title: Non-invasive metabolomic profiling of embryo culture media and morphology grading to predict implantation outcome in frozen-thawed embryo transfer cycles.
abstract: OBJECTIVE
  Assessment of embryo viability is a crucial component of in vitro fertilization and currently relies largely on embryo morphology and cleavage rate. Because morphological assessment remains highly subjective, it can be unreliable in predicting embryo viability. This study investigated the metabolomic profiling of embryo culture media using near-infrared (NIR) spectroscopy for predicting the implantation potential of human embryos in frozen-thawed embryo transfer (FET) cycles.
  
  
  METHODS
  Spent embryo culture media was collected on day 4 after thawed embryo transfer (n = 621) and analysed using NIR spectroscopy. Viability scores were calculated using a predictive multivariate algorithm of fresh embryos with known pregnancy outcomes.
  
  
  RESULTS
  The mean viability indices of embryos resulting in clinical pregnancy following FET were significantly higher than those of non-implanted embryos and differed between the 0, 50, and 100 % implantation groups. Notably, the 0 % group index was significantly lower than the 100 % implantation group index (-0.787 ± 0.382 vs. 1.064 ± 0.331, P < 0.01). To predict implantation outcomes, we examined the area under the ROC curve (AUCROC), which was significantly higher for the viability than for the morphology score (0.94 vs. 0.55; P < 0.01); however, the AUCROCs for the composite and viability scores did not differ significantly (0.92 vs. 0.94; P > 0.05).
  
  
  CONCLUSIONS
  NIR metabolomic profiling of thawed embryo culture media is independent of morphology and correlates with embryo implantation potential in FET cycles. The viability score alone or in conjunction with morphologic grading is a more objective marker for implantation outcome in FET cycles than morphology alone.
authors.affiliation: Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. xiongli236@126.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Li
authors.affiliation: Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. 357251014@qq.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. fujing_givf@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.affiliation: Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. jackeyzhang0905@163.com.
authors.forename: Wen-Bi
authors.initials: WB
authors.lastname: Zhang
authors.affiliation: Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. lsy6392@163.com.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Shanghai Ji Ai Genetics & IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. steven30l9@hotmail.com.|Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. steven30l9@hotmail.com.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Sun
mesh_terms: D000328:Adult; D015925:Cryopreservation / Q000379:methods*; D003470:Culture Media / Q000032:analysis* / Q000737:chemistry; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004624:Embryo Transfer / Q000379:methods*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D055432:Metabolomics / Q000379:methods*; D011247:Pregnancy; D011256:Pregnancy Outcome; D012372:ROC Curve; D019265:Spectroscopy, Near-Infrared
chemical_list: D003470:Culture Media
keywords: Frozen-thawed embryo transfer/FET; Morphologic grading; Near infrared spectroscopy/NIR; Non-invasive embryo selection; Viability score