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However, the teratogenic potential of dydrogesterone (DYG) remains uncertain and a subject of ongoing debate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included patients undergoing embryo transfer between January 2010 and December 2018. It analyzed 124,815 embryo transfer cycles (80,103 [64.2%] fresh; 44,712 [35.8%] frozen), resulting in 52,175 live births. Newborns were stratified by maternal luteal phase support (DYG-exposed vs. unexposed). Patients with known congenital malformation risk factors were excluded. Congenital anomaly incidence was compared between groups. Stratified analysis and multivariate logistic regression models adjusting for confounders were employed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The total congenital anomaly rate was significantly lower in DYG-exposed newborns compared to unexposed groups (6.05\u2030 vs. 7.90\u2030,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.020), with particularly notable differences in musculoskeletal malformations (0.63\u2030 vs. 1.33\u2030,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.025). No significant differences were observed in other congenital anomaly categories. After stratifying by fresh or frozen cycles, DYG-exposed and unexposed groups showed no significant differences in birth defects during fresh cycles. In frozen cycles, musculoskeletal anomalies were significantly lower in the DYG group both before (0.60\u2030 vs. 2.37\u2030,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.020) and after adjustment (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.009, OR: 0.19, 95% CI: 0.05\u20130.66). Other anomaly categories remained unaffected. However, this specific association did not remain significant after rigorous correction for multiple testing with the application of both the Bonferroni and False Discovery Rate (FDR) methods. Multivariate analysis adjusted for confounders revealed no increased risk of congenital anomalies associated with DYG exposure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>First-trimester dydrogesterone therapy was not associated with an increased risk of congenital anomalies. Due to the limitations of this cohort study, further follow-up and in-depth data analysis are planned for future studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12958-025-01507-8","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T23:24:39Z","timestamp":1764890679000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Congenital anomalies after first-trimester dydrogesterone therapy during in vitro fertilization"],"prefix":"10.1186","volume":"24","author":[{"given":"Wan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"issue":"2","key":"1507_CR1","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1055\/s-0035-1545363","volume":"33","author":"EH Yanushpolsky","year":"2015","unstructured":"Yanushpolsky EH. 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Informed consent was waived due to the retrospective nature of the study (ethics approval document number IRB00006761-M2019487). Procedures performed in this study involving human participants or human tissue were in accordance with the ethical standards of the institutional and\/or national research committee, and with the 1975 Helsinki Declaration and its later amendments or comparable ethical standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5"}}