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Year : 2022  |  Volume : 25  |  Issue : 7  |  Page : 975-978

Ischemia-Modified Albumin (IMA) levels in ectopic pregnancy and early pregnancy loss

1 Department of Obstetrics and Gynecology, University of Health Sciences Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital, Istanbul, Turkey
2 Department of Biochemistry, University of Health Sciences Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital, Istanbul, Turkey
3 Department of Anesthesiology and Reanimation, University of Health Sciences Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital, Istanbul, Turkey

Date of Submission28-Apr-2021
Date of Acceptance25-May-2022
Date of Web Publication20-Jul-2022

Correspondence Address:
Dr. K Dogan
Tevfik Saglam Street, No: 11, Zuhuratbaba, Bakirkoy, Istanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njcp.njcp_1464_21

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Background: IMA is a novel marker to consider in ischemic conditions. The initial stages of pregnancy represent a physiological ischemic status. IMA levels may be changed when there is suspicion of early pregnancy complications because of increased oxidative stress. Aim: We aimed to determine and compare IMA values in cases of ectopic and healthy pregnancies as well as early pregnancy loss. Methods: This prospective case control study population (n = 91) consisted of early pregnancy loss (n = 28), ectopic pregnancy (n = 28), and an intracavitary early healthy pregnancy (n = 35). The serum IMA levels were compared in these groups. Results: Demographic parameters were similar and there was no significant difference between the three groups in terms of serum IMA concentrations. Conclusion: We suggested that IMA cannot be used clinically for the diagnosis and follow up of early pregnancy complications during the first five to six gestational weeks.

Keywords: Early pregnancy loss, ectopic pregnancy, IMA

How to cite this article:
Dogan K, Helvacioglu C, Baghaki S, Kural A, Dogan M. Ischemia-Modified Albumin (IMA) levels in ectopic pregnancy and early pregnancy loss. Niger J Clin Pract 2022;25:975-8

How to cite this URL:
Dogan K, Helvacioglu C, Baghaki S, Kural A, Dogan M. Ischemia-Modified Albumin (IMA) levels in ectopic pregnancy and early pregnancy loss. Niger J Clin Pract [serial online] 2022 [cited 2022 Sep 28];25:975-8. Available from:

   Introduction Top

Ischemia-modified albumin (IMA) is a novel sensitive biomarker and a modified form of albumin which loses its transitional metal-binding property when exposed to oxidative stress due to various reasons, such as hypoxia, acidosis, or ischemia.[1],[2] IMA was first studied in myocardial ischemia and cerebrovascular accidents.[3],[4],[5] It was also reported to increase in pregnancy, during early and late pregnancy complications such as first trimester pregnancy loss, ectopic pregnancy, pre-eclampsia, and gestational diabetes mellitus.[6],[7],[8],[9] Studies have shown that IMA may be used as a marker of hypoxic intrauterine environment and oxidative stress, both of which hinder physiological trophoblast development significantly in early pregnancy.[8],[9],[10],[11] First trimester pregnancy loss affects approximately 10–31% women of childbearing age.[12] The pathogenesis of early miscarriage is not yet clear, but some studies have shown that it might be due to pathological villous changes and disorders in placentation.[13] Placentation disorders may cause a more ischemic environment, and contribute to oxidative stress and defective placentation in early pregnancy, which may all result in early pregnancy loss.

Ectopic pregnancy, another first trimester pregnancy complication in which the fertilized ovum implants outside the uterine cavity, affects approximately 1–2% of all pregnancies.[14] It is still one of most important causes of pregnancy-related maternal morbidity and mortality.[15],[16] For this reason, prompt diagnosis of ectopic pregnancy in early gestation is particularly important, especially in developing countries with inadequate prenatal care to plan early treatment.[17] Current diagnostic tools such as ultrasonography and serum β-HCG detection are insufficient in 8–31% of the cases, due to lack of determination of pregnancy location during the first examination.[18],[19] Although several biomarkers were identified for its early diagnosis, results were conflicting and most of them were unfit for clinical use.[20],[21]

Ectopic pregnancies and first trimester pregnancy loss are known to cause oxidative stress, like other many reproductive complications such as pre-eclampsia, fetal growth restriction, and preterm labor.[22],[23] Since oxidative stress is higher in ectopic pregnancy and first trimester pregnancy loss compared with normal pregnancy, in this study, we aimed to determine and compare IMA values in cases of ectopic and healthy pregnancies as well as early pregnancy loss.

   Methods Top

This prospective case control study was carried out in the department of Obstetrics and Gynecology, University of Health Sciences Bakirkoy Dr. Sadi Konuk Teaching and Research Hospital between April 2015 and September 2016 with the approval of the local Ethics Committee (Approval number: 2015/13/03). All participants signed written informed consent forms.

The study population (n = 91) consisted of women with five to six weeks of pregnancy who were admitted to our tertiary center to standardize the study. We classified the patients in three groups: those with an intracavitary early healthy pregnancy women attending for antenatal care (n = 35), those with an ectopic pregnancy (n = 28) and those who aborted or were admitted for dilatation and curettage due to absence of fetal cardiac activity (n = 28) applying to our emergency outpatient clinic. The sample size was not calculated in our study, as there were 91 IMA kits that we could use, but the power of our study was found to be 81% in the G-power program according to the mean IMA values of the groups.

Serum samples were collected at the initial visit before treatment. If the clinician was unable to make a diagnosis on this first visit even after a vaginal ultrasound, the patient was admitted and followed up until a diagnosis of a viable intrauterine pregnancy or missed abortion or EP was confirmed. All failed pregnancy diagnoses were histologically confirmed. Ectopic pregnancy was diagnosed by β-HCG levels over 1500 IU/mL, lack of an intrauterine or cervical canal pregnancy, and a visible gestational sac in either the adnexa or tuba with transcervical ultrasonographic examination, which were performed first by an obstetrician. All patients received medical or surgical treatments, as necessary. All ectopic pregnancies were confirmed, and those with controversial diagnoses were excluded from the study.

The demographic data of each group such as age, body mass index (BMI), parity, level of education along with gestational age by last menstrual period and ultrasound were recorded.

Women with a history of ischemic diseases, diabetes mellitus, heart diseases, hypertension or any other known medical conditions, current smokers, and multiple pregnancies, were excluded from the study.

Gynecologic and transvaginal ultrasonographic examinations were performed by the same physician (K.D), using Voluson E 6 ultrasonography equipment (General Electric Healthcare, Buckinghamshire, United Kingdom).

Five milliliters of maternal blood were collected from each participant into a heparinized tube for IMA analysis before further invasive procedures, allowed to clot and centrifuged at 4000 g for 10 minutes. Serum was stored at -80 C before analysis. IMA was measured with a double-antibody sandwich enzyme-linked immune-sorbent assay (ELISA) kit (East Biopharm Co. Ltd., Hanngzhou, China). IMA-specific monoclonal antibody enzyme was added to each well, which were pre-coated with human IMA monoclonal antibodies. The samples were incubated, and biotin-labeled IMA antibodies combined with streptavidin HRP were added to form immune complexes. The samples were incubated again and washed to remove the uncombined enzyme. Chromogen solutions A and B were added to produce a blue color change. An acid solution was added to terminate the reaction and a color change to yellow was finally observed. The optical density was measured at a wavelength of 450 nm using a Perkin Elmer 1420 VICTOR 3 instrument (Waltham, USA).

Statistical analysis

Descriptive analyses were employed to define continuous variables in the data such as mean, median, mode, and standard deviation. Two or more categorical, independent, and normally distributed variables were compared with one-way Analysis of Variance (ANOVA) test. The significance level was determined as 0.05. MedCalc Statistical Software version 12.7.7 (MedCalc Software bvba, Ostend, Belgium;; 2013) was used for all statistical analyses.

   Results Top

There was no significant difference between the groups in terms of demographic parameters, including age, BMI, parity, and gestational age by LMP/ultrasound which proved that both control and experimental groups were homogeneous [Table 1].
Table 1: The comparison of demographic data and levels of IMA between study groups

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The main finding of our study is that there was no significant difference between the three groups in terms of serum IMA concentrations (p > 0.05) which does not justify IMA to be a marker of early pregnancy complications.

   Discussion Top

The timely and accurate prediction of early pregnancy outcome, such as healthy pregnancy, ectopic pregnancy, and early pregnancy loss in pregnant women with vaginal bleeding or not bears significance for clinical management, which can be expensive and involve long-term follow up with serial β-HCG assessment, ultrasonographic examination and possibly, diagnostic laparoscopy due to risk of ectopic pregnancy. All those procedures may become tiresome for the patient.[20] On the other hand, ectopic pregnancy is still one of the important health problems due to the maternal morbidity and mortality risk. Therefore, distinguishing ectopic pregnancy from abortion and healthy intrauterine pregnancy in the first weeks of pregnancy can be of great benefit in terms of early diagnosis and treatment. For this reasons, many markers have been studied and some studies have suggested that IMA may be a helpful marker for the diagnosis of early pregnancy complications due to the intrauterine hypoxic environment that occurs during early pregnancy.[20],[21],[22],[23]

But our results indicate that IMA does not reliably differentiate between possible pregnancy failure, ectopic pregnancy or a healthy intrauterine pregnancy, especially in the first five to six gestational weeks. Contrary to our results, only a few reports are available on IMA concentrations in pregnancies complicated by early pregnancy loss and ectopic pregnancy. Cengiz et al. demonstrated increased serum IMA concentrations in early pregnancy loss and Bozkaya et al. found higher serum IMA concentrations in ectopic pregnancies compared to healthy ones.[24],[25] These conflicting results may be also due to the small number of cases and the fact that our study, unlike other studies, only included the first five to six weeks of pregnancy. The major limitation of our study was the small sample size; therefore, these inconsistent findings should be further investigated with larger size of studies.

Similar to IMA, several other biomarkers including Activin-A, Follistatin, Inhibin A, Vascular Endothelial Growth Factor (VEGF), Pregnancy-Spesific-B-1-Glycoprotein, and Pregnancy-Associated Plasma Protein-A (PAPP-A) have been studied for differentiating between ectopic and abnormal intrauterine pregnancy with conflicting results.[15],[16],[21]

In conclusion, IMA is a novel marker to consider in ischemic conditions. The fact that initial stages of pregnancy represent a physiological ischemic status can induce obstetrician to study IMA levels when there is suspicion of early intrauterine pregnancy. However, literature data and our study yield controversial results regarding the predictive value of IMA for missed abortus, or ectopic pregnancy. Larger sample sized studies should be conducted to further explain the role of IMA in complications during the first five to six gestational weeks.

Our study shows that IMA cannot be used clinically for the diagnosis and follow-up of early pregnancy complications.


The authors are indebted to the nurses, residents, and consultants from the Department of Obstetrics & Gynecology, who were involved in the management of patients, and to all patients who participated in the study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Shen XL, Lin CJ, Han LL, Lin L, Pan L, Pu XD. Assessment of ischemia-modified albumin concentrations for emergency room diagnosis of acute coronary syndrome. Int J Cardiol 2011;149:296-8.  Back to cited text no. 1
Coverdale JPC, Katundu KGH, Sobczak AIS, Arya S, Blindauer CA, Stewart AJ. Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding. Prostaglandins Leukot Essent Fatty Acids 2018;135:147-57.  Back to cited text no. 2
Gunduz A, Turedi S, Mentese A, Altunayoglu V, Turan I, Karahan SC, et al. Ischemia-modified albumin concentrations in cerebrovascular accidents. Am J Emerg Med 2008;26:874-8.  Back to cited text no. 3
Anwaruddin S, Januzzi JL Jr., Baggish AL, Lewandrowski EL, Lewandrowski KB. Ischemia-modified albumin improves the usefulness of standard cardiac biomarkers for the diagnosis of myocardial ischemia in the emergency department setting. Am J Clin Pathol 2005;123:140-5.  Back to cited text no. 4
Turan T, Akyüz AR, Sahin S, Kul S, Yilmaz AS, Kara F, et al. Association between the plasma levels of IMA and coronary atherosclerotic plaque burden and ischemic burden in early phase of non-ST-segment-elevation acute coronary syndromes. Eur Rev Med Pharmacol Sci 2017;21:576-83.  Back to cited text no. 5
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Rossi A, Bortolotti N, Vescovo S, Romanello I, Forzano L, Londero AP, et al. Ischemia-modified albumin in pregnancy. Eur J Obstet Gynecol Reprod Biol 2013;170:348-51.  Back to cited text no. 10
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Horne AW, Duncan WC, Critchley HO. The need for serum biomarker development for diagnosing and excluding tubal ectopic pregnancy. Acta Obstet Gynecol Scand 2010;89:299-301.  Back to cited text no. 17
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Shaunik A, Kulp J, Appleby DH, Sammel MD, Barnhart KT. Utility of dilation and curettage in the diagnosis of pregnancy of unknown location. Am J Obstet Gynecol 2011;204:130.e1-6.  Back to cited text no. 19
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Daponte A, Pournaras S, Zintzaras E, Kallitsaris A, Lialios G, Maniatis AN, et al. The value of a single combined measurement of VEGF, glycodelin, progesterone, PAPP-A, HPL and LIF for differentiating between ectopic and abnormal intrauterine pregnancy. Hum Reprod 2005;20:3163-6.  Back to cited text no. 21
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Bozkaya G, Karaca I, Fenercioglu O, Yildirim Karaca S, Bilgili S, Uzuncan N. Evaluation of maternal serum ischemia modified albumin and total antioxidant status in ectopic pregnancy. J Matern Fetal Neonatal Med 2019;32:2003-8.  Back to cited text no. 24
Cengiz H, Dagdeviren H, Kanawati A, Suzen Çaypinar S, Yesil A, Ekin M, et al. Ischemia-modified albumin as an oxidative stress biomarker in early pregnancy loss. J Matern Fetal Neonatal Med 2016;29:1754-7.  Back to cited text no. 25


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