الفهرس 
Recurrent Pregnancy LossOnly 14 pages are availabe for public view
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Abstract
Dys-regulations in the normal maternal immune system probably operates at the maternal-fetal interface and may involve increased activity of both uterine and peripheral natural killer cells, which appear to regulate placental and trophoblast growth, local immunomodulation, and control of trophoblast invasion. These and other aspects of immunologically-mediated infertility are not well defined.
This study aimed at studying the effect of Intralipid on the success of early pregnancy (20 weeks) in women with unexplained recurrent spontaneous abortion. It also aimed at studying the effect of adding Intralipid to the standard treatment of unexplained recurrent miscarriage on the peripheral NK cells.
The study was held at Ain Shams University Maternity Hospital. It included 160 patients with history of recurrent spontaneous abortion (2 or more abortions less than 20 weeks gestation). All the patients were less than 35 years old to decrease the risk of chromosomal abnormalities.
All patients had neither history nor current evidence of abnormal glucose tolerance, abnormal thyroid function, hyperprolactinaemia or anti-phospholipid antibody syndrome. All the patients had no history of hormonal contraception or intrauterine contraceptive device usage in the 3 months preceding the current pregnancy.
The recruited Patients were further subdivided into 2 Groups: Study group including 80 Patients with unexplained recurrent spontaneous abortion who received Intralipid in addition to the low-dose aspirin and heparin, and Control group including 80 patients with unexplained recurrent spontaneous abortion who received low dose aspirin and heparin only.
The recruited patients were subjected to history taking, with particular emphasis on past medical history, past obstetric history, and menstrual history. They had general and abdominal examination done. Obstetric ultrasound (transabdominal or transvaginal) to document viability of pregnancy and to ensure the gestational age was also done. Baseline laboratory investigations: Rhesus status, complete blood count (CBC), 1 hour postprandial blood sugar, prothrombin time (PT) and activated partial thromboplastin time (aPTT) were withdrawn. Peripheral venous blood sample was taken from all included patients before starting treatment, and collected on heparinized tubes. NK cytotoxic assay was checked on each sample. All samples were checked within 24 hours after collection. Another NK cytotoxic assay was taken at 20 weeks for both groups of patients in women with ongoing pregnancy or when missed abortion if failed treatment with karyotyping of abortus.
The study found that of the 80 women in the study group receiving Intralipid, 5 (6.3%) miscarried before 20 weeks of gestation while 75 (93.7%) had successful outcome [defined as an ongoing pregnancy beyond 20 weeks of gestation]. On the contrary, among the 80 women in the control group, 39 (48.8%) miscarried before 20 weeks of gestation while 41 (51.2%) had successful outcome. This difference was statistically significant. Addition of Intralipid was significantly associated with an almost 2-fold higher rate of successful outcome. All abortus were karyotyped and had no chromosomal abnormalities.
Women of both groups were followed up until end of pregnancy to follow up secondary outcomes. Live births were significantly more frequent among study group than among control group. Addition of Intralipid was significantly associated with an almost 3-fold higher rate of live births. It is worth mentioning that from the 80 women in the study group receiving Intralipid, one woman suffered from a systemic fungal infection while another one gave birth to a baby with an external ear anomaly; microtia. Some women experienced adverse outcomes that led to perinatal death as preterm labour, IUGR and IUFD. The differences in incidence of these outcomes among the studied groups were statistically insignificant.
The study also found that there were no significant differences between study and control groups regarding initial NK cells and that in women who miscarried before 20 weeks of gestation, the mean levels of serum CD16+56+ were statistically insignificantly lower in women of study group when compared to women of control group. On the other hand, in women with ongoing pregnancy, the mean levels of serum CD16+56+ at 20 weeks of gestation were lower in women of study group who received Intralipid when compared to women of control group. These differences were statistically significant.
It is worth mentioning that the mean levels of serum CD16+56+ in women with ongoing pregnancy beyond 20 weeks, whether in study group or in control group, were lower than in those who miscarried before 20 weeks. These differences were statistically significant among the whole study population and among the study group while were not statistically significant among the control group. Regarding the difference between levels of initial NK cells and that at 20 weeks of gestation, NK cells reduction was significantly higher among study group than among control group.
Moreover, the study found that women with elevated initial NKs (≥12.0%) had significantly higher frequency of poor outcomes in study and control groups when compared to women with normal initial NKS (<12%), except for miscarriage in study group which was not significantly different between normal (<12%) and elevated (≥12.0%) initial NKs.
Furthermore, the study found that the initial NK cells had low diagnostic performance in prediction of outcomes; CD16+56+ was an insignificant predictor of successful outcome (ongoing pregnancy beyond 20 weeks) and live births.
In conclusion, the study found that Intralipid improve pregnancy outcomes in patients with unexplained recurrent spontaneous abortion thus could be used as an effective treatment for unexplained recurrent spontaneous abortion. The underlying mechanism may be associated with its ability to decrease NK cell activity.