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@ARTICLE{Bobdiwala:177603,
      author       = {S. Bobdiwala and C. Kyriacou and E. Christodoulou$^*$ and
                      J. Farren and N. Mitchell-Jones and M. Al-Memar and F. Ayim
                      and B. Chohan and E. Kirk and O. Abughazza and B.
                      Guruwadahyarhalli and S. Guha and V. Vathanan and D. Gould
                      and C. Stalder and D. Timmerman and B. Van Calster and T.
                      Bourne},
      title        = {{E}valuating cut-off levels for progesterone, β human
                      chorionic gonadotropin and β human chorionic gonadotropin
                      ratio to exclude pregnancy viability in women with a
                      pregnancy of unknown location: {A} prospective multicenter
                      cohort study.},
      journal      = {Acta obstetricia et gynecologica Scandinavica},
      volume       = {101},
      number       = {1},
      issn         = {0001-6349},
      address      = {Malden, MA},
      publisher    = {Wiley-Blackwell},
      reportid     = {DKFZ-2021-02662},
      pages        = {46-55},
      year         = {2022},
      note         = {2022 Jan;101(1):46-55},
      abstract     = {There is no global agreement on how to best determine
                      pregnancy of unknown location viability and location using
                      biomarkers. Measurements of progesterone and β human
                      chorionic gonadotropin (βhCG) are still used in clinical
                      practice to exclude the possibility of a viable intrauterine
                      pregnancy (VIUP). We evaluate the predictive value of
                      progesterone, βhCG, and βhCG ratio cut-off levels to
                      exclude a VIUP in women with a pregnancy of unknown
                      location.This was a secondary analysis of prospective
                      multicenter study data of consecutive women with a pregnancy
                      of unknown location between January 2015 and 2017 collected
                      from dedicated early pregnancy assessment units of eight
                      hospitals. Single progesterone and serial βhCG measurements
                      were taken. Women were followed up until final pregnancy
                      outcome between 11 and 14 weeks of gestation was confirmed
                      using transvaginal ultrasonography: (1) VIUP, (2) non-viable
                      intrauterine pregnancy or failed pregnancy of unknown
                      location, and (3) ectopic pregnancy or persisting pregnancy
                      of unknown location. The predictive value of cut-off levels
                      for ruling out VIUP were evaluated across a range of values
                      likely to be encountered clinically for progesterone, βhCG,
                      and βhCG ratio.Data from 2507 of 3272 $(76.6\%)$ women were
                      suitable for analysis. All had data for βhCG levels, 2248
                      $(89.7\%)$ had progesterone levels, and 1809 $(72.2\%)$ had
                      βhCG ratio. The likelihood of viability falls with the
                      progesterone level. Although the median progesterone level
                      associated with viability was 59 nmol/L, VIUP were
                      identified with levels as low as 5 nmol/L. No single βhCG
                      cut-off reliably ruled out the presence of viability with
                      certainty, even when the level was more than 3000 IU/L,
                      there were 39/358 $(11\%)$ women who had a VIUP. The
                      probability of viability decreases with the βhCG ratio.
                      Although the median βhCG ratio associated with viability
                      was 2.26, VIUP were identified with ratios as low as 1.02. A
                      progesterone level below 2 nmol/L and βhCG ratio below
                      0.87 were unlikely to be associated with viability but were
                      not definitive when considering multiple imputation.Cut-off
                      levels for βhCG, βhCG ratio, and progesterone are not safe
                      to be used clinically to exclude viability in early
                      pregnancy. Although βhCG ratio and progesterone have
                      slightly better performance in comparison, single βhCG used
                      in this manner is highly unreliable.},
      keywords     = {early pregnancy complications (Other) / ectopic pregnancy
                      (Other) / pregnancy (Other) / pregnancy of unknown location
                      (Other) / reproductive endocrinology (Other) / ultrasound
                      (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34817062},
      doi          = {10.1111/aogs.14295},
      url          = {https://inrepo02.dkfz.de/record/177603},
}