History and exam
Key diagnostic factors
common
presence of risk factors
Risk factors include: age >35 years, history of sexually transmitted disease, cigarette smoking, very high body fat, very low body fat, history of autoimmune disease, history of appendicitis, use of dopaminergic antagonist medications, cannabis use, alcohol consumption, caffeine consumption, and stress.
history of prior pelvic surgery
Myomectomy, ovarian cystectomy, or other pelvic surgery can lead to scar tissue that may affect tubal patency.
irregular menstrual cycles
The normal menstrual cycle is 21-35 days in length, followed by bleeding for 3-7 days. A history of regular menstrual cycles is highly correlated with ovulatory menstrual cycles, particularly if accompanied by moliminal symptoms such as breast tenderness, bloating, and mood changes.
Ovulatory dysfunction is a common cause of infertility.
hirsutism
Midline abdominal or other male-pattern hair growth is a common manifestation of hyper-androgenism (a key component of polycystic ovary syndrome; PCOS). Patients with PCOS have an increased risk of infertility and miscarriage.
acne
A common manifestation of hyper-androgenism (a key component of PCOS). Patients with PCOS have an increased risk of infertility and miscarriage.
palpable uterine abnormalities
Pelvic examination may reveal abnormal shape and mobility of the uterus. This may relate to a structural abnormality, such as fibroids or scarring from endometriosis.
adnexal abnormalities
Pelvic examination may reveal the presence of adnexal masses or tenderness, indicating endometriosis or infection.
uncommon
galactorrhoea
A common sign of elevated prolactin. Increased prolactin can lead to amenorrhoea and/or poor endometrial development.
Other diagnostic factors
common
dyspareunia
Pain with intercourse may be a result of restricted uterus movement from peri-uterine adhesions. This may suggest tubal disease, endometriosis, or other anatomical causes of infertility.
uncommon
cul de sac abnormalities
Pelvic examination may reveal the presence of nodularity in the cul de sac in cases related to endometriosis.
Risk factors
strong
age >35 years
The strongest predictor of pregnancy; fecundity decreases with age (due to dwindling oocyte numbers and poorer oocyte quality).[12][13] As women delay their childbearing, age is becoming significantly more important. Fertility rates decrease at age 30 years and then further decrease after 35 years of age. In fact, the probability of pregnancy decreases by about 3% to 5% for every year over 30 years of age.[29][35]
history of sexually transmitted infection
Chlamydia and gonorrhoea infections, in particular, affect fertility by causing damage to the genital anatomy.[19][36][37] Other sexually transmitted infections (e.g., Mycoplasma genitalium, Trichomonas vaginalis) may also contribute to infertility, but data are more limited.[19] These diseases are endemic in resource-rich countries. Unfortunately, most cases of chlamydia and gonorrhoea infection are asymptomatic.[19]
very high body fat
very low body fat
Most women who are 10% below their ideal body weight experience menstrual irregularities.[42] This has led to the theory that there may be a weight-related set point to maintain menses.[43] Oligomenorrhoea (menstrual cycles longer than 35 days) and amenorrhoea (absence of menstruation) are commonly found in those with eating disorders, such as anorexia nervosa, or long-distance runners.[44] Moderately elevated prolactin levels would also indicate a stress component.[45]
cigarette smoking
Chemicals in cigarette smoke seem to accelerate follicular apoptosis, as manifested by higher follicle-stimulating hormone levels in age-matched women and earlier menopause.[15][46]
Smoking may potentially affect different stages of reproduction, such as folliculogenesis, steroidogenesis, embryo transport, or endometrial integrity and function.[47]
There is limited evidence on the effect of electronic cigarette use, but early data suggest it may also be detrimental to reproductive health.[15]
weak
auto-immune disease
Systemic lupus erythematosus, thyroid dysfunction, and inflammatory bowel disease have been associated with infertility.[48]
history of appendicitis
Inflammation of the appendix can lead to tubal injury because the appendix sits adjacent to the right fallopian tube. A ruptured appendix, particularly with resultant peritonitis, will cause pelvic inflammation and potentially tubal damage.[49]
history of caesarean or instrumental vaginal delivery
Non-spontaneous vaginal delivery may be associated with a reduction in subsequent fertility. In one systematic review, emergency cesarean birth was associated with a 13% lower probability of subsequent fertility, elective cesarean birth with a 14% lower probability, and instrumental vaginal delivery with a 2% lower probability.[50] This could be due to an increased risk of intrauterine infection, uterine scarring, or a poor childbirth experience and maternal anxiety. However, some studies report that women with reduced fecundability are also more likely to have a caesarean delivery, suggesting that the relationship could be bidirectional or due to shared underlying factors.[51]
psychiatric disease
Several dopaminergic antagonist medications used to treat psychiatric diseases can suppress hypothalamic-pituitary function and increase prolactin.[52] Women seeking fertility treatment may have a higher prevalence of current or past eating disorders, which can impact fertility and subsequent pregnancy outcomes.[53]
substance misuse
While limited evidence suggests that marijuana use may be associated with anovulation and menstrual irregularities, evidence on infertility or pregnancy delay is conflicting.[15] Cannabis affects hypothalamic gonadotrophin-releasing hormone resulting in a decrease in luteinising hormone production. It may also affect luteal function by shortening the luteal phase. Marijuana smoke also contains phyto-oestrogens that may bind competitively with oestrogen to the oestrogen receptor.[54]
Cocaine has been associated with male factor infertility; however, few data demonstrate detriment to female fertility.[55]
alcohol consumption
Alcohol consumption significantly increases oestradiol and androgen levels in women.[56] Several retrospective studies demonstrated a negative correlation between chronic alcohol and reduced fecundity. These results were supported by a prospective trial demonstrating a >50% decrease in fecundity when alcohol was consumed.[57] Further studies are required to elucidate the impact of alcohol consumption on female fertility.[58]
caffeine consumption
Several retrospective studies made associations between caffeine intake and prolonged time to conception, but evidence is low-quality and conflicting.[59][60][61] One meta-analysis found that caffeine consumption increased the risk of spontaneous abortion (relative risk 1.37 for 300 mg caffeine/day and 2.32 for 600 mg caffeine/day), but overall there was no clear association between caffeine intake and fecundability or time to pregnancy.[62]
occupational or environmental exposures
Exposure to a range of occupational and environmental chemicals has been linked to reduced fertility in women.[63][64]
Systematic reviews suggest that polychlorinated biphenyls, polybrominated diphenyl ethers, and certain perfluoroalkyl and polyfluoroalkyl substances may reduce fecundability and increase the risk of infertility in women.[65][66] Evidence is limited and less consistent on the effects of other endocrine-disrupting chemicals such as phthalates, bisphenol A, and pesticides.[65][67]
Increased exposure to air pollution and road traffic noise may also increase the risk of infertility in women, although one nationwide cohort study in Denmark found that fine particulate matter air pollution was only significantly associated with a diagnosis of infertility in men.[68][69]
stress
Women with infertility are more likely to be depressed than fertile women.[70][71] In fact, the depression and anxiety scores of women with infertility are indistinguishable from women with cancer, cardiovascular disease, and HIV.[72] However, the measurement of stress in women with infertility is problematic because there is no validated assessment and the fertility problem itself may be a major contributory factor.[73]
Women who reported being most stressed while attempting pregnancy for 6 consecutive menstrual cycles had lower pregnancy rates.[74]
In addition, maternal stress may be associated with recurrent pregnancy losses.[75]
Use of this content is subject to our disclaimer