oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
The term 'subfertility' may be preferable to infertility, as many of the bars to conception are relative rather than absolute and in about 30% of cases no cause is found.
People who are concerned about their fertility should be informed that over 80% of couples in the general population will conceive within one year if:
- the woman is aged under 40 years; and
- they do not use contraception; and
- they have regular sexual intercourse.
Of those who do not conceive in the first year, about half will do so in the second year (cumulative pregnancy rate over 90%).
Infertility may be due to problems with one or both partners. Although it has been traditionally accepted that fertility is more related to the age of the female than that of the male partner, recent literature suggests trends that increased paternal age is also associated with lower fertility.
The main causes of infertility in the UK are:
- Unexplained infertility (no identified male or female cause) (25%)
- Ovulatory disorders (25%)
- Tubal damage (20%)
- Factors in the male causing infertility (30%)
- Uterine or peritoneal disorders (10%)
In about 40% of cases, disorders are found in both the man and the woman. These percentages are an approximate prevalence.
Even in the absence of systemic illness, poor general health will impair fertility.
- Aim for an ideal body mass index (BMI). In those who are overweight (BMI 25-30) and obese (BMI >30), there is a relationship between the degree of excessive weight and poor quality and quantity of sperm.
- Men who have a BMI of >30 should be informed that they are likely to have reduced fertility.
- The adverse effects of smoking on male fertility are well documented.
- Men should be informed that although there is an association between elevated scrotal temperature and reduced semen quality, it is still uncertain whether wearing loose-fitting underwear improves fertility.
- Excessive alcohol consumption also impairs fertility. The effect of lower levels of consumption has not yet been adequately researched.
- Anabolic androgenic steroids, marijuana, opioid narcotics, cocaine and methamfetamines have an adverse impact on male fertility, and adverse effects have been reported on the hypothalamic-pituitary-testicular axis, sperm function and testicular structure.
Disorders of the testis and spermatogenesis
These may be structural or hormonal.
- Persistent azoospermia is incompatible with fertility:
- Whilst a low sperm count is a poor prognostic feature, and the lower the count the worse the prognosis, it is not totally incompatible with fertility.
- Klinefelter's syndrome with karyotype XXY is associated with hypogonadism and disorders of spermatogenesis.
- Cryptorchidism is often associated with testicular dysgenesis and is a risk factor for infertility. Early orchidopexy (6-12 months of age) might be beneficial for testicular development in adulthood.
- Testicular feminisation is a condition in which there is resistance to the virilising effects of androgens, and a child with an XY karyotype appears as a girl:
- This can be much less complete and more limited resistance to androgens can lead to poor development of the testes.
- Testicular tumours are usually treated by orchidectomy, possibly followed by radiotherapy. Treatment of testicular cancer reduces fertility.
- The presence of varicocele in some men is associated with progressive testicular damage from adolescence onwards and a consequent reduction in fertility. However, although the treatment of varicocele in adolescents may be effective, there is a significant risk of overtreatment.
- Varicocele repair may be effective in men with subnormal semen analysis, a clinical varicocele and otherwise unexplained infertility.
- Trauma can cause testicular damage.
- Pituitary tumours will displace or destroy normal tissue and the production of follicle-stimulating hormone (FSH) and luteinising hormone (LH) is often the first to be affected.
- Panhypopituitarism (unrelated to pregnancy) is called Simmonds' disease.
- Hyperprolactinaemia must be severe - ≥735 mU/L (usually due to a pituitary tumour) - to have an effect on sexual function. It may impair sexual desire, testosterone production and erectile function:
- The control of prolactin is unlike the other releasing factors in that it is controlled by an inhibiting rather than a releasing factor from the hypothalamus into the hypothalamic-pituitary portal circulation.
- It is also released in response to thyrotropin-releasing factor, as is thyroid-stimulating hormone (TSH), and so it is elevated if thyroxine is low.
- The pituitary gland may be responsible for other disorders such as Cushing's disease.
Disorders of the genital tract
- Failure of adequate differentiation of the embryonic testis can cause failure of proper development of the spermatic ducts.
- In vasectomy the objective is to interrupt the vas deferens and it may be possible to reunite this in an attempt to reverse the procedure, but the success rate as measured by successful pregnancy is poor.
- Congenital urogenital abnormalities such as hypospadias can cause problems. It tends to deposit the semen in the acid environment of the vagina rather than near the friendlier environment of the cervix.
The patient's smoking, alcohol and drug (including any illicit drugs) history should be recorded.
The search for the cause of infertility or subfertility should be systematic and led by clinical features, not a blind screening process for everything:
- Coitus must be satisfactory and occurring on a frequent basis, preferably two to three times a week:
- There may be periods of time when one of the partners is away.
- Physical or emotional problems may be present.
- Erectile dysfunction can occasionally present as a complaint of infertility.
- Ejaculatory problems - particular attention must be paid to the characteristics of micturition and ejaculation:
- Presence of nocturnal emission.
- Ejaculatory ability in given circumstances.
- Primary or acquired disorder.
- Consider psychosexual aspects (eg, features of affective relationship, pre-existent psychological trauma, previous psychological therapy).
- Current guidelines recommend that patients should be asked about:
- Post-ejaculatory pain.
- Previous or present urethritis or prostatitis.
- Obstructive or irritative urinary symptoms.
- Previous scrotal enlargement or pain or surgery.
- Previous inguinal herniorrhaphy or trauma.
- Chronic sinopulmonary infection.
- Mumps after the age of puberty may have caused orchitis.
- Note previous treatment for malignancy:
- Chemotherapeutic agents, such as those used in childhood leukaemia, may result in subsequent sterility.
- Surgery and radiotherapy may be relevant if they involved the region.
- In men about to receive chemotherapy, the question of sperm banking needs to be considered. Retention of fertility for prepubertal boys with malignancy is a growing field.
- Cryptorchidism is multifactorial in origin and can be caused by genetic factors and endocrine disruption early in pregnancy.
- Cryptorchidism is often associated with testicular dysgenesis and is a risk factor for infertility and germ cell tumours.
- Evidence is still inconclusive as to whether early surgical intervention can prevent germ cell loss. In one randomised study it improved testicular growth in boys treated at the age of 9 months compared to those aged 3 years at the time of orchidopexy.
- Paternity in men with unilateral cryptorchidism is almost equal to that in men without cryptorchidism. However, bilateral cryptorchidism significantly reduces the likelihood of paternity.
- Torsion of the testis may be relevant, as failure to reduce it swiftly can compromise blood supply and cause lasting damage.
- Sexually transmitted diseases can cause infertility.
- Drug and medication history. Legal drugs taken for legitimate purposes may cause problems:
- Phenothiazines and the older typical antipsychotics as well as metoclopramide increase levels of prolactin.
- Oral and rectal sulfasalazine impair spermatogenesis. This is reversible when the drug is withdrawn or switched to mesalazine.
- Immunosuppressants - eg, for autoimmune disease or after transplantation.
- It is prudent to record the patient's blood pressure, weight and height (to calculate their BMI).
- Men with ejaculatory disorders should have their fasting glucose performed to exclude diabetes mellitus.
- A comprehensive andrological examination is indicated if semen analysis shows abnormalities compared with reference values.
- The patient should be examined for age-appropriate development of male secondary sex characteristics, gynaecomastia or hirsutism.
- Testicular site, consistency and volume should be noted.
- Examine for the presence of a varicocele, epididymal thickening or scrotal swelling.
- Examine for inguinal lymphadenopathy in those with symptoms to suggest an STI or in those with risk factors for an STI.
In the male, semen analysis in the only necessary initial investigation:
- The specimen should be produced by masturbation (and not into a condom, as they contain spermatocides) and after three days of abstinence from sexual activity.
- The specimen should be kept warm and sent to the laboratory for examination, ideally within an hour from production, although in practice this is difficult to achieve. Prior arrangement with the laboratory may be necessary to ensure that they are able to deal with the specimen on the same day as collection.
- Normal results based on World Health Organization (WHO) criteria are given below. Figures shown are lowest acceptable result (5th percentile) and 95% confidence limits in brackets:
- Semen volume (mL): 1.5 (1.4-1.7)
- Total sperm number (106 per ejaculation): 39 (33-46)
- Sperm concentration (106 per mL): 15 (12-16)
- Total motility (%): 40 (38-42)
- Progressive motility (%): 32 (31-34)
- Vitality (live spermatozoa, %): 58 (55-63)
- Sperm morphology (normal forms, %): 4 (3.0-4.0)
- Repeat confirmatory tests should ideally be undertaken three months after the initial analysis, to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoal deficiency (azoospermia or severe oligozoospermia) has been detected, the repeat test should be undertaken as soon as possible.
- After a second unsatisfactory result, an FSH level should be taken.
- It is important to differentiate between the following:
- Oligozoospermia: <15 million spermatozoa/mL
- Asthenozoospermia: <32% motile spermatozoa
- Teratozoospermia: <4% normal forms
- Impaired spermatogenesis is often associated with elevated FSH concentration.
- Testicular biopsy is the best procedure to define the histological diagnosis and the possibility of finding sperm. Spermatozoa are found in about 60% of patients with non-obstructive azoospermia (NOA).
- To increase the chances of positive sperm retrievals in men with NOA, testicular sperm extraction (single, multiple or microsurgical) should be used rather than percutaneous epididymal sperm aspiration (PESA).
People undergoing IVF treatment should be offered testing for HIV, hepatitis B and hepatitis C. Those people found to test positive for one or more of HIV, hepatitis B, or hepatitis C should be offered specialist advice and counselling and appropriate clinical management.
See separate article Infertility Treatments.
Further reading & references
- Fertility - Assessment and treatment for people with fertility problems, NICE Guidance (Feb 2013)
- Balasch J, Gratacos E; Delayed childbearing: effects on fertility and the outcome of pregnancy. Curr Opin Obstet Gynecol. 2012 Jun;24(3):187-93. doi: 10.1097/GCO.0b013e3283517908.
- Hinz S, Rais-Bahrami S, Kempkensteffen C, et al; Effect of obesity on sex hormone levels, antisperm antibodies, and fertility Urology. 2010 Oct;76(4):851-6.
- Santos EP, Lopez-Costa S, Chenlo P, et al; Impact of spontaneous smoking cessation on sperm quality: case report. Andrologia. 2011 Dec;43(6):431-5. doi: 10.1111/j.1439-0272.2010.01089.x. Epub
- Braga DP, Halpern G, Figueira Rde C, et al; Food intake and social habits in male patients and its relationship to Fertil Steril. 2012 Jan;97(1):53-9. Epub 2011 Nov 10.
- Fronczak CM, Kim ED, Barqawi AB; The Insults of Recreational Drug Abuse on Male Fertility. J Androl. 2011 Jul 28.
- Guidelines on Male Infertility; European Association of Urologists (Mar 2013)
- Haugnes HS, Bosl GJ, Boer H, et al; Long-term and late effects of germ cell testicular cancer treatment and implications for follow-up. J Clin Oncol. 2012 Oct 20;30(30):3752-63. doi: 10.1200/JCO.2012.43.4431. Epub 2012 Sep 24.
- Maggi M, Buvat J, Corona G, et al; Hormonal Causes of Male Sexual Dysfunctions and Their Management J Sex Med. 2012 Apr 23. doi: 10.1111/j.1743-6109.2012.02735.x.
- Wyns C; Fertility preservation: current prospects and future challenges. Gynecol Endocrinol. 2013 Jan 25.
- Bostwick JR, Guthrie SK, Ellingrod VL; Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009 Jan;29(1):64-73.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Hayley Willacy
Dr Louise Newson
Prof Cathy Jackson