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Optimizing natural fertility: a committee opinion (2022)


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 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


Optmizing--Fig 1-new.png
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).

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 when
intercourse occurred on the day of ovulation (15).

Figure 2


Optimizing--Fig 2.png
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).

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


Optimizing--Fig 3.png

Figure 4


Optimizing--Fig 4.png
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.

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.

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  36. 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.
  37. Lenzi A, Lombardo F, Salacone P, Gandini L, Jannini EA. Stress, sexual dysfunctions, and male infertility. J Endocrinol Invest 2003;26:72–6.
  38. 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.
  39. 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.
  40. 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.
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  42. Zietsch B, Santtila P. No direct relationship between human female orgasm rate and number of offspring. Anim Behav 2013;86:253–5.
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  47. Steiner AZ, Long DL, Tanner C, Herring AH. Effect of vaginal lubricants on natural fertility. Obstet Gynecol 2012;120:44–51.
  48. 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.
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  50. 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.
  51. 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.
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  53. 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.
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  64. 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.
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  67. Byrne J. Periconceptional folic acid prevents miscarriage in Irish families with neural tube defects. Ir J Med Sci 2011;180:59–62.
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  69. 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.
  70. 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.
  71. 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.
  72. 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.
  73. 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.
  74. Greenlee AR, Arbuckle TE, Chyou PH. Risk factors for female infertility in an agricultural region. Epidemiology 2003;14:429–36.
  75. 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.
  76. 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.
  77. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Protein intake and ovulatory infertility. Am J Obstet Gynecol 2008;198:210.e1–7.
  78. 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.
  79. 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.
  80. 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.
  81. 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.
  82. 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.
  83. Vanegas JC, Afeiche MC, Gaskins AJ, Mínguez-Alarcon 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.
  84. 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.
  85. 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.
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  89. 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.
  90. Winter E, Wang J, Davies MJ, Norman R. Early pregnancy loss following assisted reproductive technology treatment. Hum Reprod 2002;17:3220–3.
  91. 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.
  92. Zenzes MT. Smoking and reproduction: gene damage to human gametes and embryos. Hum Reprod Update 2000;6:122–31.
  93. Stillman RJ, Rosenberg MJ, Sachs BP. Smoking and reproduction. Fertil Steril 1986;46:545–66.
  94. 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.
  95. Practice Committee of the American Society for Reproductive Medicine. Smoking and infertility: a committee opinion. Fertil Steril 2018;110:611–8.
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  97. 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.
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  100. 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.
  101. Miller NS, Gold MS. The human sexual response and alcohol and drugs. J Subst Abuse Treat 1988;5:171–7.
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  104. 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.
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  107. Mueller BA, Daling JR, Weiss NS, Moore DE. Recreational drug use and the risk of primary infertility. Epidemiology 1990;1:195–200.
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Practice Documents

ASRM Practice Documents have been developed to assist physicians with clinical decisions regarding the care of their patients.
Practice Committee Documents teaser

Current evaluation of amenorrhea: a committee opinion (2024)

Amenorrhea is the absence or abnormal cessation of the menses.
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Inclusive language and environment to welcome lesbian, gay, bisexual, transgender, queer, questioning, intersex, and asexual+ patients (2024)

Creating an inclusive clinical environment to serve lesbian, gay, bisexual, transgender, queer, questioning, intersex, and asexual+ patients is vital.
Practice Committee Documents teaser

Subclinical hypothyroidism in the infertile female population: a guideline (2024)

This guideline reviews the risks and benefits of treating subclinical hypothyroidism in female patients with a history of infertility and miscarriage.
Practice Committee Documents teaser

Tobacco or marijuana use and infertility: a committee opinion (2023)

In the United States, approximately 21% of adults report some form of tobacco use, although 18% report marijuana use.

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ASRM MAC Tool 2021

The ASRM Müllerian Anomaly Classification 2021 (MAC2021) includes cervical and vaginal anomalies and standardize terminology within an interactive tool format.

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EMR Shared Phrases/Template Library

This resource includes phrases shared by ASRM physician members to provide a template for individuals to create their own EMR phrases.

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ASRM Practice Documents

These guidelines have been developed by the ASRM Practice Committee to assist physicians with clinical decisions regarding the care of their patients.

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Ethics Committee Reports are drafted by the members of the ASRM Ethics Committee on the tough ethical dilemmas of reproductive medicine.

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Practice Guidance

Coding Corner Q & A

The Coding Corner Q & A is a list of previously submitted and answered questions from ASRM members about coding. Answers are available to ASRM Members only.

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A compendium of ASRM resources concerning the Novel Corona virus (SARS-COV-2) and COVID-19.

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Patient Resources

ReproductiveFacts.org provides a wide range of information related to reproductive health and infertility through patient education fact sheets, infographics, videos, and other resources.

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Topic Resources

View more on the topic of infertility
Webinars Icon

Aug 2, 2024, 7:30 AM CT - Psychosocial Care in Fertility Treatment - International Perspectives

Panelists will discuss assessing the degree of distress in couples undergoing infertility treatment and addressing their psychosocial needs.

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Aug 15, 2024, 3:00PM CT - Fever Pitch – Startups that are improving access to fertility care

This webinar aims to help identify what factors in fertility-related startups may improve access and equity in reproductive care.

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Fertility and Sterility On Air - Seminal Article: Ernest Ng, and Zhi Chen

June issue Seminal Contribution: a randomized controlled trial studying the use of progestins for ovulation supression in predicted high responders.  Listen to the Episode
PR Bulletin Icon

ASRM announces support for HOPE with Fertility Services Act

The American Society for Reproductive Medicine is proud to endorse the HOPE with Fertility Services Act (HR 8821).

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Coding Icon

HyCoSy and CPT 74740

When Office HSG/HyCoSy is performed but no x-ray/fluoroscopic imaging is performed, only ultrasound is done, is it appropriate to bill CPT code 74740? View the Answer
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Subclinical hypothyroidism in the infertile female population: a guideline (2024)

This guideline reviews the risks and benefits of treating subclinical hypothyroidism in female patients with a history of infertility and miscarriage. View the Committee Guideline
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Survey shows strong support for increased access to fertility treatments

A new public opinion poll reveals strong support for improved access to In Vitro Fertilization (IVF). 

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Infertility Awareness

In honor of National Infertility Awareness Week (NIAW), we have rounded up some of our resources on infertility. View infertility resources
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Leave Your Mark! NIAW April 21-27

National Infertility Awareness Week Action Round-Up Click here to leave your mark during NIAW2024
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National Infertility Awareness Week 2024: Leave Your Mark

Next week is National Infertility Awareness Week, a federally recognized health observance founded to increase awareness of infertility.

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Tobacco or marijuana use and infertility: a committee opinion (2023)

In the United States, approximately 21% of adults report some form of tobacco use, although 18% report marijuana use. View Committee Opinion
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Journal Club Global: The future of REI Fellowship training: debating opportunities and threats

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Journal Club Global: Infertility and Subclinical Hypothyroidism

The impact of treating SCH on fertility, obstetric outcomes, and offspring neurocognitive development is debated in the literature. View the Video
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We are pleased that the legislation passed into law by the Alabama General Assembly will at least allow our members in the state to care for their patients.

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IVF at the SOTU: Fertility care expected to be major focus at State of the Union

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Ethical obligations in fertility treatment when intimate partners withhold information from each other: an Ethics Committee opinion (2024)

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Ethical considerations for telemedical delivery of fertility care: an Ethics Committee opinion (2024)

Telemedicine has the potential to increase access to and decrease the cost of care. View the Committee Opinion
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ASRM Responds to Proposed Alabama Legislation

We are proud of our Alabama members and their patients, who have been such incredible advocates working to motivate their legislators to protect IVF.

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Senate Budget Hearing is Well Timed Following Alabama IVF Ruling

ASRM statement regarding the Senate Budget Committee’s hearing entitled: No Rights to Speak of: The Economic Harms of Restricting Reproductive Freedom.

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ASRM Responds to Senate’s Failure to Pass Access to Family Building Act

We are disappointed by the Senate’s failure to meet the moment and pass federal legislation protecting access to in vitro fertilization (IVF).

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What's New from the Fertility and Sterility Family of Journals

Here’s a peek at this month’s issues from our family of journals! As an ASRM Member, you can access all of our journals.
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ASRM Condemns Profoundly Misguided and Dangerous Court Decision in Alabama

In LePage v Mobile Infirmary Clinic, the Alabama Supreme Court made a decision that flies in the face of medical reality and the needs of the citizens.

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NEW from ASRM Academy: Basic Infertility for Healthcare Providers

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Definition of infertility: a committee opinion (2023)

‘‘Infertility’’ is a disease, condition, or status characterized by several factors. View the Committee Opinion
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It is the responsibility of the clinician to assess for erectile dysfunction, ejaculatory dysfunction, or diminished libido in men presenting for infertility. View the Committee Opinion
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Journal Club Global - Actualización en la suplementación con progesterona en fase lútea para transferencias de embriones congelados

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Endometriosis and infertility: a committee opinion (2012)

Women with endometriosis typically present with pelvic pain, infertility, or an adnexal mass, and may require surgery. View the Committee Opinion
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The International Glossary on Infertility and Fertility Care, 2017†‡§ (2017)

Terms and definitions currently used infertility care, infertility and medically assisted reproduction (MAR) can have different meanings that are dependent upon the setting, their usage in research or clinical interventions, or among diverse populations.
View the Committee Joint Guideline
Coding Icon

Surgery Coding

I took the ASRM coding course, and in that course, coding for bilateral neosalpingostomies was coded using only a dx of N70.11 (hydrosalpinx). View the Answer
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Post Vasectomy Infertility

If a husband has had a vasectomy, does the sterilization code apply to the wife's visits? View the Answer
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Pregnancy Of Uncertain Viability Ultrasound

My staff is telling me that I am getting reimbursed for the first sonogram and OB visit (using ICD 10 code for pregnancy of uncertain viability – O36.80X0. View the Answer
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Pregnancy Ultrasound

Our practice does routine ultrasounds (sac check- 76817) at the end of an IVF cycle and bill with a diagnosis code O09.081, pregnancy resulting from ART.  View the Answer
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Self-referred New Patient

A patient self-refers to our physician for an initial new patient consultation instead of referred by another physician, how do we code for the consult? View the Answer
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Telephone Consult

Does a physician need to speak directly to a patient to code for a telephone consult (99371-99373) or can a staff member relay physician notes to patients? View the Answer
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Testing With No History of Infertility

What diagnosis codes should  providers submit to insurance carriers while trying to evaluate fertility issues? View the Answer
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Psychological Evaluation

Many REs require patients (and their spouses/partners) who are considering using donor gametes to see an infertility counselor first. View the Answer
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IUI or IVF

Should other ovarian dysfunction (diagnosis code E28.8) or unspecified ovarian dysfunction (diagnosis code E28.9) can be used for an IUI or an IVF cycle View the Answer
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Infertility Consult

Does ASRM have any examples of evaluation and management documentation for patients being seen for an initial infertility evaluation? View the Answer
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Infertility Consult by Nurse

What code is used for a nurse practitioner seeing a fertility patient for the first time? View the Answer
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Monitoring E&M

Our group would like to know if others are billing an evaluation and management code for ultrasound and blood draw visits? View the Answer
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New vs Established Patient

How soon can you bill as a new infertility patient? View the Answer
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Hysteroscopy Recurrent Implantation Failure

What is the appropriate ICD-10 code for recurrent implantation failure?  View the Answer
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General E&M Consult

Recently we have received a “re-code” on a new patient (we billed a 99203 and the insurance re-coded it to a 99213).  View the Answer
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D&C Under Ultrasound Guidance

What are the CPT codes and ICD-10 codes for coding a surgical case for a patient with history of Stage B adenocarcinoma of the cervix ... View the Answer
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Diagnosis of Infertility for IVF Procedure

How important is it to have accurate documentation of the type of infertility diagnosis for IVF procedures?  View the Answer
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Diagnostic Testing of an Infertile Couple

The Z31.41 is or is not the correct code to use for diagnostic testing of an infertile couple? And If so can if be used as the primary and only code? View the Answer
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Blood Draws

If a patient comes in only for a blood draw (venipuncture) and is seen only by the lab technician (not an MD, PA, or NP), may we bill for a (minimal) office visit? View the Answer
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Blood Tests

Patients are requesting to have lab work drawn from the female patient moved to the males account due to the female fertility coverage being maxed out.  View the Answer
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Male Infertility

A summary of common codes for Male Infertility compiled by the ASRM Coding Committee. View the Coding Summary
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ASRM müllerian anomalies classification 2021

The Task Force set goals for a new classification and chose to base it on the iconic AFS classification from 1988 because of its simplicity and recognizability. View the Committee Opinion
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Intracytoplasmic sperm injection (ICSI) for non–male factor indications: a committee opinion (2020)

Intracytoplasmic sperm injection is frequently used in combination with assisted reproductive technologies. View the Committee Document
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Moving innovation to practice: an Ethics Committee opinion (2021)

The introduction of new strategies, tests, and procedures into clinical practice raises challenging ethical issues. View the Committee Opinion
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Fertility evaluation of infertile women: a committee opinion (2021)

Diagnostic evaluation for infertility in women should be conducted in a systematic, expeditious, and cost-effective manner. View the Committee Opinion
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Fertility treatment when the prognosis is very poor or futile: an Ethics Committee opinion (2019)

The Ethics Committee recommends that in vitro fertilization (IVF) centers develop patient-centered policies regarding requests for futile treatment.  View the Committee Opinion
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Use of exogenous gonadotropins for ovulation induction in anovulatory women: a committee opinion (2020)

Pretreatment evaluation, indications, treatment regimens, and complications of gonadotropin treatment. View the Committee Opinion
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Reproductive and hormonal considerations in women at increased risk for hereditary gynecologic cancers: Society of Gynecologic Oncology and American Society for Reproductive Medicine Evidence-Based Review (2019)

Providers who care for women at risk for hereditary gynecologic cancers must consider the impact of these conditions. View the Joint Statement
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Guidance for Providers Caring for Women and Men Of Reproductive Age with Possible Zika Virus Exposure (Updated 2019)

This ASRM guidance specifically addresses Zika virus infection issues and concerns of individuals undergoing assisted reproductive technologies (ART). View the Guideline
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American Society for Reproductive Medicine position statement on uterus transplantation: a committee opinion (2018)

Following the birth of the first child from a transplanted uterus in Gothenburg, Sweden, in 2014, other centers worldwide have produced scientific reports. View the Committee Opinion
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Child-rearing ability and the provision of fertility services: an Ethics Committee opinion (2017)

Fertility programs may withhold services on the basis that patients will be unable to provide minimally adequate or safe care for offspring. View the Committee Opinion
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Removal of myomas in asymptomatic patients to improve fertility and/or reduce miscarriage rate: a guideline (2017)

This review evaluates if uterine myomas impact likelihood of pregnancy and pregnancy loss, and if myomectomy influences pregnancy outcomes. View the Guideline
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Improving the Reporting of Clinical Trials of Infertility Treatments (IMPRINT): modifying the CONSORT statement (2014)

Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public. View the Guideline