Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome

Räty, Raija; Virtanen, Arja; Koskinen, Pertti; Anttila, Leena; Forsström, J; Laitinen, Päivi; Mörsky, Pertti; Tiitinen, Aila; Ekblad, Ulla

doi:10.1093/humrep/17.2.481

Cited by 54 publications

(26 citation statements)

References 14 publications

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“…In our data mean hCG-β levels after frozen cycles were significantly higher than those after fresh cycles regardless of pregnancy outcomes. It is noteworthy that mid-trimester hCG-β levels in pregnancies achieved after frozen cycles are higher than those of fresh cycles [33,34]. The differences in hCG-β levels among these studies could be explained by various factors including day of ET, embryo biopsy, method of fertilization, method of freezing and thawing, media of embryo culture and etiology of infertility, etc.…”

Section: Discussionmentioning

confidence: 95%

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Sung

Kwak‐Kim

Koo

et al. 2016

J Assist Reprod Genet

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Purpose To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. Methods A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. Results POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/ mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/ mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-β level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-β level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-β was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-β level and fold increase of hCG-β significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. Conclusions Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of Capsule Early prediction of pregnancy outcome...

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Section: Discussionmentioning

confidence: 95%

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Sung

Kwak‐Kim

Koo

et al. 2016

J Assist Reprod Genet

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show abstract

“…Several authors have noted elevated second trimester hCG levels following frozen ET when compared to fresh ET (16–18), however these studies did not specifically assess rates of first trimester increase. We found that the association of hCG level and type of conception was constant even when we stratified our analysis based on gestational age and absolute hCG concentration, suggesting the difference in hCG rise is already apparent as early as 15 days post-IVF retrieval (and remains unaltered) (Supplemental Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Association of the very early rise of human chorionic gonadotropin with adverse outcomes in singleton pregnancies after in vitro fertilization

Morse

Barnhart

Senapati

et al. 2016

Fertility and Sterility

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Objective To determine if very early serum hCG, a marker of trophoblast differentiation, is associated with adverse perinatal outcomes in singleton pregnancies. Design Retrospective cohort study Setting University fertility program Patients 360 singleton IVF live births Interventions Serial hCG measurements were used to determine the within-woman slope for hCG (hCG rise). Main Outcomes Measures Primary outcomes included birth weight and gestational age at delivery. Statistical comparisons utilized t-test, chi-square test, and linear and logistic regression as appropriate. Results hCG rise was positively associated with birth weight but not gestational age at delivery. Infant gender, gestational age, and type of embryo transfer ("fresh" vs. frozen/thawed) were significantly associated with birth weight and confounded the associations of interest. hCG rise was slower among subjects delivering an infant with low birth weight (slope: 0.386 ±0.05 vs. 0.407 ±0.06,) or small for gestational age (slope: 0.371 ±0.07 vs. 0.406 ±0.06,). Analysis of hCG rise by quartile showed that, when compared to the first quartile (slowest), subjects with a rate of hCG rise in the fourth quartile (fastest) had a significantly decreased risk of delivering an infant of low birth weight [OR = 0.32, 95% CI (0.11–0.92)]. No relationship was noted between hCG rise and hypertensive disorders of pregnancy. Conclusions Slower, very early first trimester hCG rise is associated with low birth weight but not gestational age at delivery among singleton IVF conceptions. The rate of increase in serum hCG may reflect early trophoblast differentiation and placentation and, possibly, predict subsequent development.

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“…Pregnancies conceived by assisted reproduction techniques (ART) have been reported to be associated with changes in the biochemical parameters of screening for DS, leading to an increased false-positive rate (FPR) in the second trimester (1)(2)(3)(4)(5)(6). The effect of ART on first-trimester Down screening, which combines maternal age, nuchal translucency thickness (NT), maternal serum free b subunit human chorionic gonadotropin (fb-hCG), and pregnancy-associated plasma protein-A (PAPP-A), has been examined, but the results have been inconclusive.…”

mentioning

confidence: 99%

In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies

Matilainen

Peuhkurinen

Laitinen

et al. 2011

Fertility and Sterility

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Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome

Abstract: The present data confirm that the overall FPR in the serum screening for Down's syndrome in assisted reproduction pregnancies is high, resulting in unnecessary invasive procedures.

Cited by 54 publications

References 14 publications

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle

Association of the very early rise of human chorionic gonadotropin with adverse outcomes in singleton pregnancies after in vitro fertilization

In combined first-trimester Down syndrome screening, the false-positive rate is not higher in pregnancies conceived after assisted reproduction compared with spontaneous pregnancies

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