Introduction
Pregnancy loss (miscarriage) is described as the sudden demise of a pregnancy before the fetus reaches viability from the time of conception until 24 weeks of gestation [1234].
Recurrent miscarriages affect 0.4–1% of couples. The risk of abortion is more in early gestations, mostly in the first trimester. There is 22–57% of risk of pregnancy loss within 6 weeks of pregnancy [5].
The pathophysiological process of threatened abortion is linked to uteroplacental damage of vessels at the margin of the placenta with blood accumulating from the chorionic layer to the lining of the uterus [6].
If the subchorionic hematoma extends to the remainder of the placenta, complete abortion will occur a week after the first signs [7].
Recurrent pregnancy loss (RPL) is identified by an ultrasound or histopathological test as two or more losses [12].
The cause of RPL is multifactorial and includes uterine anomalies, immunologic causes, endocrinological disorders, thrombophilia, infections, chromosomal anomalies, and maternal autoimmune diseases. Still, no underlying cause can be found in 50–60% of all RPL. Several forms of miscarriages may be divided as follows: threatened abortion: there is uterine bleeding, and the cervical os stays closed with higher backaches and cramps [8].
Inevitable abortion
In this condition, uterine bleeding is severe and associated with abdominal cramp or lower back pain with cervical changes in the form of opening, dilatation, and effacement. In this type of abortion, pregnancy is impossible to continue [9].
Incomplete abortion
In this type of abortion, some products are expelled, whereas the others are still inside the uterus [10].
Complete abortion
In this type of abortion, all of products of conception have been expelled from the uterus completely, and the symptoms of abortion also subside. The ultrasound confirms the diagnosis of it [9].
Missed abortion
In this type of abortion, embryonic death occurs without any expulsion of the embryo, no symptoms of pregnancy, and on ultrasound, no cardiac activities [9].
Blighted ovum
This is an embryonic pregnancy. An empty sac occur when the fertilized egg implants into the uterine cavity, but the development of the fetus never begins [9].
Septic abortion
In this type of abortion, there is pelvic infection on top of any type of abortion [11].
Platelets, commonly known as thrombocytes, are responsible for decreasing blood loss by forming blood clots, avoiding infection, and facilitating recovery. When any damage occurs, platelets are inserted to cover the damage and hormone receptors are released into the blood to draw protein coagulation factors to better heal the damage. Megakaryocytes, which are large precursor cells, are formed in the bone marrow. The platelets themselves released from the bone marrow into the bloodstream are actually a part of the megabytes. Younger platelets are usually larger than older platelets, and mean platelet volume (MPV) represents the average age of platelets [12].
MPV is a measure of the average size of your platelets, a type of blood cell that helps to prevent bleeding. MPV is particularly important in determining the cause of thrombocytopenia (a low platelet count) or thrombocytosis (a high platelet count), and it can be a useful diagnostic tool even if the platelet count is normal [13].
Platelets are particularly important blood cells in hemostasis. Granules with more mediators are expected to be larger platelets and to be more active. MPV is the most frequently used indicator in previous studies as an activation point. Increased MPV was related to heart disease, diabetes mellitus, atherosclerosis, hypertension, and in particular to polycystic ovarian disease [14].
In a number of studies, variations in platelet activity and volume were assessed in both normal and complicated pregnancy (especially preeclampsia and intrauterine growth retardation) [15].
Platelets have a nuclear discoid structure and a life-long fairly stable morphology. Recent studies have shown that changes in the morphological structure of platelets lead to increasing platelet activity [16].
Various physiological and pharmacological agents may also alter the behavior of platelets. Although platelet defense and the regulation of bleeding are the most common functions of the platelet, platelets often play a part in the physiopathogenesis of thromboembolic disorders [17].
Platelets often function in placenta growth, particularly in remodeling of the spiral artery. [18].
Pregnancy is a condition with hypercoagulation. Platelets play a critical function in maintaining the equilibrium between prothrombotic activity and placental growth for prolonged pregnancy [19]. Imbalance can lead to an increased hemostasis. This will lead to uteroplacental artery thrombosis and pregnancy failure. There have been improvements in platelet numbers and function up to 12 weeks after a miscarriage.
However, it was claimed that environmental and hormonal causes may be the cause for these change as well as pregnancy and abortion itself. [20].
The increased volume of platelet is a direct indicator of the increased synthesis of the platelet. Increased MPV reflects increased circulatory platelets and the aggregation ability of platelets [21].
Materials and methods
This prospective research was performed at Al Zahraa University Hospital in Gynecology and Obstetrics Department and the General Kafer Alzyat Hospital. The study is approved by Al-Azhar Faculty of Medicine for girls ethical committee. An informed consent was obtained from all patients groups before getting them involved in the study. This study included 120 pregnant women in first trimester coming for antenatal care from Marsh 2017 to Februarys 2018 who were divided in to two groups: the study group included 60 patients with unexplained recurrent miscarriage, and the control group included 60 patients with no history of abortion.
Every woman received informed consent, and all subjects were provided verbal explanation of the purpose of the study and the method of sample collection.
All patients were in 1st trimester. Gestational age on the first day of last menses (LMD) was calculated or by ultrasonography measurement in women with unknown LMD.
Inclusion criteria were as follows: patients aged 18–40 years; body mass index not greater than 30 kg/m2; no history of use of alcohol or smoking; no chronic disease, such as hypertension, diabetes mellitus, vasculitis, or thyroid disorders; no hematological or rheumatological conditions, defined as no history of thrombosis or frequent abortion; and no uterine anomaly on ultrasonography.
Normal parental karyotype, thyroid stimulating hormone, and antiphospholipid antibody, anticardiolipin antibody, lupus anticoagulant, prothrombin time, antithrombin 3 and thrombophilia testing included proteins C and S, fasting blood sugar, and random blood sugar.
Full history was taken from the first visit, and examination also was done.
Sample collection and its analysis was done for both groups. They were investigated by serum pregnancy test and for complete blood count (CBC) [mean corpuscular volume (MCW), red blood cell distribution distance, white blood cell (WBC), platelet (PlT), and MPV]. Auto-blood counter was used to measure CBC within one hour (CELL-DYN Sapphire, Abbott, Illinois, USA). All blood samples were received from the antecubital vein into Vacutainer System (Becton Dickinson, Franklin Lakes, NJ, USA), containing 0.04 ml 7.5% K3 ethylene diamin tetra-acetic acid (K3EDTA). The MPV, Hb, WBC, and Plt range were determined as 6.9–10.6 fl, 11.5–16.5 g/dl, 3.7–10.1×103/mm3, and 155–366×103/mm3, respectively [22].
Transabdominal or transvaginal U/S was done by ultrasound Mindray DP5 in the first trimester to detect gestational age, fetal heartbeat, single or multiple pregnancy crown rumbling length, amount of liquor, reaction of placenta, any anomalies, and amniotic fluid index by measuring the deepest pocket without umbilical cord or fetal materials measured in vertical dimension (normal 2–8 cm) [23]. Then all data were documented, tabulated, and statistically analyzed.
Statistical analysis
The collected data were input into a computer and statistically analyzed using the Statistical Social Science Package version 16.0 (SPSS for Windows; Chicago, Illinois, USA) program. Software coding was conducted for statistical calculations.
Qualitative (categorical) data were expressed as frequencies and percentages. The χ2 test and the Fisher's exact test were conducted for comparisons between groups in categorical data.
Quantitative (numerical) data were represented as mean and SD, student tests were used to detect differences between groups normally distributed or interquartile and interquartile ranges, and Mann–Whitney tests were used to detect differences between groups not normally distributed.
Spearman correlation coefficients were used to estimate relationship.
The study results were considered significant when P value was lower than 0.05, and extremely significant when P value was lower than 0.01, and P value higher than 0.05 was considered nonsignificant. All P values were double tailed.
The following statistical tests and parameters were used:
Mean
∑χ is the sum of the values.
n is the number of participants.
SD: is the sum of the square of the differences of each observation from the mean.
The χ2 test:
This test was used to compare two groups regarding the distribution of different variables.
Where: O is the observed value; E is the expected value; the t statistic to test.
Whether the means are different can be calculated as follows:
Result
[Table 1] shows that age, BMI, gestational age, and systolic and diastolic blood pressures were similar between the control pregnant women and patients with RPL, with no significant difference; however, pregnant women with RPL had significantly higher gravidity (P=0.000) and lower parity (P=0.046) (Table 1).
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Table 1: Comparison between control and studied group regarding demographic data
[Table 2] shows there was a statistically significant difference between the groups regarding MPV, with P value 0.002 (Fig. 1).
Table 2: Comparison between control and studied group regarding CBC
Figure 1: Receiver operating characteristic curve for mean platelet volume between study and control group (area under curve) of 77.5%.
The pervious receiver operating characteristic curve shows that the best cutoff point for MPV to differentiate between cases and controls was found greater than 9.5, with sensitivity of 91.67% and specificity of 60.0%, with area under curve of 77.5%.
[Table 3] shows that the sensitivity, specificity, positive predictive value, and negative predictive value of the MPV were 91.67, 60.00, 69.6, and 87.8%, respectively.
Table 3: Cutoff point of the MPV and its sensitivity, specificity, positive predictive value, and negative predictive value
Discussion
Abortion is known as sudden pregnancy loss before the 20th gestational week and is the most prevalent complication of the first trimester [4].
RPL is identified by an ultrasound or histopathological test as two or more losses [12].
Platelets are highly essential blood cells in hemostasis. Larger platelets are believed to have and to be more active granules with more mediators. MPV is the most common indicator used in previous studies to mark activation. Higher MPV was linked, in particular, with coronary heart disease, diabetes mellithus, atherosclerosis, hypertension, and polycystic ovarian syndrome [14].
In thrompotic diseases, platelets also play a leading role in physiopathogenesis [24].
Pregnancy is a condition of hypercoagulation. For the continuation of a pregnancy, platelets play a delicate function in preserving the equilibrium between prothrombotic tendance and placental development [19]. Changes in platelet number and function were recorded for up to 12 weeks after a miscarriage [20]. The decreased platelet volume is a strong indication that platelet synthesis is increasing. Increased MPV reflects increased circulatory platelets and the aggregation ability of platelets [16]. Many screening tests on frequent pregnancy loss are expensive, so this research supports the ability of MPV in an easy and common CBC routine investigation to predict thromboembolic danger in repeated miscarriage. Significantly higher MPV values were observed in patients with recurrent loss in the current study. The present research indicates that there is no major variation in the P value between the tested and the control groups in CBC studies, except for MPV (0.002) (Table 2).
These results agree with the study performed by Yilmaz et al. (2015) [25], which studied 120 patients with unexplained recurrent miscarriages (group 1) who were compared with data from 120 controls (group 2). MPV increased in patients with RPL than those of patients in the control group, and mean volume platelet rates in group 1 were considerably higher (9.45±1.09 fl) than in group 2 (7.63±0.52 fl) (P=0.001).
Moreover, such findings are compatible with the analysis carried out by Ragab et al. (2013) [26], which determined the importance of platelet indices in their analysis and red cell indices for the prediction of RPL. They studied 80 pregnant women who were divided into two group: 40 pregnant people with an unexplained history of RPL and 40 controls. The total platelet concentration for pregnant women with a background of RPL was significantly higher than in the control group (P=0.02).
However, the results do not agree with the study that was conducted by Kaplanoglu et al. (2015) [27], which examined the MPV to predict spontaneous miscarriage and to assess any variations in its values during a biochemical and clinical pregnancy. They studied 305 patients with spontaneous miscarriages and 168 control subjects, and showed that the MPV was higher for healthy pregnant women than for women with miscarriages. They also showed that the MPV was statistically significantly lower in the miscarriage community (8.99±1.47 fl) than in the control group (9.66±1.64 fl) (P<0.001). The cutoff point for MPV to differentiate between cases and controls was found to be greater than 9.5 fl, with 91.67% sensitivity and 60.0% specificity, with an area under curve of 77.5%.
This study shows that the MPV had sensitivity of 91.67% and specificity of 60.0% in the prediction of abortion in the first trimester (Table 3).
Conclusion
In this study, MPV values were substantially higher in women with repeated miscarriages than in the control group. Therefore, it can be used as a predictor for early pregnancy loss. In the research group, higher MPV values support the role of thromboembolic events in triggering repeated miscarriages. MPV measurements can be done as an easy tool to estimate repeated failure of pregnancy.
Recommendations
- This study recommended that MPV of pregnancy can be used for the early prediction of abortion with sensitivity of 91.67% and specificity of 60.0%.
- Further studies must be done to increase the efficiency of prediction of abortion in the first trimester in a larger number of patients.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgements
Place of the study: Department of Gynecology and Obstetrics at Al Zahraa University Hospital and Kafer Alzyat General Hospital in antenatal clinic from March 2017 to February 2018.
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