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Spontaneous pregnancy reaches viability after low first trimester serum progesterone: A case report

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Abstract

Progesterone is produced by the corpus luteum until completion of the luteal-placental shift at approximately 6-10 weeks following last menstruation. Studies have shown that first trimester progesterone levels are predictive of pregnancy viability, and some authors support a level of 5 ng/mL as an absolute threshold to indicate viability. A 47-year-old woman with recurrent pregnancy loss was noted to have a very low first trimester progesterone level (1.2 ng/mL), but the pregnancy progressed to viability. She unfortunately delivered an intrauterine fetal demise at 27 weeks and 3 days' gestation. A single serum progesterone level of < 5 ng/mL is suggestive, but not diagnostic, of a nonviable pregnancy. Routine uterine curettage during the evaluation of a pregnancy of unknown location using this level as an absolute cutoff may result in the interruption of a desired, viable pregnancy.

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... [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Indeed, upon literature review, cases of VIUP have been reported with lower progesterone levels (3 nmol/L) and falling serial βhCG values (βhCG ratio <1) that begin as high as 167 343 IU/L, further supporting the argument that cut-off levels in the differentiation of viability in PUL are subjective and unreliable. 15,20,36,37 Systematic reviews and meta-analyses, as well as previous work performed by our group in differentiating pregnancy location, have highlighted how combining variables in prediction models outperform any variable in isolation. 3,5,24,25 In line with this, the use of isolated cut-off levels to define viability gives an inaccurate impression of diagnostic certainty that cannot be generalized. ...
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Introduction 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. Material and methods 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. Results 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. Conclusions 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.
... The absolute treatment levels for pregnancy maintenance are not known, nor is it known what level of progesterone may impair male libido. While the absolute lowest serum progesterone level to achieve a viable pregnancy is unknown, one case report described first trimester progesterone levels of 1.2 ng/mL for a pregnancy that progressed to 27 weeks [16]. ...
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... Factors explaining the effect are probably related to the increase of the IR due to a reduction of GLUT4 expression [73]. Abundant studies have shown that first trimester progesterone levels are predictive of pregnancy viability [74][75][76][77]. High serum levels of progesterone in early pregnancy are a sign of normal function of corpus luteum and placenta. ...
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