporting it. The absence of publication bias for the MR was noted (Egger coefficient, 0.84; P=0.08) (<xref rid="f5-ETM-28-1-12572" ref-type="fig">Fig. 5</xref>).</p>
<p><italic>Risk of bias in the included studies</italic>. <xref rid="tI-ETM-28-1-12572" ref-type="table">Table I</xref> summarizes the data on the risk of bias in the included studies, as assessed by NOS. Based on the 9-item scoring system, it was revealed that 11 studies had a score of 8, six had a score of 7 and the remaining two studies had a score of 9.</p>
</sec>
<sec sec-type="Discussion">
<title>Discussion</title>
<p>The present meta-analysis included 19 studies that reported 13 different reproductive and pregnancy outcomes in women who underwent ART with and without a previous history of CS. The results demonstrated that women with a previous history of CS had 9, 13, 11 and 28&#x0025; lower probability of CPR, LBR, IR and MPR, respectively. Additionally, previous CS was associated with an 8-fold higher DTR than previous NVD. These findings offer valuable insights into the clinical management of this unique patient population.</p>
<p>The rates of CS are on the rise worldwide (<xref rid="b35-ETM-28-1-12572" ref-type="bibr">35</xref>), which in turn suggests that an increasing number of women with a history of previous CS will be receiving ART treatment. Previous studies showed that having a previous CS may increase the likelihood of infertility and prolong the time required to conceive (<xref rid="b36-ETM-28-1-12572" ref-type="bibr">36</xref>,<xref rid="b37-ETM-28-1-12572" ref-type="bibr">37</xref>). Murphy <italic>et al</italic> (<xref rid="b10-ETM-28-1-12572" ref-type="bibr">10</xref>), hypothesized that this reduction in fertility might be linked to increased rates of infections, adhesions, disruption of the placental bed or other non-medical factors associated with CS, in addition to socioeconomical and cultural differences.</p>
<p>The results of the present study revealed a 9&#x0025; lower CPR and 13&#x0025; lower LBR in women with previous CS, which is consistent with the work of Zhao <italic>et al</italic> (<xref rid="b12-ETM-28-1-12572" ref-type="bibr">12</xref>). It may be speculated that this effect may be explained by several possible mechanisms. The endometrium at the CS scar site has fewer blood vessels in the endometrial stroma, less leukocyte infiltration and delayed endometrial maturation as compared with the endometrium after vaginal delivery (<xref rid="b38-ETM-28-1-12572" ref-type="bibr">38</xref>,<xref rid="b39-ETM-28-1-12572" ref-type="bibr">39</xref>). Additionally, women with previous CS tend to have increased rates of posterior placentas during subsequent conception (<xref rid="b40-ETM-28-1-12572" ref-type="bibr">40</xref>). CS also impacts the integrity of the endometrial muscle layer junction zone (<xref rid="b41-ETM-28-1-12572" ref-type="bibr">41</xref>,<xref rid="b42-ETM-28-1-12572" ref-type="bibr">42</xref>). In addition, a previous study discovered that in frozen-thawed embryo transfer cycles, a previous CS was linked to a lower LBR and increased MR (<xref rid="b16-ETM-28-1-12572" ref-type="bibr">16</xref>).</p>
<p>However, it is important to note that the present analysis did not reveal significant differences in EPR, MR and BPR between women with previous CS and NVD. The results were comparable to findings by Riemma <italic>et al</italic> (<xref rid="b43-ETM-28-1-12572" ref-type="bibr">43</xref>). It was observed that previous CS was associated with an 11&#x0025; reduction in IR and an 8-fold higher DTR. These findings are similar to findings from previous studies (<xref rid="b44-ETM-28-1-12572" ref-type="bibr">44</xref>,<xref rid="b45-ETM-28-1-12572" ref-type="bibr">45</xref>) and may be explained by an anterior diverticulum, which gathers fluid and old blood developing in the lower uterus as a result of a CS incision (<xref rid="b45-ETM-28-1-12572" ref-type="bibr">45</xref>). Blood that enters the uterus may prevent successful implantation (<xref rid="b44-ETM-28-1-12572" ref-type="bibr">44</xref>).</p>
<p>The present study had several clinical implications. The findings of the present study may aid clinicians in counselling women with previous CS about the potential impact on their prospects of achieving a clinical pregnancy and live birth through ART. In addition, the findings of the present study warrant a thorough uterine anatomy evaluation before initiating ART, especially in women with previous CS, for early identification of uterine scars, adhesions and other possible complications. The findings of the present study also emphasize the importance of optimizing embryo transfer techniques in women with previous CS to enhance successful implantation.</p>
<p>The present review is among the very few attempts that have evaluated the impact of previous CS on a comprehensive list of reproductive and pregnancy outcomes among women with ART. The increased power of the present review due to the large sample size is another major strength.</p>
<p>Despite these strengths, the present study has certain limitations. One limitation is the moderate to high heterogeneity between the studies. This heterogeneity may be explained by methodological differences such as the study design, differences in treatment protocols, embryo transfer techniques and types of CS. In addition, the possibility of language bias could not be excluded as only studies published in English were included. Moreover, most included studies were historical cohorts. Therefore, it was not possible to adjust for some potential confounders such as smoking status, embryo quality, body mass index or ovarian stimulation protocols.</p>
<p>In conclusion, the present systematic review and meta-analysis provided comprehensive insights into the impact of previous CS on reproductive and pregnancy outcomes in women undergoing ART. The findings indicated that women with previous CS may face decreased chances of CPR, LBR and successful embryo implantation during ART. These results underscore the need for tailored counselling and management strategies for this patient population.</p>
</sec>
<sec sec-type="supplementary-material">
<title>Supplementary Material</title>
<supplementary-material id="SD1-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the implantation rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD2-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the ectopic pregnancy rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD3-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the biochemical pregnancy rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD4-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Funnel plot describing publication bias for studies reporting on the clinical pregnancy rate.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD5-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Funnel plot describing publication bias for studies reporting on the live birth rate.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD6-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Funnel plot describing publication bias for studies reporting on the biochemical pregnancy rate.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD7-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Funnel plot describing publication bias for studies reporting on the ectopic pregnancy rate.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD8-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the endometrial thickness across study groups. SD, standard deviation; WMD, weighted mean difference; CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD9-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the difficult transfer rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD10-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the preterm birth rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD11-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the miscarriage rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD12-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the still birth rate across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD13-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the birth weight across study groups. SD, standard deviation; WMD, weighted mean difference; CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD14-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Forest plot showing the incidence of birth defects across study groups. CI, confidence interval.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data1.pdf"/>
</supplementary-material>
<supplementary-material id="SD15-ETM-28-1-12572" content-type="local-data">
<caption>
<title>Search strategy.</title>
</caption>
<media mimetype="application" mime-subtype="pdf" xlink:href="Supplementary_Data2.pdf"/>
</supplementary-material>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>Not applicable.</p>
</ack>
<sec sec-type="data-availability">
<title>Availability of data and materials</title>
<p>The data generated in the present study may be requested from the corresponding author.</p>
</sec>
<sec>
<title>Authors&#x0027; contributions</title>
<p>DC conceived and designed the study. DC and LC collected the data and performed the literature search. DC was involved in the writing of the manuscript. All authors have read and approved the final manuscript. DC and LC confirm the authenticity of all the raw data.</p>
</sec>
<sec>
<title>Ethics approval and consent to participate</title>
<p>Not applicable.</p>
</sec>
<sec>
<title>Patient consent for publication</title>
<p>Not applicable.</p>
</sec>
<sec sec-type="COI-statement">
<title>Competing interests</title>
<p>The authors declare that they have no competing interests</p>
</sec>
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<floats-group>
<fig id="f1-ETM-28-1-12572" position="float">
<label>Figure 1</label>
<caption><p>Preferred reporting items for systematic reviews and meta-snalyses 2020 flow diagram explaining the search strategy.</p></caption>
<graphic xlink:href="etm-28-01-12572-g00.tif" />
</fig>
<fig id="f2-ETM-28-1-12572" position="float">
<label>Figure 2</label>
<caption><p>Forest plot showing the clinical pregnancy rate across study groups. CI, confidence interval.</p></caption>
<graphic xlink:href="etm-28-01-12572-g01.tif" />
</fig>
<fig id="f3-ETM-28-1-12572" position="float">
<label>Figure 3</label>
<caption><p>Forest plot showing the live birth rate across study groups. CI, confidence interval.</p></caption>
<graphic xlink:href="etm-28-01-12572-g02.tif" />
</fig>
<fig id="f4-ETM-28-1-12572" position="float">
<label>Figure 4</label>
<caption><p>Forest plot showing the multiple pregnancy rate across study groups. CI, confidence interval.</p></caption>
<graphic xlink:href="etm-28-01-12572-g03.tif" />
</fig>
<fig id="f5-ETM-28-1-12572" position="float">
<label>Figure 5</label>
<caption><p>Funnel plot showing publication bias for studies reporting on the miscarriage rate.</p></caption>
<graphic xlink:href="etm-28-01-12572-g04.tif" />
</fig>
<table-wrap id="tI-ETM-28-1-12572" position="float">
<label>Table I</label>
<caption><p>Characteristics of the 19 included studies.</p></caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="middle">First author, year</th>
<th align="center" valign="middle">Country</th>
<th align="center" valign="middle">Sample size</th>
<th align="center" valign="middle">Study type</th>
<th align="center" valign="middle">Study duration</th>
<th align="center" valign="middle">Eligibility</th>
<th align="center" valign="middle">Age (median and range/mean SD)</th>
<th align="center" valign="middle">Outcomes</th>
<th align="center" valign="middle">Quality of study (NOS)</th>
<th align="center" valign="middle">(Refs.)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Gale <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">Canada</td>
<td align="center" valign="middle">962</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 1, 2013 to September 1, 2019</td>
<td align="left" valign="middle">Cases: Patients with at least one prior delivery beyond 20 weeks&#x0027; gestation who underwent their first ET after a delivery; patients in the caesarean delivery group had a history of one or more caesarean deliveries, regardless of prior VD history</td>
<td align="left" valign="middle">Cases: 35.2&#x00B1;4.2</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR and SBR</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">(<xref rid="b26-ETM-28-1-12572" ref-type="bibr">26</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD; the first fresh ET</td>
<td align="left" valign="middle">Controls: 34.9&#x00B1;4.1</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Cai <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">8,494</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2014 to July 2020</td>
<td align="left" valign="middle">Cases: Women undergoing IVF/ICSI with a previous CS</td>
<td align="left" valign="middle">Cases: 36.49&#x00B1;4.19</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR and IR</td>
<td align="center" valign="middle">9</td>
<td align="center" valign="middle">(<xref rid="b27-ETM-28-1-12572" ref-type="bibr">27</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 37.32&#x00B1;4.86</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Wang <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">4,158</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2015 to April 2019</td>
<td align="left" valign="middle">Cases: Patients included in this study at least one previous delivery (including CS and VD)</td>
<td align="left" valign="middle">Cases: 35.52&#x00B1;4.71</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, PBR and SBR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b29-ETM-28-1-12572" ref-type="bibr">29</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 36.81&#x00B1;5.00</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">993</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2014 to January 2020</td>
<td align="left" valign="middle">Cases: Women who received their first FET cycle after a freeze-all policy, had a history of only one parturition (after 28 weeks of pregnancy) and were aged &#x003C;40 years with previous CS</td>
<td align="left" valign="middle">Cases: 33.5&#x00B1;3.7</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, PBR and MPR</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">(<xref rid="b28-ETM-28-1-12572" ref-type="bibr">28</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 33.8&#x00B1;3.9</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Bayram <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">Germany</td>
<td align="center" valign="middle">412</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">March 2017 to October 2019</td>
<td align="left" valign="middle">Cases: Patients with secondary infertility and at least one previous caesarean delivery</td>
<td align="left" valign="middle">Cases: 35.0 (4.6)</td>
<td align="left" valign="middle">CPR, LBR and ET</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b30-ETM-28-1-12572" ref-type="bibr">30</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 34.1 (5.0)</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Diao <italic>et al</italic>, 2021</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">760</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2015 to December 2019</td>
<td align="left" valign="middle">Cases: All women with secondary infertility and a history of delivery who underwent IVF/ICSI-ET treatment (patients having a history of a previous delivery beyond 5 months gestation; on treatment with either a long mid-luteal GnRH antagonist or GnRH antagonist ovarian stimulation protocol; undergoing a first fresh ET)</td>
<td align="left" valign="middle">Cases: 35.11&#x00B1;3.97</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR and BW</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b31-ETM-28-1-12572" ref-type="bibr">31</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 35.05&#x00B1;4.51</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Asoglu <italic>et al</italic>, 2021</td>
<td align="left" valign="middle">Turkey</td>
<td align="center" valign="middle">150</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">2017-2018</td>
<td align="left" valign="middle">Cases: Women undergoing IVF/ICSI with a previous CS</td>
<td align="left" valign="middle">Cases: 34.5&#x00B1;5</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR and MPR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b23-ETM-28-1-12572" ref-type="bibr">23</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 34.6&#x00B1;4.8</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Chen <italic>et al</italic>, 2021</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">5,479</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">2014-2017</td>
<td align="left" valign="middle">Cases: All women with secondary infertility and a history of delivery who underwent IVF/ICSI-ETtreatment with at least one good embryo; FSH &#x2264;10 mIU/ml; BMI &#x2264;30 kg/m<sup>2</sup>; endometrial thickness of ET day &#x2265;8 mm&#x005D;</td>
<td align="left" valign="middle">Not reported</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, PBR and MPR</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">(<xref rid="b25-ETM-28-1-12572" ref-type="bibr">25</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Wang <italic>et al</italic>, 2020</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">1,076</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2015 to December 2016</td>
<td align="left" valign="middle">Cases: Women undergoing IVF/ICSI with a previous CS</td>
<td align="left" valign="middle">Cases: 35.4&#x00B1;4.5</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, PBR, SBR, ET and IR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b22-ETM-28-1-12572" ref-type="bibr">22</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Women undergoing IVF/ICSI with a previous VD</td>
<td align="left" valign="middle">Controls: 37.4&#x00B1;5.2</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Huang <italic>et al</italic>, 2020</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">2,046</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2013 to December 2018</td>
<td align="left" valign="middle">Cases: Infertile women with a prior live birth delivery and undergoing their first FET cycles after a freeze-all policy</td>
<td align="left" valign="middle">Cases: 37.2&#x00B1;5.5</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, MPR, ET and IR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b16-ETM-28-1-12572" ref-type="bibr">16</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with history of VD only</td>
<td align="left" valign="middle">Controls: 36.2&#x00B1;5</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Vissers <italic>et al</italic>, 2020</td>
<td align="left" valign="middle">Netherlands</td>
<td align="center" valign="middle">1,317</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">2006 to 2016</td>
<td align="left" valign="middle">Cases: Infertile women with only one previous CS; the first</td>
<td align="left" valign="middle">Cases: 36.6&#x00B1;3.6</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR,PBR, SBR,ET,BW, IR and DTR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b24-ETM-28-1-12572" ref-type="bibr">24</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD; the first fresh ET first fresh ET</td>
<td align="left" valign="middle">Controls: 36.2&#x00B1;3.8</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Lawrenz <italic>et al</italic>, 2020</td>
<td align="left" valign="middle">UAE</td>
<td align="center" valign="middle">495</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">2018-2019</td>
<td align="left" valign="middle">Cases: Infertile women with only one previous CS; the first fresh ET</td>
<td align="left" valign="middle">Cases: 37.1&#x00B1;3.6</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR and BPR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b21-ETM-28-1-12572" ref-type="bibr">21</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD; the first fresh ET</td>
<td align="left" valign="middle">Controls: 38.4&#x00B1;3.2</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Jacob <italic>et al</italic>, 2019</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">1,793</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">2015-2016</td>
<td align="left" valign="middle">Cases: Infertile women with only one previous CS; the first fresh ET</td>
<td align="left" valign="middle">Cases: 35.4&#x00B1;3.3</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, PBR, MPR, SBR, BD and BW</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">(<xref rid="b32-ETM-28-1-12572" ref-type="bibr">32</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD; the first fresh ET</td>
<td align="left" valign="middle">Controls: 36.1&#x00B1;3.7</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Van den Tweel <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">Netherlands</td>
<td align="center" valign="middle">530</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2005 to June 2016</td>
<td align="left" valign="middle">Cases: Subfertile women with previous CS undergoing IVF/ICSI (with a previous live birth who tried for a second child using IVF/ICSI and had at least one ET)</td>
<td align="left" valign="middle">Cases: 34.5&#x00B1;3.8</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR and BPR</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">(<xref rid="b18-ETM-28-1-12572" ref-type="bibr">18</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Subfertile women with previous VD receiving IVF/ICSI</td>
<td align="left" valign="middle">Controls: 34.4&#x00B1;3.9</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Wang <italic>et al</italic>, 2017</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">310</td>
<td align="left" valign="middle">Retrospective case control</td>
<td align="left" valign="middle">January 2013 to December 2015</td>
<td align="left" valign="middle">Cases: Subfertile women with prior CS undergoing IVF/ICSC and fresh ET</td>
<td align="left" valign="middle">Cases: 33.9&#x00B1;3.1</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, MPR, SBR, IR, ET, BW and DTR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b19-ETM-28-1-12572" ref-type="bibr">19</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD and undergoing IVF-ET</td>
<td align="left" valign="middle">Controls: 34.1&#x00B1;3.1</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Patounakis <italic>et al</italic>, 2016</td>
<td align="left" valign="middle">USA</td>
<td align="center" valign="middle">194</td>
<td align="left" valign="middle">Prospective cohort</td>
<td align="left" valign="middle">March 2008 to May 2014</td>
<td align="left" valign="middle">Cases: Infertile women with single or multiple previous CS (women with a history of a previous delivery beyond 20 weeks of gestation)</td>
<td align="left" valign="middle">Cases: 35.3&#x00B1;4.2</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, ET and DTR</td>
<td align="center" valign="middle">9</td>
<td align="center" valign="middle">(<xref rid="b17-ETM-28-1-12572" ref-type="bibr">17</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with previous VD</td>
<td align="left" valign="middle">Controls: 35.6&#x00B1;4.3</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Zhang <italic>et al</italic>, 2016</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">231</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">January 2012 to September 2014</td>
<td align="left" valign="middle">Cases: Infertile women with previous CS undergoing IVF-ET</td>
<td align="left" valign="middle">Cases: 33.5&#x00B1;3.7</td>
<td align="left" valign="middle">CPR, EPR, LBR, MR, BPR, PBR, MPR, SBR, ET,BD, IR and BW</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b20-ETM-28-1-12572" ref-type="bibr">20</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with previous VD undergoing IVF-ET</td>
<td align="left" valign="middle">Controls: 33.8&#x00B1;3.8</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Friedenthal <italic>et al</italic>, 2021</td>
<td align="left" valign="middle">USA</td>
<td align="center" valign="middle">525</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">2012 to 2020</td>
<td align="left" valign="middle">Cases: Subfertile women with prior CS undergoing IVF-ET</td>
<td align="left" valign="middle">Cases: 37.4&#x00B1;3.6</td>
<td align="left" valign="middle">ET, IR, PBR, MR and LBR</td>
<td align="center" valign="middle">8</td>
<td align="center" valign="middle">(<xref rid="b33-ETM-28-1-12572" ref-type="bibr">33</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD undergoing IVF-ET</td>
<td align="left" valign="middle">Controls: 36.9&#x00B1;3.9</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
<tr>
<td align="left" valign="middle">Lin <italic>et al</italic>, 2022</td>
<td align="left" valign="middle">China</td>
<td align="center" valign="middle">9,124</td>
<td align="left" valign="middle">Retrospective cohort</td>
<td align="left" valign="middle">April 2014 to April 2020</td>
<td align="left" valign="middle">Cases: Subfertile women with prior CS undergoing IVF-ET</td>
<td align="left" valign="middle">Not reported</td>
<td align="left" valign="middle">PBR</td>
<td align="center" valign="middle">7</td>
<td align="center" valign="middle">(<xref rid="b34-ETM-28-1-12572" ref-type="bibr">34</xref>)</td>
</tr>
<tr>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">Controls: Infertile women with only one previous VD undergoing IVF-ET</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
<td align="left" valign="middle">&#x00A0;</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn><p>SD, standard deviation; NOS, Newcastle Ottawa Scale; ET, embryo transfer; VD, vaginal delivery; CPR, clinical pregnancy test; EPR, ectopic pregnancy rate; LBR, live birth rate; MR, miscarriage rate; SBR, still brith rate; IVF/ICSI, in vitro fertilisation/intracytoplasmic sperm injection; BPR, biochemical pregnancy rate; IR, implantation rate; MPR, multiple pregnancy rate; BW, birth weight; DTR, difficult transfer rate; BD, birth defects; PBR, preterm birth rate.</p></fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</article>
