Clinicians may be asked to provide advice about sexual and lifestyle practices relating to procreation. This document will provide practitioners with recommendations, based on a consensus of expert opinion, for counseling women and men about how they might optimize the likelihood of achieving natural, non-medically-assisted pregnancy when there is no history of infertility or reason to question their potential fertility. Any patient encounter with nonpregnant women or men with reproductive potential is an opportunity to counsel them about wellness and healthy habits to optimize reproductive outcomes (1, 2).
Fertility varies among populations and declines with age in both women and men, but the effects of age are much more pronounced in women (6, 7) (Fig. 1). There is an age-related decline in the chances of pregnancy and live birth, corresponding to an increased risk of aneuploidy and miscarriage with maternal aging (8). In a landmark study in Hutterites, whose societal pressure is to reproduce until menopause, pregnancies occurred rarely during the 40s, with the average age of the mother at the last pregnancy just before turning 41 years old. Markers of ovarian reserve also decline with increasing age but are poor predictors of fecundity in noninfertile women (9, 10). Although semen parameters in men also decline detectably after 35 years of age, male fertility does not appear to be appreciably affected before the age of approximately 50 (11).
FERTILITY AND AGING
Fertility is defined as the capacity to produce a child. The likelihood of conception is generally highest in the first few months of unprotected intercourse and declines gradually thereafter (3). Approximately 80% of couples will conceive in the first 6 months of attempting pregnancy (3). Monthly fecundability (the probability of pregnancy per month) is greatest in the first 3 months (3). Relative fertility is decreased by about half at age 40 compared with women in their late 20s and early 30s, the time of peak fertility (4, 5).Fertility varies among populations and declines with age in both women and men, but the effects of age are much more pronounced in women (6, 7) (Fig. 1). There is an age-related decline in the chances of pregnancy and live birth, corresponding to an increased risk of aneuploidy and miscarriage with maternal aging (8). In a landmark study in Hutterites, whose societal pressure is to reproduce until menopause, pregnancies occurred rarely during the 40s, with the average age of the mother at the last pregnancy just before turning 41 years old. Markers of ovarian reserve also decline with increasing age but are poor predictors of fecundity in noninfertile women (9, 10). Although semen parameters in men also decline detectably after 35 years of age, male fertility does not appear to be appreciably affected before the age of approximately 50 (11).
Figure 1
Infertility is a disease, defined as the failure to achieve a successful pregnancy after 12 months or more of regular unprotected vaginal intercourse (12). Earlier evaluation and treatment may be justified on the basis of the medical history and physical findings and is warranted after 6 months without conception for women aged 35 years and older due to the accelerated decline in fertility (8, 12).
intercourse occurred on the day of ovulation (15).
THE FERTILE WINDOW
For counseling purposes, the ‘‘fertile window’’ is best defined as the 6-day interval ending on the day of ovulation (13, 14). At least in theory, the viability of both oocytes and sperm should be maximal during that time. In a study of 221 presumed fertile women, peak fecundability was observed when intercourse occurred within 2 days before ovulation (14) (Fig. 2). In another family planning study, the investigators combined data obtained from two cohorts, one using basal body temperature monitoring and the other using analysis of urinary estrogen and progesterone metabolites, to determine the likely time of ovulation. The likelihood of pregnancy was greatest when intercourse occurred the day before ovulation and started to decline whenintercourse occurred on the day of ovulation (15).
Figure 2
Among women who described their menstrual cycles as ‘‘generally regular,’’ the likelihood of conception resulting from a single act of intercourse increases during the putative fertile window (16). The probability of clinical pregnancy increases from 3.2% on cycle day 8 to 9.4% on cycle day 12 and decreases to less than 2% on cycle day 21. Although it is thought that age does not affect the length or timing of the fertile window in relationship to ovulation, the likelihood of success decreases with increasing age (Fig. 3) (17).
Although evidence suggests that daily intercourse during the fertile window may confer a slight advantage, specific recommendations regarding the frequency of intercourse may induce unnecessary stress in the couple. In one study, cycle fecundity was similar with intercourse that occurred daily, every other day, and even every 3 days in the fertile window, but was lowest when intercourse occurred only once in the fertile window (14). Couples should be informed that reproductive efficiency increases with the frequency of intercourse and is highest when intercourse occurs every 1 to 2 days during the fertile window, but be advised that the optimal frequency of intercourse is best defined by their own preference within that context. Intercourse more frequently than every 1 to 2 days is not associated with lower fecundity, and couples should not be advised to limit the frequency of intercourse when trying to achieve pregnancy.
The calendar method is based on the length of the menstrual cycle. For all women, the length of the luteal phase is presumed to be approximately 14 days. Thus, the day of ovulation is set at cycle day 14 for a woman with a 28-day cycle, day 16 for a woman with a 30-day cycle, etc. The fertile window is set as the presumed day of ovulation and the 5 days prior (cycle days 9–14 in a woman with a 28-day cycle, cycle days 11–16 in a woman with a 30-day cycle, and so forth). Smart phone calendar apps, which use the calendar method, are becoming a popular first-line or adjunct fertility-awareness method (22). However the ability of appbased technology to precisely predict an individual’s fertile window or ovulation day may not add to the clinical utility of traditional practices (23).
A study of 949 volunteers comparing urinary luteinizing hormone (LH) testing with multiple different downloadable calendar apps revealed a maximum accuracy of 21% in predicting the day of ovulation (24). The major pitfall of these predictors is that they are based on the assumption that the timing and duration of a woman’s fertile window are consistent and dependent on cycle length characteristics, despite knowledge that cycles are much more variable (25, 26). Patients should be empowered to use this technology to assist in understanding their own personal cycle characteristics and trends; however this should be accompanied by a candid review of the shortcomings of the calendar method, with and without apps, for ovulation tracking.
Ovulation detection devices monitor urinary LH excretion to determine the day of ovulation. Some of these also monitor urinary estrone glucuronide levels to delineate other days in the fertile window (days of ‘‘high’’ but not ‘‘peak’’ fertility). Although numerous studies have validated the accuracy of methods for detecting the midcycle urinary LH surge (1, 2, 27), ovulation may occur any time within the 2 days thereafter (28, 29), and false-positive test results occur in approximately 7% of cycles (29). The use of ovulation detection devices has been shown in a randomized controlled trial to decrease the time to pregnancy (30).
The quality of the cervical mucus (as detected by vaginal secretions at the introitus) provides an inexpensive and private index of when ovulation may be expected. The estimated probability of conception, in relation to the characteristics of cervical/vaginal secretions, is shown in Figure 4. The probability is highest when the mucus is slippery and clear (31), but such mucus is not a prerequisite for pregnancy to occur. The volume of cervical mucus increases with plasma estrogen concentrations over the 5 to 6 days preceding ovulation and reaches its peak within 2 to 3 days before ovulation (32). A retrospective cohort study including 1,681 cycles observed that pregnancy rates were highest (approximately 38%) when intercourse occurred on the day of peak mucus (day 0) and were appreciably lower (approximately 15% to 20%) on the day before or the day after the peak (33).
FREQUENCY OF INTERCOURSE
Information has emerged over the past decade that may help to define an optimal frequency of intercourse. Whereas abstinence intervals greater than 5 days may adversely affect sperm counts, abstinence intervals as short as 2 days are associated with normal sperm densities (18). A widely held misconception is that frequent ejaculations decrease male fertility. A retrospective study that analyzed almost 10,000 semen specimens observed that in men with normal semen quality, sperm concentrations and motility remained normal, even with daily ejaculation (19). Surprisingly, in men with oligozoospermia, sperm concentration and motility may be highest with daily ejaculation (19). Abstinence intervals generally also do not appear to affect sperm morphology, as judged by ‘‘strict’’ criteria (20). However, after longer abstinence intervals of 10 days or more, semen parameters begin to deteriorate. Although studies of semen parameters provide useful quantitative data, these data may not accurately predict the functional integrity or capacity of sperm.Although evidence suggests that daily intercourse during the fertile window may confer a slight advantage, specific recommendations regarding the frequency of intercourse may induce unnecessary stress in the couple. In one study, cycle fecundity was similar with intercourse that occurred daily, every other day, and even every 3 days in the fertile window, but was lowest when intercourse occurred only once in the fertile window (14). Couples should be informed that reproductive efficiency increases with the frequency of intercourse and is highest when intercourse occurs every 1 to 2 days during the fertile window, but be advised that the optimal frequency of intercourse is best defined by their own preference within that context. Intercourse more frequently than every 1 to 2 days is not associated with lower fecundity, and couples should not be advised to limit the frequency of intercourse when trying to achieve pregnancy.
FERTILITY-AWARENESS METHODS
The timing of the fertile window within a given cycle can vary considerably, even in women who have regular cycles. Use of fertility-tracking methods to determine the fertile window and appropriately time intercourse is associated with an increased probability of conceiving in an ovulatory cycle (21). Fertility-tracking methods include the calendar method (with or without the assistance of a smart phone app), cervical mucus monitoring, ovulation detection devices, and basal body temperature tracking.The calendar method is based on the length of the menstrual cycle. For all women, the length of the luteal phase is presumed to be approximately 14 days. Thus, the day of ovulation is set at cycle day 14 for a woman with a 28-day cycle, day 16 for a woman with a 30-day cycle, etc. The fertile window is set as the presumed day of ovulation and the 5 days prior (cycle days 9–14 in a woman with a 28-day cycle, cycle days 11–16 in a woman with a 30-day cycle, and so forth). Smart phone calendar apps, which use the calendar method, are becoming a popular first-line or adjunct fertility-awareness method (22). However the ability of appbased technology to precisely predict an individual’s fertile window or ovulation day may not add to the clinical utility of traditional practices (23).
A study of 949 volunteers comparing urinary luteinizing hormone (LH) testing with multiple different downloadable calendar apps revealed a maximum accuracy of 21% in predicting the day of ovulation (24). The major pitfall of these predictors is that they are based on the assumption that the timing and duration of a woman’s fertile window are consistent and dependent on cycle length characteristics, despite knowledge that cycles are much more variable (25, 26). Patients should be empowered to use this technology to assist in understanding their own personal cycle characteristics and trends; however this should be accompanied by a candid review of the shortcomings of the calendar method, with and without apps, for ovulation tracking.
Ovulation detection devices monitor urinary LH excretion to determine the day of ovulation. Some of these also monitor urinary estrone glucuronide levels to delineate other days in the fertile window (days of ‘‘high’’ but not ‘‘peak’’ fertility). Although numerous studies have validated the accuracy of methods for detecting the midcycle urinary LH surge (1, 2, 27), ovulation may occur any time within the 2 days thereafter (28, 29), and false-positive test results occur in approximately 7% of cycles (29). The use of ovulation detection devices has been shown in a randomized controlled trial to decrease the time to pregnancy (30).
The quality of the cervical mucus (as detected by vaginal secretions at the introitus) provides an inexpensive and private index of when ovulation may be expected. The estimated probability of conception, in relation to the characteristics of cervical/vaginal secretions, is shown in Figure 4. The probability is highest when the mucus is slippery and clear (31), but such mucus is not a prerequisite for pregnancy to occur. The volume of cervical mucus increases with plasma estrogen concentrations over the 5 to 6 days preceding ovulation and reaches its peak within 2 to 3 days before ovulation (32). A retrospective cohort study including 1,681 cycles observed that pregnancy rates were highest (approximately 38%) when intercourse occurred on the day of peak mucus (day 0) and were appreciably lower (approximately 15% to 20%) on the day before or the day after the peak (33).
Figure 3
Figure 4
A prospective study including 2,832 cycles observed that changes in cervical mucus characteristics correlated closely with basal body temperature and predicted the time of peak fertility more accurately than a menstrual calendar (34). Cervical mucus monitoring in retrospective cohort studies is associated with a higher probability of conceiving in a given cycle (21, 35). One large study found that changes in cervical mucus across the fertile interval predicted the day-specific probability of conception as well as or better than basal body temperature or urinary LH monitoring (36).
Although some women may find fertility-awareness methods empowering, others may find that they induce unnecessary stress. The stress associated with trying to conceive can reduce sexual esteem, satisfaction, and the frequency of intercourse. These parameters are further aggravated when the timing of intercourse is linked to ovulation prediction methods or follows a strict schedule (37, 38). If fertility-awareness methods are employed, their use should guide the timing of frequent intercourse and not replace the approach to frequent intercourse every 1 to 2 days during the fertile window.
Sperm deposited at the cervix at midcycle are found in the fallopian tubes within 15 minutes (39). Furthermore, sperm traverse the fallopian tubes and are expelled into the peritoneal cavity rather than collecting in the ampullary portion of the fallopian tube (39). Studies in which labeled particles were placed in the posterior vaginal fornix at varying times of the cycle observed their transport into the fallopian tubes within as little as 2 minutes during the follicular phase (40). It is interesting that the particles were observed only in the tube adjacent to the ovary containing the dominant follicle and not in the contralateral tube. The number of transported particles increased with the size of the dominant follicle and after administration of oxytocin to simulate the increase in oxytocin observed in women during intercourse and orgasm. There is no evidence that coital position affects fecundability. Sperm can be found in the cervical canal seconds after ejaculation, regardless of coital position. Although female orgasm may promote sperm transport, there is no known relationship between orgasm and fertility (41, 42). There also is no convincing evidence for any relationship between specific coital practices and infant gender.
Some vaginal lubricants may decrease fertility on the basis of their observed effects on sperm survival in vitro. Whereas commercially available water-based lubricants inhibit sperm motility in vitro by 60% to 100% within 60 minutes of incubation, canola oil has no similar detrimental effect (43). Some over-the-counter lubricants, olive oil, and saliva diluted to concentrations even as low as 6.25% adversely affect sperm motility and velocity, but mineral oil has no such effect (44–46). Hydroxyethylcellulose-based lubricants also have no demonstrable adverse impact on semen parameters (46). Although some lubricants adversely affect sperm parameters in vitro, the use of lubricants in couples attempting conception was shown not to affect cycle fecundability compared with nonuse (47, 48).
Multiple cohort studies have assessed the association between dietary patterns, macronutrients, micronutrients, and fertility. The Nurses’ Health Study II assessed the efficacy of an investigator-denfined ‘‘fertility diet,’’ which encouraged higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low-glycemic carbohydrates, high-fat dairy, multivitamins, and iron from plants and supplements. The study demonstrated that increasing adherence to the ‘‘fertility diet’’ was associated with a lower risk of infertility related to ovulatory dysfunction (relative risk [RR] 0.34; 95% confidence interval [CI], 0.23–0.48) (52).
There are other studies that have evaluated diet in relation to outcomes in women utilizing assisted reproductive technologies (ART). It is unclear if these data apply to women attempting to optimize natural fertility, but given the overall lack of robust data, they are discussed here. For example, and contrary to what was found in couples not utilizing ART, increasing adherence to the ‘‘fertility diet’’ in the Nurses’ Health Study II was not associated with rates of pregnancy or live birth in women utilizing ART (53). Another cohort study assessing a slightly different ‘‘pro-fertility diet’’ (higher intakes of supplemental folic acid, vitamin B12, vitamin D, low-pesticide produces, whole grains, dairy, soy foods, and seafood rather than meats) demonstrated an increased probability of live birth among women utilizing ART who had higher pretreatment adherence to the pro-fertility diet (54). Similarly, studies have found that greater adherence to the Mediterranean diet (high intakes of vegetables, fruits, low-fat dairy, olive oil, fish, and poultry) or the Dutch diet (high intakes of whole grains, monounsaturated or polyunsaturated oils, vegetables, fruits, meat or meat replacements, and fish) was associated with higher rates of positive pregnancy tests (55), ongoing clinical pregnancy (56, 57), and live birth (56) following in vitro fertilization.
Alternatively, other cohort studies found no associations between higher adherence to the Mediterranean diet and rates of positive pregnancy tests (53, 56, 58), clinical pregnancy (53, 58), or live births (59) following use of ART. Likewise, no associations have been found between higher adherence to a ‘‘health-conscious low-processed’’ diet (higher intakes of vegetables, fruits, whole grains, nuts and legumes, long-chain omega-3 fats, polyunsaturated fat, and alcohol and lower intakes of sugar-sweetened beverages, fruit juice, red and processed meat, trans fat, and sodium) (55); the alternative health eating index 2010 diet (high intakes of fruits, vegetables, whole grains, fish, and legumes and low intakes of mayonnaise, snacks, and meat products) (53); diets with high intakes of seafood and vegetables (60); or a ‘‘Western’’ diet (high intakes of oil, meat, and chicken) (60) with rates of biochemical pregnancy, clinical pregnancy, or live birth after use of ART. Randomized, controlled trials are needed.
Although the results of cohort studies have been somewhat inconsistent, some investigators have suggested that aside from overall dietary patterns, individual micronutrients and macronutrients, such as multivitamins (61, 62), folic acid (63–68), long-chain omega-3 fatty acids (69–71), full-fat dairy (72–75), whole grains (76), vegetables (77), fish (78), and soy isoflavones (79–83), may have beneficial effects on fertility. Other micronutrients and macronutrients, such as trans fatty acids (52, 75), meat (77, 84), carbohydrates, and glycemic load (85), have been reported to have a negative impact on fertility. Again, better studies and randomized, controlled trials are needed.
Overall, although a healthy lifestyle may help to improve fertility in women with ovulatory dysfunction, there is little evidence that dietary variations, such as vegetarian diets, low-fat diets, vitamin-enriched diets, antioxidants, or herbal remedies, improve fertility in women without ovulatory dysfunction or affect the sex of the infant. In general, robust evidence is lacking that dietary and lifestyle interventions improve natural fertility, although dietary and lifestyle modifications may be recommended to improve overall health.
In contrast, data obtained by self-report from 29,844 pregnant Danish women suggested that time to conception was shorter for women who drank wine than for women who consumed no alcohol (100). However, a study of 1,769 postpartum Italian women found no relationship between alcohol consumption and difficulty conceiving (97).
Higher levels of alcohol consumption by women (more than two drinks per day, with one drink containing 10 g of ethanol) probably are best avoided when attempting pregnancy, but there is limited evidence to indicate that more moderate alcohol consumption adversely affects fertility. Of course, alcohol consumption should cease altogether during pregnancy, because alcohol has well-documented detrimental effects on fetal development, and no ‘‘safe’’ level of alcohol consumption has been established (98).
Chronic alcohol dependence in males has been associated with lower sperm counts, sperm motility, sperm morphology scores, seminal fluid volume, and serum testosterone levels (19, 20, 37). In one survey study, partners of men with heavy alcohol consumption had a longer time to pregnancy than partners of mild drinkers and nondrinkers (99). Although significant alcohol consumption has been associated with detrimental hormonal and semen markers in males, a dose– response pattern has not been established, and there is a lack of evidence for any effect of moderate alcohol consumption on male fertility (13, 37). Alcohol abuse is also associated with an increased risk of sexual dysfunction in males and females, with increased risks of ejaculatory dysfunction, premature ejaculation, decreased sexual desire, dyspareunia, and vaginal dryness (101–103).
However, in a systematic review of 28 articles on persistent organic pollutants and fecundability of couples, there was a high level of evidence supporting adverse effects of female exposure to polychlorinated biphenyls on time to pregnancy and weak evidence supporting adverse effects of female exposure to polybrominated diphenyl ethers and select perand polyfluoroalkyl substances on time to pregnancy (120). There was little or no support for associations between female exposure to organochlorine pesticides and time to pregnancy and too few studies of male exposure to any of the persistent organic pollutants and fecundability to draw conclusions. Overall, reproductive-aged men and women seeking conception should be encouraged, to the extent possible, to limit their exposure to endocrine-disrupting chemicals in food, air, water, and personal care products.
The potential adverse effect of air pollution on fertility is another area of growing concern (121). Higher exposure to ambient air pollution has been linked to lower fertility rates in Europe (122), the United States (123), and China (124). Previoustudies have shown that couples who live closer to major roadways have a higher risk of infertility (125) and longer time to pregnancy (126) than couples who live farther away. Moreover, women with higher preconception and early pregnancy exposure to nitrogen dioxides and fine particulate matter, such as experienced when living close to a major roadway, have been shown to have decreased fecundability (127, 128) and higher risk of miscarriage (53, 129, 130) than women with lower exposure. Numerous studies have also linked increased air pollution exposure to impaired semen parameters (131), including higher sperm DNA fragmentation and aneuploidy, lower sperm morphology and motility, and altered reproductive hormone levels. Overall, it remains to be determined whether the effects of air pollution on sperm parameters translate into effects on the fertility of couples.
Acknowledgments: This report was developed under the direction of the Practice Committees of the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs of the individual patient, the available resources, and institutional or clinical practice limitations. The Practice Committees and the Boards of Directors of the ASRM and SART have approved this report. This document was reviewed by ASRM members, and their input was considered in the preparation of the final document.
The following members of the ASRM Practice Committee participated in the development of this document: Alan Penzias, M.D., Ricardo Azziz, M.D., M.P.H., M.B.A., Kristin Bendikson, M.D., Tommaso Falcone, M.D., Karl Hansen, M.D., Ph.D., Micah Hill, D.O., Sangita Jindal, Ph.D., Suleena Kalra, M.D., M.S.C.E., Jennifer Mersereau, M.D., Richard Reindollar, M.D., Chevis N. Shannon, Dr.P.H., M.P.H., M.B.A., Anne Steiner, M.D., M.P.H., Cigdem Tanrikut, M.D., Hugh Taylor, M.D., and Belinda Yauger, M.D. The Practice Committee acknowledges the special contributions of Micah Hill, D.O. (chair), Eric Forman, M.D., Audrey Gaskins, Sc.D., Mae Healy, D.O., and Anne Martini, D.O., in association with the Society for Reproductive Endocrinology and Infertility Practice Committee in the preparation of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. Members of the Committee who were found to have conflicts of interest based on the relationships disclosed did not participate in the discussion or development of this document.
Although some women may find fertility-awareness methods empowering, others may find that they induce unnecessary stress. The stress associated with trying to conceive can reduce sexual esteem, satisfaction, and the frequency of intercourse. These parameters are further aggravated when the timing of intercourse is linked to ovulation prediction methods or follows a strict schedule (37, 38). If fertility-awareness methods are employed, their use should guide the timing of frequent intercourse and not replace the approach to frequent intercourse every 1 to 2 days during the fertile window.
COITAL PRACTICES
Postcoital routines may become ritualized for couples trying to conceive. Although many women think that remaining supine for an interval after intercourse facilitates sperm transport and prevents leakage of semen from the vagina, this belief has no scientific foundation.Sperm deposited at the cervix at midcycle are found in the fallopian tubes within 15 minutes (39). Furthermore, sperm traverse the fallopian tubes and are expelled into the peritoneal cavity rather than collecting in the ampullary portion of the fallopian tube (39). Studies in which labeled particles were placed in the posterior vaginal fornix at varying times of the cycle observed their transport into the fallopian tubes within as little as 2 minutes during the follicular phase (40). It is interesting that the particles were observed only in the tube adjacent to the ovary containing the dominant follicle and not in the contralateral tube. The number of transported particles increased with the size of the dominant follicle and after administration of oxytocin to simulate the increase in oxytocin observed in women during intercourse and orgasm. There is no evidence that coital position affects fecundability. Sperm can be found in the cervical canal seconds after ejaculation, regardless of coital position. Although female orgasm may promote sperm transport, there is no known relationship between orgasm and fertility (41, 42). There also is no convincing evidence for any relationship between specific coital practices and infant gender.
Some vaginal lubricants may decrease fertility on the basis of their observed effects on sperm survival in vitro. Whereas commercially available water-based lubricants inhibit sperm motility in vitro by 60% to 100% within 60 minutes of incubation, canola oil has no similar detrimental effect (43). Some over-the-counter lubricants, olive oil, and saliva diluted to concentrations even as low as 6.25% adversely affect sperm motility and velocity, but mineral oil has no such effect (44–46). Hydroxyethylcellulose-based lubricants also have no demonstrable adverse impact on semen parameters (46). Although some lubricants adversely affect sperm parameters in vitro, the use of lubricants in couples attempting conception was shown not to affect cycle fecundability compared with nonuse (47, 48).
DIET AND LIFESTYLE
Diet
Fertility rates are decreased in women who are either very thin or obese, but data regarding the effects of normal variations in diet on fertility in ovulatory women are few (49). Elevated blood mercury levels from heavy seafood consumption have been associated with infertility (50). Women attempting to conceive should be advised to take a folic acid supplement (at least 400 mg daily) to reduce the risk of neural tube defects (51).Multiple cohort studies have assessed the association between dietary patterns, macronutrients, micronutrients, and fertility. The Nurses’ Health Study II assessed the efficacy of an investigator-denfined ‘‘fertility diet,’’ which encouraged higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low-glycemic carbohydrates, high-fat dairy, multivitamins, and iron from plants and supplements. The study demonstrated that increasing adherence to the ‘‘fertility diet’’ was associated with a lower risk of infertility related to ovulatory dysfunction (relative risk [RR] 0.34; 95% confidence interval [CI], 0.23–0.48) (52).
There are other studies that have evaluated diet in relation to outcomes in women utilizing assisted reproductive technologies (ART). It is unclear if these data apply to women attempting to optimize natural fertility, but given the overall lack of robust data, they are discussed here. For example, and contrary to what was found in couples not utilizing ART, increasing adherence to the ‘‘fertility diet’’ in the Nurses’ Health Study II was not associated with rates of pregnancy or live birth in women utilizing ART (53). Another cohort study assessing a slightly different ‘‘pro-fertility diet’’ (higher intakes of supplemental folic acid, vitamin B12, vitamin D, low-pesticide produces, whole grains, dairy, soy foods, and seafood rather than meats) demonstrated an increased probability of live birth among women utilizing ART who had higher pretreatment adherence to the pro-fertility diet (54). Similarly, studies have found that greater adherence to the Mediterranean diet (high intakes of vegetables, fruits, low-fat dairy, olive oil, fish, and poultry) or the Dutch diet (high intakes of whole grains, monounsaturated or polyunsaturated oils, vegetables, fruits, meat or meat replacements, and fish) was associated with higher rates of positive pregnancy tests (55), ongoing clinical pregnancy (56, 57), and live birth (56) following in vitro fertilization.
Alternatively, other cohort studies found no associations between higher adherence to the Mediterranean diet and rates of positive pregnancy tests (53, 56, 58), clinical pregnancy (53, 58), or live births (59) following use of ART. Likewise, no associations have been found between higher adherence to a ‘‘health-conscious low-processed’’ diet (higher intakes of vegetables, fruits, whole grains, nuts and legumes, long-chain omega-3 fats, polyunsaturated fat, and alcohol and lower intakes of sugar-sweetened beverages, fruit juice, red and processed meat, trans fat, and sodium) (55); the alternative health eating index 2010 diet (high intakes of fruits, vegetables, whole grains, fish, and legumes and low intakes of mayonnaise, snacks, and meat products) (53); diets with high intakes of seafood and vegetables (60); or a ‘‘Western’’ diet (high intakes of oil, meat, and chicken) (60) with rates of biochemical pregnancy, clinical pregnancy, or live birth after use of ART. Randomized, controlled trials are needed.
Although the results of cohort studies have been somewhat inconsistent, some investigators have suggested that aside from overall dietary patterns, individual micronutrients and macronutrients, such as multivitamins (61, 62), folic acid (63–68), long-chain omega-3 fatty acids (69–71), full-fat dairy (72–75), whole grains (76), vegetables (77), fish (78), and soy isoflavones (79–83), may have beneficial effects on fertility. Other micronutrients and macronutrients, such as trans fatty acids (52, 75), meat (77, 84), carbohydrates, and glycemic load (85), have been reported to have a negative impact on fertility. Again, better studies and randomized, controlled trials are needed.
Overall, although a healthy lifestyle may help to improve fertility in women with ovulatory dysfunction, there is little evidence that dietary variations, such as vegetarian diets, low-fat diets, vitamin-enriched diets, antioxidants, or herbal remedies, improve fertility in women without ovulatory dysfunction or affect the sex of the infant. In general, robust evidence is lacking that dietary and lifestyle interventions improve natural fertility, although dietary and lifestyle modifications may be recommended to improve overall health.
Smoking
Smoking has substantial adverse effects on fertility. A large meta-analysis comparing 10,928 smoking women with 19,128 nonsmoking women found that smoking women were significantly more likely to be infertile (OR, 1.60; 95% CI, 1.34–1.91) (86). The observation that menopause occurs, on average, 1 to 4 years earlier in smoking than in nonsmoking women suggests that smoking may accelerate the rate of follicular depletion (87, 88), although histologic studies have not confirmed this relationship (89). Smoking also is associated with an increased risk of miscarriage, in both naturally conceived pregnancies and those resulting from ART (90, 91). Although decreases in sperm density and motility and abnormalities in sperm morphology have been observed in men who smoke, the available data do not demonstrate conclusively that smoking decreases male fertility (92–94). The effects of smoking on fertility in men and women and the mechanisms that may explain its adverse impact are discussed at length in a separate Practice Committee report (95).Alcohol
The effect of alcohol on female fertility has not been clearly established. Whereas some studies have concluded that alcohol has a detrimental effect, others have suggested that alcohol may enhance fertility. A cohort study of 7,393 women in Stockholm observed that the risk of infertility was significantly increased (relative risk [RR], 1.59; 95% CI, 1.09–2.31) among women who consumed two alcoholic drinks per day and decreased (RR, 0.64; 95% CI, 0.46–0.90) in those who consumed less than one drink per day (96). Other studies have also shown a trend toward higher alcohol consumption and decreased conception (96–99).In contrast, data obtained by self-report from 29,844 pregnant Danish women suggested that time to conception was shorter for women who drank wine than for women who consumed no alcohol (100). However, a study of 1,769 postpartum Italian women found no relationship between alcohol consumption and difficulty conceiving (97).
Higher levels of alcohol consumption by women (more than two drinks per day, with one drink containing 10 g of ethanol) probably are best avoided when attempting pregnancy, but there is limited evidence to indicate that more moderate alcohol consumption adversely affects fertility. Of course, alcohol consumption should cease altogether during pregnancy, because alcohol has well-documented detrimental effects on fetal development, and no ‘‘safe’’ level of alcohol consumption has been established (98).
Chronic alcohol dependence in males has been associated with lower sperm counts, sperm motility, sperm morphology scores, seminal fluid volume, and serum testosterone levels (19, 20, 37). In one survey study, partners of men with heavy alcohol consumption had a longer time to pregnancy than partners of mild drinkers and nondrinkers (99). Although significant alcohol consumption has been associated with detrimental hormonal and semen markers in males, a dose– response pattern has not been established, and there is a lack of evidence for any effect of moderate alcohol consumption on male fertility (13, 37). Alcohol abuse is also associated with an increased risk of sexual dysfunction in males and females, with increased risks of ejaculatory dysfunction, premature ejaculation, decreased sexual desire, dyspareunia, and vaginal dryness (101–103).
Caffeine
High levels of caffeine consumption (500 mg; >5 cups of coffee per day or its equivalent) have been associated with decreased fertility (OR, 1.45; 95% CI, 1.03–2.04) (97). During pregnancy, caffeine consumption over 200 to 300 mg per day (2–3 cups per day) may increase the risk of miscarriage (104–106) but does not affect the risk of congenital anomalies. Overall, moderate caffeine consumption (1– 2 cups of coffee per day or its equivalent) before or during pregnancy has no apparent adverse effects on fertility or pregnancy outcomes. Caffeine consumption has no effect on semen parameters in men (94).Cannabis and Other Recreational Drugs
One study found that the prevalence of infertility was increased in ovulatory women who reported using cannabis (RR, 1.7; CI 95%, 1.0–3.0) (107). Men who smoke cannabis have been reported to have 29% lower sperm counts than men who have never smoked cannabis, and a dose-dependent effect of cannabis on sperm counts has been reported (108–110). Cannaboid agonists can inhibit sperm hyperactivated motility and acrosomal reactions necessary for sperm binding to the zona pellucida, suggesting the potential for cannabis use to decrease fertilization pathways (110–114). However, data from the National Survey of Family Growth and North American Preconception Cohort Study demonstrated no association between male or female cannabis use and time to pregnancy (115, 116). The American College of Obstetricians and Gynecologists recommends that women who are pregnant or may become pregnant should discontinue cannabis use because of the adverse effects of smoking and potential concerns for impaired fetal neurodevelopment (117). The use of other recreational drugs by men and women desiring pregnancy s also discouraged because of the risks of pregnancy and neonatal complications.Environmental Exposures
A growing body of evidence suggests that exposure to synthetic and naturally occurring environmental chemicals in food, water, air, and consumer products may contribute to reduced fertility in men and women. Of particular concern are endocrine-disrupting chemicals, a class of exogenous compounds that alter the hormonal and homoeostatic systems of organisms, resulting in adverse health effects (118). In a scoping review of 12 articles on nonpersistent exposure to endocrine-disrupting chemicals and time to pregnancy, the evidence largely indicated little to no association between exposure of women or men to the most commonly studied chemicals, such as phthalates, bisphenol A, and triclosan, and time to pregnancy (119).However, in a systematic review of 28 articles on persistent organic pollutants and fecundability of couples, there was a high level of evidence supporting adverse effects of female exposure to polychlorinated biphenyls on time to pregnancy and weak evidence supporting adverse effects of female exposure to polybrominated diphenyl ethers and select perand polyfluoroalkyl substances on time to pregnancy (120). There was little or no support for associations between female exposure to organochlorine pesticides and time to pregnancy and too few studies of male exposure to any of the persistent organic pollutants and fecundability to draw conclusions. Overall, reproductive-aged men and women seeking conception should be encouraged, to the extent possible, to limit their exposure to endocrine-disrupting chemicals in food, air, water, and personal care products.
The potential adverse effect of air pollution on fertility is another area of growing concern (121). Higher exposure to ambient air pollution has been linked to lower fertility rates in Europe (122), the United States (123), and China (124). Previoustudies have shown that couples who live closer to major roadways have a higher risk of infertility (125) and longer time to pregnancy (126) than couples who live farther away. Moreover, women with higher preconception and early pregnancy exposure to nitrogen dioxides and fine particulate matter, such as experienced when living close to a major roadway, have been shown to have decreased fecundability (127, 128) and higher risk of miscarriage (53, 129, 130) than women with lower exposure. Numerous studies have also linked increased air pollution exposure to impaired semen parameters (131), including higher sperm DNA fragmentation and aneuploidy, lower sperm morphology and motility, and altered reproductive hormone levels. Overall, it remains to be determined whether the effects of air pollution on sperm parameters translate into effects on the fertility of couples.
SUMMARY
- The chances of pregnancy and live birth for women significantly decrease after age 35, as the risks of aneuploidy and miscarriage increase.
- The ‘‘fertile window’’ spans the 6-day interval ending on the day of ovulation. Frequent intercourse (every 1–2 days) during the fertile window yields the highest pregnancy rates, but results achieved with less frequent intercourse (2–3 times per week) are nearly equivalent. Couples should not be advised to limit the frequency of intercourse when trying to achieve pregnancy.
- The use of fertility-awareness methods, such as ovulation detection kits and cervical mucus monitoring, has been shown to increase the probability of conceiving in a given menstrual cycle.
- There is insufficient evidence that a specific diet or intake of particular macronutrients can improve natural fertility. Daily folic acid supplementation in women decreases the risk of neural tube defects in their children.
- Specific coital positions and postcoital routines have no impact on fertility.
- Alcohol abuse, recreational drugs, smoking, and high caffeine intake may all negatively impact fertility.
- Higher exposure to certain endocrine-disrupting chemicals, such as polychlorinated biphenyls, and to air pollution may adversely impact fertility in women.
CONCLUSION
- Time to conception increases with age. For women over 35, consultation with a reproductive specialist should be considered after 6 months of unsuccessful efforts to conceive.
- Intercourse every 1 to 2 days during the fertile window can help maximize fecundability.
- For couples who are unable to have regular frequent intercourse, fertility-awareness methods may help time frequent intercourse to the fertile window and decrease time to pregnancy.
- Smoking and recreational drugs should be discouraged in men and women attempting pregnancy. Alcohol and caffeine use should be limited to minimal to moderate use while trying to conceive.
- A healthy lifestyle and diet should be encouraged in men and women attempting to achieve pregnancy for their effects on general health.
- Women wishing to become pregnant should take a daily folic acid supplement (400 mg).
- Reproductive-aged men and women should be encouraged, to the extent possible, to limit their exposure to endocrine-disrupting chemicals in food, air, water, and personal care products, and to air pollution.
Acknowledgments: This report was developed under the direction of the Practice Committees of the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management may be appropriate, taking into account the needs of the individual patient, the available resources, and institutional or clinical practice limitations. The Practice Committees and the Boards of Directors of the ASRM and SART have approved this report. This document was reviewed by ASRM members, and their input was considered in the preparation of the final document.
The following members of the ASRM Practice Committee participated in the development of this document: Alan Penzias, M.D., Ricardo Azziz, M.D., M.P.H., M.B.A., Kristin Bendikson, M.D., Tommaso Falcone, M.D., Karl Hansen, M.D., Ph.D., Micah Hill, D.O., Sangita Jindal, Ph.D., Suleena Kalra, M.D., M.S.C.E., Jennifer Mersereau, M.D., Richard Reindollar, M.D., Chevis N. Shannon, Dr.P.H., M.P.H., M.B.A., Anne Steiner, M.D., M.P.H., Cigdem Tanrikut, M.D., Hugh Taylor, M.D., and Belinda Yauger, M.D. The Practice Committee acknowledges the special contributions of Micah Hill, D.O. (chair), Eric Forman, M.D., Audrey Gaskins, Sc.D., Mae Healy, D.O., and Anne Martini, D.O., in association with the Society for Reproductive Endocrinology and Infertility Practice Committee in the preparation of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. Members of the Committee who were found to have conflicts of interest based on the relationships disclosed did not participate in the discussion or development of this document.
REFERENCES
- Nielsen MS, Barton SD, Hatasaka HH, Stanford JB. Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick. Fertil Steril 2001;76:384–7.
- Tanabe K, Susumu N, Hand K, Nishii K, Ishikawa I, Nozawa S. Prediction of the potentially fertile period by urinary hormone measurements using a new home-use monitor: comparison with laboratory hormone analyses. Hum Reprod 2001;16:1619–24.
- Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod 2003;18:1959–66.
- Wesselink AK, Rothman KJ, Hatch EE, Mikkelsen EM, Sørensen HT, Wise LA. Age and fecundability in a North American preconception cohort study. Am J Obstet Gynecol 2017:667.e1–8.
- Steiner AZ, Jukic AM. Impact of female age and nulligravidity on fecundity in an older reproductive age cohort. Fertil Steril 2016;105:1584–8.
- Howe G, Westhoff C, Vessey M, Yeates D. Effects of age, cigarette smoking, and other factors on fertility: findings in a large prospective study. Br Med J 1985;290:1697–700.
- Larsen U, Menken J, Trussell J. Age and infertility. Science 1986;26:1389–94.
- Practice Committee of the American Society for Reproductive Medicine. Evaluation of the infertile woman: a committee opinion. Fertil Steril. In press.
- American College of Obstetricians and Gynecologists. The use of antimullerian hormone in women not seeking fertility care, 773. Available at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/ articles/2019/04/the-use-of-antimullerian-hormone-in-women-not-seeking-fertility-care. Accessed February 26, 2021.
- Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, Baird DD. Association between biomarkers of ovarian reserve and infertility among older women of reproductive age. J Am Med Assoc 2017;318: 1367–76.
- Dunson DB, Baird DD, Colombo B. Increased infertility with age in men and women. Am J Obstet Gynecol 2004;103:51–6.
- Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: A committee opinion. Fertil Steril 2020;113:533–5.
- Brosens I, Gordts S, Puttemans P, Campo R, Gordts S, Brosens J. Managing infertility with fertility-awareness methods. Sex Reprod Menopause 2006; 4:13–6.
- Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N Engl J Med 1995;333:1517–21.
- Dunson DB, Baird DD, Wilcox AJ, Weinberg CR. Day-specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation. Hum Reprod 1999;14:1835–9.
- Wilcox AJ, Dunson DB, Weinberg CR, Trussell J, Day Baird D. Likelihood of conception with a single act of intercourse: providing benchmark rates for assessment of post-coital contraceptives. Contraception 2001;63:211–5.
- Stanford JB, Dunson DB. Effects of sexual intercourse patterns in time to pregnancy studies. Am J Epidemiol 2007;165:1088–95.
- Elzanaty S, Malm J, Giwercman A. Duration of sexual abstinence: epididymal and accessory sex gland secretions and their relationship to sperm motility. Hum Reprod 2005;20:221–5.
- Levitas E, Lunenfeld E, Weiss N, Friger M, Har-Vardi I, Koifman A, et al. Relationship between the duration of sexual abstinence and semen quality: analysis of 9,489 semen samples. Fertil Steril 2005;83:1680–6.
- Check JH, Epstein R, Long R. Effect of time interval between ejaculations on semen parameters. Arch Androl 1995;27:93–5.
- Stanford JB, Willis SK, Hatch EE, Rothman KJ, Wise LA. Fecundability in relation to use of fertility awareness indicators in a North American preconception cohort study. Fertil Steril 2019;112:892–9.
- Soumpasis I, Grace B, Johnson S. Real-life insights on menstrual cycles and ovulation using big data. Hum Reprod Open 2020;2020:hoaa011.
- Setton R, Tierney C, Tsai T. The accuracy of web sites and cellular phone applications in predicting the fertile window. Obstet Gynecol 2016;128:58–63.
- Johnson S, Marriott L, Zinaman M. Can apps and calendar methods predict ovulation with accuracy? Curr Med Res Opin 2018;34:1587–94.
- Johnson SR, Miro F, Barrett S, Ellis JE. Levels of urinary human chorionic gonadotrophin (hCG) following conception and variability of menstrual cycle length in a cohort of women attempting to conceive. Curr Med Res Opin 2009;25:741–8.
- Keulers MJ, Hamilton CJ, Franx A, Evers JL, Bots RS. The length of the fertile window is associated with the chance of spontaneously conceiving an ongoing pregnancy in subfertile couples. Hum Reprod 2007;22:1652–6.
- Miller PB, Soules MR. The usefulness of a urinary LH kit for ovulation prediction during menstrual cycles of normal women. Obstet Gynecol 1996; 87:13–7.
- Pearlstone AC, Surrey ES. The temporal relation between the urine LH surge and sonographic evidence of ovulation: determinants and clinical significance. Obstet Gynecol 1994;83:184–8.
- McGovern PG, Myers ER, Silva S, Coutifaris C, Carson SA, Legro RS, et al. Absence of secretory endometrium after false-positive home urine luteinizing hormone testing. Fertil Steril 2004;82:1273–7.
- Robinson JE, Wakelin M, Ellis JE. Increased pregnancy rate with use of the Clearblue Easy fertility monitor. Fertil Steril 2007;87:329–34.
- Scarpa B, Dunson DB, Colombo B. Cervical mucus secretions on the day of intercourse: an accurate marker of highly fertile days. Eur J Obstet Gynaecol Reprod Biol 2006;125:72–8.
- Stanford JB, White GL, Hatasaka H. Timing intercourse to achieve pregnancy: current evidence. Obstet Gynecol 2002;100:1333–41.
- Stanford JB, Smith KR, Dunson DB. Vulvar mucus observations and the probability of pregnancy. Obstet Gynecol 2003;101:1285–93.
- Dunson DB, Sinai I, Colombo B. The relationship between cervical secretions and the daily probabilities of pregnancy: effectiveness of the TwoDay Algorithm. Hum Reprod 2001;16:2278–82.
- Evans-Hoeker E, Pritchard DA, Long DL, Herring AH, Stanford JB, Steiner AZ. Cervical mucus monitoring prevalence and associated fecundability in women trying to conceive. Fertil Steril 2013;100:1033– 8.e1.
- Bigelow JL, Dunson DB, Stanford JB, Ecochard R, Gnoth C, Colombo B. Mucus observations in the fertile window: a better predictor of conception than timing of intercourse. Hum Reprod 2004;19:889–92.
- Lenzi A, Lombardo F, Salacone P, Gandini L, Jannini EA. Stress, sexual dysfunctions, and male infertility. J Endocrinol Invest 2003;26:72–6.
- Andrews FM, Abbey A, Halman LJ. Is fertility-problem stress different? The dynamics of stress in fertile and infertile couples. Fertil Steril 1992;57: 1247–53.
- Settlage DS, Motoshima M, Tredway DR. Sperm transport from the external cervical os to the fallopian tubes in women: a time and quantitation study. Fertil Steril 1973;24:655–61.
- Kunz G, Beil D, Deininger H, Wildt L, Leyendecker G. The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy. Hum Reprod 1996;11:627–32.
- King R, Dempsey M, Valentine KA. Measuring sperm backflow following female orgasm: a new method. Socioaffect Neurosci Psychol 2016;6: 31927.
- Zietsch B, Santtila P. No direct relationship between human female orgasm rate and number of offspring. Anim Behav 2013;86:253–5.
- Kutteh WH, Chao CH, Ritter JO, Byrd W. Vaginal lubricants for the infertile couple: effect on sperm activity. Int J Fertil Menopausal Stud 1996;41: 400–4.
- Anderson L, Lewis SE, McClure N. The effects of coital lubricants on sperm motility in vitro. Hum Reprod 1998;13:3351–6.
- Tulandi T, Plouffe L Jr, McInnes RA. Effect of saliva on sperm motility and activity. Fertil Steril 1982;8:721–3.
- Agarwal A, Deepinder F, Cocuzza M, Short RA, Evenson DP. Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study. Fertil Steril 2008;89:375–9.
- Steiner AZ, Long DL, Tanner C, Herring AH. Effect of vaginal lubricants on natural fertility. Obstet Gynecol 2012;120:44–51.
- McInerney KA, Hahn KA, Hatch EE, Mikkelsen EM, Steiner AZ, Rothman KJ, et al. Lubricant use during intercourse and time to pregnancy: a prospective cohort study. BJOG 2018;125:1541–8.
- Clark AM, Thornley B, Tomlinson L, Galletley C, Norman RJ. Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum Reprod 1998;13:1502–5.
- Choy CM, Lam CW, Cheung LT, Briton-Jones CM, Cheung LP, Haines CJ. Infertility, blood mercury concentrations and dietary seafood consumption: a case-control study. BJOG 2002;109:1121–5.
- Lumley J, Watson L, Watson M, Bower C. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database Syst Rev 2001;3:CD001056.
- Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in the prevention of ovulatory disorder infertility. Obstet Gynecol 2007;110: 1050–8.
- Gaskins AJ, Nassan FL, Chiu YH, Arvizu M, Williams PL, Keller MG, et al. Dietary patterns and outcomes of assisted reproduction. Am J Obstet Gynecol 2019;220:567.e1–18.
- Gaskins AJ, Mínguez-Alarcon L, Fong KC, Abu Awad Y, Di Q, Chavarro JE, et al. Supplemental folate and the relationship between traffic-related air pollution and livebirth among women undergoing assisted reproduction. Am J Epidemiol 2019;188:1595–604.
- Vujkovic M, de Vries JH, Lindemans J, Macklon NS, van der Spek PJ, Steegers EA, et al. The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertil Steril 2010;94: 2096–101.
- Karayiannis D, Kontogianni MD, Mendorou C, Mastrominas M, Yiannakouris N. Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility. Hum Reprod 2018; 33:494–502.
- Twigt JM, Bolhuis ME, Steegers EA, Hammiche F, van Inzen WG, Laven JS, et al. The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment. Hum Reprod 2012; 27:2526–31.
- Sun H, Lin Y, Lin D, Zou C, Zou X, Fu L, et al. Mediterranean diet improves embryo yield in IVF: a prospective cohort study. Reprod Biol Endocrinol 2019;17:73.
- Ricci E, Bravi F, Noli S, Somigliana E, Cipriani S, Castiglioni M, et al. Mediterranean diet and outcomes of assisted reproduction: an Italian cohort study. Am J Obstet Gynecol 2019;221:627.e1–14.
- Sugawa M, Okubo H, Sasaki S, Nakagawa Y, Kobayashi T, Kato K. Lack of a meaningful association between dietary patterns and in vitro fertilization outcome among Japanese women. Reprod Med Biol 2018;17:466–73.
- Czeizel E, Kollega-Tarsoly E, Kalina A, Pal M, Pados G. Cholesterol levels in young men and women planning conception. Article in Hu. Orv Hetil 1996; 137:125–8.
- Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility. Fertil Steril 2008;89:668–76.
- Gaskins AJ, Mumford SL, Chavarro JE, Zhang C, Pollack AZ, Wactawski-Wende J, et al. The impact of dietary folate intake on reproductive function in premenopausal women: a prospective cohort study. PLoS One 2012;7: e46276.
- Cueto HT, Riis AH, Hatch EE, Wise LA, Rothman KJ, Sørensen HT, et al. Folic acid supplementation and fecundability: a Danish prospective cohort study. Eur J Clin Nutr 2016;70:66–71.
- Szymanski W, Kazdepka-Zieminska A. Wp1yw stezenia homocysteiny w p1ynie pecherzykowym na stopien dojrza1osci komorki jajowej [Effect of homocysteine concentration in follicular fluid on a degree of oocyte maturity]. Ginekol Pol 2003;74:1392–6.
- Gaskins AJ, Rich-Edwards JW, Hauser R, Williams PL, Gillman MW, Ginsburg ES, et al. Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth. Obstet Gynecol 2014;124:23–31.
- Byrne J. Periconceptional folic acid prevents miscarriage in Irish families with neural tube defects. Ir J Med Sci 2011;180:59–62.
- Gaskins AJ, Afeiche MC, Wright DL, Toth TL, Williams PL, Gillman MW, et al. Dietary folate and reproductive success among women undergoing assisted reproduction. Obstet Gynecol 2014;124:801–9.
- Mumford SL, Chavarro JE, Zhang C, Perkins NJ, Sjaarda LA, Pollack AZ, et al. Dietary fat intake and reproductive hormone concentrations and ovulation in regularly menstruating women. Am J Clin Nutr 2016;103: 868–77.
- Chiu YH, Karmon AE, Gaskins AJ, Arvizu M, Williams PL, Souter I, et al. Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction. Hum Reprod 2018;33:156–65.
- Mirabi P, Chaichi MJ, Esmaeilzadeh S, Ali Jorsaraei SG, Bijani A, Ehsani M, et al. The role of fatty acids on ICSI outcomes: a prospective cohort study. Lipids Health Dis 2017;16:18.
- Afeiche MC, Chiu YH, Gaskins AJ, Williams PL, Souter I, Wright DL, et al. Dairy intake in relation to in vitro fertilization outcomes among women from a fertility clinic. Hum Reprod 2016;31:563–71.
- Chavarro JE, Rich-Edwards JW, Rosner B, Willett WC. A prospective study of dairy foods intake and anovulatory infertility. Hum Reprod 2007;22:1340–7.
- Greenlee AR, Arbuckle TE, Chyou PH. Risk factors for female infertility in an agricultural region. Epidemiology 2003;14:429–36.
- Wise LA, Wesselink AK, Tucker KL, Saklani S, Mikkelsen EM, Cueto H, et al. Dietary fat intake and fecundability in 2 preconception cohort studies. Am J Epidemiol 2018;187:60–74.
- Gaskins AJ, Chiu YH, Williams PL, Keller MG, Toth TL, Hauser R, et al. Maternal whole grain intake and outcomes of in vitro fertilization. Fertil Steril 2016;105:1503–10.e4.
- Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Protein intake and ovulatory infertility. Am J Obstet Gynecol 2008;198:210.e1–7.
- Gaskins AJ, Sundaram R, Buck Louis GM, Chavarro JE. Seafood intake, sexual activity, and time to pregnancy. J Clin Endocrinol Metab 2018;103: 2680–8.
- Jacobsen BK, Jaceldo-Siegl K, Knutsen SF, Fan J, Oda K, Fraser GE. Soy isoflavone intake and the likelihood of ever becoming a mother: the Adventist Health Study-2. Int J Womens Health 2014;6:377–84.
- Shahin AY, Ismail AM, Zahran KM, Makhlouf AM. Adding phytoestrogens to clomiphene induction in unexplained infertility patients—a randomized trial. Reprod Biomed Online 2008;16:580–8.
- Unfer V, Casini ML, Costabile L, Mignosa M, Gerli S, Di Renzo GC. High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial. J Soc Gynecol Investig 2004;11:323–8.
- Unfer V, Casini ML, Gerli S, Costabile L, Mignosa M, Di Renzo GC. Phytoestrogens may improve the pregnancy rate in in vitro fertilization-embryo transfer cycles: a prospective, controlled, randomized trial. Fertil Steril 2004;82:1509–13.
- Vanegas JC, Afeiche MC, Gaskins AJ, Mínguez-Alarcon L, Williams PL, Wright DL, et al. Soy food intake and treatment outcomes of women undergoing assisted reproductive technology. Fertil Steril 2015;103:749– 55.e2.
- Braga DP, Halpern G, Setti AS, Figueira RC, Iaconelli A Jr, Borges E Jr. The impact of food intake and social habits on embryo quality and the likelihood of blastocyst formation. Reprod Biomed Online 2015;31:30–8.
- Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility. Eur J Clin Nutr 2009;63:78–86.
- Augood C, Duckitt K, Templeton AA. Smoking and female infertility: a systematic review and meta-analysis. Hum Reprod 1998;13:1532–9.
- Adena MA, Gallagher HG. Cigarette smoking and the age at menopause. Ann Hum Biol 1982;9:121–30.
- Mattison DR, Plowchalk DR, Meadows MJ, Miller MM, Malek A, London S. The effect of smoking on oogenesis, fertilization, and implantation. Semin Reprod Endocrinol 1989;7:291–304.
- Peck JD, Quaas AM, Craig LB, Soules MR, Klein NA, Hansen KR. Lifestyle factors associated with histologically derived human ovarian nongrowing follicle count in reproductive age women. Hum Reprod 2016; 31:150–7.
- Winter E, Wang J, Davies MJ, Norman R. Early pregnancy loss following assisted reproductive technology treatment. Hum Reprod 2002;17:3220–3.
- Ness RB, Grisso JA, Hirschinger N, Markovic N, Shaw LM, Day NL, et al. Cocaine and tobacco use and the risk of spontaneous abortion. N Engl J Med 1999;340:333–9.
- Zenzes MT. Smoking and reproduction: gene damage to human gametes and embryos. Hum Reprod Update 2000;6:122–31.
- Stillman RJ, Rosenberg MJ, Sachs BP. Smoking and reproduction. Fertil Steril 1986;46:545–66.
- Povey AC, Clyma JA, McNamee R, Moore HD, Baillie H, Pacey AA, et al. Modifiable and non-modifiable risk factors for poor semen quality: a case-referent study. Hum Reprod 2012;27:2799–806.
- Practice Committee of the American Society for Reproductive Medicine. Smoking and infertility: a committee opinion. Fertil Steril 2018;110:611–8.
- Eggert J, Theobald H, Engfeldt P. Effects of alcohol consumption on female fertility during an 18-year period. Fertil Steril 2004;81:379–83.
- Jensen TK, Hjollund HI, Henriksen TB, Scheike T, Kolstad H, Giwercman A, et al. Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy. Bt Med J 1998;317:505–10.
- Hakim RB, Gray RH, Zacur H. Alcohol and caffeine consumption and decreased fertility. Fertil Steril 1998;70:632.
- Hassan MA, Killick SR. Negative lifestyle is associated with a significant reduction in fecundity. Fertil Steril 2004;81:384–92.
- Tolstrup JS, Kjaer SK, Holst C, Sharif H, Munk C, Osler M, et al. Alcohol use as a predictor for infertility in a representative population of Danish women. Acta Obstet Gynecol Scand 2003;82:744–9.
- Miller NS, Gold MS. The human sexual response and alcohol and drugs. J Subst Abuse Treat 1988;5:171–7.
- Grover S, Mattoo SK, Pendharkar S, Kandappan V. Sexual dysfunction in patients with alcohol and opioid dependence. Indian J Psychol Med 2014;36:355–65.
- Cocores JA, Miller NS, Pottash AC, Gold MS. Sexual dysfunction in abusers of cocaine and alcohol. Am J Drug Alcohol Abuse 1988;14:169–73.
- Bolumar F, Olsen J, Rebagliato M, Bisanti L. Caffeine intake and delayed conception: a European multicenter study on infertility and subfecundity. European Study Group on Infertility Subfecundity. Am J Epidemiol 1997; 15:324–34.
- Wilcox A, Weinberg C, Baird D. Caffeinated beverages and decreased fertility. Lancet 1988;2:1453–6.
- Signorello LB, McLaughlin JK. Maternal caffeine consumption and spontaneous abortion: a review of the epidemiologic evidence. Epidemiology 2004;15:229–39.
- Mueller BA, Daling JR, Weiss NS, Moore DE. Recreational drug use and the risk of primary infertility. Epidemiology 1990;1:195–200.
- Kolodny RC, Masters WH, Kolodner RM, Toro G. Depression of plasma testosterone levels after chronic intensive marihuana use. N Engl J Med 1974;290:872–4.
- Gundersen TD, Jørgensen N, Andersson AM, Bang AK, Nordkap L, Skakkebæk NE, et al. Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men. Am J Epidemiol 2015;182:473–81.
- Payne KS, Mazur DJ, Hotaling JM, Pastuszak AW. Cannabis and male fertility: a systematic review. J Urol 2019;202:674–81.
- Rossato M, Ion Popa F, Ferigo M, Clari G, Foresta C. Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 2005;90:984–91.
- Maccarrone M, Barboni B, Paradisi A, Bernabo N, Gasperi V, Pistilli MG, et al. Characterization of the endocannabinoid system in boar spermatozoa and implications for sperm capacitation and acrosome reaction. J Cell Sci 2005;118:4393–404.
- Schuel H, Burkman LJ, Lippes J, Crickard K, Mahony MC, Giuffrida A, et al. Evidence that anandamide-signaling regulates human sperm functions required for fertilization. Mol Reprod Dev 2002;63:376–87.
- Whan LB, West MC, McClure N, Lewis SE. Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro. Fertil Steril 2006;85:653–60.
- Kasman AM, Thoma ME, McLain AC, Eisenberg ML. Association between use of marijuana and time to pregnancy in men and women: findings from the National Survey of Family Growth. Fertil Steril 2018;109:866–71.
- Wise LA, Wesselink AK, Hatch EE, Rothman KJ, Mikkelsen EM, Sørensen HT, et al. Marijuana use and fecundability in a North American preconception cohort study. J Epidemiol Community Health 2018;72: 208–15.
- American College of Obstetricians and Gynecologists. Committee Opinion No. 722: Marijuana use during pregnancy and lactation. Obstet Gynecol 2017;130:e205–9.
- Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev 2009;30:293–342.
- Hipwell AE, Kahn LG, Factor-Litvak P, Porucznik CA, Siegel EL, Fichorova RN, et al. Program collaborators for Environmental influences on Child Health Outcomes. Exposure to non-persistent chemicals in consumer products and fecundability: a systematic review. Hum Reprod Update 2019;25:51–71.
- Kahn LG, Harley KG, Siegel EL, Zhu Y, Factor-Litvak P, Porucznik CA, et al. Persistent organic pollutants and couple fecundability: a systematic review. Hum Reprod Update 2021;27:339–66.
- Carre J, Gatimel N, Moreau J, Parinaud J, Leandri R. Does air pollution play a role in infertility?: a systematic review. Environ Health 2017;16:82.
- Nieuwenhuijsen MJ, Basagana X, Dadvand P, Martinez D, Cirach M, Beelen R, et al. Air pollution and human fertility rates. Environ Int 2014;70:9–14.
- Xue T, Zhu T. Association between fertility rate reduction and pregestational exposure to ambient fine particles in the United States, 2003-2011. Environ Int 2018;121:955–62.
- Xue T, Zhu T. Increment of ambient exposure to fine particles and the reduced human fertility rate in China, 2000-2010. Sci Total Environ 2018;642:497–504.
- Mahalingaiah S, Winter MR, Aschengrau A. Association of prenatal and early life exposure to tetrachloroethylene (PCE) with polycystic ovary syndrome and other reproductive disorders in the Cape Cod Health Study: a retrospective cohort study. Reprod Toxicol 2016;65:87–94.
- Mendola P, Sundaram R, Louis GMB, Sun L, Wallace ME, Smarr MM, et al. Proximity to major roadways and prospectively-measured time-to-preg-nancy and infertility. Sci Total Environ 2017;576:172–7.
- Nobles CJ, Schisterman EF, Ha S, Buck Louis GM, Sherman S, Mendola P. Time-varying cycle average and daily variation in ambient air pollution and fecundability. Hum Reprod 2018;33:166–76.
- Slama R, Bottagisi S, Solansky I, Lepeule J, Giorgis-Allemand L, Sram R. Short-term impact of atmospheric pollution on fecundability. Epidemiology 2013;24:871–9.
- Ha S, Sundaram R, Buck Louis GM, Nobles C, Seeni I, Sherman S, et al. Ambient air pollution and the risk of pregnancy loss: a prospective cohort study. Fertil Steril 2018;109:148–53.
- Zhang L, Liu W, Hou K, Lin J, Zhou C, Tong X, et al. Air pollution-induced missed abortion risk for pregnancies. Nat Sustain 2019;2: 1011–7.
- Deng Z, Chen F, Zhang M, Lan L, Qiao Z, Cui Y, et al. Association between air pollution and sperm quality: a systematic review and meta-analysis. Environ Pollut 2016;208(Pt B):663–9.
Practice Documents
ASRM Practice Documents have been developed to assist physicians with clinical decisions regarding the care of their patients.The use of preimplantation genetic testing for aneuploidy: a committee opinion (2024)
PGT-A use in the U.S. is rising, but its value as a routine IVF screening test is unclear, with mixed results from various studies.Evidence-based diagnosis and treatment for uterine septum: a guideline (2024)
To provide evidence-based recommendations regarding the diagnosis and effectiveness of surgical treatment of a uterine septum.The use of hormonal contraceptives in fertility treatments: a committee opinion (2024)
Hormonal contraception aids in the timing of ART cycles, reduce ovarian cysts at IVF cycle initiation, and optimize visualization before hysteroscopy.Current evaluation of amenorrhea: a committee opinion (2024)
Amenorrhea is the absence or abnormal cessation of the menses.Topic Resources
View more on the topic of infertility