Pregnancy Outcome After Levonorgestrel-only EC Failure
Pregnancy Outcome After Levonorgestrel-only EC Failure
BACKGROUND: Levonorgestrel (LNG), as a dedicated emergency contraception (EC) product, has been available over-the-counter in China for 10 years. Until now, only a small number of deliveries after LNG-EC failure have been documented.
METHODS: This study was a prospective comparative cohort study. A group of 332 pregnant women who had used LNG-EC during the conception cycle was recruited, and matched to a group of 332 pregnant women without the exposure to LNG. Congenital malformations, perinatal complications and delivery circumstances were investigated in this study.
RESULTS: There were 31 pregnant women in the study group and 28 in the comparison group miscarried within 14 weeks of gestation. In the study and comparison groups, four malformations were found in each group. In the study group, both birthweight (3416 versus 3345 g, P = 0.040) and the sex ratio of birth (boys/girls, 1.14 versus 0.90, P = 0.153) were higher than in the comparison group. There were no statistically significant differences in the incidence of miscarriage or malformation or in the neonatal outcome between the two groups.
CONCLUSIONS: There was no association between the use of LNG-EC pills and the risk of major congenital malformations, pregnancy complications or any other adverse pregnancy outcomes in our study.
Levonorgestrel (LNG) administered at a dose of 1.5 mg (given either as a single 1.5 mg dose or two 0.75 mg doses taken 12 h apart) is a safe and well-tolerated method for emergency contraception (EC) (Cheng et al., 2008). In China, LNG is marketed in packs containing either two or four 0.75 mg tablets, or one tablet of 1.5 mg of LNG. When taken within 72 h after intercourse, the method prevents ~85% of the pregnancies that will occur without treatment (WHO, 1998; von Hertzen et al., 2002; Sarkar, 2003). Single dose (1.5 mg) administration has a similar effectiveness as the standard two-dose regimen (0.75 mg twice, 12 h apart) (Cheng et al., 2008; von Hertzen et al., 2002).
The mechanisms of LNG-EC action have not been fully characterized. It is generally believed that LNG can prevent or delay ovulation (Croxatto et al., 2001; Marions et al., 2002), modify endometrial receptivity, thicken cervical mucus and impair the formation of the corpus luteum (Croxatto et al., 2001). Recent animal studies convincingly show that LNG does not interfere with post-fertilization events (Croxatto et al., 2003; Müller et al., 2003).
The currently reported pregnancy (failure) rate with LNG-EC is between 0.2 and 3.0% after one single coital act (Cheng et al., 2008), making LNG-EC less effective than regular contraceptive methods (pregnancy rates for combined oral contraceptives in the first year of use are reported from 0.3% for perfect use to 8% for typical use, and for intrauterine devices pregnancy rates are reported as 0.1-2.2% for up to 12 years of exposure) (Grimes, 2007; Hatcher and Nelson, 2007).
LNG-EC has been available over-the-counter (OTC) since 1998 in China and up to 2005, it was estimated that over 30 million boxes were sold annually there (Cheng, personal data). Similar to women in Britain and Sweden (Blanchard et al., 2003; Larsson et al., 2004), Chinese women are more likely to purchase EC directly from pharmacies than to obtain it with a doctor's prescription. Young unmarried women under 24 years of age are the main EC users in China (Kang et al., 2007a, b). Because LNG-EC is extensively used in China, the absolute number of EC failures observed is higher when compared with that in other countries. When LNG-EC fails, some nulliparous women in China choose to continue their pregnancies.
In the context of LNG-EC failure, only limited data have been available on the effect of the pregnancy outcomes. Some animal studies have indicated a dose-dependent virilization of female fetuses related to LNG's androgenic character (Grumbach, 1959; Gindi and Ahmed-Nasr, 1993). But other authors consider that there is not enough evidence to prove the relationship between the oral contraception pills and the pudendum abnormalities (Bracken, 1990; Raman-Wilms et al., 1995). In more than 6000 published cases of LNG-EC use, there have been no reports on adverse birth outcomes, but only a small number of normal deliveries after LNG-EC failure have actually been documented (Camp et al., 2003). Recently, De Santis et al. (2005) reported a study of 36 women exposed to LNG compared with a control group (80 cases), which showed no statistical differences between the groups in terms of spontaneous or legal abortion, major congenital malformations, prepartum or peripartum complications or adverse pregnancy outcomes.
The purpose of this study is to further explore the possible consequences of LNG-EC exposure on subsequent pregnancy outcomes. We compared fetal development and pregnancy outcome in a cohort of pregnant women who decided to continue their pregnancies after LNG-EC ingestion to that in a group of healthy pregnant women unexposed to the LNG-EC presenting in our hospital outpatient clinic during the same time period. In this prospective study, we also investigated the possible relationships between the doses of LNG taken and the risks of adverse pregnancy outcomes.
Abstract and Introduction
Abstract
BACKGROUND: Levonorgestrel (LNG), as a dedicated emergency contraception (EC) product, has been available over-the-counter in China for 10 years. Until now, only a small number of deliveries after LNG-EC failure have been documented.
METHODS: This study was a prospective comparative cohort study. A group of 332 pregnant women who had used LNG-EC during the conception cycle was recruited, and matched to a group of 332 pregnant women without the exposure to LNG. Congenital malformations, perinatal complications and delivery circumstances were investigated in this study.
RESULTS: There were 31 pregnant women in the study group and 28 in the comparison group miscarried within 14 weeks of gestation. In the study and comparison groups, four malformations were found in each group. In the study group, both birthweight (3416 versus 3345 g, P = 0.040) and the sex ratio of birth (boys/girls, 1.14 versus 0.90, P = 0.153) were higher than in the comparison group. There were no statistically significant differences in the incidence of miscarriage or malformation or in the neonatal outcome between the two groups.
CONCLUSIONS: There was no association between the use of LNG-EC pills and the risk of major congenital malformations, pregnancy complications or any other adverse pregnancy outcomes in our study.
Introduction
Levonorgestrel (LNG) administered at a dose of 1.5 mg (given either as a single 1.5 mg dose or two 0.75 mg doses taken 12 h apart) is a safe and well-tolerated method for emergency contraception (EC) (Cheng et al., 2008). In China, LNG is marketed in packs containing either two or four 0.75 mg tablets, or one tablet of 1.5 mg of LNG. When taken within 72 h after intercourse, the method prevents ~85% of the pregnancies that will occur without treatment (WHO, 1998; von Hertzen et al., 2002; Sarkar, 2003). Single dose (1.5 mg) administration has a similar effectiveness as the standard two-dose regimen (0.75 mg twice, 12 h apart) (Cheng et al., 2008; von Hertzen et al., 2002).
The mechanisms of LNG-EC action have not been fully characterized. It is generally believed that LNG can prevent or delay ovulation (Croxatto et al., 2001; Marions et al., 2002), modify endometrial receptivity, thicken cervical mucus and impair the formation of the corpus luteum (Croxatto et al., 2001). Recent animal studies convincingly show that LNG does not interfere with post-fertilization events (Croxatto et al., 2003; Müller et al., 2003).
The currently reported pregnancy (failure) rate with LNG-EC is between 0.2 and 3.0% after one single coital act (Cheng et al., 2008), making LNG-EC less effective than regular contraceptive methods (pregnancy rates for combined oral contraceptives in the first year of use are reported from 0.3% for perfect use to 8% for typical use, and for intrauterine devices pregnancy rates are reported as 0.1-2.2% for up to 12 years of exposure) (Grimes, 2007; Hatcher and Nelson, 2007).
LNG-EC has been available over-the-counter (OTC) since 1998 in China and up to 2005, it was estimated that over 30 million boxes were sold annually there (Cheng, personal data). Similar to women in Britain and Sweden (Blanchard et al., 2003; Larsson et al., 2004), Chinese women are more likely to purchase EC directly from pharmacies than to obtain it with a doctor's prescription. Young unmarried women under 24 years of age are the main EC users in China (Kang et al., 2007a, b). Because LNG-EC is extensively used in China, the absolute number of EC failures observed is higher when compared with that in other countries. When LNG-EC fails, some nulliparous women in China choose to continue their pregnancies.
In the context of LNG-EC failure, only limited data have been available on the effect of the pregnancy outcomes. Some animal studies have indicated a dose-dependent virilization of female fetuses related to LNG's androgenic character (Grumbach, 1959; Gindi and Ahmed-Nasr, 1993). But other authors consider that there is not enough evidence to prove the relationship between the oral contraception pills and the pudendum abnormalities (Bracken, 1990; Raman-Wilms et al., 1995). In more than 6000 published cases of LNG-EC use, there have been no reports on adverse birth outcomes, but only a small number of normal deliveries after LNG-EC failure have actually been documented (Camp et al., 2003). Recently, De Santis et al. (2005) reported a study of 36 women exposed to LNG compared with a control group (80 cases), which showed no statistical differences between the groups in terms of spontaneous or legal abortion, major congenital malformations, prepartum or peripartum complications or adverse pregnancy outcomes.
The purpose of this study is to further explore the possible consequences of LNG-EC exposure on subsequent pregnancy outcomes. We compared fetal development and pregnancy outcome in a cohort of pregnant women who decided to continue their pregnancies after LNG-EC ingestion to that in a group of healthy pregnant women unexposed to the LNG-EC presenting in our hospital outpatient clinic during the same time period. In this prospective study, we also investigated the possible relationships between the doses of LNG taken and the risks of adverse pregnancy outcomes.