Association of Maternal Factors With Delayed Implantation
Background: Late implantation and the pattern of early rise in hCG have been associated with early pregnancy loss. We explored factors that might be predictive of these markers of poor embryonic health in spontaneously conceived pregnancies.
Methods: Participants in the North Carolina Early Pregnancy Study collected daily first-morning urine specimens while attempting to conceive. Samples were assayed for estrogen and progesterone metabolites (to identify day of ovulation) and hCG (to detect conception). Data were available for 190 pregnancies, 48 of which ended in early loss (within 6 weeks of the last menstrual period). We used logistic regression to identify characteristics associated with late implantation (≥10 days post-ovulation). For pregnancies surviving at least 6 weeks (n= 142), we used linear mixed models to identify factors associated with variations in hCG rise in the first 7 days from detection.
Results: Later implantation was associated with current maternal smoking [odds ratio (OR): 5.7; 95% confidence interval (CI): 1.1–30] and with oocytes that were likely to have been fertilized late in their post-ovulatory lifespan (OR: 5.1; CI: 1.9–16). Older women had a faster rise in hCG (P= 0.01), as did women who had relatively late menarche (P for trend = 0.02). Women exposed in utero to diethylstilbestrol showed an unusual pattern of slow initial hCG rise followed by a fast increase, a pattern significantly different from that of unexposed women (P= 0.002).
Conclusions: Although limited by small numbers and infrequent exposures, our analyses suggest that a woman's exposures both early in life and at the time of pregnancy may influence early development of the conceptus.
hCG is secreted by trophoblast cells of the early conceptus and the developing placenta, and performs vital functions in early pregnancy. These include maintenance of the corpus luteum (Zeleznik and Pohl, 2006) and formation of the placental syncytium (Yang et al., 2003). The appearance of hCG in maternal urine can be used as a marker of embryonic implantation (Wilcox et al., 1999). Delayed implantation has been associated with early pregnancy loss (Wilcox et al., 1999). Lower hCG levels and slower rates of hCG rise early in pregnancy are seen in ectopic pregnancies (Kadar et al., 1981; Check et al., 1992; Seeber et al., 2006) and have been associated with pregnancy loss (Check et al., 1992; Bjercke et al., 1999; Urbancsek et al., 2002; Baird et al., 2003; Alahakoon et al., 2004; Stone et al., 2006; Shamonki et al., 2009) (reviewed in Chung and Allen, 2008). Most of these studies have been based on clinical populations undergoing fertility treatment, which may not be representative of spontaneously conceived pregnancies. Given that timing of implantation and early pregnancy hCG rise may be markers of pregnancy health, we explored maternal and pregnancy characteristics that may influence these markers. We studied a cohort of women with spontaneously conceived pregnancies under observation from before the time of conception.
Abstract and Introduction
Abstract
Background: Late implantation and the pattern of early rise in hCG have been associated with early pregnancy loss. We explored factors that might be predictive of these markers of poor embryonic health in spontaneously conceived pregnancies.
Methods: Participants in the North Carolina Early Pregnancy Study collected daily first-morning urine specimens while attempting to conceive. Samples were assayed for estrogen and progesterone metabolites (to identify day of ovulation) and hCG (to detect conception). Data were available for 190 pregnancies, 48 of which ended in early loss (within 6 weeks of the last menstrual period). We used logistic regression to identify characteristics associated with late implantation (≥10 days post-ovulation). For pregnancies surviving at least 6 weeks (n= 142), we used linear mixed models to identify factors associated with variations in hCG rise in the first 7 days from detection.
Results: Later implantation was associated with current maternal smoking [odds ratio (OR): 5.7; 95% confidence interval (CI): 1.1–30] and with oocytes that were likely to have been fertilized late in their post-ovulatory lifespan (OR: 5.1; CI: 1.9–16). Older women had a faster rise in hCG (P= 0.01), as did women who had relatively late menarche (P for trend = 0.02). Women exposed in utero to diethylstilbestrol showed an unusual pattern of slow initial hCG rise followed by a fast increase, a pattern significantly different from that of unexposed women (P= 0.002).
Conclusions: Although limited by small numbers and infrequent exposures, our analyses suggest that a woman's exposures both early in life and at the time of pregnancy may influence early development of the conceptus.
Introduction
hCG is secreted by trophoblast cells of the early conceptus and the developing placenta, and performs vital functions in early pregnancy. These include maintenance of the corpus luteum (Zeleznik and Pohl, 2006) and formation of the placental syncytium (Yang et al., 2003). The appearance of hCG in maternal urine can be used as a marker of embryonic implantation (Wilcox et al., 1999). Delayed implantation has been associated with early pregnancy loss (Wilcox et al., 1999). Lower hCG levels and slower rates of hCG rise early in pregnancy are seen in ectopic pregnancies (Kadar et al., 1981; Check et al., 1992; Seeber et al., 2006) and have been associated with pregnancy loss (Check et al., 1992; Bjercke et al., 1999; Urbancsek et al., 2002; Baird et al., 2003; Alahakoon et al., 2004; Stone et al., 2006; Shamonki et al., 2009) (reviewed in Chung and Allen, 2008). Most of these studies have been based on clinical populations undergoing fertility treatment, which may not be representative of spontaneously conceived pregnancies. Given that timing of implantation and early pregnancy hCG rise may be markers of pregnancy health, we explored maternal and pregnancy characteristics that may influence these markers. We studied a cohort of women with spontaneously conceived pregnancies under observation from before the time of conception.
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