Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy

Study population

From 1992 to 1995 a total of 430 couples were recruited after a nationwide mailing of personal letters to 52 255 trade union members (metalworkers, office workers, nurses, and day care workers) who were 20-35 years old, lived with a partner, and had no children. Couples without previous reproductive experience who intended to discontinue contraception to become pregnant were eligible for enrolment. The exact number of eligible couples in the source population of 52 255 people was unknown. Under the assumption that 75% of pregnancies in Denmark are planned, an average participation rate of 16% was estimated by using data from union, age, parity, and calendar specific birth rates obtained from the Danish civil registration system. A detailed description of the study cohort is provided elsewhere.21

Enrolment and follow up

The couples were enrolled into the study when they discontinued birth control and were followed for six menstrual cycles or until a clinically recognised pregnancy. The couples were enrolled at two centres in Denmark: the department of occupational medicine in Aarhus (west centre) and the department of growth and reproduction in Copenhagen (east centre). At enrolment both partners filled in a questionnaire on demographic, medical, reproductive, occupational, and lifestyle factors and the men provided a semen sample. During follow up the women recorded vaginal bleeding and sexual intercourse daily, and one additional semen sample was collected during the menstrual period of each cycle. Finally, couples completed a monthly questionnaire on changes in occupational exposures and lifestyle factors.

The couples were asked to report on smoking and intake of alcohol and caffeine as average daily or weekly consumption during the week before completion of the questionnaire. Smoking habits were reported as the average number of cigarettes, cigars, or pipes smoked a day. The key question on intake of alcohol intake was: “How much did you consume of the following beverages during the last week: bottles of beer (0.33 l), glasses of wine and spirits (about 12 g alcohol in each).” The total weekly alcohol intake (number of drinks) was calculated by summing the intake of beer, wine, and spirits. Intake of coffee, tea, and beverages containing chocolate was measured as the average number of cups a day, and consumption of cola drinks was measured as the average weekly number of bottles [0.25 l] consumed to estimate each person's daily caffeine intake.22If the information on lifestyle factors was missing in a monthly questionnaire the person was assumed to have consumed the same amount of caffeine and alcohol or smoked the same number of cigarettes as during the previous month.

The participants were also asked: “Did your mother smoke when she was pregnant with you?” and to report whether this information was provided by their mother or not. Body mass index was calculated as weight divided by height squared (kg/m²). Reported diseases associated with fecundability (salpingitis, ovarian cysts, gonorrhoea, peritonitis, epididymitis, adult parotitis, testicular cancer, and cryptorchidism) were transformed into one variable (present or not present) for both men and women.

Women recorded sexual intercourse daily, but this information was missing for 336 cycles (available for 1325 cycles). If the information was missing in one cycle the frequency of sexual intercourse was assumed to be the same as during the previous months, but in 205 cycles (88 couples) no diary information on sexual intercourses was obtained because the women became pregnant in the first cycle before the diaries were handed out. Therefore, this information was not used, and we excluded cycles with no intercourse from day 11 to 20 in the cycle as no couples who refrained from intercourse in that period became pregnant (47 cycles).

The number of cycles to pregnancy or to the end of follow up were calculated from the day the couples discontinued contraception. Day 1 of the cycle was defined as the day of onset of menstrual bleeding. If the discontinuation was 10 days or more before the first day of the next menstrual bleeding or the expected day of the next menstrual bleeding (calculated from last menstrual bleeding and cycle length) the cycle was counted as the first. For other couples the first cycle was that after the first menstrual bleeding after discontinuation of contraception. Couples who dropped out of the study before the six follow up cycles were censored at the cycle in which they stopped participation (n=22). Data were available on 1661 cycles. Seven couples were excluded because of azoospermia. A total of 423 couples with 1596 cycles were included in the analyses.

Statistical analyses

Alcohol intake was categorised before the analyses into five levels; 0, 1-5, 6-10, 11-15, and >15 drinks a week and was also entered as a continuous variable. Furthermore, we computed the mean alcohol intake for all reported cycles. We also compared couples with a weekly alcohol intake of over five drinks in the entire follow up period with couples with a lower weekly intake in all cycles (this was performed for men and women separately). No significant interaction between alcohol intake and caffeine or smoking was found. Accordingly no interaction terms were entered in the multiple logistic regression analyses, but smoking and caffeine intake were entered as confounders.

The time to pregnancy by level of alcohol intake was analysed by survival analysis techniques, which are equivalent to logistic regression on the total number of observed cycles with the outcome “pregnant/not pregnant.” Fecundability denotes the probability of obtaining a clinically recognised pregnancy in a menstrual cycle among couples not pregnant in the previous cycles. The fecundability odds ratio measures the odds of conception among exposed couples divided by the odds among those not exposed. Other variables mentioned above were excluded stepwise and if the point estimate of the association between alcohol intake and fecundability changed by less than 10% after exclusion, the variable was removed from the final model. Those variables which did not affect point estimates by 10% or more were also not significant at the 5% level.

Potential confounders were examined in bivariate analyses by comparing couples who became pregnant within six cycles with couples who did not. The following variables were related to becoming pregnant during follow up: the woman's age, smoking in either partner or smoking exposure in utero, diseases in the reproductive system of either partner, sperm concentration (categorised as <10, 10-19, 20-49, and >49 million/ml), duration of menstrual cycle, use of oral contraceptives as last method of birth control, and the woman's body mass index. Variables not associated with fecundability were centre of enrolment, age at menarche, the man's body mass index, the man's age, and caffeine intake of both partners.

The square root transformed continuous alcohol intake was entered into the multivariate model. Furthermore, dummy variables were created for each source of alcohol intake. Also, men and women who reported alcohol intake from only beer, only wine, or from other sources were included in all analyses to determine the independent effect of each. Fecundability odds ratios are presented with 95% confidence intervals.

Possible bias

The rate of pregnancies per cycle and the proportion of women who became pregnant during six cycles with unprotected intercourse (65%) was slightly lower in this study than in some of the previously published follow up studies.1426 Study designs and methods differed, however, and the populations are not necessarily comparable. Recruitment bias may explain the low pregnancy rate in six cycles if couples with suspected fertility problems are included more often. To avoid this source of bias, couples should be unaware of their reproductive capacity and have used contraception before the study, but couples using less reliable methods of contraception for a longer time might suspect fertility problems. Bias in relation to the reported associations between fecundability and alcohol intake is likely only if infertile couples with high alcohol intake were oversampled. This is unlikely as alcohol intake is not an established risk factor for infertility.

The exclusion of couples with unplanned pregnancies may cause selection bias, and the magnitude of this bias cannot be ruled out as only couples planning a pregnancy were invited to take part in the study. If alcohol intake is associated with irregular use of birth control, or the use of less effective methods, the fecundability of alcohol consumers will be underestimated. Also, the repetitive measurement of alcohol intake during follow up may change the intake. The alcohol intake was, however, relatively constant across cycles.

Effect of alcohol on women's fertility

The observed reduction of female fecundability even among women with a low alcohol intake (five drinks a week) was unexpected and has not previously been reported.,16^–20The observation that higher alcohol intake is associated with reduced fecundability is supported by previous studies. 17 18 The biological evidence for a detrimental effect of alcohol on female fecundability,1^–3 27 may indicate an effect of a moderate intake at critical time periods around the time of conception. We obtained information on alcohol intake around ovulation but most other studies have relied on more general exposure data, such as average alcohol intake before conception, that was obtained only once during follow up or retrospectively (with recall of up to several years). This is more likely to lead to misclassification and underreporting of exposure. One study among women receiving artificial donor insemination reported slightly higher fecundability in women consuming 1-10 glasses of alcoholic beverage the week before insemination than in women with no alcohol intake.19 The women were not asked about changes in alcohol intake over the study period, and a quarter of the women who became pregnant reported a different alcohol intake after the the study period than during it.

Two studies found no effect even of high weekly alcohol intake (more than 12 drinks) on fecundability. 16 28 In one study the mean time from exposure to questioning was almost 10 years, and recall bias probably explains the negative findings.28 The other study included only a few women from one occupational group, and 60% had tried to conceive before enrolment in the study.16 Two other studies found no association between alcohol intake and fecundability at low exposures, but a detrimental effect was found among women who consumed more than eight drinks a week. 17 18 Data were obtained retrospectively during pregnancy, which may have affected the results.

Several retrospective studies have found no significant unadjusted effect of alcohol intake in women, 14 29 30 and some studies that have included alcohol intake as a confounder in the multivariate analysis of other risk factors have found no independent effect. 12 20 31 32 Several case-control studies have found that infertile women who seek medical care have a significantly higher alcohol intake than women who become pregnant naturally. 6 8 33 These studies are vulnerable to selection bias, however, as only half of all couples with infertility problems seek medical care. 34 35 Also, the couples with problems may have to remember their intake further back in time than those without problems (controls), which may cause bias, and couples with problems may have changed their drinking habits because of their infertility. One study included no information on when alcoholexposure was assessed, and exposure was measured as no use or frequent use.8 The quality of our data on alcohol exposure may thus be better than other published studies with respect to accuracy and time specificity, and that may explain our findings of decreased fecundability even at low alcohol exposures.

No effect of men's alcohol intake on fecundability was observed, which is consistent with other studies. 16 18 28 Only a few studies have evaluated the effect of alcohol intake on semen quality and no association has been found.,36^–39

We found an association between women's alcohol intake and decreased fecundability even among women who had five or fewer drinks a week, which would indicate that fecundability is reduced in a high proportion of women because of alcohol intake. This finding needs further corroboration, but it seems reasonable to encourage women to reduce their intake of alcohol or not to drink at all when they are trying to become pregnant.