Maternal consumption of coffee during pregnancy and stillbirth and infant death in first year of life: prospective study Cigarette smoking, alcohol consumption, and caffeine intake and fecundability. Caffeine and caffeinated beverage consumption and risk of spontaneous abortion. Psychological distress by type of fertility barrier. Caffeine consumption and miscarriage: a prospective cohort study. Coffee and Caffeine Consumption in Relation to Sex Hormone–Binding Globulin and Risk of Type 2 Diabetes in Postmenopausal Women alcohol, smoking, and caffeine in relation to fecundability, with effect modification by NAT2. Does caffeine and alcohol intake before pregnancy predict the occurrence of spontaneous abortion? Association of Genetic Polymorphisms with Serum Estrogens Measured Multiple Times During a 2-Year Period in Premenopausal Women Caffeine intake and delayed conception: a European multicenter study on infertility and subfecundity. European Study Group on Infertility Subfecundity. The Associations of Maternal Caffeine Consumption and Nausea with Spontaneous Abortion A prospective study of the effects of female and male caffeine consumption on the reproductive endpoints of IVF and gamete intra-Fallopian transfer. Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study. Moderate caffeine use and the risk of spontaneous abortion and intrauterine growth retardation. Coffee consumption and risk of hospitalized miscarriage before 12 weeks of gestation. The nuts and bolts of PROSPERO: an international prospective register of systematic reviews Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy. Caffeinated Beverages, Decaffeinated Coffee, and Spontaneous Abortion Effects of Caffeine Consumption by Women and Men on the Outcome of In Vitro Fertilization. Risk Factors for Early Pregnancy Loss Are caffeinated beverages risk factors for delayed conception? Alcohol and caffeine consumption and decreased fertility. Differences in fertility associated with caffeinated beverage consumption. Is caffeine consumption a risk factor for osteoporosis? Caffeinated Beverage and Soda Consumption and Time to Pregnancy
Abstract Objective : To study the association between coffee consumption during pregnancy and the risk of stillbirth and infant death in the first year of life . Design : Prospect i ve follow up study . Setting : Aarhus University Hospital , Denmark , 1989 - 96 . Participants : 18 478 singleton pregnancies in women with valid information about coffee consumption during pregnancy . Main outcome measures : Stillbirth ( delivery of a dead fetus at ≥28 weeks ' gestation ) and infant death ( death of a liveborn infant during the first year of life ) . Results : Pregnant women who drank eight or more cups of coffee per day during pregnancy had an increased risk of stillbirth compared with women who did not drink coffee ( odds ratio=3.0 , 95 % confidence interval 1.5 to 5.9 ) . After adjustment for smoking habits and alcohol intake during pregnancy , the relative risk of stillbirth decreased slightly . Adjustment for parity , maternal age , marital status , years of education , occupational status , and body mass index did not substantially change the estimates of association . There was no significant association between coffee consumption and death in the first year of life after adjustment for smoking habits during pregnancy . Conclusion : Drinking coffee during pregnancy is associated with an increased risk of stillbirth but not with infant death . What is already known on this topic Results from studies in monkeys suggest that high daily doses of caffeine in pregnancy increase the risk of stillbirth , but evidence from studies in humans has been lacking What this study adds Pregnant women who drank eight or more cups of coffee a day had more than twice the risk of stillbirth compared with women who did not drink coffee during BACKGROUND In a prospect i ve study the effect of the behavioral risk factors of both partners on fecundability  was studied . METHODS Information was collected on smoking habits , alcohol consumption , and caffeine intake ( e.g. coffee , tea , and cola consumption ) by interviewing 259 female nonmedical hospital workers , i.e. , clerical staff , cleaners , kitchen and restaurant workers , and their partners , who were planning a pregnancy . The occurrence of pregnancy was tested prospect ively during the 12 months after enrollment . RESULTS Among the participants as well as among their partners , smoking a moderate number of cigarettes ( 1 - 10/day ) was associated with higher fecundability ( i.e. , the probability of becoming pregnant each month ) than among those not smoking ( participant : OR = 1.4 ( 95 % CI , 0.9 - 2.2 ) ; partner : OR = 2.1 ( 95 % CI , 1.2 - 3.5 ) ) . The level of alcohol consumption in the female partner was not related to fecundability . However , in the male partner , there was a positive influence for drinking more than 10 alcoholic drinks per week compared with that observed for those drinking less than 5 ( OR = 1.6 ; 95 % CI , 1.0 - 2.4 ) . Participants with a moderate caffeine intake ( 400 - 700 mg/day ) showed a higher fecundability than those with a lower intake level ( ORadjusted = 2.1 ( 95 % CI , 1.2 - 3.7 ) ) . Heavy caffeine intake ( > 700 mg/day ) among partners was negatively related to fecundability when compared with the lowest intake level ( ORadjusted = 0.6 ( 95 % CI , 0.3 - 0.97 ) ) . CONCLUSIONS This study does not support the hypothesis that moderate cigarette smoking , caffeine intake , and alcohol consumption have an adverse influence on fecundability STUDY QUESTION Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion ( SAB )  ? SUMMARY ANSWER While preconceptional caffeine consumption was not material ly associated with an increased risk of SAB , consumption during early pregnancy was associated with a small increased risk of SAB , although the relation was not linear . WHAT IS KNOWN ALREADY Caffeine has been hypothesized as a risk factor for SAB since the 1980s ; however , results from previous studies have been conflicting . STUDY DESIGN , SIZE , DURATION This prospect i ve cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010 . PARTICIPANTS / MATERIAL S , SETTING , METHODS Participants were women who conceived after entry into the Snart-Gravid cohort and who were aged 18 - 40 , in a stable relationship with a male partner , and did not use fertility treatments to conceive . Women reported their daily caffeine and caffeinated beverage consumption on question naires before conception and during early pregnancy . All exposure measurements were prospect i ve with respect to outcome ascertainment . We estimated hazard ratios ( HRs ) of SAB for categories of caffeine consumption in milligrams ( mg ) per day and the corresponding 95 % confidence intervals ( CIs ) using Cox proportional hazards regression models with gestational weeks as the time scale . MAIN RESULTS AND THE ROLE OF CHANCE There were 732 women ( 14.3 % ) who were identified as having a SAB . In the preconceptional period , caffeine consumption was not material ly associated with SAB risk ( HR comparing ≥300 with < 100 mg/day : 1.09 ; 95 % CI : 0.89 , 1.33 ) . In early pregnancy , the HRs for 100 - 199 , 200 - 299 and ≥300 mg/day of caffeine consumption were 1.62 ( 95 % CI : 1.19 , 2.22 ) , 1.48 ( 95 % CI : 1.03 , 2.13 ) and 1.23 ( 95 % CI : 0.61 , 2.46 ) , respectively , compared with that for < 100 mg/day . LIMITATIONS , REASONS FOR CAUTION The observed results may be affected by non-differential exposure misclassification , reverse causation and residual confounding . WIDER IMPLICATION S OF THE FINDINGS This is the largest study to date of prospect ively measured , preconception caffeine consumption and risk of SAB . We were able to reduce the likelihood of differential left truncation bias and recall bias present in other analyses . STUDY FUNDING /COMPETING INTERESTS Snart-Gravid was funded by the NICHD ( R21 - 050264 ) . Dr. Hahn 's work was funded in part by the BU Reproductive , Perinatal , and Pediatric Epidemiology Training Grant NIH # T32HD052458 . There are no competing interests BACKGROUND We examined  fertility-specific distress ( FSD ) and general distress by type of fertility barrier ( FB ) . METHODS In a r and om sample telephone survey , 580 US women reported their fertility intentions and histories . Six groups of women were identified : ( i ) no FBs , ( ii ) infertile with intent , ( iii ) infertile without intent , ( iv ) other fertility problems , ( v ) miscarriages and ( vi ) situational barriers . Multiple regression analyses were used to compare groups with FBs . RESULTS Sixty-one percent reported FBs and 28 % reported an inability to conceive for at least 12 months . The infertile with intent group had the highest FSD , which was largely explained by ( a ) self- identification as infertile and ( b ) seeking medical help for fertility . The no FB group had a mean Center for Epidemiological Studies Depression scale score above the commonly used cut-off of 16 , although 23 % of the women with FBs did score above 16 . CONCLUSIONS FBs are common . Self- identification as infertile is the largest source of FSD . More women with FBs had elevated general distress than women without FBs ; mean general distress was below 16 for all FB groups . It may be that , for some women ( even those with children ) , FBs can have lasting emotional consequences , but many women do heal from the emotional distress that may accompany fertility difficulties Caffeine consumption has been equivocally associated with  miscarriage  , despite an absence of prospect i ve longitudinal measurement of caffeine intake during sensitive windows of human development . In response to this critical data gap , we analyzed daily caffeine consumption while attempting pregnancy through 12 menstrual cycles at risk for pregnancy and found that caffeine consumption did not increase the risk or hazard of miscarriage  , even after adjusting for relevant covariates OBJECTIVE Coffee consumption has been inversely associated with  type 2 diabetes risk , but its mechanisms are largely unknown . We aim ed to examine whether plasma levels of sex hormones and sex hormone – binding globulin ( SHBG ) may account for the inverse association between coffee consumption and type 2 diabetes risk . RESEARCH DESIGN AND METHODS We conducted a case-control study nested in the prospect i ve Women 's Health Study ( WHS ) . During a median follow-up of 10 years , 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age , race , duration of follow-up , and time of blood draw . RESULTS Caffeinated coffee was positively associated with SHBG but not with sex hormones . Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming ≥4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers ( P for trend = 0.01 ) . In contrast , neither decaffeinated coffee nor tea was associated with SHBG or sex hormones . The multivariable-adjusted odds ratio ( OR ) of type 2 diabetes for women consuming ≥4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 ( 95 % CI 0.23–0.94 ; P for trend = 0.047 ) . The association was largely attenuated after further adjusting for SHBG ( OR 0.71 [ 95 % CI 0.31–1.61 ] ; P for trend = 0.47 ) . In addition , carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming ≥2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG . CONCLUSIONS Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women PURPOSE Common polymorphisms in the N-acetyltransferase-2 ( NAT2 ) metabolic enzyme determine slow or rapid acetylator phenotypes . We investigated the effects of alcohol , smoking , and caffeine on fecundability , and determined whether the effects were modified by NAT2 . METHODS Three NAT2 polymorphisms were genotyped in 319 women office workers participating in a prospect i ve pregnancy study ( 1990 - 1994 ) . Women were ages 20 - 41 and at risk for pregnancy . Discrete-time survival analysis was used to determine the effects of alcohol , smoking , and caffeine on fecundability and evaluate effect modification by NAT2 . RESULTS We followed 319 women ( 161 slow acetylators , 158 rapid ) for an average of 8 menstrual cycles , result ing in 124 pregnancies . There was no effect of caffeine on fecundability . Drinking ≥1 alcoholic drink per day and current smoking were significantly associated with reduced fecundability , but only among slow acetylators ( adjusted fecundability odds ratio [ FOR ] for smoking = 0.34 ; 95 % confidence interval , 0.22 - 0.90 ; adjusted FOR for ≥1 drink per day = 0.20 ; 0.05 - 0.92 ) . There was no effect among rapid acetylators . CONCLUSIONS NAT2 status significantly modified the effects of alcohol and smoking on fecundability , emphasizing the importance of incorporating genetic and metabolic information in studies of reproductive health . Replication of this study is warranted BACKGROUND Consumption of caffeine and alcohol is suspected to affect pregnancy outcome . Use of both stimulants is widespread and even minor effects on fetal viability are of public health interest . METHODS We performed a nested case-control study using prospect i ve data from a population -based cohort comprising 11088 women aged 20 - 29 years . From this cohort , women who experienced either a spontaneous abortion ( n = 303 ) or who gave birth ( n = 1381 ) during follow-up [ mean time : 2.1 years ( range : 1.6 - 3.4 ) ] were selected . Associations between self-reported exposures to caffeine and /or alcohol at enrolment and spontaneous abortion were analysed by means of logistic regression . RESULTS Compared with women with a pre-pregnancy intake of < 75 mg caffeine per day , the adjusted odds ratio ( 95 % confidence interval ) for spontaneous abortion was 1.26 ( 0.77 - 2.06 ) , 1.45 ( 0.87 - 2.41 ) , 1.44 ( 0.87 - 2.37 ) and 1.72 ( 1.00 - 2.96 ) for a pre-pregnancy intake on 75 - 300 , 301 - 500 , 501 - 900 and > 900 mg caffeine per day respectively ( P = 0.05 for trend ) . A pre-pregnancy intake of alcohol was not a predictor for spontaneous abortion . CONCLUSIONS A high intake of caffeine prior to pregnancy seems to be associated with an increased risk of spontaneous abortion , whereas a low-to-moderate alcohol intake does not influence the risk There is evidence that circulating estrogens are associated with breast cancer risk . In this study of premenopausal women , we explored the association of polymorphisms in genes in the estrogen synthesis and metabolism pathways with serum and urinary levels of estrone ( E1 ) and estradiol ( E2 ) and with the urinary ratio of 2-hydroxyestrone (2-OHE1)/16α-hydroxyestrone ( 16α-OHE1 ) . This analysis included 220 women , who were participants in a 2-year r and omized soy intervention .  Blood specimens were collected in the luteal phase of the menstrual cycle an average of 4.4 times over 2 years . Overnight urinary specimens were collected on the same cycle day , only at baseline . Levels of E1 , E2 , 2-OHE1 , and 16α-OHE1 were measured by enzyme immunoassays . The DNA sample s were analyzed by PCR/RFLP for the COMT Val158Met , CYP1A1 * 2A , CYP1A1 * 2B , CYP1A2 * 1F , CYP1B1 Val432Leu , and CYP17 T27C polymorphisms . We applied mixed models to investigate the relations between genotypes and repeated serum hormone measurements and generalized linear models to assess associations between genotypes and urinary estrogen metabolites . The CYP1A2 C allele was significantly associated with lower serum E2 levels ; in CC genotype carriers , serum E2 levels were 26.3 % lower than in homo- and heterozygous common allele carriers combined ( P = 0.01 ) . CYP1A2 * 1F also affected the urinary 2-OHE1/16α-OHE1 ratio ; carriers of the variant C allele had a markedly lower ratio than individuals with the AA genotype ( 1.37 versus 1.76 ; P = 0.002 ) . These data suggest that CYP1A2 * 1F is associated with lower circulating levels of E2 , and that it may be a susceptibility locus for breast cancer The effects of caffeine consumption on delayed conception were evaluated in a European multicenter study on risk factors of infertility . Information was collected retrospectively on time of unprotected intercourse for the first pregnancy and the most recent waiting time episode in a r and omly selected sample of 3,187 women aged 25 - 44 years from five European countries ( Denmark , Germany , Italy , Pol and , and Spain ) between August 1991 and February 1993 . The consumption of caffeinated beverages at the beginning of the waiting time was used to estimate daily caffeine intake , which was categorized as 0 - 100 , 101 - 300 , 301 - 500 , and > or = 501 mg . Risk of subfecundity ( > or = 9.5 months ) and the fecundability ratio , respectively , were assessed by logistic regression and Cox proportional hazard analyses , adjusting for age , parity , smoking , alcohol consumption , frequency of intercourse , educational level , working status , use of oral contraceptives , and country . A significantly increased odds ratio ( OR ) of 1.45 ( 95 % confidence interval ( CI ) 1.03 - 2.04 ) for subfecundity in the first pregnancy was observed for women drinking more than 500 mg of caffeine per day , the effect being relatively stronger in smokers ( OR = 1.56 , 95 % CI 0.92 - 2.63 ) than in nonsmokers ( OR = 1.38 , 95 % CI 0.85 - 2.23 ) . Women in the highest level of consumption had an increase in the time leading to the first pregnancy of 11 % ( hazard ratio = 0.90 , 95 % CI 0.78 - 1.03 ) . These associations were observed consistently in all countries as well as for the most recent waiting time episode . The authors conclude that high levels of caffeine intake may delay conception among fertile women To examine whether maternal caffeine consumption is associated with the risk of spontaneous abortion , we analyzed data from a population -based prospect i ve study . The study population comprised 575 women delivering singleton livebirths and 75 women who had spontaneous abortions . The subjects were predominantly white , middle-class women enrolled before pregnancy . Study participants were traced to delivery of a liveborn , singleton infant or a spontaneous abortion . Of the 71 women who did not experience nausea , 29.6 % had a spontaneous abortion , compared with 7.2 % of 514 women who did experience nausea . Maternal caffeine consumption before pregnancy , or in women without nausea , did not increase the risk of spontaneous abortion , whereas maternal caffeine consumption during the first trimester after nausea started might increase risk of spontaneous abortion ( risk ratio = 5.4 , 95 % confidence interval = 2.0–14.6 for caffeine consumption ≥300 mg per day compared with < 20 mg per day ) . These results suggest that maternal caffeine consumption during pregnancy may influence fetal viability in women with nausea BACKGROUND This study evaluated the timing and amount of caffeine intake by women and men undergoing IVF and gamete intra-Fallopian transfer ( GIFT ) on oocyte retrieval , sperm parameters , fertilization , multiple gestations , miscarriage , and live births . METHODS A prospect i ve study of 221 couples was conducted in Southern California between 1993 and 1998 . " Usual " caffeine intake during lifetime and 1 year prior to attempt , caffeine intake during the week of the initial clinic visit , as well as intake during the week of the procedure , was evaluated from beverages ( coffee , soda , tea ) and chocolates . RESULTS Not achieving a live birth was significantly associated with " usual " female caffeine consumption [ adjusted odds ratios ( 95 % confidence intervals ) : 3.1 ( 1.1 , 9.7 ) and 3.9 ( 1.3 , 11.6 ) for intake of > 2 - 50 and 50 mg/day , compared with 0 - 2 mg/day ] and consumption during the week of the initial visit [ 2.9 ( 1.1 , 7.5 ) and 3.8 ( 1.4 , 10.7 ) ] female compared with 0 - 2 mg/day , although caffeine use was low . Infant gestational age decreased by 3.8 ( -6.9 , -0.7 ) or 3.5 ( -6.7 , -0.3 ) weeks for women who consumed > 50 mg/day of caffeine " usually " or during the week of the initial visit . The odds of having multiple gestations increased by 2.2 ( 1.1 , 4.4 ) and 3.0 ( 1.2 , 7.4 ) for men who increased their " usual " intake or intake during the week of the initial visit by an extra 100 mg/day . Caffeine intake was not significantly associated with other outcomes . CONCLUSIONS This is the first IVF/GIFT study to report any effect of caffeine on live births , gestational age , and multiple gestations . If these findings are replicated , caffeine use should be minimized prior to and while undergoing IVF/GIFT OBJECTIVE The objective of the study was to examine whether the risk of miscarriage  is associated with caffeine consumption during pregnancy after controlling for pregnancy-related symptoms . STUDY DESIGN This was a population -based prospect i ve cohort study . RESULTS An increasing dose of daily caffeine intake during pregnancy was associated with an increased risk of miscarriage , compared with no caffeine intake , with an adjusted hazard ratio ( aHR ) of 1.42 ( 95 % confidence interval 0.93 to 2.15 ) for caffeine intake of less than 200 mg/day , and aHR of 2.23 ( 1.34 to 3.69 ) for intake of 200 or more mg/day , respectively . Nausea or vomiting during pregnancy did not material ly affect this observed association , nor did the change in intake pattern of caffeine during pregnancy . In addition , the magnitude of the association appeared to be stronger among women without a history of miscarriage ( aHR 2.33 , 1.48 to 3.67 ) than that among women with such a history ( aHR 0.81 , 0.34 to 1.94 ) . CONCLUSION Our results demonstrated that high doses of caffeine intake during pregnancy increase the risk of miscarriage  , independent of pregnancy-related symptoms OBJECTIVE To examine the relationship between caffeine consumption during pregnancy and the occurrence of  spontaneous abortion and intrauterine growth retardation .  DESIGN , SETTING , AND PATIENTS A cohort of 431 women , enrolled in a multicenter study within 21 days of conception , was monitored throughout pregnancy to determine ( 1 ) caffeine exposure , ( 2 ) exposure to other risk factors , ( 3 ) fetal growth as assessed by ultrasonography , and ( 4 ) pregnancy outcome . OUTCOME MEASURES Spontaneous abortion , intrauterine growth , birth weight , and head circumference . RESULTS The mean ( + /- SD ) first-trimester  caffeine consumption was not significantly higher in women who aborted ( 125.9 + /- 123.1 mg ) than in women who delivered liveborn infants ( 111.6 + /- 107.0 mg ) ( P = 34 ) . The adjusted odds ratio ( OR ) for spontaneous abortion was 1.15 ( 95 % confidence interval [ CI ] , 0.89 to 1.49 ) . Early fetal growth , assessed by crown-rump length on ultrasonographic examination , was not affected by caffeine . Although the group consuming the most caffeine ( > 300 mg/d ) had a significantly higher proportion of babies with birth weights and head circumferences below the 10th percentile in the crude analysis , the association with caffeine was no longer significant when other risk factors ( notably smoking ) were taken into account . The adjusted ORs were 1.11 ( 95 % CI , 0.88 to 1.40 ) for decreased birth weight and 1.09 ( 95 % CI , 0.86 to 1.37 ) for smaller head circumference . CONCLUSIONS Close monitoring of a cohort identified very soon after conception enabled us to identify all abortions after 21 days postconception , monitor intrauterine growth prospect ively , and track caffeine use . Despite this intensive surveillance , we found no evidence that moderate caffeine use increased the risk of spontaneous abortion , intrauterine growth retardation , or microcephaly after accounting for other risk factors In order to analyse the association between drinking coffee in pregnancy and risk of spontaneous abortion , a case-controlled study was conducted in Milan , Northern Italy . Cases were 782 women with spontaneous abortion within the 12th week of gestation . The control group was recruited from women who gave birth at term ( > 37 weeks gestation ) to healthy infants on r and omly selected days at the same hospitals where cases had been identified : 1543 controls were interviewed . A total of 561 ( 72 % ) cases of spontaneous abortion and 877 ( 57 % ) controls reported coffee drinking during the first trimester of the index pregnancy . The corresponding multivariate odds ratios of spontaneous abortion , in comparison with non-drinkers , were 1.2 , 1.8 and 4.0 , respectively , for drinkers of 1 , 2 or 3 , and 4 or more cups of coffee per day . No relationship emerged between maternal decaffeinated coffee , tea and cola drinking in pregnancy , as well as paternal coffee consumption , and risk of spontaneous abortion . With regard to duration in years of coffee drinking , the estimated multivariate odds ratios of spontaneous abortion were , in comparison with non-coffee drinkers , 1.1 ( 95 % confidence interval ( CI ) 0.9 - 1.4 ) and 1.9 ( 95 % CI 1.5 - 2.6 ) for women reporting a duration of coffee consumption < or = 10 or > 10 years . In conclusion , coffee drinking early in pregnancy was associated with an increased risk of abortion . This has biological implication s , but epidemiological inference on the causality is difficult and still open to debate Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions Fecundability has been defined as the ability to achieve a recognized pregnancy . Several studies on caffeine and fecundability have been conducted but have been inconclusive . This may be explained partly by lack of stratification by smoking . Furthermore , few research ers have tried to separate the effect of caffeine from different sources ( coffee , tea , cola , and chocolate ) . Clearly , the relationship between caffeine and fecundability needs further research , given the high prevalence of caffeine intake among women of childbearing age . We examined the independent and combined effects of smoking and caffeine intake from different sources on the probability of conception .  From 1992 to 1995 , a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old , lived with a partner , and had no previous reproductive experience . At enrollment and in six cycles of follow-up , both partners filled out a question naire on different factors including smoking habits and their intake of coffee , tea , chocolate , cola beverages , and chocolate bars . In all , 1596 cycles and 423 couples were included in the analyses . The cycle-specific association between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle ( pregnant or not pregnant ) in a Cox discrete model calculating the fecundability odds-ratio ( FR ) . Compared to nonsmoking women with caffeine intake less than 300 mg/d , nonsmoking women who consumed 300 to 700 mg/d caffeine had a FR of 0.88 [ 95 % confidence interval ( CI ) 0.60 - 1.31 ] , whereas women with a higher caffeine intake had a FR = 0.63 ( 95 % CI 0.25 - 1.60 ) after adjusting for female body mass index and alcohol intake , diseases of the female reproductive organs , semen quality , and duration of menstrual cycle . No dose-response relationship was found among smokers . Among males , the same decline in point estimates of the FR was present . Smoking women whose only source of caffeine was coffee ( > 300 mg/d ) had a reduced fecundability odds-ratio ( FR = 0.34 ; 95 % CI 0.12 - 0.98 ) . An interaction between caffeine and smoking is biologically plausible , and the lack of effect among smokers may be due to faster metabolism of caffeine . Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake We examined the relations between  spontaneous abortion and the consumption of caffeine , individual caffeine‐containing beverages ( coffee , tea , and soda ) , and decaffeinated coffee in a prospect i ve study of 5,144 pregnant women . We collected information about potential risk factors for spontaneous abortion , including consumption of caffeinated beverages and decaffeinated coffee before and during pregnancy , by interview in the first trimester . Neither total estimated caffeine nor individual caffeinated beverage consumption during the first trimester was associated with an appreciable increase in risk for spontaneous abortion . The adjusted odds ratio for consumption of greater than 300 mg per day of caffeine was 1.3 [ 95 % confidence interval ( CI ) = 0.8–2.1 ] after adjustment for maternal age , pregnancy history , cigarette and alcohol consumption , employment , race , gestational age at interview , and marital and socioeconomic status . The adjusted odds ratio for spontaneous abortion related to consumption of three or more cups of decaffeinated coffee during the first trimester was 2.4 ( 95 % CI = 1.3–4.7 ) in the same model . Although we could not demonstrate this with available data , we suspect that this association was due to bias result ing from the relations among fetal viability , symptoms of pregnancy such as nausea , and consumption patterns during pregnancy OBJECTIVE The objective of this study was to estimate the association between caffeine consumption and  in vitro fertilization ( IVF ) outcomes .  METHODS A total of 2474 couples were prospect ively enrolled prior to undergoing their first cycle of IVF , contributing a total of 4716 IVF cycles . Discrete survival analysis adjusting for observed confounders was applied to quantify the relation between caffeine consumption and livebirth . Secondary outcomes of interest were oocyte retrieval , peak estradiol level , implantation rate , and fertilization rate . RESULTS Overall , caffeine consumption by women was not significantly associated with livebirth ( ptrend=0.74 ) . Compared with women who do not drink caffeine , the likelihood of livebirth was not significantly different for women who drank low ( > 0 - 800 mg/week ; odds ratio [OR]=1.00 , 95 % confidence interval [CI])=0.83 - 1.21 ) , moderate ( > 800 - 1400 mg/week ; OR=0.89 , 95 % CI=0.71 - 1.12 ) , or high levels of caffeine ( > 1400 mg/week ; OR=1.07 , 95 % CI=0.85 - 1.34 ) . Greater caffeine intake by women was associated with a significantly lower peak estradiol level ( ptrend=0.03 ) , but was not associated with the number of oocytes retrieved ( ptrend=0.75 ) , fertilization rate ( ptrend=0.10 ) , or implantation rate ( ptrend=0.23 ) . There was no significant association between caffeine intake by men and livebirth ( ptrend=0.27 ) , fertilization ( ptrend=0.72 ) , or implantation ( ptrend=0.24 ) . The individual effects of consumption of coffee , tea , or soda by women or men were not related to livebirth . CONCLUSION Caffeine consumption by women or men was not associated with  IVF outcomes We looked at risk of early  pregnancy loss among 171 women who conceived while participating in a prospect i ve study . Twenty-five percent of biochemically detected pregnancies ended within six weeks of the last menstrual period ; all but two of these losses were clinical ly unrecognized . While our sample is small , it is the first to allow description of possible associations between risk of early pregnancy loss and maternal characteristics or exposures . We looked at risk in relation to a woman 's age , pregnancy history , weight , education , prenatal DES exposure , cigarette smoking , use of caffeinated and alcoholic beverages , marijuana , cigarette smoking by baby 's father , and other variables . None of these factors was definitely associated with early pregnancy loss . Still , the possibility of real effects can not be excluded and deserves further The association between time to conceive reported by 2817 fertile women who had recently had a liveborn child and consumption of coffee , tea , and " cola " drinks has been investigated . No evidence for an adverse effect of caffeine was found . For levels of consumption ranging from less than one cup of coffee per week ( 501 mg caffeine per month ) to more than two cups of coffee per day ( 7000 mg per month ) , the average time to conceive was similar . The fecundability ratio adjusted for known risk factors for time to conceive was 1.03 ( 95 % confidence interval 0.92 - 1.16 ) between those who consumed more than 7000 mg caffeine per month and those who consumed 500 mg or less per month . Furthermore caffeine consumption was not associated with  infertility  in 1818 infertile women and their primiparous controls OBJECTIVE To examine the effects of alcohol and caffeine on  conception . DESIGN Prospect i ve observational study . SETTING Healthy volunteers in two manufacturing facilities . PATIENT(S ) One hundred twenty-four women who provided daily urine sample s for measurement of steroid hormones and hCG , and prospect i ve information about alcohol and caffeine consumption .  MAIN OUTCOME MEASURE(S ) Probability of conception per 100 menstrual cycles . RESULT ( S ) There was > 50 % reduction in the probability of conception during a menstrual cycle during which participants consumed alcohol . Caffeine consumption did not independently affect the probability of conception but may enhance alcohol 's negative effect . Women who abstained from alcohol and consumed less than one cup of coffee or its equivalent per day conceived 26.9 pregnancies per 100 menstrual cycles compared with 10.5 per 100 menstrual cycles among those who consumed any alcohol and more than one cup of coffee per day . CONCLUSIONS This study revealed an independent dose-related negative effect of alcohol consumption on the ability to conceive . Our results suggest that women who are attempting to conceive should abstain from consuming alcohol OBJECTIVES The effect of caffeine consumption on fertility was examined prospect ively in 210 women . METHODS Women reported on caffeinated beverage consumption and pregnancy status monthly . Odds ratios for becoming pregnant were calculated for both high and moderate vs low consumption . RESULTS No significant association was found for any of the caffeinated beverages except tea . Drinking one-half cup or more of tea daily approximately doubled the odds of conception per cycle . CONCLUSIONS These data suggest that caffeine may not be the responsible agent for variation in fertility associated with consumption of the beverages examined High caffeine consumption has been proposed as a risk factor for osteoporotic fracture , but the evidence associating high caffeine intake with low bone density is inconsistent . We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified r and om sample of white women residing in Rochester , Minnesota . After age adjustment , there was no association between overall caffeine consumption and bone mineral at five of the six sites . In the femoral shaft , however , there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages . When caffeine intake was categorized by source , no consistent influence of coffee , tea , or other caffeinated beverage consumption could be detected on bone mineral . Caffeine intake was , however , positively associated with cigarette smoking and alcohol consumption . After adjusting for age , caffeine consumption was not correlated with biochemical indices of bone turnover , circulating concentrations of estradiol and estrone , or other dietary and musculoskeletal variables . These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis . Among elderly women , however , in whom calcium balance performance is impaired , high caffeine intake may predispose to cortical bone loss from the proximal femur Background : Many epidemiologic studies have evaluated the association between caffeine and fertility , with inconsistent results . Some studies suggest that various caffeine-containing beverages may affect fertility differently . Methods : We evaluated the relation of caffeine , coffee , tea , and sodas with time to pregnancy  in a prospect i ve cohort study of 3628 women planning a pregnancy , in Denmark ( 2007–2010 ) . Women reported beverage intake at baseline and every 8 weeks during follow-up until they became pregnant or for up to 12 cycles . We used discrete-time Cox proportional hazards regression to estimate fecundability ratios ( FRs ) and 95 % confidence intervals ( CIs ) , controlling for potential confounders . Results : There was little relation between fecundability and caffeine intake of 300 + mg/day compared with < 100 mg/day ( FR = 1.04 [ 95 % CI = 0.90–1.21 ] ) or coffee intake of 3 + servings/day compared with none ( 1.05 [ 0.85–1.33 ] ) . Soda consumption was associated with reduced fecundability : for all types of sodas combined , the adjusted FRs were 0.89 ( 0.80–0.98 ) , 0.85 ( 0.71–1.02 ) , 0.84 ( 0.57–1.25 ) , and 0.48 ( 0.21–1.13 ) for < 1 , 1 , 2 , and 3 + servings per day , respectively , compared with none . Tea drinking was associated with a slight increase in fecundability , with FR = 1.27 ( 0.98–1.64 ) for 2 + servings/day versus none . Conclusion : In this prospect i ve study of time to pregnancy , the association between caffeine intake and fertility differed by beverage type . Although we controlled for many confounders , our findings of reduced fecundability among soda drinkers and increased fecundability among tea drinkers could have result ed from confounding by unmeasured lifestyle characteristics
Objective The aim was to investigate whether coffee or caffeine consumption is associated with reproductive endpoints among women with natural fertility ( ie , time to pregnancy [ TTP ] and spontaneous abortion [ SAB ] ) and among women in fertility treatment ( ie , clinical pregnancy rate or live birth rate ) .