The role of human chorionic gonadatropin (hCG) in the maintenance of early pregnancy is well known. Recent data suggests that hCG may play a role in the maintenance of the later stages of pregnancy as well, by directly and indirectly promoting uterine quiescence. If hCG acts as an endogenous tocolytic in normal pregnancy, then it may be an ideal candidate for therapy of preterm labor as well. We present compelling in vitro as well as in vivo data, which support the role of hCG in the maintenance of normal uterine quiescence. Additionally, we will present in vivo and in vitro data that confirms the ability of hCG to directly promote relaxation of uterine contractions. This review provides a basis for future study of the use of hCG in clinical obstetrics. Given the limited effectiveness of tocolytic therapies available at the time, hCG may provide a promising pharmacological approach to the pervasive problem of preterm labor in human pregnancy. While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics.
hCG tocolytic preterm labor treatment, human chorionic gonadotropin uterine quiescence pregnancy, hCG endogenous tocolytic normal pregnancy maintenance, Kurtzman Rao hCG preterm labor tocolysis, hCG uterine relaxation contractions in vitro in vivo, novel tocolytic therapy hCG preterm birth, human chorionic gonadotropin myometrial relaxation, hCG role clinical obstetrics preterm labor prevention, pregnancy maintenance hCG beyond early gestation, tocolytic effectiveness hCG pharmacological approach
PMID 11394205 11394205 DOI 10.1055/s-2001-13912 10.1055/s-2001-13912 Kurtzman et al. 2001, Kurtzman 2001
Cite this article
Kurtzman, J. T., Wilson, H., & Rao, C. V. (2001). A proposed role for hCG in clinical obstetrics. Seminars in reproductive medicine, 19(1), 63-68. https://doi.org/10.1055/s-2001-13912
Kurtzman JT, Wilson H, Rao CV. A proposed role for hCG in clinical obstetrics. Semin Reprod Med. 2001;19(1):63-68. doi:10.1055/s-2001-13912
Kurtzman, J. T., et al. "A proposed role for hCG in clinical obstetrics." Seminars in reproductive medicine, vol. 19, no. 1, 2001, pp. 63-68.
Previous studies have demonstrated that human myometrium contains receptors for human chorionic gonadotropin (hCG) and that hCG can inhibit myometrial contractions in vitro. To use for the first time hCG as a tocolytic agent in the treatment of preterm labor. The study group included 100 women with preterm labor; 50 were assigned to receive HCC and 50 placebo. Assignment was made with stratification according to four categories of gestational age between 20–35 weeks. One half of the surviving infants were followed-up at 18 months. The protocol of the dosage consisted of one single dose of hCG 5,000 IV and 10,000 units of hCG in 500 dextrose as a drip of 20 drops per minute. The mean length of time from randomization to delivery differs significantly for the two groups: 28.8 days for the hCG group and 15 days for the placebo treatment group (highly statistically significant, P <0.001). There was statistically significant difference (P <0.05) between the two groups regarding the induction of delivery before 37 weeks and the proportion of infants weighing less than 2,500 g. Human chorionic gonadotropin treatment was associated with an improvement score on the Bayley psychomotor development index. Human chorionic gonadotropin exhibits potent tocolysis with no fetal side effects. This preliminary study suggests that HCG may be a candidate for tocolytic therapy of preterm labor.
We compared nifedipine and ritodrine for treatment of preterm labor with respect to neonatal outcome. We conducted an open randomized multicenter study of neonatal outcome in 185 women who received either oral nifedipine (n = 95) or intravenous (IV) ritodrine (n = 90) for treatment of preterm labor. Secondary outcome measures included neonatal mortality and morbidity, especially neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), and intracranial bleeding. There were no significant differences in umbilical artery pH values and Apgar scores between groups. Nifedipine was associated with lower admission rates to the NICU (49% versus 66%; odds ratio 0. 51, confidence interval 0.28, 0.93) compared with ritodrine, and lower incidences of RDS (21% versus 37%; 0.46, 0.24, 0.89), intracranial bleeding (18% versus 31%; 0.48, 0.24, 0.96), and neonatal jaundice (52% versus 67%; 0.53, 0.29, 0.97). Logistic regression analysis showed that even after correction for gestational age at birth, newborn risk of RDS, intracranial bleeding, or neonatal jaundice was significantly lower in the nifedipine group than the ritodrine group. Nifedipine for treatment of preterm labor was associated with a lower incidence of neonatal morbidity than ritodrine. That difference appeared to be partly because of the higher tocolytic efficacy of nifedipine and partly because of an intrinsic beneficial effect of nifedipine, or the lack of harmful effects when compared with ritodrine.
To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. TABULATION, INTEGRATION, Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
To characterize the continuum between normal and preterm labor to prevent spontaneous preterm birth and low birth weight. Between August 1, 1992, and November 30, 1993, obstetric patients from a large managed care medical group were assigned in rotation to five private practice offices for pregnancy care. In the study office (374 births), a systematic approach of visit-by-visit screening, patient education, selective office evaluation of cervical change by transvaginal ultrasound examination, outpatient modification of activity, and graded oral or subcutaneous tocolysis was used; inpatient tocolysis was used only when outpatient management failed. In the comparison offices (1391 births), transvaginal ultrasound was not used and conventional methods were used at the discretion of the attending physicians. Birth weights below 1500 g (P = .008; odds ratio [OR] 0.08, 95% confidence interval [CI] 0.05-1.32), 2000 g (P = .21; OR 0.21, 95% CI 0.05-0.88), and 2500 g (P = .008; OR 0.44, 95% CI 0.23-0.83) occurred significantly less often in the study group than in the comparison group. The difference in spontaneous preterm births under 2500 g was also significant (P < .001; OR 0.08, 95% CI 0.01-0.58). By emphasizing transvaginal ultrasound and graded outpatient tocolysis, the diagnosis and management of preterm prelabor was associated with a reduction in the rate of spontaneous preterm birth and low birth weight infants.