Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause

Hunt, Lauren; McInerney-Leo, Aideen; Sinnott, Stephen; Sutton, Bridget M.; Cincotta, Robert; Duncombe, Gregory; Chua, Jackie; Peterson, Madelyn

doi:10.1007/s10815-017-0996-1

Cited by 13 publications

(11 citation statements)

References 57 publications

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“…It has been suggested that hormonal treatment is the most important cause of altered biochemical markers in IVF pregnancies. The supra-physiologic oestrogen level and premature progesterone secretion due to ovarian stimulation may result in a non-synchronous uterine environment, a suboptimal placenta-endometrial interface and impaired placentation [6,8,11,31]. This hypothesis was supported by findings that first-trimester maternal serum PAPP-A levels are affected by the oestradiol level at the time of oocyte retrieval and by the number of oocytes in IVF cycles [27,32].…”

Section: Discussionmentioning

confidence: 93%

Maternal serum levels of angiogenic markers and markers of placentation in pregnancies conceived with fresh and vitrified-warmed blastocyst transfer

Reljič

Porović

2019

J Assist Reprod Genet

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The aim of the study was to compare the levels of angiogenic markers and markers of placentation between pregnancies conceived with fresh (ET) and vitrified-warmed blastocyst transfer (FET). Methods Women with singleton pregnancies resulting from fresh ET or FET during the period between 2013 and 2017 were included in this prospective observational study. Fresh ET was performed in a stimulated and FET in natural cycle. At 6-7 weeks of gestation, after ultrasound confirmation of a single gestational sac with a viable embryo, serum levels of free β-hCG, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PIGF) and fms-like tyrosine kinase (sFlt-1) were measured. Data on the patients' characteristics, pregnancy complications and outcomes were collected from a questionnaire and National Perinatal Information System of Slovenia. Results Among 211 pregnancies, 126 were achieved with fresh ET and 85 with FET. There were no significant differences in perinatal outcome, pregnancy complication and PIGF level between the fresh ET and FET group. Women achieving pregnancy with FET had significant higher levels of free β-hCG (40.20 ± 30.62 IU/L vs. 28.74 ± 23.52, p = 0.002), PAPP-A (0.09 ± 0.06 vs. 0.06 ± 0.05 IU/L, p = 0.004) and sFlt-1 (596.19 ± 283.06 vs. 436.53 ± 248.23 pg/L, p < 0.0001) compared to women having conceived with fresh ET. There were no significant differences in the levels of evaluated biomarkers between patients with different pregnancy outcomes and complications. Conclusion Levels of angiogenic markers and markers of placentation differ between pregnancies achieved with fresh ET and FET which may reflect altered implantation and early placentation with some forms of assisted reproductive technologies.

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Section: Discussionmentioning

confidence: 93%

Maternal serum levels of angiogenic markers and markers of placentation in pregnancies conceived with fresh and vitrified-warmed blastocyst transfer

Reljič

Porović

2019

J Assist Reprod Genet

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“…Women who become pregnant after undergoing ovarian stimulation, which results in high levels of estradiol, show significantly lower levels of PAPP-A as compared to women who become pregnant naturally [32,33]. This has been measured at the end of the first trimester in connection with prenatal screening, and the reference interval for normal PAPP-A levels is reduced if the woman underwent ovarian stimulation.…”

Section: Introductionmentioning

confidence: 99%

Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development

Bøtkjær

Pors

Petersen

et al. 2019

J Assist Reprod Genet

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Purpose The IGF signaling cascade exerts important regulatory functions in human ovarian folliculogenesis. The scope of this study was to evaluate the transcription profile of insulin-like growth factor (IGF) genes during human ovarian follicle development and to analyze follicle fluid levels of key IGF proteins. Methods Gene expression profiling was performed with microarray gene analysis. The analysis was assessed from ovarian follicles and granulosa cells (GCs) obtained from isolated stage-specific human ovarian follicles, including preantral follicles, small antral follicles, and preovulatory follicles. Numerous genes involved in the IGF signaling pathway was evaluated and key genes were validated by qPCR from GCs. Protein levels of various IGF components of human follicular fluid (FF) were measured by ELISA and time-resolved immunofluorometric assays (TRIFMA). Results The gene expression levels of PAPPA, IGF2, IGF receptors and intracellular IGF-activated genes increased with increasing follicle size. This was especially prominent in the late preovulatory stage where IGF2 expression peaked. Protein levels of intact IGF binding protein-4 decreased significantly in FF from large preovulatory follicles compared with small antral follicles concomitant with higher protein levels of PAPP-A. The IGF modulators IGF-2 receptor, IGFBPs, stanniocalcins, and IGF-2 mRNA binding proteins were all observed to be expressed in the different follicle stages. Conclusions This study confirms and highlights the importance of PAPP-A regulating bioactive IGF levels throughout folliculogenesis and especially for the high rate of granulosa cell proliferation and expression of key ovarian hormones important in the last part of the follicular phase of the menstrual cycle.

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“…Based on the cause of infertility, it is possible to become pregnant for infertile women by using assisted reproduction technology. Various studies have shown that children born through infertility treatments, particularly IVF, have more congenital anomalies than normal births (7)(8)(9)(10)(11)(12). Prevention of chromosomal abnormalities is only possible via doing the screening tests, detecting malformations, and terming this pregnancy with family consent.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that children who are born via fertility treatment, particularly IVF, have more congenital anomalies than the babies from normal-conception (3-7). Hunt et al (8) showed that PAPP-A levels in those who have been treated by assisted fertility methods, such as IVF, were higher than those who became pregnant spontaneously. It could be a result of the ICSI technique through microinjection that makes bleeding in zona pellucida so that the placenta and biochemical tests in the first trimester can be affected (8).…”

Section: ) Genetic Council After Examinations To Interpret and Justimentioning

confidence: 99%

“…Hunt et al (8) showed that PAPP-A levels in those who have been treated by assisted fertility methods, such as IVF, were higher than those who became pregnant spontaneously. It could be a result of the ICSI technique through microinjection that makes bleeding in zona pellucida so that the placenta and biochemical tests in the first trimester can be affected (8). Human intervention and laboratory conditions in assisted reproductive techniques may affect the fetus growth and development.…”

Section: ) Genetic Council After Examinations To Interpret and Justimentioning

confidence: 99%

See 1 more Smart Citation

Impact of Assisted Reproductive Technology on Embryonic Health Screening Tests: A Case-Control Study

Soltani

Karimi

Khashavi³

et al. 2020

Hormozgan medical journal

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Background: More than one million children throughout the world are born by using fertility techniques. In this process, human intervention and laboratory conditions may have an impact on the growth and development of the fetus. Objectives: The present study aimed to consider the effect of assisted reproductive techniques on the results of embryonic health screening tests. Methods: In this case-control study, among clients who went to the Infertility Center of the Ome Leila Hospital in Bandar Abbas Province, we selected 200 pregnant women who were impregnated via assisted reproductive techniques as the case group and 200 natural pregnant women as the control group by sample random sampling. Checklists were filled out and data analyzed by the SPSS version 21 and chi-square tests by using an interview with pregnant women and investigating the embryonic screening tests. Results: Most of the participants in the study were housewives and had primary infertility. Their BMI was normal. There was no significant difference between the final results of the embryonic screening test in the two groups at the first trimester (P > 0.05). However, in the second trimester, there was a significant difference between them. The positive results were higher in the case group in comparison with the control group (P = 0.001). The mean of all types of screening tests in the first trimester in both groups was not different, significantly (P < 0.05), although in the second trimester, the mean of all the testis, including BHCG (P = 0.006) and AFP (P = 0.018) in both case and control groups, was significantly different. The mean of BHCG and AFP was higher in the case group, while the mean of Estradiol and Inhibin, NB, and NT were not really different (P < 0.05). Conclusions: Our study showed that embryonic screening tests, particularly the BHCG and AFP tests, would be affected by applying the assisted reproductive techniques. For the couples who had a history of infertility and used reproductive methods, screening tests are essential in the first and second trimester.

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Low first-trimester PAPP-A in IVF (fresh and frozen-thawed) pregnancies, likely due to a biological cause

Cited by 13 publications

References 57 publications

Maternal serum levels of angiogenic markers and markers of placentation in pregnancies conceived with fresh and vitrified-warmed blastocyst transfer

Maternal serum levels of angiogenic markers and markers of placentation in pregnancies conceived with fresh and vitrified-warmed blastocyst transfer

Transcription profile of the insulin-like growth factor signaling pathway during human ovarian follicular development

Impact of Assisted Reproductive Technology on Embryonic Health Screening Tests: A Case-Control Study

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