الفهرس 
MISCARRIAGEOnly 14 pages are availabe for public view
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Abstract
S
pontaneous miscarriage is the involuntary termination of pregnancy before 20 weeks of gestation or spontaneous expulsion of fetus below 500 g (Speroff and Fritz, 2011).
Recurrent pregnancy loss (RPL) is defined as three or more spontaneous losses (not necessarily consecutive) (Lee et al., 2000; Kim et al., 2004; Steinburg and Schneider, 2009).
Spontaneous miscarriage accounts for about 15% of pregnancies. 1% of it is recurrent (McNamee et al., 2012).
More than 80% of abortion occurs in the first 12 weeks of pregnancy; at least half result from chromosomal anomalies (Cunningham et al., 2010).
Over than90% of the chromosomal abnormalities observed among abortuses are numerical. Trisomy accounts for 50- 60%, monosomy (45 XO) accounts for 25% and polyploidy accounts for 15- 20%. The reminder is split between structural abnormalities (translocation, inversion) and mosaicism (Phillip et al., 2003; Cunningham et al., 2010).
Developmental uterine defects are associated with poor reproductive outcome. These poor outcomes are more profound in cases of septate uteri (Chan et al., 2011).
The pregnancy outcomes with intrauterine adhesions are generally poor, these percentages are much improved after adhesiolysis; the prognosis is generally correlate with the severity of the disease (Al- Inany, 2001; Cunningham et al., 2010).
Cervical insufficiency is a cause for second trimester abortion or asymptomatic rupture of membrane before loss in the third trimester (Cunningham et al., 2010).
Spontaneous abortion increases in women with insulin -dependent diabetes. The risk is related to the degree of metabolic control in the first trimester. Women who had spontaneous miscarriages had statistically significantly higher HgbA1c levels (Melanie and Richard, 2010).
There is no definitive evidence that hypothyroidism is a cause of abortion in humans. In women who have had RPL, some studies have shown an increased incidence of anti-thyroid anti-bodies compared with controls, though the published data are largely conflicting in this issue (Melanie and Richard, 2010).
Women with PCOS who conceive either spontaneously or after ovulation induction have a much higher risk of miscarriage (Diamanti-Kandarakis E, 2008).
There is no convincing evidence that LPD is associated with abortion (Bukulmez and Arici, 2004; Melanie and Richard, 2010).
Infections are uncommon cause of early abortion. Infection may be primarily intra-uterine or may result from trans-placental transmission from the mother (American College of Obstetricians and Gynecologists, 2004; Melanie and Richard, 2010).
The autoimmune disorders like systemic lupus erythematosus and the antiphospholipid syndrome (APS). Alloimmune disorders involve an abnormal maternal immune response to fetal or placental antigens may be a cause of recurrent pregnancy loss (Speroff and Fritz, 2005).
Recent clinical and experimental observations suggest that the pathophysiology of pregnancy failure in patients with APS may involve inflammation at the maternal-fetal interface and disruption of normal trophoblast function and survival, rather than a pro-thrombotic event (Abrahams, 2009).
Inherited thrombophilia resulting from genetic mutation in clotting factors have emerged as a potentially important cause of recurrent pregnancy losses, but a great number of women with these mutations have completely normal reproductive performance (Speroff and Fritz, 2011).
There is evidence that obesity may increase the general risk of miscarriage (Metwally et al., 2008; Vinter et al., 2012).
Many studies support the conclusion that cigarette smoking increases the risk of spontaneous miscarriage in a dose dependent manner, while others failed to support this association (Wisborg et al., 2003; Maconochie et al., 2007).
Maconochie et al. (2007) reported that a low level of alcohol consumption during pregnancy was not associated with a significant risk of abortion; Andersen and his colleagues (2012) reported that even low amounts of alcohol consumption during early pregnancy increased the risk of spontaneous abortion substantially.
Anesthetic gases, organic solvent and heavy metals (mercury, lead) have been implicated as causative agents of miscarriage (Gardella et al., 2000).
Radiation in sufficient doses is a recognized abortificient. The human dose to affect abortion is not precisely known (Cunningham et al., 2010).
Uncomplicated abdominal or pelvic surgery performed during early pregnancy does not appear to increase the risk of abortion. An important exception involves early removal of the corpus luteum cyst or the ovary in which the corpus luteum reside (Cunningham et al., 2010).
Chromosomal abnormalities in sperm (paternal factor) have been associated with abortion (Carrell and colleagues, 2003).
Spontaneous abortion is categorized as threatened, inevitable, incomplete, complete, or missed. Abortion can be further categorized as sporadic or recurrent (Zeqiri et al., 2010).
Ectopic pregnancy, gestational trophoblastic diseases (GTD) and implantation bleeding are differential diagnosis for miscarriage.
Progesterone is a C-21 steroid hormone, belongs to a class of hormones called Progestogens (Schumacher et al., 2004).
Progesterone is produced in the adrenal glands, the gonads (specifically after ovulation in the corpus luteum), and the brain. And during pregnancy, it is secreted from corpus luteum and placenta (Talwar and Srivastava, 2003).
The maintenance of normal pregnancy up to 7 to 8 weeks of pregnancy is dependent on progesterone synthesis by corpus luteum under the influence of human chorionic gonadotropin, from the 7th week onward the placenta take over the dominant role of steroid production (Speroff and Fritz, 2011).
Progesterone prepares and maintains the endometrium to allow implantation (Cunningham, Leveno et al., 2010).
Progesterone is known to have inhibitory effects on smooth muscle contraction (Speroff and Fritz, 2011).
Cholesterol is the precursor of all steroid hormones. Low density lipoproteins (LDL) are the near exclusive form of cholesterol that used for progesterone biosynthesis (Cunningham et al., 2010).
After LDL-cholesterol uptake, progesterone is synthesized from cholesterol in a two-step enzymatic reaction. First, cholesterol is converted to pregnenolone within the mitochondria. In a reaction catalyzed by cytochrome p450 cholesterol side-chain cleavage enzyme, Pregnenolone leave the mitochondria and converted to progesterone in the endoplasmic reticulum by 3B-hydroxysteroid dehydrogenase (Cunningham et al., 2010).
Progesterone circulating in plasma bound to transcortin. Transcortin actually has a higher affinity for progesterone than for cortisol (Harper’s et al., 2003).
There are two active metabolites of progesterone that increase significantly during pregnancy. There is about a 10-fold increase of the 5 α- reduced metabolites, 5-α pregnane-3, 20-dione. This compound contributes to the resistance in pregnancy against the vasopressor action of angiotensin II (Speroff and Fritz, 2011).
Most progesterone actions on the female reproductive tract are mediated through nuclear hormone receptors (Connelly and colleagues, 2002). The best understood isoforms are the progesterone receptors type A (PR-A) and B (PR-B). Both arise from single gene, and regulate transcription of target genes. These receptors have unique actions (Peluso, 2007). The endometrial glands and stroma appears to have different expression patterns for these receptors that vary over the menstrual cycle (Cunningham et al., 2010).
Serum progesterone measurement is a reliable biochemical test in establishing the diagnosis of early pregnancy failure (Deeks et al., 2012).
Transvaginal ultrasound has revolutionized the diagnosis of early pregnancy as it can detect a pregnancy at an earlier stage, whether it is normal and therefore reassuring, or abnormal and require intervention (Sawyer and Jurkovic, 2007).
A smaller than expected gestational sac can be a predictor of poor pregnancy outcome, both alone and in combination with other parameters. The difference is only becoming apparent from 5 weeks onwards. Unfortunately, the predictive value of a smaller than expected GSD in isolation is variable and highly dependent upon other presenting factors (Jauniaux et al., 2005).
Mean GSD: CRL ratios have also been used to predict pregnancy outcome with varying degrees of accuracy (Choong et al., 2003).
Abnormal developmental pattern of FHR and/or bradycardia has been associated with subsequent miscarriage (Chittacharoen and Herabutya, 2004).
Embryonic bradycardia and absence of yolk sac or even a smaller yolk sac diameter than expected for any gestational age are predictors of poor pregnancy outcome during the first 12 weeks (Varelas et al., 2007).
The shape of the gestational sac, the echogenicity of the placenta, the thickness of the trophoblast and the presence of an intrauterine hematoma (IUHS) have all been proposed as sonographic markers associated with early spontaneous miscarriage (Jauniaux et al., 2005).
The four major criteria of pregnancy failure on which the diagnosis can be reliably made are: The finding of an embryo with a CRL of 6 mm or more on transvaginal ultrasound without a heartbeat, The finding of a gestation sac of mean diameter 20 mm or more without a yolk sac, or a sac greater than 25 mm MSD without a visible embryo (Choong et al., 2003; Elson et al., 2003; Ashgar and Fatima, 2011).
The four minor criteria for diagnosing pregnancy failure include a thin decidual reaction, a poorly reflective decidual reaction, and absence of the double decidual sac sign and a low position of the sac in the uterus. Because they are non-specific and unreliable they should not be used alone to diagnose pregnancy failure (Chiang et al., 2004; Ashgar and Fatima, 2011).
This study aimed to predict abortion using blood progesterone and some ultrasonographic measurements at the 7th week of gestation. It was found that the abortion rate is 11.5% from the 7th week till the 20th week of gestation.
The ultrasound measurements used in this study include the mean gestational sac diameter (MSD), the crown-rump length (CRL), the mean sac diameter to crown-rump length ratio (MSD_CRL), and the fetal heart rate (FHR) were used to predict the outcome of pregnancy.
It was found that MSD, MSD-CRL and FHR were highly valid markers and better positive than negative with higher sensitivity compared to progesterone and CRL.
In conclusion; this study found that the use of MSD, MSD-CRL ratio and FHR is significant in predicting pregnancy outcome this is which supported by the results of studies by (Burwinkel et al., 1993; Tadmor et al., 1994; Doubilet et al., 2000; Makrydimas et al., 2003; Daemen et al., 2007; Varelas et al., 2008; Metin Altay et al., 2009, Fatma and colleagues, 2011). But CRL is not significant.
Also this study found that the measurement of serum progesterone for prediction of pregnancy outcome is non- significant which is supported by the results of the studies of (Carmona et al., 2003; Darwish et al., 2005; Kim and his colleagues, 2012). On the other hand there is many studies support the use of serum progesterone measurement in the prediction of the fate of pregnancy (Al-sebai et al., 2005; Altay et al., 2009; Ben et al., 2012). A study of Lijun & colleagues (2011) support that the use of serum progesterone in the prediction of pregnancy outcome of threatened abortion with other biomarker (β-hCG) increase its accuracy and reliability compared to serum progesterone alone or β-hCG alone.