A study on stress, depression and NK cytotoxic potential in women with recurrent spontaneous abortion.
ABSTRACT It has been recognized that acute and chronic stress has an impact on the immune system. Acute stress may have a stimulating effect on the immune system, while in the case of chronic stress specially depression, the immune system could be down-regulated. However, an association between depression and a higher number of circulating white blood cells with increased activity has been reported. Elevation in immune cell numbers and alteration in cytokine profiles are documented for women suffering sporadic spontaneous abortion with a high stress score. In spite of these contradictory results and to make a new approach in immunological (NK activity) as well as psychological parameters (stress/depression) in women suffering from recurrent spontaneous abortion (RSA) the present study was planned. Forty-five women with a history of RSA and a matched control group were participated in this study. A questionnaire for life events known as life change units (LCU) and the Beck Depression Inventory (BDI) outlines were used and the socio-psychological events were recorded after visiting and interview. Fresh peripheral blood lymphocytes were taken as a source of NK activity and K562 cell line were used as NK sensitive target. The experiments were performed and the cells were analyzed with a flow-cytometer. The stress and the depression scores were determined 245+/-83.6 and 27.6+/-8.8 for women with RSA and 224+/-79.6 and 19.4+/-7.1 for non-RSA group respectively. There was an association between life stress scores and depression scores with r=0.65 and P=0.000 for RSA women. A correlation with r =-0.34 and P = 0.02 was found between depression scores and NK cytotoxicity. The Pearson correlation test showed a lack of relationship between high stress score and NK activity with the r=0.011 and P=0.95, but r=-0.30 and P=0.072 was obtained for high depression scores and NK cytotoxicity. Therefore, it could be suggested that in the case of women with a history of recurrent spontaneous abortion, modulation for immunological parameters (i.e immunotherapy) concurrently with managing psychological aspects (stress/depression) could be modified for the benefit of the patients.
[show abstract] [hide abstract]
ABSTRACT: Stress is thought to be abortogenic and psycho-neuro-immunological pathways have been suggested to be involved in triggering miscarriages. From experiments in pregnant mice exposed to stress some insights into the underlying mechanisms have been gained, delineating immunological imbalances as a cause of pregnancy failure. In order to test the validity of the conclusions drawn from murine experiments and the role of stress in human pregnancy loss, the following study was performed. We used an established perceived stress questionnaire and measured the stress score of women with a confirmed diagnosis of first trimester spontaneous abortion (n = 94). Decidual tissue was investigated by immunohistochemistry and in-situ hybridization to detect the presence and distribution of immunocompetent decidual cells [CD56(+) natural killer (NK) cells, CD8(+)and CD3(+) T cells, tryptase(+) mast cells (MCT(+)) and tumour necrosis factor (TNF)-alpha(+) cells]. The patient cohort was divided into women experiencing low or high levels of stress. In the decidua of women with high stress scores we observed significantly higher numbers of MCT(+), CD8(+) T cells and TNF-alpha(+) cells per mm(2) tissue (P < or = 0.05). No significant differences between individuals with lower or higher stress scores could be observed with respect to decidual CD56(+) NK and CD3(+) T cells. Using a questionnaire to score perceived stress in humans may be a valid approach to assess non-biased stress scores. Stress-triggered abortion in humans, identified by a questionnaire, can be linked to immunological imbalances.Human Reproduction 07/2001; 16(7):1505-11. · 4.47 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: The study aim was to clarify the role of anxiety and depression on the outcome in assisted reproductive treatment. Previous studies on this topic have shown contradicting results, which may have been caused by population characteristics, the design of the study, or small sample sizes. In a multicentre prospective study, 291 out of 359 (81%) consecutively invited women agreed to participate. Before down-regulation by means of gonadotrophin-releasing hormone (GnRH) analogues in a long IVF protocol, patients were asked to complete the Dutch version of the State and Trait Anxiety Inventory to measure anxiety, and the Dutch version of the Beck Depression Inventory (BDI) to measure depression. Multiple logistic regression analysis was used to analyse known predictors of pregnancy and psychological factors and their relationship with treatment outcome. A significant relationship was shown between baseline psychological factors and the probability to become pregnant after IVF/intracytoplasmic sperm injection (ICSI) treatment, controlling for other factors. State anxiety had a slightly stronger correlation (P = 0.01) with treatment outcome than depression (P = 0.03). Pre-existing psychological factors are independently related to treatment outcome in IVF/ICSI, and should therefore be taken into account in patient counselling. Psychological factors may be improved by intervention, whereas demographic and gynaecological factors cannot. Future studies should be directed towards underlying mechanisms involved and the role of evidence-based distress reduction in order to improve treatment results.Human Reproduction 08/2001; 16(7):1420-3. · 4.47 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: It is by now widely recognized that acute and chronic stress have an impact on the immune system. Acute stress may have a stimulating effect on the immune system, while in the case of chronic stress--and in particular in depression--the immune system may be down-regulated. However, there is considerable individual variability in the immune response to stress. This seems to a large extent to be determined by the subject's way of dealing with stress. The perception and evaluation of a stressor and the specific ways of stress coping may in different ways be related to various aspects of the stress response: sympathetic nervous system (SNS) activation and activation of the hypothalamic-pituitary-adrenal (HPA) axis, both systems affecting the immune system. Prolonged exposure to stressors or to severe life stresses may outweigh the person's coping resources leading to feelings of depression. The affective changes with the accompanying changes in the HPA axis are one of the hypothesized mechanisms underlying the immune changes in depression. It should be noted that the relationship between depression and immunity is affected by several other factors, such as gender and age and other personal resources. Increasing the subject's abilities to cope with stress and to reduce the negative affect by psychological interventions may on the other hand have a beneficial effect on the immune system.Psychiatry Research 02/1999; 85(1):7-15. · 2.52 Impact Factor
Copyright © 2006, IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY. All rights reserved. 9
Iran J Allergy Asthma Immunol
March 2006; 5(1): 9-16
A study on Stress, Depression and NK Cytotoxic Potential
in Women with Recurrent Spontaneous Abortion
Alireza Andalib, Abass Rezaie, Farzad Oreizy, Katayoun Shafiei, and Sima Baluchi
Department of Immunology and Psychology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
Received: 7 October 2005; Received in revised form: 26 February 2006; Accepted: 28 February 2006
It has been recognized that acute and chronic stress has an impact on the immune
system. Acute stress may have a stimulating effect on the immune system, while in the case
of chronic stress specially depression, the immune system could be down-regulated.
However, an association between depression and a higher number of circulating white blood
cells with increased activity has been reported. Elevation in immune cell numbers and
alteration in cytokine profiles are documented for women suffering sporadic spontaneous
abortion with a high stress score. In spite of these contradictory results and to make a new
approach in immunological (NK activity) as well as psychological parameters
(stress/depression) in women suffering from recurrent spontaneous abortion (RSA) the
present study was planned.
Forty-five women with a history of RSA and a matched control group were participated
in this study. A questionnaire for life events known as life change units (LCU) and the Beck
Depression Inventory (BDI) outlines were used and the socio-psychological events were
recorded after visiting and interview. Fresh peripheral blood lymphocytes were taken as a
source of NK activity and K562 cell line were used as NK sensitive target. The experiments
were performed and the cells were analyzed with a flow-cytometer.
The stress and the depression scores were determined 245±83.6 and 27.6±8.8 for
women with RSA and 224±79.6 and 19.4±7.1 for non-RSA group respectively. There was
an association between life stress scores and depression scores with r=0.65 and P=0.000 for
RSA women. A correlation with r = -0.34 and P = 0.02 was found between depression
scores and NK cytotoxicity. The Pearson correlation test showed a lack of relationship
between high stress score and NK activity with the r=0.011 and P=0.95, but r= -0.30 and
P=0.072 was obtained for high depression scores and NK cytotoxicity. Therefore, it could
be suggested that in the case of women with a history of recurrent spontaneous abortion,
modulation for immunological parameters (i.e immunotherapy) concurrently with managing
psychological aspects (stress/depression) could be modified for the benefit of the patients.
Key words: Cytotoxicity, Immunologic; NK cells; Flow cytometry; Spontaneous
abortion; Stress; Suppression
Corresponding Author: Alireza Andalib, PhD;
Department of Immunology, Isfahan University of Medical Sciences,
Isfahan, Iran. Tel: (+98 311) 792 2431, Fax: (+98 311) 668 8597,
The psycho-neuro-immuno-endocrine network has
A. Andalib, et al.
10/ IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY Vol. 5, No. 1, March 2006
been proposed to be involved in abortion.1,2 It has been
reported that some patients suffering from recurrent
abortion may present with psychological disorder.3
Some investigators tried to explain the influence of
psychological stress on pregnancy outcome by elevated
stress hormones (catecholamines, cortisol) that reduce
fetal vascularization and oxygen supply which may
possibly induce abortion.4 Furthermore, with regard to
immunological parameters Arck et al demonstrated
significant increase in the numbers of CD8+ T cells, as
well as TNFα and Tryptase+ mast cells in the deciduas
of women suffering sporadic spontaneous abortion with
a high stress score compared with control group.1
Chronic stress can lead to fewer circulating B, T and
NK cells, as well as decreasing proliferation responses
of lymphocytes and reducing NK cell activity.5,6 In
contrast to the down regulation with the longer lasting
chronic stress, acute stress such as examination seems
rather to have an activating effect on immune
parameter.5,7 An increase in IL-1β, IL-2 and soluble
ICAM-1 plasma concentrations was seen following
experiencing acute stress.8 Depression is also
associated with a higher number of circulating white
blood cells, primarily neutrophils and total number of
lymphocyte (NK, B and T cells) and their activities.6 In
addition, depression was shown to be associated with
alteration in cytokine profiles. Immune system cells, in
particular lymphocytes and macrophages have specific,
high-affinity and saturable binding sites for most
neuro-endocrine peptides. However, studies of isolated
immune cells in culture show that hormones have a
variety of effects on these cells. For example, estrogen
decreases cell-mediated immunity and suppressor cells
which permit enhanced B lymphocyte activation and
antibody production. In animal models, hormone
effects in immune system have been shown to be
complex with different effects depending on the strain
and the specific disease.9,10 NK cells are element of
innate immune system and account for 5-15% of
peripheral blood lymphocytes population.11 These cells
have the ability to both lyse target cells and provide an
early immune regulation cytokines without prior
immunization.11,12 New insight into NK biology has
suggested major role of NK cells in infection control
and uterine function in pregnancy.12 Recent studies
show that NK cells play important role in the control of
migration and differentiation of trophoblasts and
implantation of embryo through secreting various
cytokine.13,14. Several recent studies have indicated that
RSA is associated with and alteration in endometrial
and peripheral leukocyte population. In addition,
significant higher number of activated leukocytes have
been shown in deciduas and specially increased in NK
cell population in relation with pregnancy failure.15,16
Therefore, the present study has focused on immuno-
logical and psychological aspects to have a new
approach for looking at these aspects simultaneously, it
is hoped that medical laboratory available tests as well
as psychological care in clinic would benefit patients
who suffer socio-medical problems.
MATERIALS AND METHODS
Forty-five women with history of three or more
RSA were included, women with anatomical, genetical,
hormonal or infection causes were excluded after
visiting and interview by specialist. In addition, a non-
RSA control group was included in the present study
consisting of forty-five healthy multiparous women
with no history of abortion.
consideration, the specialist has interviewed selected
cases, regarding stress as well as depression. The
assistant co-worker in this project performed interviews
and filled in all the valid questionnaire forms.
Stress Score Assessment
Holmes and Rahe social re-adjustment rating scale
was used for a total amount of stress that an individual
might have experienced. Stress in women was recorded
as a valid approach to assess non-biased stress scores
based on life stress questionnaire. Therefore, by adding
up the relative stress values, known as Life Change
Units (LCU), for various events the total score
determined. Persons with a low stress tolerance may
find themselves overstressed with a score of 150. A
score of 250 or more is considered high. The test is
used to determine disease susceptibility. With a score
of 150 or less an individual has a 37% chance of
becoming seriously ill. Between 150 to 300, it jumps to
51%, with over 300 scores; there is an 80% chance of a
serious illness in the next 2 years.17,18
The scale of scores for stress assessment stands for
150; which means an individual would be glad and/or
normal, but there might be a slight risk of illness (but
still needs to take care of his/herself). The scores
between 150 and 250 would be considered as low stress
value, and the shift to 300 scores would be supposed
for mild to moderate condition. The score 300+ means
NK Cytotoxic Potential in Spontaneous Abortion
Vol. 5, No. 1, March 2006 IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY /11
extreme care and/or at a greatly increased risk of
serious illness. Questionnaire life events have been
considered based on the Arck et al 2001.1,17
The Beck Depression Inventory (BDI) is a 21 item
self-report rating inventory measures characteristic
attitudes and symptoms of depression. This inventory is
a self-administered 21 item self-report scale measuring
supposed manifestations of depression. The BDI
demonstrates high interval consistency, with alpha
coefficient of 0.88 and 0.81 for psychiatric and non-
psychiatric populations, respectively. Clinical rating for
psychiatric patients are reported as high to moderate
ranging from 0.55 to 0.96 with r = 0.72. The highest
score on each of the twenty-one questions is three, the
highest possible total for the whole test is sixty-three,
and the lowest possible score for the whole test is zero.
Total score levels for depression assessment are as
follows: 5-9 would be considered normal, 10-18 is mild
to moderate depression, 19-29 stands for moderate to
severe depression and 30-63 considered for severe
Natural Killer Potential Assessment
Peripheral blood was collected in EDTA and then
peripheral blood lymphocytes (PBL) were separated
using a Ficoll-Hypaque
(lymphoprep; Norway). Lymphocytes were isolated,
washed and brought to a concentration of 5x 105
cells/ml in RPMI 1640 + 10% FCS (Gibco, Germany).
The K562 tumor cell line (obtained from pasteur
Institute-Iran), maintained in continuous suspension
culture in RPMI 1640+10% FCS, supplemented with
L-glutamine, 100 µg/ml streptomycine, 100U/ml
penicillin (Jaber-Ebn-Hayyan, Iran). The K562 is an
NK-sensitive human erythromyelocytic leukemia cell
line.22 These cells were used as sensitive target cells for
evaluation natural killer cell cytotoxicity in vitro assay.
The non-radioactive method assessment for NK cell
cytotoxicity was modified from the procedure of Vital
et al (1989) and Gilman (1999)(23;24). A working
solution was prepared by adding 0.5ug/ml of propidium
iodide (PI, Sigma) in RPMI 1640+10% FCS.
6:1 12:125:1 50:1
NK cytotoxicity Percentage
Figure 1. The NK cytotoxicity assessment in PBL samples obtained from the women with RSA and non-RSA. The kinetic of
NK cytotoxicity is summarized, the representative NK cytotoxicity from four different samples with the ratio of 6:1, 12:1,
25:1 and 50:1 has been illustrated. The sample numbers 1 and 3 were taken from non RSA group, and the others were from
RSA women. These show variation cytotoxicity potential in different individuals. The outcome results in the groups were
achieved from the data analysis and it is indicated in table 1.
A. Andalib, et al.
12/ IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY Vol. 5, No. 1, March 2006
Figure 2. The dot plot has been defined as fluorescence light-2 (FL2) versus fluorescence light-1 (FL1) detectors that shows
the fluorescence intensity in distinctive stained cell populations (i.e. gated specific population). Dead K562 cells form a well-
defined population with distinctive fluorescence staining with PI (green gated). The dot-plot is illustrated the representative
for target dead cells (green) and live population (red) based on the PI dye staining in comparison with the control cells (red
population only) for K562. The calculation of cytotoxicity is based on the two different gated cells with the proportion of cell
population based on the acquisition data on system.
The lymphocytes (as effectors) and K562 (as target)
cell lines were mixed and cultured in the same tube
with Effector: Target ratios of 50: 1, 25:1, 12:1 and 6:1
respectively. Briefly: the tubes containing the mixed
cells were centrifuged for 3 min at 300g at room
temperature, then kept in 37°C for 150 minutes in a
humified 5% CO2 incubator, then the tubes were
resuspended. In the working solution, a concentration
of 1x105 cell/ml was prepared to avoid recycling of NK
cells. The samples were then incubated for 1 h at 37°C,
5% CO2, then the cell concentration brought to 1x106
cell/ml and was ready for running by flow cytometre.
In order to monitor the spontaneous death rate, the only
target cells were incubated accompanied with the
processing. The final concentrations of 1x105 cells/ml
have been running as control. The cells were analyzed
with a FACScalibour flow cytometry (Becton-
Dickinson, USA). A representative dot plot is shown
for cell analysis by flow-cytometre (Figure 1).
1x104cells were run in each event and the data obtained
were analysed using a cell Quest software installed in
the flow system. The percentage of dead target cell was
calculated as: the percentage of dead target cell in the
test tube including effector cells subtracted the
percentage of dead target cells in control tube with
absence of effector cells (Figure 2).
The data was analysed using SPSS software
installed in IUMS computer network. The Student t-test
was used to test statistical significances of the mean
values for ages, NK cells activity and the scores
obtained. Correlations were determined by the Pearson
test. The significance level was set at p value < 0.05 for
all the tested data.
The analysis results of psychological parameters as
well as cell mediated cytotoxicity of women with
history of RSA and multiparous control group are
summarized in Table 1. The mean age was 29.7±4.5
NK Cytotoxic Potential in Spontaneous Abortion
Vol. 5, No. 1, March 2006 IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY /13
years for RSA women and 31.1 ± 3.8 years for the
control group. The mean ± SD of gravidity was 3.3 ±
0.7 for control group, and the mean number of
spontaneous abortion were 3.4 ± 0.7 in the RSA group.
The life event scores of the stress questionnaire
were calculated 254 ± 83.6 for women with RSA and
224 ± 79.6 for women in control group. The
comparison between the means does not reach to a
statistical significant level (P= 0.086). The depression
score means were determined 27.6 ± 8.8 in RSA
women and 19.4 ± 7.1 in control group respectively.
The difference between the two means is statically
significant (P= 0.000). The analyses indicate an
association between life stress scores and depression
scores in RSA women with r = 0.65, P=0.000 and it
was determined with r = 0.45 and P= 0.002 for control
group respectively. The NK cell activity in the two
groups has been indicated in Table 1. The regression
analysis was performed for stress as well as depression
scores with NK cytotoxicity in both RSA and non-RSA
women. The association between NK cytotoxicity and
stress scores were determined with the r = -0.054, P=
0.79 for the ratio 50:1 of Effector: Target cells. In
addition, similar data was obtained for the other ratios
tested. Therefore, the lack of correlation was concluded
for this association speculation. A weak negative
correlation between the depression scores and NK
cytotoxicity was seen with r = -0.34 and P= 0.02 in
RSA women for the ratio of 50:1. Similar data was
seen for the other ratios tested. There was no
relationship between stress scores and NK cytotoxicity
in non-RSA group (data not shown). However, the
depression scores and the percentage of NK
cytotoxicity show a weak negative correlation (r = -
0.36 and P= 0.014 for the ratio of 50:1) for non RSA
group. The regression analyses for the other ratios
show a similar trend as mentioned before.
Moreover, the scores of high depression and high
stress in the women were analyzed (Table 1). The
patients were divided into two sub-groups, low (< 249)
and high (>250) for stress scores, along with low (< 19)
and high (≥ 19) for depression scores. The mean ± SD
was determined 311±57 (N=26) for the high-stress sub-
group, and 30±7.6 (N= 37) for high-depression sub-
group. The association between the high stress and the
high depression scores was significant (r= 0.422, P=
0.045). The Pearson correlation test shows a lack of
relationship between high stress score and NK
cytotoxicity (r= 0.011, P = 0.95, N= 26). The same
analysis for high depression scores and NK cytotoxicity
was determined with r = -0.30 and P= 0.072, N= 37. In
non-RSA women, there was also no association for
either high stress sub-group or high depression sub-
group and NK cytotoxicity (P≥ 0.05). Moreover, the
analysis performed for looking at the relationship
between the stress or depression scores and the ages of
the women involved in this study, however, no
consistent association was found.
Table 1. NK cytotoxicity potential, depression and stress
scores measurements in women with RSA and non-RSA
High stress Score
The fresh peripheral lymphocytes were the source of NK cell
activity for both RSA and non-RSA women. The tests were
prepared 2-3 times for each sample and mean±SD for each ratio
tested are presented. The P value shows the comparison between
the two mean groups. The stress and depression scores obtained
according to a standard questionnaire described in material and
method section. E:T stands for Effector lymphocytes used in
experiment process and K562 as Target cells according to
procedure described in the text.
The present study was an attempt to look at an
aspect of psychological parameters in relationship with
functional immune system in part. According to the
literature survey the mechanisms involved in some
unexplained miscarriages have speculated to be related
with interface of immunological functions. For
instance, it has been reported that emotional stress is
often followed by increased susceptibility to infections.
Natural killer cells in first line of immunological
defence play a major role in the immediate immune
response controlling this susceptibility.25 In addition, it
has been suggested that catecholamines are responsible
for altered cellular immunity after stress.26 Moreover,
alteration in cytokine profile balances and cellular
patterns such as T, B and mast cells were considered
for women who had abortion experiences with
psychiatric histories.1,27 Our data show an elevated
stress score (not statistically significant) as well as
292 ± 37
25 ± 6.1
311 ± 57
30 ± 7.6
A. Andalib, et al.
14/ IRANIAN JOURNAL OF ALLERGY, ASTHMA AND IMMUNOLOGY Vol. 5, No. 1, March 2006
increased depression score (P=0.000) in RSA women in
comparison with the non-RSA women. According to
the questionnaire used in this study the mean stress
scores obtained in non-RSA population were scaled in
mild to moderate grade, so the explanation of this high-
background may need a social attention and should be
discussed in detail, but, it is out of the focus of the
present study. This study indicated that both increased
NK cytotoxicity and the augmented psychopathlogical
scores were seen in the RSA women. Similar
association was concluded partially by Arck and
Hori.1,2,28 However, there are some contradictory
reports which do not support this concept.29 The result
of present study shows that women with RSA
experience have considerable psychological disorder
(which could be seen by the high stress/depression
scores). One possible reason is that abortion could be a
psychological trauma and stressful life event, this
chronic stress might cause depression in these groups
of women, and the depression may influence the
hormonal status as well as immunological factors.
There are several reports that show it in spite of that the
women who had association between stress and
abortion, but there was not correlation with their
pregnancy outcome. These reports also considered the
physiological markers i.e. hormones concentration.
However, our investigation did not cover the women’s
hormones, but several investigators have discussed
hormonal changes in recurrent miscarriage in recent
years.1,27 From all the aspects of immune system,
although we evaluate the natural killer activity, but not
hormonal state, the relationships between lymphocytes
and hormonal status have been noted elsewhere.26,30
For instance, it has been suggested that the
accumulation and survival of uterine mucosal
lymphocytes of NK cells are hormonally indirect
dependent.10,31 At this time, there are enough reports
that show TH1/TH2 cytokine imbalance at a feto-
maternal interface, and it has been supposed that
immunological function could influence of some
unexplained miscarriage.10,28 Hence, it could be
concluded that women with a history of abortion might
be at risk of abortion due to influence the immune
mediator either indirectly (hormonal alteration) or
directly (cytokine profile imbalance TH1/TH2).
Furthermore, there are more investigations which
indicated increased levels of abortogenic type TH1 cell
cytokines and decreased levels of pregnancy protective
cytokines (TH2) that could be linked to stress-triggered
embryonic loss.32,33 In experimental model it has been
shown that stress promotes neurotransmitter substance
P release in tissues and this substance increase the
production of decidual tumor necrosis factor (TNFα) by
CD8+ T cells.34 However, linkage of immune-hormone
system by various mechanisms may protect the
pregnancy outcome. For instance progesterone-induced
blocking factor (PIBF) induces increased production of
TH2-type cytokines by stimulating asymmetric
antibody synthesis by B cells which might contribute to
protection of the fetus.30 As mentioned above, all the
aspects discussed could be considered for the RSA and
similar cases involved.
immunotherapy would be recommended for down -
regulated NK activity, and psychotherapy has been
reported to result in a successful pregnancy outcome in
patients with a history of recurrent spontaneous
abortion.35 Although we consider two aspects related to
RSA women, more aspects should be considered being
able to handle an abortion state. Using a helping system
for improvement of individual stress managing
capabilities may be possible approach for benefit to
patients together with using appropriate immuno-
This work was financially supported in part by the
council of research in Isfahan University of Medical
Sciences and registered by ID number 81229. The
authors would like to express high appreciation to Dr.
Reza Bagherian from the psychology department in
IUMS for his kind consultations.
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Klapp BF. Stress and immune mediators in miscarriage.
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