MATERIALS AND METHODS

This study was designed as a randomized clinical trial. From February 2000 to February 2002, pregnant women with pretem labor, who were admitted to Khorram Abad hospitals, in the west of Iran, were invited to participate. One hundred and one cases who consented were randomly allocated to 2 different intervention groups, named A and B. Group A and B consisted of 50 and 51 pregnant women, respectively.

A diagnosis of preterm labor was made in patients between 20 weeks and 36 weeks, six days of gestation if uterine contractions at a frequency of four per 20 min or eight per 60 min and were accompanied by one of the following: premature rupture of membrane, cervical dilation greater than 2 cm, effacement exceeding 50% , or a change in cervical dilation or effacement detected by serial examinations. The patients placed in the lateral recumbent position and externally monitored for fetal heart tones and contractions. If uterine contractions were present at least every 15 min, an intravenous bolus of 500 mL of normal saline was administered. This rapid intravascular expansion can diminish the contractions of an irritable uterus and help the physician differentiate this condition from preterm labor. By this method patients could be included.

Exclusion criteria were premature rupture of membrane, cervical dilatation more than 4 cm placental abruption diabetes mellitus, cardiorespiratory diseases, genitourinary infections, anatomical anomalies of the pelvis and fetal anomalies.

For patients of group A, intravenous HCG was administered in an initial dose of 5000 IU.

Then 10000 IU of HCG in 500 mL of D5W was administered by the order of 20 drops per minute intravenously. The protocol was continued until the time that contractions discontinued.

Patients of group B received a loading dose of 4 g intravenously (1 g/min) Magnesium sulphate. A continuous infusion of 2 g h^-1 was then administrated. The infusion was continued until 12 h of uterine quiescence is achieved. In both groups, if contractions continued by previous or a higher force and frequency, or dilatation progressed the patient was excluded and management of patient was continued out of the study protocols. So patients could be switched to another tocolytic regimen if they continued to have contractions after 6 h of therapy.

All of the patients were under observe in the hospital until 24 h of the end of drug infusion. Also, both of the groups received dexamethasone, 5 mg bid for 4 doses. Patients were under control until the end of pregnancy.

In this study data such as maternal. gestational age when the diagnosis of perterm labor was achieved, delay of labor due to treatment protocols, frequency of complications in both groups were registered.

Data were collected using questioners and clinical examination. Results were analyzed using descriptive statistics, distributional indices. Independent t-test was occupied to compare maternal age, gravidity, time of admission and neonatal birth weight between two groups.

RESULTS

Both groups were similar to each other regarding maternal age and gestational age (Table 1). The only multiple gestations enrolled were twins and 4 patients in each group had a twin gestation. The incidence of success was similar between the groups at 37(74%) and 36 (73%), HCG and magnesium sulphate. Delivery was delayed 48 h in 45(90.3%) and 44(88%) patients in the HCG and magnesium sulphate groups (Table 2).

There was not any complication in group A and all of the patients in group B had complications such as thirst, flashing, headache, vertigo, nausea and vomiting (Table 3). NO sever complication was detected during the study. There was no significant difference between the outcomes between study groups (Table 2).

The mean of neonatal birth weight in group A was 2334±631.03. This mean for group B was 2287.25±498.7. There parameters were not statistically different (p-value = 0.68).

Table 1:	Demographic characteristics

Table 2:	The comparison of tocolytic function and outcomes in the groups

Table 3:	The frequency of complications in HCG and Magnesium sulphate intervention groups

There was not any perinatal mortality in the two groups. In each of study groups 9(0.18% in group A and 17.65% in group B) neonates were admitted to NICU, due to respiratory distress. All of the neonates and mothers were discharged by a stable position and with no problem.

DISCUSSION

Human myometrium contain HCG/lh receptors. There are fewer of these receptors during labor compared to no labor at preterm or term deliveries. Exogenous HCG can directly inhibit oxytocin-stimulated human myometrial contraction (Ambrus and Rao, 1998). These finding suggest that HCG may directly maintain myometrial quiescence during pregnancy (Eta et al., 1994; Toppozada et al., 1998). As maintenance of uterine quiescence may involve down-regulation of myometrial gap junctions, we investigated the effect of HCG on connexin 43 (cx-43) gene expression from RNA to protein and morphological gap junctions (Ambrus and Rao, 1998). Present results demonstrated that HCG could be one of the hormones responsible for maintaining uterine quiescence by down-regulating myometrial gap junctions during pregnancy. The HCG action is concentration and time dependent, hormone special and mediated by protein kinase-A signaling and appears to involve progesterone receptors (Kurtzman et al., 1999). We choose magnesium sulphate as the control drug because it is our first-line tocolytic. Although the overall efficacy of magnesium sulphate as a tocolytic is arguable (Edward et al., 2004; Canadian Preterm Labor Group, 1992). It has been used for more than 3 decades. The frequency of maternal side effects has been a consistent concern and it appears that the margin between maternal safety and efficacy of magnesium sulphate infusion for tocolysis is quite narrow (Atkinson et al., 1995). We likewise noted a high incidence of maternal side effects (100%) and no dis continuation rate in the magnesium sulphate group. This is consistent with an earlier study (Bennet, 1997) showing a 10% discontinuation rate in patients treated with magnesium sulphate infusion for tocolysis with an overall 31% incidence of reported side effects (Macwhorter-Edward 2004). In Behnam (2001) study an overall 100% incidence of reported side effects. Despite the encouraging results of recent studies (Adrienne et al., 2005; Kornyei et al., 2003) demonstrating improved methods of predict prematurity and prevent preterm labor, the incidence of preterm delivery has remained stable during the last 20 years (Adrienne et al., 2005) clearly new methods to arrest acute preterm labor are needed. HCG is a new drug that inhibit human myometrial contractions. The ability of HCG to inhibit preterm delivery may be mediated further by directly suppressing myometrial responsiveness to stimulatory eicosanoids (Zuo et al., 1994b). HCG-may also increase the formation of eicosanoids that prompt myometrial relaxation, such as prostacyclin (Swanson et al., 1992; Toth and Rao, 1994) In the present study demonstrated that HCG comparable clinical efficacy in delaying delivery for 48 h in direct comparison with magnesium sulphate. Our study may have two limitations and could be improved in several ways. First we may have over diagnosed preterm labor and treated some women in both groups un necessarily. When preterm labor in diagnosed on the basis of contraction alone, between 30 and 70% of women will resolve without treatment. In this circumstance many more patients would be required to determine a benefit of HCG. It is likely that, despite the entry criteria, many of our patients were not in true groups is the result of our definition of preterm labor. Second, we did not exclude twins in our study. The dynamics of premature uterine contractions in twins may be different from those in singleton pregnancies, because of uterine over distension, but strict entry criteria and the blind randomization process should have eliminated of bias. In addition, there was no difference in the number of twins in each randomized group. Accumulating data suggest that prolonged tocolytic treatment is not effective in improving neonatal outcome and remains controversial. There is a strong consensus, however that in those patients who present with active labor before 34 weeks of gestation that a 48 h delay in delivery until a full course of dexamethasone is completed, will have improved neonatal outcomes (Savvidou et al., 1998).

CONCLUSIONS

This study suggests that HCG may be a therapeutic candidate for inhibition of preterm labor in human pregnancy, due to its effectiveness and not prominent demonstrated complications. Further work is needed to delineate the mechanism of action, as well as the safety and efficacy of HCG for use in the prevention of human preterm delivery. In order to find the most effective dose of, HCG further studies are suggested.