High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India
Objective The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients. Methods This retrospective analytical study...
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| Veröffentlicht in: | International journal of gynecology and obstetrics 2024-09, Vol.166 (3), p.1263-1272 |
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| creator | Kuriakose, Santhosh Dhanasooraj, Dhananjayan Shiny, P. M. Shammy, S. Sona, V. P. Manjula, Anupama A. Ramachandran, Amrutha Vijaykumar, Bindu Susan, Nayana Dinesan, M. Sankar, Uma V. Ramachandran, Kavitha Sreedharan, P. S. |
| description | Objective
The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.
Methods
This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.
Results
Among 151 cases enrolled, 39 were unique POLE‐mutated cases. Significant associations were high‐grade tumors, myometrial invasion >50%, and Lymph‐vascular space invasion (LVSI). The median follow‐up was 40 months (95% confidence interval [CI], 34–46). A lower mean disease‐specific survival (DSS) of 51.7 months (95% CI, 43.7–59.6) was noted in the POLE‐mutated group compared with 72.11 months (95% CI, 67.60–76.62) for the POLE wild‐type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE‐mutated group was noted. In advanced stages (FIGO stages II–IV), a nine‐fold HR for DSS and overall survival (OS) compared with POLE wild‐type was identified. After controlling for treatment effects using Cox proportional HR, advanced‐stage POLE‐mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE‐wild‐type tumors of the same stage.
Conclusion
This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE‐mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.
Synopsis
The present study identified unique POLE mutations, termed “non‐pathogenic”, in an endometrial cancer cohort of Indian ethnicity, characterized by poor survival, which was pronounced in advanced stages. |
| doi_str_mv | 10.1002/ijgo.15486 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3033008711</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3033008711</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2886-efacb48b1713013684855dfebcba8b8fb42d133ebfb02c0fbd2a693f608b84803</originalsourceid><addsrcrecordid>eNp9kM1KAzEUhYMotlY3PoBkKcLUZDI_6VJK1UqhgroekkzSRmaSmsxYupE-gg-gL9cnMbXq0tVdnO98XA4Apxj1MULxpX6e2T5OE5rtgS6m-SAiST7YB90QoiiPB3EHHHn_jBDCOcaHoENommMSp13wdqtnc7hw8pVV0ggJrYKb9YexZrN-X7BmbmfSaLFZf8L76WQE67ZhjbYGLnUTeta6ULYzY732UBvIoLBz65qtR5rS1rJxmlVQsCB3UDlbwwfbhu7YlJodgwPFKi9Pfm4PPF2PHoe30WR6Mx5eTSIRU5pFUjHBE8rD-wRhktGEpmmpJBecUU4VT-ISEyK54igWSPEyZtmAqAyFNKGI9MD5zhuefWmlb4paeyGrihlpW18QRAhCNKwT0IsdKpz13klVLJyumVsVGBXbvYvt3sX33gE--_G2vJblH_o7cADwDljqSq7-URXju5vpTvoFe5GPkw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3033008711</pqid></control><display><type>article</type><title>High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Kuriakose, Santhosh ; Dhanasooraj, Dhananjayan ; Shiny, P. M. ; Shammy, S. ; Sona, V. P. ; Manjula, Anupama A. ; Ramachandran, Amrutha ; Vijaykumar, Bindu ; Susan, Nayana ; Dinesan, M. ; Sankar, Uma V. ; Ramachandran, Kavitha ; Sreedharan, P. S.</creator><creatorcontrib>Kuriakose, Santhosh ; Dhanasooraj, Dhananjayan ; Shiny, P. M. ; Shammy, S. ; Sona, V. P. ; Manjula, Anupama A. ; Ramachandran, Amrutha ; Vijaykumar, Bindu ; Susan, Nayana ; Dinesan, M. ; Sankar, Uma V. ; Ramachandran, Kavitha ; Sreedharan, P. S.</creatorcontrib><description>Objective
The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.
Methods
This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.
Results
Among 151 cases enrolled, 39 were unique POLE‐mutated cases. Significant associations were high‐grade tumors, myometrial invasion >50%, and Lymph‐vascular space invasion (LVSI). The median follow‐up was 40 months (95% confidence interval [CI], 34–46). A lower mean disease‐specific survival (DSS) of 51.7 months (95% CI, 43.7–59.6) was noted in the POLE‐mutated group compared with 72.11 months (95% CI, 67.60–76.62) for the POLE wild‐type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE‐mutated group was noted. In advanced stages (FIGO stages II–IV), a nine‐fold HR for DSS and overall survival (OS) compared with POLE wild‐type was identified. After controlling for treatment effects using Cox proportional HR, advanced‐stage POLE‐mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE‐wild‐type tumors of the same stage.
Conclusion
This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE‐mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.
Synopsis
The present study identified unique POLE mutations, termed “non‐pathogenic”, in an endometrial cancer cohort of Indian ethnicity, characterized by poor survival, which was pronounced in advanced stages.</description><identifier>ISSN: 0020-7292</identifier><identifier>ISSN: 1879-3479</identifier><identifier>EISSN: 1879-3479</identifier><identifier>DOI: 10.1002/ijgo.15486</identifier><identifier>PMID: 38571325</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; DNA Polymerase II - genetics ; endometrial carcinoma ; Endometrial Neoplasms - genetics ; Endometrial Neoplasms - mortality ; Endometrial Neoplasms - pathology ; Female ; Humans ; India ; Middle Aged ; Mutation ; Neoplasm Staging ; POLE mutation ; Poly-ADP-Ribose Binding Proteins - genetics ; polymerase epsilon (POLE) gene ; Prevalence ; Prognosis ; Retrospective Studies ; Sanger sequencing</subject><ispartof>International journal of gynecology and obstetrics, 2024-09, Vol.166 (3), p.1263-1272</ispartof><rights>2024 International Federation of Gynecology and Obstetrics.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2886-efacb48b1713013684855dfebcba8b8fb42d133ebfb02c0fbd2a693f608b84803</cites><orcidid>0000-0001-7876-6813 ; 0000-0002-0565-8501</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijgo.15486$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijgo.15486$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38571325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuriakose, Santhosh</creatorcontrib><creatorcontrib>Dhanasooraj, Dhananjayan</creatorcontrib><creatorcontrib>Shiny, P. M.</creatorcontrib><creatorcontrib>Shammy, S.</creatorcontrib><creatorcontrib>Sona, V. P.</creatorcontrib><creatorcontrib>Manjula, Anupama A.</creatorcontrib><creatorcontrib>Ramachandran, Amrutha</creatorcontrib><creatorcontrib>Vijaykumar, Bindu</creatorcontrib><creatorcontrib>Susan, Nayana</creatorcontrib><creatorcontrib>Dinesan, M.</creatorcontrib><creatorcontrib>Sankar, Uma V.</creatorcontrib><creatorcontrib>Ramachandran, Kavitha</creatorcontrib><creatorcontrib>Sreedharan, P. S.</creatorcontrib><title>High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India</title><title>International journal of gynecology and obstetrics</title><addtitle>Int J Gynaecol Obstet</addtitle><description>Objective
The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.
Methods
This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.
Results
Among 151 cases enrolled, 39 were unique POLE‐mutated cases. Significant associations were high‐grade tumors, myometrial invasion >50%, and Lymph‐vascular space invasion (LVSI). The median follow‐up was 40 months (95% confidence interval [CI], 34–46). A lower mean disease‐specific survival (DSS) of 51.7 months (95% CI, 43.7–59.6) was noted in the POLE‐mutated group compared with 72.11 months (95% CI, 67.60–76.62) for the POLE wild‐type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE‐mutated group was noted. In advanced stages (FIGO stages II–IV), a nine‐fold HR for DSS and overall survival (OS) compared with POLE wild‐type was identified. After controlling for treatment effects using Cox proportional HR, advanced‐stage POLE‐mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE‐wild‐type tumors of the same stage.
Conclusion
This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE‐mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.
Synopsis
The present study identified unique POLE mutations, termed “non‐pathogenic”, in an endometrial cancer cohort of Indian ethnicity, characterized by poor survival, which was pronounced in advanced stages.</description><subject>Adult</subject><subject>Aged</subject><subject>DNA Polymerase II - genetics</subject><subject>endometrial carcinoma</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometrial Neoplasms - mortality</subject><subject>Endometrial Neoplasms - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>India</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Staging</subject><subject>POLE mutation</subject><subject>Poly-ADP-Ribose Binding Proteins - genetics</subject><subject>polymerase epsilon (POLE) gene</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Sanger sequencing</subject><issn>0020-7292</issn><issn>1879-3479</issn><issn>1879-3479</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1KAzEUhYMotlY3PoBkKcLUZDI_6VJK1UqhgroekkzSRmaSmsxYupE-gg-gL9cnMbXq0tVdnO98XA4Apxj1MULxpX6e2T5OE5rtgS6m-SAiST7YB90QoiiPB3EHHHn_jBDCOcaHoENommMSp13wdqtnc7hw8pVV0ggJrYKb9YexZrN-X7BmbmfSaLFZf8L76WQE67ZhjbYGLnUTeta6ULYzY732UBvIoLBz65qtR5rS1rJxmlVQsCB3UDlbwwfbhu7YlJodgwPFKi9Pfm4PPF2PHoe30WR6Mx5eTSIRU5pFUjHBE8rD-wRhktGEpmmpJBecUU4VT-ISEyK54igWSPEyZtmAqAyFNKGI9MD5zhuefWmlb4paeyGrihlpW18QRAhCNKwT0IsdKpz13klVLJyumVsVGBXbvYvt3sX33gE--_G2vJblH_o7cADwDljqSq7-URXju5vpTvoFe5GPkw</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Kuriakose, Santhosh</creator><creator>Dhanasooraj, Dhananjayan</creator><creator>Shiny, P. M.</creator><creator>Shammy, S.</creator><creator>Sona, V. P.</creator><creator>Manjula, Anupama A.</creator><creator>Ramachandran, Amrutha</creator><creator>Vijaykumar, Bindu</creator><creator>Susan, Nayana</creator><creator>Dinesan, M.</creator><creator>Sankar, Uma V.</creator><creator>Ramachandran, Kavitha</creator><creator>Sreedharan, P. S.</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7876-6813</orcidid><orcidid>https://orcid.org/0000-0002-0565-8501</orcidid></search><sort><creationdate>202409</creationdate><title>High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India</title><author>Kuriakose, Santhosh ; Dhanasooraj, Dhananjayan ; Shiny, P. M. ; Shammy, S. ; Sona, V. P. ; Manjula, Anupama A. ; Ramachandran, Amrutha ; Vijaykumar, Bindu ; Susan, Nayana ; Dinesan, M. ; Sankar, Uma V. ; Ramachandran, Kavitha ; Sreedharan, P. S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2886-efacb48b1713013684855dfebcba8b8fb42d133ebfb02c0fbd2a693f608b84803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>DNA Polymerase II - genetics</topic><topic>endometrial carcinoma</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometrial Neoplasms - mortality</topic><topic>Endometrial Neoplasms - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>India</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Staging</topic><topic>POLE mutation</topic><topic>Poly-ADP-Ribose Binding Proteins - genetics</topic><topic>polymerase epsilon (POLE) gene</topic><topic>Prevalence</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Sanger sequencing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kuriakose, Santhosh</creatorcontrib><creatorcontrib>Dhanasooraj, Dhananjayan</creatorcontrib><creatorcontrib>Shiny, P. M.</creatorcontrib><creatorcontrib>Shammy, S.</creatorcontrib><creatorcontrib>Sona, V. P.</creatorcontrib><creatorcontrib>Manjula, Anupama A.</creatorcontrib><creatorcontrib>Ramachandran, Amrutha</creatorcontrib><creatorcontrib>Vijaykumar, Bindu</creatorcontrib><creatorcontrib>Susan, Nayana</creatorcontrib><creatorcontrib>Dinesan, M.</creatorcontrib><creatorcontrib>Sankar, Uma V.</creatorcontrib><creatorcontrib>Ramachandran, Kavitha</creatorcontrib><creatorcontrib>Sreedharan, P. S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of gynecology and obstetrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuriakose, Santhosh</au><au>Dhanasooraj, Dhananjayan</au><au>Shiny, P. M.</au><au>Shammy, S.</au><au>Sona, V. P.</au><au>Manjula, Anupama A.</au><au>Ramachandran, Amrutha</au><au>Vijaykumar, Bindu</au><au>Susan, Nayana</au><au>Dinesan, M.</au><au>Sankar, Uma V.</au><au>Ramachandran, Kavitha</au><au>Sreedharan, P. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India</atitle><jtitle>International journal of gynecology and obstetrics</jtitle><addtitle>Int J Gynaecol Obstet</addtitle><date>2024-09</date><risdate>2024</risdate><volume>166</volume><issue>3</issue><spage>1263</spage><epage>1272</epage><pages>1263-1272</pages><issn>0020-7292</issn><issn>1879-3479</issn><eissn>1879-3479</eissn><abstract>Objective
The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.
Methods
This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.
Results
Among 151 cases enrolled, 39 were unique POLE‐mutated cases. Significant associations were high‐grade tumors, myometrial invasion >50%, and Lymph‐vascular space invasion (LVSI). The median follow‐up was 40 months (95% confidence interval [CI], 34–46). A lower mean disease‐specific survival (DSS) of 51.7 months (95% CI, 43.7–59.6) was noted in the POLE‐mutated group compared with 72.11 months (95% CI, 67.60–76.62) for the POLE wild‐type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE‐mutated group was noted. In advanced stages (FIGO stages II–IV), a nine‐fold HR for DSS and overall survival (OS) compared with POLE wild‐type was identified. After controlling for treatment effects using Cox proportional HR, advanced‐stage POLE‐mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE‐wild‐type tumors of the same stage.
Conclusion
This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE‐mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.
Synopsis
The present study identified unique POLE mutations, termed “non‐pathogenic”, in an endometrial cancer cohort of Indian ethnicity, characterized by poor survival, which was pronounced in advanced stages.</abstract><cop>United States</cop><pmid>38571325</pmid><doi>10.1002/ijgo.15486</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-7876-6813</orcidid><orcidid>https://orcid.org/0000-0002-0565-8501</orcidid></addata></record> |
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| ispartof | International journal of gynecology and obstetrics, 2024-09, Vol.166 (3), p.1263-1272 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Aged DNA Polymerase II - genetics endometrial carcinoma Endometrial Neoplasms - genetics Endometrial Neoplasms - mortality Endometrial Neoplasms - pathology Female Humans India Middle Aged Mutation Neoplasm Staging POLE mutation Poly-ADP-Ribose Binding Proteins - genetics polymerase epsilon (POLE) gene Prevalence Prognosis Retrospective Studies Sanger sequencing |
| title | High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India |
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