The median age was 29, and about two-thirds of the women had previously been pregnant (Table ). About half of pregnancies in the study had implantation on Day 10 or later. Only 11 pregnancies (6%) were to women who were self-reported smokers. Seven pregnancies (5%) were to women who reported prenatal diethylstilbestrol (DES) exposure, and 47 (28%) pregnancies were to women who reported that their mother had smoked while pregnant with them.
Distribution of maternal and pregnancy characteristics within the two study samples, all conceptions (n= 189) and clinical pregnancies only (n= 142).
Time from ovulation to implantation
Women who were current smokers had five times the odds of late implantation as never or former smokers [odds ratio (OR) (95% confidence interval, CI): 5.3 (1.3, 36), P= 0.03] (Fig. ). There were not enough current smokers to evaluate a dose–response relationship. The association between husband's smoking and late implantation was also positive but weaker [OR (CI): 1.8 (0.64, 5.7)].
ORs and 95% CIs for late implantation (≥10 days post-ovulation).
Implantation was also later among conceptions that resulted from a long oocyte-waiting time [OR (CI): 5.1 (1.9, 16), P= 0.0008] (Fig. ). Late implantation was more common in exposed early losses, but not exclusive to them. When we restricted analysis to clinical pregnancies, the association between oocyte-waiting time and late implantation was still evident, but attenuated [OR (CI): 2.2 (0.63, 8.0)].
Given our previous observation that a long oocyte-waiting time led to early loss (Wilcox et al., 1998
), we explored whether that association might be mediated by late implantation. We included both oocyte-waiting time and late implantation as predictors in a logistic regression of early loss. While the effect of oocyte-waiting time was attenuated when adjusted for late implantation (from an OR of 3.9 to 2.7), it was still significantly associated with early loss (P
Women who reported that their mother had smoked while pregnant with them had less late implantation [OR (CI): 0.48 (0.23, 0.96), P= 0.04]. The odds of late implantation also tended to be lower for women who had lived with one or more household smokers (mother, father or other) during their childhood (P= 0.11) (Fig. ).
We explored the robustness of these associations with current smoking and prenatal exposure to maternal smoking by limiting the analysis to clinical pregnancies. The association between current smoking and late implantation was similar [5.5 (1.2, 39)] and the protective association of prenatal exposure to maternal smoking and late implantation was slightly stronger, 0.35 (0.14, 0.83). After further restricting to only live births (i.e. excluding the 15 clinical miscarriages), the associations again became slightly stronger [current smoking, 6.1 (1.3, 44) and prenatal maternal smoking exposure 0.31 (0.11, 0.77)].
Season of the year [previously associated with early loss in these data (Weinberg et al., 1994
)] was not associated with the timing of implantation (P
= 0.97, data not shown).
Rate of hCG rise
Three factors were associated with the steepness of the initial hCG rise: age, age of menarche and DES. Older women had a faster rise (P= 0.01) (Fig. ). This could not be attributed to their increased gravidity which was not associated with rate of rise (P= 0.25). When pregnancy losses were removed, the P-value increased to 0.08. The P-value for age when age at menarche was included in the model was unchanged (0.01). Excluding the DES-exposed women led to a stronger P-value (P= 0.006). Age at menarche was weakly associated with hCG rise, with women who were younger at menarche having a slower hCG rise (P= 0.09) (Fig. ). A linear trend test of the age at menarche categories was significant, P= 0.02. This P-value was not affected by adjustment for BMI (P= 0.02) or removing the pregnancy losses (P= 0.03); however removing the DES-exposed participants increased the P-value (0.06). Exposure to DES in utero was associated with a distinct pattern of hCG increase (P= 0.002) (Fig. ). Exposed women had a slower hCG rise up to Day 4 and then a faster rise thereafter. Interpretation of this finding is limited by the fact that only four pregnancies were to DES-exposed mothers. Removing the pregnancy losses did not alter the P-value (P= 0.002).
Average relative increase in hCG over the first 7 days of pregnancy beginning with the day of implantation (Day 1), stratified by participant age at intake, P= 0.01. Solid line represents women 29 or older; the dotted line represents women under 29.
Figure 3 Average relative increase in hCG over the first 7 days of pregnancy beginning with the day of implantation (Day 1), stratified by age at menarche, P= 0.01. The solid line represents women <12 at menarche, the small dashed line represents women (more ...)
Figure 4 Average relative increase in hCG over the first 7 days of pregnancy beginning with the day of implantation (Day 1), stratified by in utero exposure to DES, P= 0.002. The solid line represents women not exposed to DES in utero; the dotted line represents (more ...)