Postgraduate Medical Institute, Hull and York Medical School, Academic Department of Obstetrics and Gynaecology, Hull, UK
1 To whom correspondence should be addressed at: Womens and Childrens Hospital, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, UK. e-mail: mamhassan{at}yahoo.com
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Abstract |
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Key words: contraception/fecundity/fertility/lifestyle/time to pregnancy
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Introduction |
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A huge literature on the efficacy and safety of various contraceptive methods already exists (Vessey et al, 1982; Hannaford and Kay, 1998
; World Health Organization Scientific Group, 1998
; Beral et al, 1999
; Hannaford, 2000
) while the effects of the modern and new methods on subsequent fertility are yet to be substantiated. Such effects may be viewed as a spectrum extending from contraceptive failure to impaired fertility. Contraceptive failure may reflect a high fecundity of the couple or a reduced efficacy of the contraceptive method or may reflect the couples inadequate contraceptive knowledge, their fear of side-effects or their belief that they are less fecund to the extent of using unreliable methods for contraception or using effective methods inconsistently (Milsom et al, 1991
; Jones and Forrest, 1992
; Baird et al, 1994
; Rosenberg et al, 1995
; Olsen et al, 1998
; Peterson et al, 1998
; Ranjit et al, 2001
). On the other hand, while the immediate return of fertility after discontinuing barrier contraception is to be expected, the effect of hormonal contraception and of the intrauterine contraceptive devices, which have multiple contraceptive effects, on future fertility is less certain (Whitelaw, 1967
; Vessey et al, 1978
). In addition, the effect of all the methods on future fertility may be compounded by other factors such as the individual and lifestyle characteristics of the couples.
This study aimed to evaluate the impact of each of the commonly used contraceptive methods on subsequent fecundity as measured by the time to pregnancy (TTP) and the conception rates for users of each method after discontinuing contraception, before and after adjustment for the effects of the individual and lifestyle factors. The effect of the duration of contraceptive use, overall and for the individual methods, was also evaluated.
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Materials and methods |
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The questionnaire was validated in a way similar to that used for earlier questionnaires (Hassan and Killick, 2003a,b; Hassan and Killick, 2004
). An independent assessor interviewed women in the clinic after self-completing the questionnaire to ensure that they had understood exactly what information was required from each question. Another group was asked to complete the questionnaire on two occasions, 2 weeks apart, to ensure that their answers were consistent. Approval was obtained from the Local Research Ethics Committees in both centres. No conflicts of interest existed. The response rate (ratio of returned questionnaires to the distributed ones) was >98% and the sample included 2841 completed questionnaires.
Data analysis was carried out using SPSS (Statistical Package for Social Sciences). The outcome measures were the mean TTP, conception rate (CR) and odds ratio (OR) of subfecundity (TTP >12 months) after discontinuing each contraceptive method compared with those after condom use overall and in relation to short- and long-term use (2 or >2 years). Statistical tests used in the analysis were non-parametric (MannWhitney U-test; KruskalWallis,
2-test) tests and regression models (general linear model for TTP and binary logistic regression for subfecundity). Survival analysis was not used, as there were no censored data in this sample. Statistical significance was indicated by P < 0.05.
The individual and lifestyle characteristics were compared according to the contraceptive methods to identify factors that may have biased the effect of contraceptive use on later fecundity. The mean TTP after discontinuing each contraceptive method was compared with that after condom use, overall and in relation to duration of use. The effect of contraceptive duration on subsequent TTP for each method was studied. CR in 6, 12 and 24 months after discontinuing each method and the OR of subfecundity relative to condom use were calculated, overall and for short and long-term use. Regression analysis was used to adjust for potential confounders (e.g. both partners age, weight, smoking and alcohol consumption, tea/coffee intake and recreational drug use as well as parity, coital frequency, menstrual pattern and age at menarche).
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Results |
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Using stepwise logistic regression, of the factors introduced into the model, a significant effect on the likelihood of subfecundity was detected with age (P < 0.0001), womens weight (P < 0.0001), partners smoking (P = 0.02), womens smoking (P = 0.04), partners alcohol consumption (P = 0.01), parity (P = 0.007), the duration of contraceptive use (P = 0.009), the contraceptive method used before pregnancy [COC (P = 0.004), injectables (P < 0.0001) or implant (P = 0.01) compared with condom use] and the menstrual pattern (P < 0.0001), all adjusted for the effects of the other factors.
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Discussion |
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A modest significant decline in fecundity after stopping COC use was found. Mean TTP of previous COC users was 3 months longer, the OR of subfecundity was doubled and they were 2.5-fold more likely to take >2 years to conceive, compared with condom users. The overall effect is similar to that shown by studies of high-dose COC (Pardthaisong and Gray, 1981; Linn et al, 1982
; Vessey et al, 1986
) and the residual effect of COC use on fertility seems to be dose-independent. Similar to other studies (Papiernik and Rozenbaum, 1975
; Harlap, 1979
; Weisberg, 1982
; Harlap and Baras, 1984
; Speroff, 1989
; Bracken et al, 1990
) the effect of COC use, compared with condom use, was more evident in older women and those who had weight or menstrual disturbances, i.e. those with potentially compromised ovarian function. The negative effect of previous COC use on subsequent fertility could probably be due to transient persistence of ovarian suppression or anovulation, particularly in susceptible women (Hull et al, 1981a
; Thomas and Forrest, 1983
). In clinical terms, however, and apart from cases of low ovarian function, this and other studies show that the effect of previous COC use on subsequent fertility is trivial (Portuondo et al, 1979
; Lahteenmaki et al, 1980
; Hull et al, 1981b
; Huggins and Cullins, 1990
; Hassan et al, 1994
; Chasan-Taber et al, 1997
).
The above results, which showed a progressive decline in subsequent fecundity after prolonged COC use, do not agree with the results of the study by Farrow et al. (2002), in which they suggested that previous prolonged use of oral contraception is associated with improved fecundity. There are several possible explanations for this difference. First, in the study by Farrow et al. unintentional pregnancies were excluded. Short-term contraceptive users are more likely to have experienced an unintentional pregnancy, and this was mirrored in the relatively small proportion of short-term users (<2 years) analysed in their study (18.0%) compared with short-term users in our sample (51.3%). An unintentional pregnancy may reflect high fecundity, and exclusion of these unintentional pregnancies means that short-term users would mistakenly seem less fecund compared with long-term users. We felt that inclusion of these would be practically more reflective. Second, less fertile women are less likely to use an effective contraceptive method such as COC, especially in the long-term. Consequently long-term users would appear relatively more fertile due to self-selection. Third, long-term contraceptive users are relatively older and hence less likely to persist in trying for pregnancy than short-term users. Consequently, potentially subfertile long-term contraceptive users are more likely to be excluded from studies of pregnant samples than short-term users, and long-term users may appear more fecund than short-term users, another source of selection bias. Therefore, we felt that, in order to assess the effect of duration of use of each contraceptive method, we should control for these and other biasing factors by using groups of condom users with matched durations of use for comparison purposes (Tables III and V). No such comparisons between COC use and the use of other contraceptive methods have been made in the study by Farrow et al. Finally, in the study by Farrow et al., early pregnancies were excluded and no differentiation between the use of COC or POP, which have been shown to have different effects on subsequent fecundity, was made.
Similarly, previous use of the injectables was associated with a significant reduction in subsequent fecundity (Schwallie and Assenzo, 1974; Ellinas, 1977
; Fraser, 1982
; Kaunitz, 1996
). Mean TTP was 3-fold longer, conception rate was halved and odds of subfecundity increased to 5.5-fold relative to condom use. The delay in the return of fertility after injectable use was >1 year (Kaunitz, 1998
) and in this study was even longer with prolonged use, in older women, obese women and those with menstrual disturbances. This cannot entirely be explained by delayed clearance of the residual drug from the body (Pardthaisong et al, 1980
; Pardthaisong, 1984
). As with previous COC use, the effect of the injectables on subsequent fertility could at least partly be due to residual ovarian suppression after stopping use (Saxena et al, 1980
; Garza-Flores et al, 1985
). These results apply to depot medroxyprogesterone acetate, the only injectable contraceptive currently licensed for long-term use in the UK. Studies investigating previous use of other injectables, e.g. norethisterone oenanthate (Fotherby et al, 1984
; Indian Council of Medical Research, 1986
) and Cyclofem (Bassol and Garza-Flores, 1994
; Bahamondes et al, 1997
) did not show a detrimental effect on later fertility.
Only short-term IUD use was associated with a negative effect on later fecundity in this sample. Compared with condom use, short-term IUD users had 1.6-fold longer TTP and were 2.9-fold more likely to be subfecund, but none of the long-term users was subfecund. This effect may be explained by occurrence of events for which IUD use was prematurely discontinued and which have negatively affected fecundity (World Health Organization Task Force, 1984; Sandmire, 1986
; Skjeldestad and Bratt, 1988
; Wilson, 1989
; Gayer and Henry-Suchet, 1990
). It could perhaps be due to a residual foreign body reaction in the short term that tends to settle with long-term use. It should be remembered that IUD users who consequently develop tubal subfertility are excluded from this study, and the effect of previous IUD use, especially long term, on subsequent fertility could have been underestimated. Results of other studies are inconsistent; some showing absence of a detrimental effect (Randic et al, 1977
; Vessey et al, 1983
; Randic et al, 1985
; Batar, 1986
; Skjeldestad and Bratt, 1987
; Gupta et al, 1989
; Bastianelli et al, 1998
; Delbarge et al, 2002
) and others showing a negative effect with long-term use (Tietze, 1968
; Anwar et al, 1993
; Doll et al, 2001
).
All IUS users in this study conceived within 1 month of its removal, whereas, unlike other studies (Belhadj et al, 1986; Affandi et al, 1987
; Diaz et al, 1987
; Andersson et al, 1992
; Sivin et al, 1992
; Glasier, 2002
), previous implant use was associated with a significant negative effect on subsequent fecundity. These results, however, should be interpreted with caution in view of the small numbers studied (13 and four respectively). The results of this study, like those of previous studies (Chi, 1993
; Perheentupa et al, 2003
), indicate that previous POP use is not associated with a detrimental effect on subsequent fertility. Those who denied past use of contraception in this sample had a significantly reduced fecundity. This could be explained by prior knowledge of their reduced fertility (26.3%) or their very sporadic coital frequency (29.5%).
Based on the above results, it appears that the contraceptive methods that act principally by ovarian suppression such as COC and the injectables might have a transient residual negative effect on subsequent fertility, particularly in the women who already have potentially compromised ovarian function. In such women, other methods, e.g. POP, provide effective means of contraception without a significant impact on later fertility. However, COC users should be reassured that the effect on later fertility is small. Further studies involving large numbers of IUS and implant users, in order to ratify their effects on later fecundity, are warranted.
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Acknowledgement |
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Submitted on August 8, 2003; accepted on October 1, 2003.