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Negative lifestyle is associated with a significant reduction in fecundity

  • Mohamed A.M Hassan
    Correspondence
    Reprint requests: Mohamed A. M. Hassan, M.Sc., Women's and Children's Hospital, Hull Royal Infirmary, Anlaby Road, Hull HU3 2JZ, United Kingdom (FAX: 0044-1482-382781).
    Affiliations
    The University of Hull, Postgraduate Medical Institute, Hull and York Medical School, Academic Department of Obstetrics and Gynaecology, Women's and Children's Hospital, Hull Royal Infirmary, Hull, United Kingdom
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  • Stephen R Killick
    Affiliations
    The University of Hull, Postgraduate Medical Institute, Hull and York Medical School, Academic Department of Obstetrics and Gynaecology, Women's and Children's Hospital, Hull Royal Infirmary, Hull, United Kingdom
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      Abstract

      Objective

      To evaluate the association patterns and quantify the effects of lifestyle on time to pregnancy (TTP).

      Design

      Observational study.

      Setting

      Teaching hospitals in Hull, United Kingdom.

      Patient(s)

      Two thousand and one hundred twelve consecutive pregnant women.

      Intervention(s)

      A questionnaire inquiring about TTP, contraceptive use, pregnancy planning, previous subfertility/pregnancies, age, and lifestyle characteristics of either partner.

      Main outcome measure(s)

      We compared TTP, conception rates, and relative risk of subfecundity between subgroups with different lifestyle characteristics.

      Result(s)

      We found that TTP was significantly longer if the woman or partner smoked >15 cigarettes/day (P<.001 and .04, respectively), the partner consumed >20 alcohol units/week (P<.001), the woman's body mass index was >25 kg/m2 (P<.001), their coffee and/or tea intake was >6 cups/day (P=.04), or if they were socially deprived (P<.001). Each of these effects remained unchanged after adjusting for the potential confounders. The relative-risks of subfecundity with each of these variables ranged between 1.4 to 1.9 (1.4 to 3.6 after adjustment). The effects of coital frequency and recreational drug use were insignificant. Couples who had >4 negative lifestyle variables had a sevenfold longer TTP; their conception probabilities fell by 60%, and they were 7.3-fold more likely to be subfecund than those without negative variables.

      Conclusion(s)

      Lifestyle has a significant and cumulative impact on fecundity. Dose-dependent effects occur with smoking, alcohol, and tea/coffee consumption. Appropriate counseling could result in substantial reductions in the referrals for fertility investigations and treatments.

      Keywords

      Half of the couples trying for a pregnancy succeed within 3 months, increasing to over 85% by end of the first year (
      • Bongaarts J.
      A method for the estimation of fecundability.
      ). An unsuccessful waiting time to pregnancy (TTP) despite frequent unprotected intercourse of >12 months is usually used to define subfertility (
      ESHRE Capri workshop
      Guidelines to the prevalence, diagnosis, treatment and management of infertility.
      ) and is commonly employed as an indication for commencing investigations (
      • Hull M.G.R.
      • Glazener C.M.A.
      • Kelly N.J.
      • Conway D.I.
      • Foster P.A.
      • Hinton R.A.
      • et al.
      Population study of causes, treatment, and outcome of infertility.
      ). However, 30% of the subfertile couples have no identifiable medical cause, (
      • Templeton A.
      Infertility-epidemiology, aetiology and effective management.
      ) and over 70% of these unexplained cases conceive within a further 24 months of trying without any medical intervention (
      • Hull M.G.R.
      Infertility treatment relative effectiveness of conventional and assisted conception methods.
      ). Differences in the individual and lifestyle characteristics have been suggested to have a role, though poorly quantified, in the cause of subfertility (
      • Van Noord-Zaadstra B.M.
      • Looman C.W.
      • Alsbach H.
      • Habbema J.D.
      • te Velde E.R.
      • Karbaat J.
      Delaying childbearing effect of age on fecundity and outcome of pregnancy.
      ,
      • Kidd S.A.
      • Eskenazi B.
      • Wyrobek A.J.
      Effects of male age on semen quality and fertility a review of the literature.
      ,
      • Howe G.
      • Westhoff C.
      • Vessey M.
      • Yeates D.
      Effects of age, cigarette smoking, and other factors on fertility findings in a large prospective study.
      ,
      • Feichtinger W.
      Environmental factors and fertility.
      ,
      • Bolumer F.
      • Olsen J.
      • Rebagliato M.
      • Saez-Lloret I.
      • Bisanti L.
      Body mass index and delayed conception a European multicentre study on infertility and subfecundity.
      ,
      • Chia S.E.
      • Lim S.T.
      • Tay S.K.
      • Lim S.T.
      Factors associated with male infertility a case-control study of 218 infertile and 240 fertile men.
      ). If lifestyle variables could be modified, then this might assist in the spontaneous achievement of pregnancy in cases of unexplained subfertility or in the success of fertility treatments (
      • Clark A.M.
      • Thornley B.
      • Tomlinson L.
      • Galletley C.
      • Norman R.J.
      Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment.
      ,
      • Rosevear S.K.
      • Holt D.W.
      • Lee T.D.
      • Ford W.C.
      • Wardle P.G.
      • Hull M.G.
      Smoking and decreased fertilisation rates in vitro.
      ).
      Public expectation that medical treatment is increasingly possible and available leads to an ever increasing demand for the use of medical resources (
      • Templeton A.
      • Fraser C.
      • Thompson B.
      Infertility-epidemiology and referral practice.
      ). Prevention, a main goal of the primary health care system, remains the most attractive and cost-effective approach to the majority of medical problems. Subfertility is no exception. Sound evidence-based advice given by general practitioners and through family planning clinics to couples planning for pregnancy could result, if the magnitude of the effects were great enough, in a substantial reduction in the referrals for medical investigation and in a consequent savings in resources.
      The aim of this study was to evaluate the association patterns and to quantify the absolute and relative effects of lifestyle variables—including obesity, smoking, alcohol consumption, coffee and tea intake, recreational drug use, coital frequency, and standard of living—on fecundity, measured by the time interval of exposure to unprotected intercourse from the discontinuation of contraception until pregnancy (TTP).

      Materials and methods

      A survey was conducted in Hull and East Yorkshire (September 2000 to May 2001). Consecutive women attending the antenatal clinics were asked to self-complete a questionnaire inquiring about TTP (the interval of exposure to unprotected intercourse from discontinuing birth control methods until conception), contraceptive use, pregnancy planning, previous fertility problems/pregnancies, gynecologic disease, and individual and lifestyle characteristics of either partner including their age, weight, height, smoking, alcohol consumption, coffee and tea intake, recreational drug use, and the couple's coital frequency. Using the electoral ward, the postal code was linked to the Index of Multiple Deprivation (IMD), which was used as an indicator of the living standard.
      The IMD (
      • Noble M.
      • Penhale B.
      • Smith G.
      • Wright G.
      • Dibben C.
      • Owen T.
      • et al.
      Indices of deprivation 2000.
      ) is a compound index made up of six ward-level domain indices, each of which is composed of a number of indicators (33 in total) to describe aspects of this deprivation at a ward level as comprehensively as possible. These indices (contribution of each domain to the overall index) include: income (25%), employment (25%), education and training (15%), health deprivation and disability (15%), geographical access to services (10%), and housing (10%). The indicators measure deprivation independently of population size. The domain indices are also assigned a rank based on the electoral wards in England (8414), with the most deprived ward of each index given a rank of 1, and the least deprived ward given a rank of 8414. The IMD is ranked in the same way. The IMD score represents the combined sum of the weighted, exponentially transformed domain rank of the domain score. The bigger the IMD score, the more deprived the ward. The ranks show how a ward compares with all the other wards, whereas the scores indicate the distances between each rank position, as these will vary.
      Approval was obtained from the local research ethics committee (the UK equivalent of an institutional review board). There are no conflicts of interest. The response was over 99%, and the sample included 2112 completed questionnaires. Results of the component of the survey examining the effect of age on fecundity have already been published (

      Hassan MAM, Killick S. Evidence for the decline in male fertility with increasing age. Fertil Steril 2003;79(Suppl 3):1520–7

      ).
      Data analysis was carried out using a computer package (SPSS; SPSS, Inc., Chicago, IL). The outcome measures were the mean TTP, conception rates, and subfecundity proportions of various subgroups for each of the lifestyle variables. Subfecund couples were those who had TTP >12 months. Differences in the individual and lifestyle variables between fecund and subfecund couples were evaluated using the Mann-Whitney U-test. Each variable was correlated to TTP using Spearman's correlation coefficient, then subgrouped.
      The mean TTP of subgroups of each variable were compared before and after adjustment for the potential confounders in a general linear model using univariate analysis. The conception rates of these subgroups were determined, and the relative risk (RR) of taking TTP >12 or >24 months was calculated before and after adjustment using binary logistic regression. The TTP, conception rates, and RR of subfecundity for groups with different numbers of negative lifestyle variables were compared to study the absolute effect of negative lifestyle on fecundity. Variables in the regression models included women's age, weight, parity, smoking, alcohol consumption, coffee intake, menstrual pattern, contraceptive use, and also their partners' age, smoking, alcohol consumption, and the couples' coital frequency and living standard.

      Results

      Of the 2112 consecutive pregnant women surveyed, 136 women did not report TTP. Of the remaining 1976, 1128 (57.1%) conceived within 3 months, a number that rose to 1604 (81.2%) by end of the first year. Of the 372 (18.8%) subfecund couples, 190 (9.6%) conceived in the second year. The subfecund women and their partners were significantly older (P <.001), more obese (P <.001), smoked more cigarettes (P = .002 and .04), consumed more alcohol (P =.6 and .02), had longer contraceptive use (P <.001); their recreational drug use and coital frequency were not significantly different when compared with fecund couples (Table 1).
      TABLE 1Differences in individual and lifestyle variables for fecund and subfecund couples.
      Variable
      = Mean.
      Fecund (CI)
      = Mean.
      Subfecund (CI)
      = Mean.
      P value
      Women's age (27.4 y)27.2 (26.9–27.4)29.2 (28.6–29.7)<.001
      Men's age (30.3 y)29.8 (29.5–30.1)32.7 (32.0–33.4)<.001
      Women's obesity: BMI (25.7 kg/m2)25.4 (25.2–25.7)26.6 (26.1–27.1)<.001
      Women's obesity: weight (69.1 kg)68.3 (67.6–69.0)72.1 (70.6–73.6)<.001
      Women's smoking
      Excluding nonconsumers. Hassan. Lifestyle and fecundity. Fertil Steril 2004.
      (11.1 cigarette/d)
      10.5 (10.0–11.0)12.9 (11.6–14.3).002
      Men's smoking
      Excluding nonconsumers. Hassan. Lifestyle and fecundity. Fertil Steril 2004.
      (15.6 cigarette/d)
      15.3 (14.7–16.0)16.7 (15.4–18.1).040
      Women's alcohol
      Excluding nonconsumers. Hassan. Lifestyle and fecundity. Fertil Steril 2004.
      (3.6 unit/wk)
      3.6 (3.4–3.8)3.5 (3.1–4.0).600
      Men's alcohol
      Excluding nonconsumers. Hassan. Lifestyle and fecundity. Fertil Steril 2004.
      (10.3 unit/wk)
      9.8 (9.3–10.4)11.5 (10.3–12.7).020
      Women's tea and coffee (3.7 cup/d)3.7 (3.5–3.8)3.7 (3.4–4.0).900
      Coital frequency (1.9 times/wk)1.9 (1.8–1.9)1.9 (1.8–2.0).700
      Previous pregnancies (1.5 pregnancies)1.5 (1.4–1.6)1.4 (1.4–1.6).200
      Note: CI = 95% confidence interval; statistical test = Mann-Whitney.
      a = Mean.
      b Excluding nonconsumers.Hassan. Lifestyle and fecundity. Fertil Steril 2004.

       Women and men's smoking

      Of the couples surveyed, 72.6% of the women and 59.5% of the partners were nonsmokers, while 4.2% and 17.4%, respectively, used to smoke >15 cigarettes/day. A statistically significant reduction in fecundity occurred with heavy but not with light smoking (Fig. 1A, B). Heavy smokers (>15 cigarettes/day) among women had a twofold longer TTP (P <.001), while the TTP of light smokers was not significantly different from that of nonsmokers. The effect of women's heavy smoking remained statistically significant; men's heavy smoking became insignificant after adjustment for the potential confounders (Table 2). Heavy smokers were more likely to be subfecund than nonsmokers; RR (95% CI) = 1.9 (1.4–2.6) in women and 1.4 (1.1–1.8) in men (3.6 [1.9–7.1], 1.4 [0.9–2.1] after adjustment), while the conception rate within 12 months for light smokers was not different from that for nonsmokers (Table 3).
      Figure thumbnail GR1
      FIGURE 1Effect of each of the lifestyle variables on fecundity, expressed as time to pregnancy (TTP) in months. The values in each figure represent the mean TTP for each of the subgroups of the lifestyle variables, and the error bars represent the standard error of the mean. (A) Women's smoking and (B) men's smoking. The number of cigarettes/day smoked by women and their partners, respectively, were (I) nonsmokers, (II) ≤5, (III) 6–10, (IV) 11–15, (V) 16–20, and (VI) >20. (P values are <.001 and .05, respectively.) (C) Women's alcohol consumption and (D) men's alcohol consumption. The amounts of alcohol in units/week consumed by women and their partners, respectively, were: (I) nonconsumers, (II) ≤5, (III) 6–10, (IV) 11–15, (V) 16–20, and (VI) >20. (P values are .05 and .009, respectively.) (E) Women's coffee and tea intake. The amount of women's coffee and tea per day in cups/day was: (I) nonconsumers, (II) ≤5, (III) 6–10, (IV) 11–15, (V) 16–20, and (VI) >20. (P = .01.) (F) Women's obesity presented by BMI. Women's BMI in kg/m2 were: (I) <19, (II) 19–24, (III) 25–29, (IV) 30–34, (V) 35–39, and (VI) >39. (P < .001.)
      Hassan. Lifestyle and fecundity.Fertil Steril 2004.
      TABLE 2Effect of lifestyle variables on time to pregnancy (TTP).
      VariableGroupsUnadjusted TTP (months)Adjusted TTP
      Factors in the model: women's age, weight, smoking, alcohol consumption, tea/coffee intake, drug abuse, parity, contraceptive use, and menstrual pattern, and men's age, smoking, alcohol consumption, drug abuse, coital frequency, and living standard. Hassan. Lifestyle and fecundity.Fertil Steril 2004.
      (months)
      (CI)
      Mean.
      Statistical test(CI)
      Mean.
      Statistical test
      Women's smoking (cigarette/d)None9.3 (8.6–10.1)F = 12.09.1 (8.2–9.9)F = 12.2
      Light (≤15)9.8 (8.3–11.2)(P <.001)11.1 (9.4–12.9)(P <.001)
      Heavy (>15)17.4 (14.2–20.6)18.7 (14.9–22.4)
      Men's smoking (cigarette/d)None9.6 (8.7–10.4)F = 3.19.2 (8.2–10.1)F = 2.6
      Light (≤15)9.0 (7.6–10.5)(P = .045)11.2 (9.6–12.8)(P = .08)
      Heavy (>15)11.7 (10.0–13.4)10.8 (8.8–12.7)
      Women's alcohol (unit/wk)None8.7 (8.0–9.5)F = 3.49.3 (8.4–10.2)F = 2.3
      Mild (≤20)7.6 (6.8–8.5)(P = .07)7.6 (6.7–8.6)(P = .08)
      Heavy (>20)
      Men's alcohol (unit/wk)None10.0 (8.5–11.4)F = 17.89.3 (7.7–11.0)F = 7.8
      Mild (≤20)9.4 (8.6–10.2)(P <.001)9.6 (8.8–10.5)(P <.001)
      Heavy (>20)18.6 (15.7–21.3)16.7 (13.2–20.2)
      Women's tea and coffee (cup/d)Mild (<7)8.1 (7.5–8.7)F = 4.28.4 (7.7–9.1)F = 2.5
      Heavy (≥7)10.3 (8.3–12.2)(P = .04)10.4 (8.1–12.8)(P = .1)
      Women's obesity (BMI)<19 kg/m229.0 (18.5–39.5)F = 13.125.5 (15.1–35.9)F = 10.5
      19–24 kg/m26.8 (5.5–8.1)(P <.001)6.9 (5.5–8.4)(P <.001)
      25–39 kg/m210.6 (9.8–11.4)10.9 (10.0–11.7)
      >39 kg/m213.3 (8.3–18.4)14.0 (8.8–19.3)
      Living standardHigh standard7.1 (5.6–8.7)F = 14.66.8 (5.0–8.5)F = 16.5
      Low standard10.7 (9.8–11.5)(P <.001)11.0 (10.0–11.9)(P <.001)
      Recreational drug useNever8.5 (7.9–9.1)F = 0.48.5 (7.9–9.2)F = 0.1
      Previous/current11.0 (3.6–18.4)(P = .5)8.1 (0.3–15.9)(P = .9)
      Coital frequencyOnce or less/week9.2 (8.0–10.4)F = 0.99.2 (7.9–10.6)F = 0.6
      2–4 times/week10.0 (9.2–10.9)(P = .4)10.1 (9.1–11.0)(P = .6)
      ≥5 times/week9.1 (7.1–11.0)10.3 (8.2–12.5)
      Number of negative lifestyle variablesNone3.4 (0.2–6.6)F = 17.02.9 (0.0–6.3)F = 6.5
      One5.7 (4.4–7.1)(P <.001)6.0 (4.4–7.6)(P <.001)
      Two8.5 (7.2–9.8)8.5 (7.2–9.7)
      Three12.7 (10.9–14.4)11.8 (9.9–13.7)
      Four15.1 (12.4–17.8)15.3 (11.8–18.7)
      Five or more25.0 (16.3–33.7)21.1 (12.0–30.3)
      Note: CI = 95% Confidence Interval; F = analysis of variance.
      a Mean.
      b Factors in the model: women's age, weight, smoking, alcohol consumption, tea/coffee intake, drug abuse, parity, contraceptive use, and menstrual pattern, and men's age, smoking, alcohol consumption, drug abuse, coital frequency, and living standard.Hassan. Lifestyle and fecundity.Fertil Steril 2004.
      TABLE 3Relative risk of subfecundity for various subgroups of lifestyle variables.
      VariablesGroupsRelative risk of subfecundity (TTP >12 months)
      UnadjustedAdjusted
      Factors in the model: women's age, weight, smoking, alcohol consumption, tea/coffee intake, drug abuse, parity, contraceptive use, and menstrual pattern, and men's age, smoking, alcohol consumption, drug abuse, coital frequency, and living standard. Hassan. Lifestyle and fecundity.Fertil Steril 2004.
      %RR (CI)
      RR = relative risk; CI = 95% confidence interval; test = binary logistic regression.
      P valueRR (CI)
      RR = relative risk; CI = 95% confidence interval; test = binary logistic regression.
      P value
      Women's smoking (cigarette/d)None21.01.01.0
      Light (≤15)23.31.1 (0.9–1.4).4001.5 (1.1–2.2).0400
      Heavy (>15)40.01.9 (1.4–2.6).0013.6 (1.9–7.1).0001
      Men's smoking (cigarette/d)None21.21.01.0
      Light (≤15)19.60.9 (0.7–1.2).6001.2 (0.8–1.7).4000
      Heavy (>15)29.51.4 (1.1–1.8).0081.4 (0.9–2.1).0900
      Women's alcohol (unit/wk)None20.01.01.0
      Mild (≤20)17.40.9 (0.7–1.1).2000.8 (0.6–1.0).0900
      Heavy (>20)
      Men's alcohol (unit/wk)None17.81.01.0
      Mild (≤20)19.51.1 (0.9–1.4).5001.3 (0.9–1.9).2000
      Heavy (>20)33.31.9 (1.3–2.7).0012.2 (1.1–4.4).0300
      Women's coffee and tea (cup/d)Mild (<7)18.21.01.0
      Heavy (≤7)27.11.5 (1.1–1.9).0071.7 (1.1–2.7).0200
      Women's BMI<19 kg/m240.03.5 (1.6–7.8).0204.8 (1.2–19.7).0300
      19–24 kg/m211.41.01.0
      25–39 kg/m221.11.9 (1.4–2.4)<.0012.2 (1.6–3.2)<.0001
      >39 kg/m242.93.8 (2.3–6.2)<.0016.9 (2.9–16.8)<.0001
      Living standardHigh standard17.61.01.0
      Low standard24.31.4 (1.1–1.8).0251.6 (1.1–2.3).0300
      Recreational drug useNever19.21.01.0
      Previous/current33.31.7 (0.8–3.9).3001.6 (0.3–7.8).6000
      Coital frequency≤1/week19.81.01.0
      2–4 time/week23.71.2 (1.0–1.5).1001.2 (0.8–1.6).4000
      ≥5 time/week18.10.9 (0.6–1.3).7001.0 (0.6–1.7).9000
      Number of negative lifestyle variablesNone6.91.01.0
      One13.41.9 (0.7–5.2).2002.2 (0.7–6.4).2000
      Two20.43.0 (1.1–7.8).0103.3 (1.1–9.6).0300
      Three29.04.2 (1.6–11.1)<.0014.4 (1.4–13.6).0100
      Four36.65.3 (2.0–14.2)<.0016.5 (1.8–23.7).0040
      Five or more50.07.3 (2.2–23.4).0057.2 (1.1–49.7).0400
      a RR = relative risk; CI = 95% confidence interval; test = binary logistic regression.
      b Factors in the model: women's age, weight, smoking, alcohol consumption, tea/coffee intake, drug abuse, parity, contraceptive use, and menstrual pattern, and men's age, smoking, alcohol consumption, drug abuse, coital frequency, and living standard.Hassan. Lifestyle and fecundity.Fertil Steril 2004.

       Women and men's alcohol consumption

      Of the survey participants, 58.2% of the women and 23.8% of their partners did not consume alcohol or had stopped drinking before trying for pregnancy; 12.0% of the partners but none of the women used to consume >20 units/week. Heavy men's alcohol consumption (>20 unit/week) was associated with a significant reduction in fecundity (twofold longer TTP, P <.001), but no similar effect was detected with women's alcohol consumption as, in this sample, the amount they used to consume did not exceed 15 units/week (see Fig. 1C, D). Moderate alcohol consumption, neither in women nor in their partners, was found to have an effect on TTP compared with nonconsumers. Similar results were obtained after adjustment (see Table 2). Heavy men's alcohol consumption was associated with a higher likelihood of subfecundity RR = 1.9 (1.3–2.7) (after adjustment = 2.2 [1.1–4.4]). The pregnancy rates in association with moderate women or men's alcohol consumption were not significantly different from the rates of nonconsumers (see Table 3).

       Women's tea and coffee intake

      Although 10.7% of the women did not drink tea or coffee, 19.1% consumed >5 cups/day. A longer TTP with heavy coffee or tea intake (P =.04) became insignificant after adjustment (see Fig. 1E, Table 1). Women who used to consume seven or more cups of tea or coffee/day were 1.5-fold (1.1–1.9) more likely to be subfecund (1.7 [1.1–2.7] after adjustment).

       Women's obesity

      Among those surveyed, 2.6% of all women had a body mass index (BMI) <19 kg/m2, and 17.9% had a BMI >30 kg/m2 before pregnancy. The effect of body mass on fecundity appeared to be bimodal. Underweight women (BMI <19 kg/m2) had a fourfold longer TTP than that of the women who had a normal BMI (19 to 24 kg/m2). Women who had a prepregnancy weight >80 kg or BMI >25 kg/m2 took twofold longer TTP (P <.001) (see Fig. 1F). The effects remained unchanged after adjustment for the other lifestyle variables, the woman's age, and the menstrual pattern (see Table 2). Underweight women were 3.5-fold (1.6–7.8) and morbidly obese women were 3.8-fold (2.3–6.2) more likely to be subfecund than those who had a normal BMI (4.8 [1.2–19.7] and 6.9 [2.9–16.8] after adjustment, respectively) (see Table 3).

       Living standard

      The IMD score revealed that 22.1% of the couples had a deprivation score <20 (high standard), and 21.2% had a score >60 (low standard). Socially deprived couples took significantly longer TTP (P <.001) and were more likely to be subfecund (RR [CI] = 1.4 [1.1–1.8] before, and 1.6 [1.1–2.3] after adjustment) than those who had high living standard (see TABLE 2, TABLE 3).

       Recreational drug use

      Only 3.0% of the women admitted previous or current drug use, and only 0.7% reported knowledge of their partner's previous or current use. Recreational drug use, in this sample, was not found to be associated with a statistically significant effect on TTP or the subfecund proportions, compared with those of individuals who had never used recreational drugs (see TABLE 2, TABLE 3).

       Coital frequency

      Infrequent intercourse was reported by 10.9% of the couples (less than once/week), and 12.2% reported frequent intercourse (five times or more/week). No statistically significant affect on TTP or conception rate was found for coital frequency in this sample (see TABLE 2, TABLE 3).

       Absolute effect of negative lifestyle

      The negative lifestyle variables were women's heavy smoking, men's heavy smoking (>15 cigarettes/day), heavy alcohol consumption (>20 units/week), heavy tea or coffee intake (>6 cups/day), prepregnancy BMI >25 kg/m2, social deprivation (score >60), and women's age >35 or men's age >45 years at the time of discontinuing contraception. Among those surveyed, 5.7% of the couples had none of these variables, 31.9% had one, 36.1% had two, 18.1% had three, and 8.2% had four or more variables.
      The increase in the number of the negative lifestyle variables was persistently associated with a significant and progressive reduction in fecundity. The mean TTP increased 2.5-fold with two variables, 3.7-fold with three variables, and 4.4-fold with four variables. Couples who had more than four negative variables had a 7.3-fold longer TTP than those who had no negative variables (Fig. 2; see Table 2). There was a statistically significant progressive decline in the conception rates within 6 and 12 months with the rise in numbers of negative lifestyle variables (Fig. 3). The conception probabilities, within 6 months, were found to fall from 0.9 with one variable to 0.77 with two, 0.48 with three down to 0.45 with four variables, and no pregnancies were achieved within 6 months in association with five or more variables. The conception probabilities within 12 months fell from 0.93 with one variable to 0.82 with two, 0.67 with three, down to 0.38 in association with four negative variables. Compared with the couples who had no negative variables, the RR (CI) of subfecundity rose from 1.9 (0.7–5.2) with one variable to 3.0 (1.1–7.8) with two, 4.2 (1.6–11.1) with three, 5.3 (2.0–14.2) with four, up to 7.3 (2.2–23.4) in association with five or more negative variables (2.2 [0.7–6.4], 3.3 [1.1–9.6], 4.4 [1.4–13.6], 6.5 [1.8–23.7], 7.2 [1.1–49.7] after adjustment, respectively) (see Table 3).
      Figure thumbnail GR2
      FIGURE 2The absolute cumulative effect of increasing numbers of negative lifestyle variables on fecundity, expressed as time to pregnancy (TTP) in months. These variables include women's smoking >15 cigarettes/day, men's smoking >15 cigarettes/day, men's alcohol >20 units/week, women's coffee/tea intake ≥7 cups/day, women's weight >70 kg, social deprivation score >60, women's age >35 years, and/or partners' age >45 years at the time of discontinuing contraception. The bold values represent the mean TTP for subgroups with increasing numbers of the negative lifestyle variables, and the error bars represent the standard error of the mean. The dashed lines point to the subgroups between which the shown P values were calculated.
      Hassan. Lifestyle and fecundity.Fertil Steril 2004.
      Figure thumbnail GR3
      FIGURE 3The effect of increasing numbers of negative lifestyle variables on the cumulative conception rates within 1 year for a pregnant population. These variables include women's smoking >15 cigarettes/day, men's smoking >15 cigarettes/day, men's alcohol >20 units/week, women's coffee or tea intake >7 cups/day, women's weight >70 kg, social deprivation score >60, women's age >35 years, and/or partners' age >45 years at the time of discontinuing contraception. The lines represent the cumulative conception rates for subgroups with different numbers of negative lifestyle variables as follows: ○ No negative variables; ■ One negative variable; × Two negative variables; ▵ Three negative variables; ♦ Four or more negative variables.
      Hassan. Lifestyle and fecundity.Fertil Steril 2004.

      Discussion

      The methodology of this study has been previously discussed elsewhere (

      Hassan MAM, Killick S. Evidence for the decline in male fertility with increasing age. Fertil Steril 2003;79(Suppl 3):1520–7

      ). Using time to a current pregnancy excluded from the analysis those who had failed to conceive or had given up the pregnancy attempt (
      • Basso O.
      • Juul S.
      • Olsen J.
      Time to pregnancy as a correlate of fecundity differential persistence in trying to become pregnant as a source of bias.
      ,
      • Jensen T.K.
      • Scheike T.
      • Keiding N.
      • Schaumburg I.
      • Grandjean P.
      Selection bias in determining the age dependence of waiting time to pregnancy.
      ,
      • Juul S.
      • Keiding N.
      • Tvede M.
      Retrospectively sampled time to pregnancy data may make age-decreasing fecundity look increasing. European Infertility and Subfecundity Group.
      ). However, such selective sampling is not expected to have a significant effect on the results or conclusions, as lifestyle variables are not expected to lead to absolute sterility. In addition, an underestimation rather than overestimation of the negative effect, of the negative lifestyle, on fecundity would result from excluding the small minority who gave up the pregnancy attempt (
      • Olsen J.
      • Juul S.
      • Basso O.
      Measuring time to pregnancy methodological issues to consider.
      ). The effect of negative lifestyle on fecundity was similar in planned and unplanned pregnancies. Furthermore, studies comparing the effects of exposures on TTP among pregnancy planners with those in current pregnancies have shown similar results (
      • Bolumar F.
      • Olsen J.
      • Boldsen J.
      Smoking reduces the biological capacity of conception. Results from a European multicenter study. The European Study Group on Infertility and Subfecundity.
      ).
      Data analysis aimed not only to detect but also to quantify the relative and absolute effects of lifestyle factors on fecundity. This was achieved in two ways; by comparing the mean TTP, then by comparing the conception rates and calculating the RR of subfecundity for various subgroups of each lifestyle factor and for groups with different numbers of the negative lifestyle factors. General linear and logistic regression models were used to control for confounders to assess the effect of each of the lifestyle variables independently.
      The harmful effects of smoking and heavy alcohol drinking on the general health are well accepted. Several studies have shown the negative effects of smoking (
      • Baird D.D.
      • Wilcox A.J.
      Cigarette smoking associated with delayed conception.
      ,
      • Weinberg C.R.
      • Wilcox A.J.
      • Baird D.D.
      Reduced fecundability in women with prenatal exposure to cigarette smoking.
      ,
      • Suonio S.
      • Saarikoski S.
      • Kauhanen O.
      • Metsapelto A.
      • Terho J.
      • Vohlonen I.
      Smoking does affect fecundity.
      ,
      • Joesoef M.R.
      • Beral V.
      • Aral S.O.
      • Rolfs R.T.
      • Cramer D.W.
      Fertility and use of cigarettes, alcohol, marijuana, and cocaine.
      ,
      • Alderete E.
      • Eskenazi B.
      • Sholtz R.
      Effect of cigarette smoking and coffee drinking on time to conception.
      ,
      • Hughes E.G.
      • Brennan B.G.
      Does cigarette smoking impair natural or assisted fecundity?.
      ,
      • Vine M.F.
      Smoking and male reproduction a review.
      ,
      • Bolumar F.
      • Olsen J.
      • Boldsen J.
      Smoking reduces fecundity a European multicenter study on infertility and subfecundity. The European Study Group on Infertility and Subfecundity.
      ,
      • Curtis K.M.
      • Savitz D.A.
      • Arcbukle T.E.
      Effects of cigarette smoking, caffeine consumption, and alcohol intake on fecundability.
      ,
      • Augood C.
      • Duckitt K.
      • Templeton A.A.
      Smoking and female infertility a systematic review and meta-analysis.
      ) and alcohol consumption (
      • Grodstein F.
      • Goldman M.B.
      • Cramer D.W.
      Infertility in women and moderate alcohol use.
      ,
      • Hakim R.B.
      • Gray R.H.
      • Zacur H.
      Alcohol and caffeine consumption and decreased fertility.
      ,
      • Jensen T.K.
      • Hjollund N.H.
      • Henriksen T.B.
      • Scheike T.
      • Kolstad H.
      • Giwercman A.
      • et al.
      Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy.
      ) on fertility. Smoking has been shown to affect gamete quality (
      • Weisberg E.
      Smoking and reproductive health.
      ,
      • Vine M.F.
      • Tse C.K.
      • Hu P.
      • Truong K.Y.
      Cigarette smoking and semen quality.
      ,
      • Rubes J.
      • Lowe X.
      • Moore 2nd, D.
      • Perreault S.
      • Slott V.
      • Evenson D.
      • et al.
      Smoking cigarettes is associated with increased sperm disomy in teenage men.
      ,
      • Wong W.Y.
      • Thomas C.M.
      • Merkus H.M.
      • Zielhuis G.A.
      • Doesburg W.H.
      • Steegers-Theunissen R.P.
      Cigarette smoking and the risk of male factor subfertility minor association between cotinine in seminal plasma and semen morphology.
      ,
      • Zenzes M.T.
      • Wang P.
      • Casper R.F.
      Cigarette smoking may affect meiotic mutation of human oocytes.
      ), impair fertilization (
      • Rosevear S.K.
      • Holt D.W.
      • Lee T.D.
      • Ford W.C.
      • Wardle P.G.
      • Hull M.G.
      Smoking and decreased fertilisation rates in vitro.
      ,
      • Weigert M.
      • Hofstetter G.
      • Kaipl D.
      • Gottlich H.
      • Krischker U.
      • Bichler K.
      • et al.
      The effect of smoking on oocyte quality and hormonal parameters of patients undergoing in vitro fertilization-embryo transfer.
      ), or result in early miscarriage. The effect of alcohol consumption on fertility has been suggested to be related to hormonal and ovulatory abnormalities (
      • Gill J.
      The effects of moderate alcohol consumption on female hormone levels and reproductive function.
      ). Couples who are trying for pregnancy are usually advised to give up smoking and stop drinking, but this advice may be difficult or even impossible for some couples to follow, which may add more stress and strain to an already threatened relationship and further jeopardize their chances of conception (
      • Hjollund N.H.
      • Jensen T.K.
      • Bonde J.P.
      • Henriksen T.B.
      • Andersson A.M.
      • Kolstad H.A.
      • et al.
      Distress and reduced fertility a follow up study of first-pregnancy planners.
      ,
      • Stoleru S.
      • Teglas J.P.
      • Fermanian J.
      • Spira A.
      Psychological factors in the aetiology of infertility a prospective cohort study.
      ,
      • Sanders K.A.
      • Bruce N.W.
      A prospective study of psychological stress and fertility in women.
      ). It is important, therefore, to quantify and base the advice given on clear evidence.
      Based on the above results, the effects of smoking and alcohol consumption on fecundity appear to be dose-dependent. A significant negative effect was demonstrated only with heavy smoking (>15 cigarettes/day, women or men). Light smoking has not been found to affect TTP or the conception probabilities compared with nonsmoking. The effect of women's alcohol consumption on fecundity in this sample was insignificant. This may be due to the relatively small amount they consumed. The effect of the male partner's alcohol consumption on fecundity was only significant when the amount consumed exceeded 20 units/week; a smaller amount has not been shown to have a statistically significant effect. The absence of a statistically significant effect in association with moderate alcohol consumption is consistent with the results of other studies (
      • Zaadstra B.
      M, Looman CW, te Velede ER, Habbema JD, Karbaat J. Moderate drinking no impact on female fecundity.
      ,
      • Folrack E.I.
      • Zielhuis G.A.
      • Rolland R.
      Cigarette smoking, alcohol consumption and caffeine intake and fecundability.
      ). The negative effect of heavy caffeine intake is also consistent with the results of other studies (
      • Wilcox A.
      • Weinberg C.
      • Baird D.
      Caffeinated beverages and decreased fertility.
      ,
      • Olsen J.
      Cigarette smoking, tea and coffee drinking and subfecundity.
      ,
      • Bolumar F.
      • Olsen J.
      • Rebagliato M.
      • Bisanti L.
      Caffeine intake and delayed conception a European multicenter study on infertility and subfecundity.
      ,
      • Jensen T.K.
      • Henriksen T.B.
      • Hjollund N.H.
      • Scheike T.
      • Kolstad H.
      • Giwercman A.
      • et al.
      Caffeine intake and fecundability a follow up study among 430 Danish couples planning their first pregnancy.
      ).
      The effect of body mass on fecundity was bimodal. Sporadic ovulation in underweight women is not unexpected, and this would explain the statistically significant reduction in fecundity of these women. A statistically significant negative effect of women's obesity on fecundity was demonstrated. This effect was independent of other lifestyle variables, the women's age, and the menstrual pattern, and was similar whether the absolute weight or BMI was used in the analysis. The effect of obesity on fertility might be a direct effect (
      • Zaadstra B.M.
      • Seidell J.C.
      • Van Noord P.A.
      • te Velde E.R.
      • Habbema J.D.
      • Vrieswijk B.
      • et al.
      Fat and female fecundity prospective study of effect of body fat distribution on conception rates.
      ,
      • Jarow J.P.
      • Kirkland J.
      • Koritnik D.R.
      • Cefalu W.T.
      Effect of obesity and fertility status on sex steroid levels in men.
      ,
      • Foreyt J.P.
      • Poston 2nd, W.S.
      Obesity a never-ending cycle?.
      ); be caused by disturbance in leptin (
      • Messinis I.E.
      • Milingos S.D.
      Leptin in human reproduction.
      ,
      • Magni P.
      • Motta M.
      • Martini L.
      Leptin a possible link between food intake, energy expenditure, and reproductive function.
      ,
      • Alfer J.
      • Muller-Schottle F.
      • Classen-linke I.
      • von Rango U.
      • Happel L.
      • Beier-Hellwig K.
      • et al.
      The endometrium as a novel target for leptin differences in fertility and subfertility.
      ,
      • Imani B.
      • Eijkemans M.J.
      • de Jong F.H.
      • Payne N.N.
      • Bouchard P.
      • Giudice L.C.
      • et al.
      Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.
      ), an important factor for both body fat mass regulation and reproductive function; or be the result of polycystic ovary syndrome (
      • Franks S.
      • Kiddy D.
      • Sharp P.
      • Singh A.
      • Reed M.
      • Seppala M.
      • et al.
      Obesity and polycystic ovary syndrome.
      ,
      • Pettigrew R.
      • Hamilton-Fairley D.
      Obesity and female reproductive function.
      ), a prevalent condition among obese women. In these cases, weight loss has been shown to improve both the chances of spontaneous conception and the success of fertility treatments (
      • Kiddy D.S.
      • Hamilton-Fairley D.
      • Bush A.
      • Short F.
      • Anyaoku V.
      • Reed M.J.
      • et al.
      Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome.
      ,
      • Pasquali R.
      • Casimirri F.
      • Vicennati V.
      Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome.
      ,
      • Norman R.J.
      • Clark A.M.
      Obesity and reproductive disorders a review.
      ,
      • Kably-Ambe A.
      • Barron-Vallejo J.
      • Limon-Luque L.M.
      Effect of body mass index and follicular synchrony in the ovarian response to ovulation induction with menotropins.
      ).
      In this sample, the statistically insignificant effect of recreational drug use on fecundity is probably a result of the tiny proportion that admitted having ever used drugs. Other studies have demonstrated a negative effect (
      • Mueller B.A.
      • Daling J.R.
      • Weiss N.S.
      • Moore D.E.
      Recreational drug use and the risk of primary infertility.
      ). Also, results from this study, in agreement with other studies (
      • Agarwal S.K.
      • Haney A.F.
      Does recommending timed intercourse really help the infertile couple?.
      ,
      • Tur-Kaspa I.
      • Maor Y.
      • Levran D.
      • Yonish M.
      • Mashiach S.
      • Dor J.
      How often should infertile men have intercourse?.
      ), are not supportive of the belief that frequent or timed intercourse enhances fecundity. These provide an evidence-based answer to a question commonly asked by couples striving for pregnancy.
      The detrimental effect on fecundity of social deprivation (as identified by using the IMD) could not be attributed to other lifestyle variables as it remained statistically significant after adjustment. Residence in more deprived areas is associated with personal disadvantage (
      • Sloggett A.
      • Joshi H.
      Deprivation indicators as predictors of life events 1981–1992 based on the UK ONS Longitudinal Study.
      ), but the mechanism by which social deprivation affects fertility is unclear. Further research is obviously needed.
      Increasingly in recent decades, couples, especially those with career ambitions, choose to delay having children until later age (
      • Martin S.P.
      Diverging fertility among U.S. women who delay childbearing past age 30.
      ). Therefore, trying for a pregnancy at women's age of 35 years or more and/or men's age of 45 years or more was considered among the negative lifestyle factors. About two-thirds of the couples in this sample had two or more negative lifestyle variables, and the results of this study indicate that the detrimental effect of negative lifestyle factors on fecundity is cumulative. The TTP was progressively longer (2.4-fold with two, up to 7.3-fold with five or more variables) and the conception probabilities were persistently lower (0.82 with two, down to 0.38 with four variables) with increased numbers of negative lifestyle variables. Couples who had five or more negative variables were 7.3-fold more likely to be subfecund compared with those without any of these variables.
      Subfertile couples who are seeking medical intervention often disregard lifestyle factors as having adverse effects on fertility (
      • Olatunbosun O.A.
      • Edouard L.
      • Pierson R.A.
      How important is health promotion in the lifestyle of infertile couples?.
      ). Promoting a healthier lifestyle among the couples planning or trying for pregnancy is important not only for their general health but also for prevention of subfertility, as evident from the data in our study. Primary health care providers are in a unique position to provide education, counseling, and support to these couples (
      • Whitman-Elia G.F.
      • Baxley E.G.
      A primary care approach to the infertile couple.
      ). Based on our results, should these couples lead a healthy lifestyle, a reduction in subfecundity by over half would result. This, in the long term, could lead to a substantial decline in the referrals for medical investigations and fertility treatments.

      References

        • Bongaarts J.
        A method for the estimation of fecundability.
        Demography. 1975; 12: 645-660
        • ESHRE Capri workshop
        Guidelines to the prevalence, diagnosis, treatment and management of infertility.
        Hum Reprod. 1996; 11: 1775-1807
        • Hull M.G.R.
        • Glazener C.M.A.
        • Kelly N.J.
        • Conway D.I.
        • Foster P.A.
        • Hinton R.A.
        • et al.
        Population study of causes, treatment, and outcome of infertility.
        BMJ. 1985; 291: 1693-1697
        • Templeton A.
        Infertility-epidemiology, aetiology and effective management.
        Health Bull. 1995; 53: 294-298
        • Hull M.G.R.
        Infertility treatment.
        Hum Reprod. 1992; 7: 785-796
        • Van Noord-Zaadstra B.M.
        • Looman C.W.
        • Alsbach H.
        • Habbema J.D.
        • te Velde E.R.
        • Karbaat J.
        Delaying childbearing.
        BMJ. 1991; 302: 1361-1365
        • Kidd S.A.
        • Eskenazi B.
        • Wyrobek A.J.
        Effects of male age on semen quality and fertility.
        Fertil Steril. 2001; 75: 237-248
        • Howe G.
        • Westhoff C.
        • Vessey M.
        • Yeates D.
        Effects of age, cigarette smoking, and other factors on fertility.
        BMJ. 1985; 290: 1697-1700
        • Feichtinger W.
        Environmental factors and fertility.
        Hum Reprod. 1991; 6: 1170-1175
        • Bolumer F.
        • Olsen J.
        • Rebagliato M.
        • Saez-Lloret I.
        • Bisanti L.
        Body mass index and delayed conception.
        Am J Epidemiol. 2000; 151: 1072-1079
        • Chia S.E.
        • Lim S.T.
        • Tay S.K.
        • Lim S.T.
        Factors associated with male infertility.
        Br J Obstet Gynaecol. 2000; 107: 55-61
        • Clark A.M.
        • Thornley B.
        • Tomlinson L.
        • Galletley C.
        • Norman R.J.
        Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment.
        Hum Reprod. 1998; 13: 1502-1505
        • Rosevear S.K.
        • Holt D.W.
        • Lee T.D.
        • Ford W.C.
        • Wardle P.G.
        • Hull M.G.
        Smoking and decreased fertilisation rates in vitro.
        Lancet. 1992; 340: 1195-1196
        • Templeton A.
        • Fraser C.
        • Thompson B.
        Infertility-epidemiology and referral practice.
        Hum Reprod. 1991; 6: 1391-1394
        • Noble M.
        • Penhale B.
        • Smith G.
        • Wright G.
        • Dibben C.
        • Owen T.
        • et al.
        Indices of deprivation 2000.
        Department of the Environment, Transport and the Regions (DETR), London2000
      1. Hassan MAM, Killick S. Evidence for the decline in male fertility with increasing age. Fertil Steril 2003;79(Suppl 3):1520–7

        • Basso O.
        • Juul S.
        • Olsen J.
        Time to pregnancy as a correlate of fecundity.
        Int J Epidemiol. 2000; 29: 856-861
        • Jensen T.K.
        • Scheike T.
        • Keiding N.
        • Schaumburg I.
        • Grandjean P.
        Selection bias in determining the age dependence of waiting time to pregnancy.
        Am J Epidemiol. 2000; 152: 565-572
        • Juul S.
        • Keiding N.
        • Tvede M.
        Retrospectively sampled time to pregnancy data may make age-decreasing fecundity look increasing. European Infertility and Subfecundity Group.
        Epidemiology. 2000; 11: 717-719
        • Olsen J.
        • Juul S.
        • Basso O.
        Measuring time to pregnancy.
        Hum Reprod. 1998; 13: 1751-1756
        • Bolumar F.
        • Olsen J.
        • Boldsen J.
        Smoking reduces the biological capacity of conception. Results from a European multicenter study. The European Study Group on Infertility and Subfecundity.
        Ugeskr Laeger. 1997; 159: 4526-4532
        • Baird D.D.
        • Wilcox A.J.
        Cigarette smoking associated with delayed conception.
        JAMA. 1985; 253: 2979-2983
        • Weinberg C.R.
        • Wilcox A.J.
        • Baird D.D.
        Reduced fecundability in women with prenatal exposure to cigarette smoking.
        Am J Epidemiol. 1989; 129: 1072-1078
        • Suonio S.
        • Saarikoski S.
        • Kauhanen O.
        • Metsapelto A.
        • Terho J.
        • Vohlonen I.
        Smoking does affect fecundity.
        Eur J Obstet Gynecol Reprod Biol. 1990; 34: 89-95
        • Joesoef M.R.
        • Beral V.
        • Aral S.O.
        • Rolfs R.T.
        • Cramer D.W.
        Fertility and use of cigarettes, alcohol, marijuana, and cocaine.
        Ann Epidemiol. 1994; 4: 423
        • Alderete E.
        • Eskenazi B.
        • Sholtz R.
        Effect of cigarette smoking and coffee drinking on time to conception.
        Epidemiology. 1995; 6: 403-408
        • Hughes E.G.
        • Brennan B.G.
        Does cigarette smoking impair natural or assisted fecundity?.
        Fertil Steril. 1996; 66: 679-689
        • Vine M.F.
        Smoking and male reproduction.
        Int J Androl. 1996; 19: 323-337
        • Bolumar F.
        • Olsen J.
        • Boldsen J.
        Smoking reduces fecundity.
        Am J Epidemiol. 1996; 143: 578-587
        • Curtis K.M.
        • Savitz D.A.
        • Arcbukle T.E.
        Effects of cigarette smoking, caffeine consumption, and alcohol intake on fecundability.
        Am J Epidemiol. 1997; 146: 32-41
        • Augood C.
        • Duckitt K.
        • Templeton A.A.
        Smoking and female infertility.
        Hum Reprod. 1998; 13: 1532-1539
        • Grodstein F.
        • Goldman M.B.
        • Cramer D.W.
        Infertility in women and moderate alcohol use.
        Am J Public Health. 1994; 84: 1429-1432
        • Hakim R.B.
        • Gray R.H.
        • Zacur H.
        Alcohol and caffeine consumption and decreased fertility.
        Fertil Steril. 1998; 70: 632-637
        • Jensen T.K.
        • Hjollund N.H.
        • Henriksen T.B.
        • Scheike T.
        • Kolstad H.
        • Giwercman A.
        • et al.
        Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy.
        BMJ. 1998; 317: 505-510
        • Weisberg E.
        Smoking and reproductive health.
        Clin Reprod Fertil. 1985; 3: 175-186
        • Vine M.F.
        • Tse C.K.
        • Hu P.
        • Truong K.Y.
        Cigarette smoking and semen quality.
        Fertil Steril. 1996; 65: 835-842
        • Rubes J.
        • Lowe X.
        • Moore 2nd, D.
        • Perreault S.
        • Slott V.
        • Evenson D.
        • et al.
        Smoking cigarettes is associated with increased sperm disomy in teenage men.
        Fertil Steril. 1998; 70: 715-723
        • Wong W.Y.
        • Thomas C.M.
        • Merkus H.M.
        • Zielhuis G.A.
        • Doesburg W.H.
        • Steegers-Theunissen R.P.
        Cigarette smoking and the risk of male factor subfertility.
        Fertil Steril. 2000; 74: 930-935
        • Zenzes M.T.
        • Wang P.
        • Casper R.F.
        Cigarette smoking may affect meiotic mutation of human oocytes.
        Hum Reprod. 1995; 10: 3213-3217
        • Weigert M.
        • Hofstetter G.
        • Kaipl D.
        • Gottlich H.
        • Krischker U.
        • Bichler K.
        • et al.
        The effect of smoking on oocyte quality and hormonal parameters of patients undergoing in vitro fertilization-embryo transfer.
        J Assist Reprod Genet. 1999; 16: 287-293
        • Gill J.
        The effects of moderate alcohol consumption on female hormone levels and reproductive function.
        Alcohol Alcohol. 2000; 35: 417-423
        • Hjollund N.H.
        • Jensen T.K.
        • Bonde J.P.
        • Henriksen T.B.
        • Andersson A.M.
        • Kolstad H.A.
        • et al.
        Distress and reduced fertility.
        Fertil Steril. 1999; 72: 47-53
        • Stoleru S.
        • Teglas J.P.
        • Fermanian J.
        • Spira A.
        Psychological factors in the aetiology of infertility.
        Hum Reprod. 1993; 8: 1039-1046
        • Sanders K.A.
        • Bruce N.W.
        A prospective study of psychological stress and fertility in women.
        Hum Reprod. 1997; 12: 2324-2329
        • Zaadstra B.
        M, Looman CW, te Velede ER, Habbema JD, Karbaat J. Moderate drinking.
        Fertil Steril. 1994; 62: 948-954
        • Folrack E.I.
        • Zielhuis G.A.
        • Rolland R.
        Cigarette smoking, alcohol consumption and caffeine intake and fecundability.
        Prev Med. 1994; 23: 175-180
        • Wilcox A.
        • Weinberg C.
        • Baird D.
        Caffeinated beverages and decreased fertility.
        Lancet. 1988; 2: 1453-1456
        • Olsen J.
        Cigarette smoking, tea and coffee drinking and subfecundity.
        Am J Epidemiol. 1991; 133: 734-739
        • Bolumar F.
        • Olsen J.
        • Rebagliato M.
        • Bisanti L.
        Caffeine intake and delayed conception.
        Am J Epidemiol. 1997; 145: 324-334
        • Jensen T.K.
        • Henriksen T.B.
        • Hjollund N.H.
        • Scheike T.
        • Kolstad H.
        • Giwercman A.
        • et al.
        Caffeine intake and fecundability.
        Reprod Toxicol. 1998; 12: 289-295
        • Zaadstra B.M.
        • Seidell J.C.
        • Van Noord P.A.
        • te Velde E.R.
        • Habbema J.D.
        • Vrieswijk B.
        • et al.
        Fat and female fecundity.
        BMJ. 1993; 306: 484-487
        • Jarow J.P.
        • Kirkland J.
        • Koritnik D.R.
        • Cefalu W.T.
        Effect of obesity and fertility status on sex steroid levels in men.
        Urology. 1993; 42: 171-174
        • Foreyt J.P.
        • Poston 2nd, W.S.
        Obesity.
        Int J Fertil Wom Med. 1998; 43: 111-116
        • Messinis I.E.
        • Milingos S.D.
        Leptin in human reproduction.
        Hum Reprod Update. 1999; 5: 52-63
        • Magni P.
        • Motta M.
        • Martini L.
        Leptin.
        Regul Pept. 2000; 92: 51-56
        • Alfer J.
        • Muller-Schottle F.
        • Classen-linke I.
        • von Rango U.
        • Happel L.
        • Beier-Hellwig K.
        • et al.
        The endometrium as a novel target for leptin.
        Mol Hum Reprod. 2000; 6: 595-601
        • Imani B.
        • Eijkemans M.J.
        • de Jong F.H.
        • Payne N.N.
        • Bouchard P.
        • Giudice L.C.
        • et al.
        Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.
        J Clin Endocrinol Metab. 2000; 85: 676-682
        • Franks S.
        • Kiddy D.
        • Sharp P.
        • Singh A.
        • Reed M.
        • Seppala M.
        • et al.
        Obesity and polycystic ovary syndrome.
        Ann NY Acad Sci. 1991; 626: 201-206
        • Pettigrew R.
        • Hamilton-Fairley D.
        Obesity and female reproductive function.
        Br Med Bull. 1997; 53: 341-358
        • Kiddy D.S.
        • Hamilton-Fairley D.
        • Bush A.
        • Short F.
        • Anyaoku V.
        • Reed M.J.
        • et al.
        Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome.
        Clin Endocrinol. 1992; 36: 105-111
        • Pasquali R.
        • Casimirri F.
        • Vicennati V.
        Weight control and its beneficial effect on fertility in women with obesity and polycystic ovary syndrome.
        Hum Reprod. 1997; 12: 82-87
        • Norman R.J.
        • Clark A.M.
        Obesity and reproductive disorders.
        Reprod Fertil Dev. 1998; 10: 55-63
        • Kably-Ambe A.
        • Barron-Vallejo J.
        • Limon-Luque L.M.
        Effect of body mass index and follicular synchrony in the ovarian response to ovulation induction with menotropins.
        Int J Fertil Wom Med. 1999; 44: 156-159
        • Mueller B.A.
        • Daling J.R.
        • Weiss N.S.
        • Moore D.E.
        Recreational drug use and the risk of primary infertility.
        Epidemiology. 1990; 1: 189-192
        • Agarwal S.K.
        • Haney A.F.
        Does recommending timed intercourse really help the infertile couple?.
        Obstet Gynecol. 1994; 84: 307-310
        • Tur-Kaspa I.
        • Maor Y.
        • Levran D.
        • Yonish M.
        • Mashiach S.
        • Dor J.
        How often should infertile men have intercourse?.
        Fertil Steril. 1994; 62: 370-375
        • Sloggett A.
        • Joshi H.
        Deprivation indicators as predictors of life events 1981–1992 based on the UK ONS Longitudinal Study.
        J Epidemiol Community Health. 1998; 52: 228-233
        • Martin S.P.
        Diverging fertility among U.S. women who delay childbearing past age 30.
        Demography. 2000; 37: 523-533
        • Olatunbosun O.A.
        • Edouard L.
        • Pierson R.A.
        How important is health promotion in the lifestyle of infertile couples?.
        Clin Exp Obstet Gynecol. 1997; 24: 183-186
        • Whitman-Elia G.F.
        • Baxley E.G.
        A primary care approach to the infertile couple.
        J Am Board Fam Pract. 2001; 14: 33-45