{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T21:58:15Z","timestamp":1785362295437,"version":"3.55.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Fertilization and early-cleavage failure are the major causes of assisted reproductive technology failure, but genotype-guided care is underused. We conducted whole-exome sequencing with Sanger confirmation in 20 men from couples with unexplained fertilization and cleavage failure after\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    fertilization or intracytoplasmic sperm injection (ICSI). Then, further sperm transmission electron microscopy, immunofluorescence, and, where appropriate, embryo quantitative parental contamination test (qPCT) and kinship analysis were integrated in selected cases. Six novel variants were found in four families: two each in dynein axonemal heavy chain 10 (\n                    <jats:italic toggle=\"yes\">DNAH10<\/jats:italic>\n                    ) and dynein axonemal heavy chain 12 (\n                    <jats:italic toggle=\"yes\">DNAH12<\/jats:italic>\n                    ) and one in cilia and flagella associated protein 47 (\n                    <jats:italic toggle=\"yes\">CFAP47<\/jats:italic>\n                    ) and phospholipase C zeta 1 (\n                    <jats:italic toggle=\"yes\">PLCZ1<\/jats:italic>\n                    ), respectively.\n                    <jats:italic toggle=\"yes\">DNAH10\/DNAH12<\/jats:italic>\n                    variants segregated with multiple morphological abnormalities of the sperm flagella and showed \u201c9+2\u201d axonemal disruption and reduced dynein signals. Hemizygous\n                    <jats:italic toggle=\"yes\">CFAP47<\/jats:italic>\n                    c.8006C&gt;T is associated with cleavage failure and altered PLCZ1 localization. Homozygous\n                    <jats:italic toggle=\"yes\">PLCZ1<\/jats:italic>\n                    c.589C&gt;T in a consanguineous pedigree coincided with multinuclear (\u22653 pronuclei) zygotes, and qPCT\/kinship indicated excess paternal contribution, consistent with suspected polyspermy in multinuclear zygotes. Management-matched genotype: ICSI restored fertilization in\n                    <jats:italic toggle=\"yes\">DNAH10\/DNAH12<\/jats:italic>\n                    deficiency, whereas ICSI plus assisted oocyte activation (AOA) improved cleavage and yielded ongoing pregnancies in\n                    <jats:italic toggle=\"yes\">CFAP47\/PLCZ1<\/jats:italic>\n                    deficiency. These findings outline potentially actionable clinical strategies\u2013ICSI for axonemal dynein defects and ICSI plus AOA for activation pathway defects\u2013and support targeted genetic testing plus embryo qPCT\/kinship in selected cases.\n                  <\/jats:p>","DOI":"10.4103\/aja202629","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T07:00:07Z","timestamp":1785308407000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Genotype-based management of fertilization and cleavage failure: case-series evidence from DNAH10, DNAH12, CFAP47, and PLCZ1"],"prefix":"10.4103","author":[{"given":"Ke-Er","family":"Gan","sequence":"first","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"},{"name":"Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ling","family":"Zhong","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"},{"name":"Center of Reproductive Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Bang","family":"Ou","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Kun","family":"Liang","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhou","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuerxunayi","family":"Yalikun","sequence":"additional","affiliation":[{"name":"IVF Center, The First People\u2019s Hospital of Kashi Prefecture, Kashi 843800, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan","family":"Li","sequence":"additional","affiliation":[{"name":"Yikon Genomics, Suzhou 215000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 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