It is Time to Evaluate Human Chorionic Gonadotropin for the Treatment of Preterm Births

Abstract

Births between 20th to 37 th completed gestational weeks are considered preterm. More births occur during late (34-36 weeks) than in early (before 34 weeks) preterm period. Preterm births account for more infant deaths than any other cause. The prematurely born infants have breathing problems, feeding difficulties, cerebral palsy, developmental delays, vision problems and hearing impairment. These complications are generally more severe in early than in late preterm born infants. Preterm infants require medical care in neonatal intensive care units for several weeks after birth. The surviving infants are at a greater risk for early death and life-long neurological and cognitive difficulties. All this medical care costs billions of US healthcare dollars. In addition, parents go through considerable amount of guilt and emotional trauma.The incidence of preterm births is about 9% in US and higher in third world countries. Despite the basic science and clinical research advances to better understand and control preterm births, the rates are increasing. The current therapies include β-androgenic agonists, calcium channel blockers, non-steroidal anti-inflammatory compounds, nitric oxide donors, oxytocin antagonists, etc. Among them Magnesium sulfate (MgSO 4 ) is a popular first line therapy. Most of these drugs are only used for about 24-48 hours, so that the patients can be treated with corticosteroids to promote fetal lung maturity. The infants with relatively mature lungs have better survival chances. There is a clear unmet need to improve upon the current therapies to better control and treat preterm births.The paradigm shift on human chorionic gonadotropin (hCG) actions revealed that it can act on human myometrium.1 It contains hCG/luteinizing hormone receptors and their activation results in an inhibition of contractions.1-5 These findings are consistent with the notion that hCG promotes myometrial quiescence, which is a prerequisite for pregnancy initiation and continuation. 5 The quiescence declines as pregnancy advances, which permits myometrial stimulants to dominate so that they can facilitate normal labor progression. 5 The maintenance of myometrial quiescence by hCG suggests, that it could be used for suppression of prematurely activated myometrial contractions, that are responsible for preterm births. 5,6 In fact, hCG has been shown to be effective in preventing preterm birth in a mouse model. 7There are now five clinical studies testing hCG in the treatment of preterm births. 8-12Four of them were on women with active labor and the fifth was on women with a previous history of preterm births. [8][9][10][11][12] The studies on women with active labor were compared with MgSO 4 treatment. [8][9][10][11] The results showed that while hCG was equally effective, it did not have the side effects of MgSO 4 . [8][9][10][11] In the prophylactic study, hCG was found to be equally effective as vaginal micronized progesterone tablets with a better compliance rate than progesterone. 12Despite this encouraging data, t...

There is no turning back on the paradigm shift on the actions of human chorionic gonadotropin and luteinizing hormone

“…70-72 i. Decreasing hCG influence toward the end of pregnancy may allow myometrial stimulants to dominate for the successful progression of labor. 52,73 The possible hCG/LH involvement in the above normal events should include the contributions of sex steroid hormones, growth factors, cytokines, chemokines, etc. Moreover, it should lead to an increased appreciation that many more inputs than previously thought could be necessary for a complete normal response.…”