Offer all couples who are concerned about their fertility an initial assessment (history and examination) in primary care.

Assess couples who are concerned about infertility to identify those:

Who need early investigation or referral.

Who have modifiable factors (e.g. overweight, heavy smoking).

Take a full medical, sexual, and social history, including:

The woman's age (fertility decreases with age).

Children born to the woman, and previous pregnancies and miscarriages (with the same or a different partner). It is important to consider a new partner's fertility history.

Length of time trying to conceive.

Frequency of sexual intercourse (including any difficulties with intercourse), as the chances of conception improve with regular sexual intercourse.

Length of time since stopping contraception and type of contraception. Check that there are no problems that may explain the inability to conceive, such as a 'lost' intrauterine contraceptive device.

History and symptoms that may indicate ovulatory problems:

Menstrual cycle details, including length of cycle and menorrhagia. Oligomenorrhoea or amenorrhoea may indicate lack of or infrequent ovulation. Ask about symptoms and signs of ovulation (e.g. ovulatory discomfort, dysmenorrhoea).

Galactorrhoea or hirsutism.

Systemic disease, including thyroid dysfunction, diabetes, and inflammatory bowel disease.

Excessive exercise, weight loss, or psychological distress.

History and symptoms that may indicate tubal, uterine, or cervical factors:

Symptoms of pelvic inflammatory disease or endometriosis, such as dyspareunia and dysmenorrhoea.

History of sexually transmitted diseases or pelvic inflammatory disease.

Cervical smear history (including any investigations or treatment for an abnormal smear) and previous pelvic surgery, such as appendicitis, ovarian cyst.

Intermenstrual or postcoital bleeding.

Drug history: see Drugs in Causes of infertility in women.

Details of occupation for possible exposure to hazards that can reduce fertility, such as pesticides, nitrous oxide, formaldehyde, and solvents.

Lifestyle factors that may affect fertility (e.g. smoking, weight gain).

Perform physical examination to identify problems that may contribute to infertility:

Pelvic examination may identify such factors as vaginal infection or tenderness indicating endometriosis or pelvic inflammatory disease. Bimanual examination may reveal fibroids or an ovarian cyst.

Look for obesity (associated with lower fertility), hirsutism and acne (associated with polycystic ovary syndrome), and galactorrhoea (suggestive of hyperprolactinaemia).

Take a full medical, sexual, and social history, including:

Children born to the man (with the same or a different partner).

Length of time trying to conceive, and frequency and difficulties of sexual intercourse.

Symptoms or history that may suggest primary spermatogenic failure or obstructive azoospermia:

History of mumps, sexually transmitted diseases, or testicular trauma.

Previous urogenital abnormality and treatment (e.g. undescended testis or orchidopexy).

Systemic diseases (e.g. cardiac failure, chronic renal failure, neoplasia, uncontrolled diabetes, liver cirrhosis, thyrotoxicosis).

Previous surgery (e.g. hernia repair, orchidopexy).

Ejaculatory or erectile dysfunction.

Drug history: see Drugs in Causes of infertility in men.

Details of occupation for possible exposure to pesticides, X-rays, solvents, paints, or chemicals from smelting or welding.

Lifestyle factors that may affect fertility, such as smoking, alcohol intake, illicit drugs, excessive travelling that limits optimal coital timing, excessive exercise, stress, or social or occupational situations that may cause testicular hyperthermia.

Perform physical examination to identify factors that may contribute to infertility:

Scrotal examination may reveal lumps (cancer, varicocele, or hernia); small, soft testes (which may indicate hypogonadism); or undescended testes.

The penis should be examined, including a check of the position of the urethral meatus, for structural abnormalities.

Assess secondary sexual characteristics. In hypogonadism, there may be a decrease in beard and body hair growth and a decrease in muscle mass.

Look for gynaecomastia, which may indicate hypogonadism.

General advice

Involve both partners in all aspects of management. Discussion of wishes, plans, beliefs, and motives is important.

Offer information about normal patterns of conception. For many couples, this will provide reassurance that they have a good chance of conception and may be all that they need.

In general, do not advise investigations for infertility until the couple has been unable to conceive after 1 year of unprotected intercourse.

Advise regular sexual intercourse (two or three times weekly) throughout the woman's cycle; this should ensure that intercourse falls within the fertile period. Do not recommend the use of temperature charts or luteinizing hormone detection methods.

Inform couples that stress in either partner can affect their relationship and is likely to reduce libido and frequency of intercourse, which can contribute to fertility problems.

Provide up-to-date information. Information on infertility is often available locally. National sources of up-to-date information include the Human Fertilisation and Embryology Authority (www.hfea.gov.uk), Infertility Network UK (www.infertilitynetworkuk.com) and British Infertility Counselling Association (www.bica.net).

General health issues

Advise women on preparation for pregnancy (e.g. taking folic acid), check rubella status, and offer cervical screening in accordance with the national cervical screening programme.

For further information, see the CKS topic on Pre-conception - advice and management.

Smoking

Advise women who smoke that smoking is likely to reduce their fertility.

Advise women that passive smoking is likely to reduce their chances of conceiving.

Advise men that smoking is associated with reduced semen quality and that stopping smoking will improve their general health.

Offer women and men referral to a smoking cessation programme. See the CKS topic on Smoking cessation for more information.

Weight

Advise women to aim for a body mass index (BMI) of 19–25 kg/m²:

In particular, encourage weight loss in women with a BMI greater than 29 kg/m², as weight loss is likely to increase their chance of ovulation and therefore conception.

Advise women with a BMI less than 19 kg/m² and either amenorrhoea or irregular menstruation that gaining weight is likely to increase their chance of conception.

Inform women that participating in a group programme involving exercise and dietary advice increases the chances of pregnancy.

Advise men with a body mass index greater than 29 kg/m² that they are likely to have reduced fertility and that they should lose weight.

Occupational risks

Advise anyone concerned about occupational risks to their health, including their fertility, to seek specialist advice. Advice may be obtained from:

Occupational health at their place of work for some people.

The Health and Safety Executive, which provides detailed information on occupational risks. Advice about individual circumstances can be sought by contacting an contacting an adviser.

Other risk factors

Inform women that evidence is inconsistent on the effect of alcohol on fertility, but alcohol poses a definite risk to the fetus, and the Department of Health now recommends consumption of no alcohol at all whilst trying to conceive. Women who choose to drink should consume no more than 1–2 units of alcohol once or twice weekly and should not get intoxicated, to minimize risk to the baby.

Inform men that alcohol consumption within the Department of Health's recommendations of 3–4 units daily is unlikely to affect their fertility. Excessive alcohol consumption can be detrimental to semen quality.

Inform women and men that there is no consistent evidence of an association between consumption of caffeinated beverages and fertility problems.

Inform men that although an elevated scrotal temperature is associated with reduced semen quality, it is uncertain whether wearing loose-fitting underwear improves semen quality.

Advise people trying to conceive that the effectiveness of complementary therapies has not been properly evaluated, and these therapies are not recommended.

Advise women and men that the use of illicit drugs may affect fertility. Offer users of illicit drugs referral to a specialist drugs and alcohol service.

Start investigations in couples who have not conceived after 1 year of regular unprotected sexual intercourse.

Offer investigations earlier than 1 year to couples who have been identified as less likely to conceive.

Early investigations may be prompted by the same factors that prompt an early referral (see When to refer).

Measure mid-luteal phase progesterone in all women to confirm ovulation. The sample should be taken 7 days before the expected period (day 21 in a 28-day cycle).

The following additional tests may be needed:

In women with prolonged irregular menstrual cycles, depending on the timing of menstrual periods, serum progesterone may need to be measured later (e.g. on day 28 of a 35-day cycle) to confirm ovulation, and repeated weekly thereafter until the next menstrual cycle starts.

In women with irregular menstrual cycles, measure serum gonadotrophins (follicle-stimulating hormone and luteinizing hormone).

In women with symptoms of thyroid disease, perform thyroid function tests.

In women with an ovulatory disorder, galactorrhoea, or a suspected pituitary tumour, measure prolactin.

Screen for chlamydia.

Arrange for semen analysis.

If the result of the first semen sample is normal, there is no need to do a repeat confirmatory test.

If the result of the first semen sample is abnormal, order a repeat test:

Testing should ideally be repeated 3 months after the initial test, to allow time for the cycle of spermatozoa to be completed.

It may be appropriate to test earlier (e.g. if the man is very anxious regarding the test result and prefers to have the test done earlier). In these circumstances, or if there is a gross spermatozoa deficiency (azoospermia or severe oligospermia), perform the repeat test within 2–4 weeks.

If the repeat test result is normal, the semen should be regarded as normal and no further testing is required.

Men who have two abnormal semen examination results should be referred for further assessment.

Screen for chlamydia.

Do not recommend:

Basal body temperature charts.

Use of ovulation predictor kits.

Postcoital testing.

Screening for antisperm antibodies.

Referral criteria for people presenting with infertility may vary among health authorities.

If the woman is younger than 35 years: in general, consider referral if history, examination, and investigations are normal in both partners and the couple has not conceived after 18 months.

Provide earlier referral for women 35 years of age or older or if an abnormality in the history, examination, or investigations suggests that earlier secondary care involvement is required.

Earlier referral (i.e. duration of infertility less than 18 months) may also be prompted by factors listed in Table 1.

Ensure that the couple have been offered counselling before, during, and after investigation and treatment, regardless of the outcome of these procedures, and explain that fertility problems and their investigation and treatment can cause psychological stress. Usually counselling will be arranged by the specialist infertility team. Infertility counsellors are provided by all licensed clinics in the UK, and the British Infertility Counselling Association (www.bica.net).

Assessments in secondary and tertiary care:

Investigations in women normally include tubal patency tests:

Women who are not known to have comorbid conditions (e.g. pelvic inflammatory disease, endometriosis, or previous ectopic pregnancy) should be offered hysterosalpingography or hysterosalpingo-contrast ultrasonography.

Women thought to have comorbid conditions should be offered diagnostic laparoscopy and dye so that tubal and other pelvic abnormalities can be assessed at the same time.

Investigations in men include an assessment of the sperm, starting with a review of results obtained from primary care investigations:

In men with abnormal sperm, a more detailed examination is done, which may include microbiological tests, sperm culture, endocrine tests, imaging of the urogenital tract, and testicular biopsy.

Types of infertility treatment:

There are three main types of fertility treatment (see Types of infertility treatment):

Further information on many aspects of infertility treatments can be found on the website of the Human Fertilisation and Embryology Authority (HFEA, www.hfea.gov.uk). This body is responsible for regulating all NHS and private clinics offering infertility treatments to ensure compliance with the Human Fertilisation and Embryology Act 1990:

Information provided by the HFEA to patients, donors, and healthcare professionals includes:

The HFEA guide to infertility, which is written for people who are having or considering fertility treatment.

Detailed information on all UK fertility clinics, including the services they provided and their success rates.

Depending on the treatment, problems that may occur with assisted conception include:

Ovarian hyperstimulation syndrome:

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic and potentially life-threatening complication of superovulation [National Collaborating Centre for Women's and Children's Health, 2004]:

OHSS can occur after any form of supraphysiological ovarian stimulation, including clomifene and gonadotrophin ovulation induction.

Mild forms of OHSS are common and affect up to 33% of in vitro fertilization (IVF) cycles. Moderate or severe OHSS complicates 3–8% of IVF cycles [RCOG, 2006]. Severe manifestations of OHSS can lead to thrombosis, renal and liver dysfunction, and acute respiratory distress syndrome, causing serious morbidity.

Onset of OHSS can be [RCOG, 2006]:

Early: within 9 days after the ovulatory dose of human chorionic gonadotrophin (hCG).

Late: after 9 days, reflecting endogenous hCG stimulation arising from successful implantation.

Symptoms and signs include:

Feeling unwell, nausea, vomiting.

Abdominal pain, distension, or both, caused by enlarged ovaries and acute ascites.

Bowel disturbance: constipation or diarrhoea.

Dark, concentrated urine due to reduced renal perfusion and low urine output.

Dyspnoea due to splinting of the diaphragm secondary to ascites or pleural effusion.

Leg and vulval oedema.

Consider alternative diagnoses, such as complications of an ovarian cyst (torsion, haemorrhage), pelvic infection, intra-abdominal haemorrhage, ectopic pregnancy, and appendicitis [RCOG, 2006].

Seek urgent advice from a specialist unit if OHSS is suspected. The severity of OHSS can worsen over time, and even initially mild presentations should be kept under review [RCOG, 2006].

Ectopic pregnancy:

Ectopic pregnancy occurs in about 4% of pregnancies after assisted conception [Braude and Rowell, 2003]:

Heterotopic (one embryo in the uterus and one in the tube) pregnancy is rare naturally (1 in 30,000 pregnancies), but the rate may be as high as 1 in 100 pregnancies in women who have had assisted conception [Tal et al, 1996].

Pelvic infection:

The egg extraction procedure poses a risk of pelvic infection. As a result, pelvic pain and other signs of infection may develop in the weeks after the procedure:

Infection might be introduced into the ovary during the extraction procedure, which involves passing a needle through the vaginal wall into the ovary.

The risk of serious pelvic infection is likely to be less than 1 in 500 procedures.

Multiple pregnancy:

Multiple pregnancy is the greatest health risk associated with fertility treatment:

The risk of multiple birth is high with in vitro fertilization (IVF):

In the UK, 1 in 4 births after IVF (including intracytoplasmic sperm injection [ICSI]) result in twins or triplets. In contrast, the incidence is 1 in 80 births after natural conception.

40% of IVF babies are twins. The numbers of multiple births from IVF has risen by 41% from 1995 to 2003.

The high incidence of multiple births is due to current embryo transfer practices — most women have two embryos transferred during IVF.

Multiple pregnancy poses increased risks:

Up to 25% of women carrying more than one baby have pregnancy-induced high blood pressure and are 2–3 times more likely to get diabetes than those with singleton pregnancies.

The risk of death, although low, is double for women expecting twins compared with singleton pregnancies.

Twins and triplets have much higher risks of ill health and death compared to singletons:

Around half of all twins and 90% of triplets are born prematurely or with low birth weight. The risk of death in the first week of life is five times higher for twins and nine times higher for triplets than for singletons.

Twins have a four times higher risk of cerebral palsy than singletons (around 8 in 1000 twins are affected).