Fertility: assessment and treatment for people with fertility problems

National Institute for Health and Care Excellence

This summary is from sections 1.1–1.4, and 1.8 of the full guideline. For the complete list of recommendations, please refer to the full guideline

Expectant management A formal approach that encourages conception through unprotected vaginal intercourse. It involves supportively offering an individual or couple information and advice about the regularity and timing of intercourse and any lifestyle changes which might improve their chances of conceiving. It does not involve active clinical or therapeutic interventions

Full cycle This term is used to define a full IVF treatment, which should include 1 episode of ovarian stimulation and the transfer of any resultant fresh and frozen embryo(s)

Mild male factor infertility This term is used extensively in practice and in the literature. However, no formally recognised definition is currently available. For the purpose of this guideline it is defined as when 2 or more semen analyses have 1 or more variables below the 5th centile (as defined by the World Health Organization [WHO], 2010). The effect on the chance of pregnancy occurring naturally through vaginal intercourse within 2 years would then be similar to people with unexplained infertility or mild endometriosis

Natural cycle IVF An IVF procedure in which 1 or more oocytes are collected from the ovaries during a spontaneous menstrual cycle without the use of drugs

Principles of care

Providing information

• Couples who experience problems in conceiving should be seen together because both partners are affected by decisions surrounding investigation and treatment
• People should have the opportunity to make informed decisions regarding their care and treatment via access to evidence-based information. These choices should be recognised as an integral part of the decision-making process. Verbal information should be supplemented with written information or audio-visual media
• Information regarding care and treatment options should be provided in a form that is accessible to people who have additional needs, such as people with physical, cognitive or sensory disabilities, and people who do not speak or read English

Fertility: assessment and treatment for people with fertility problems continued

Frequency and timing of sexual intercourse or artificial insemination

• People who are concerned about their fertility should be informed that vaginal sexual intercourse every 2 to 3 days optimises the chance of pregnancy
• People who are using artificial insemination to conceive should have their insemination timed around ovulation

Alcohol

• Women who are trying to become pregnant should be informed that drinking no more than 1 or 2 units of alcohol once or twice per week and avoiding episodes of intoxication reduces the risk of harming a developing fetus
• Men should be informed that alcohol consumption within the Department of Health's recommendations of 3 to 4 units per day for men is unlikely to affect their semen quality
• Men should be informed that excessive alcohol intake is detrimental to semen quality

Smoking

• Women who smoke should be informed that this is likely to reduce their fertility
• Women who smoke should be offered referral to a smoking cessation programme to support their efforts in stopping smoking
• Women should be informed that passive smoking is likely to affect their chance of conceiving
• Men who smoke should be informed that there is an association between smoking and reduced semen quality (although the impact of this on male fertility is uncertain), and that stopping smoking will improve their general health

Caffeinated beverages

• People who are concerned about their fertility should be informed that there is no consistent evidence of an association between consumption of caffeinated beverages (tea, coffee and colas) and fertility problems (See Lifestyle factors)

Obesity

• Women who have a body mass index (BMI) of 30 or over should be informed that they are likely to take longer to conceive
• Women who have a BMI of 30 or over and who are not ovulating should be informed that losing weight is likely to increase their chance of conception
• Women should be informed that participating in a group programme involving exercise and dietary advice leads to more pregnancies than weight loss advice alone
• Men who have a BMI of 30 or over should be informed that they are likely to have reduced fertility

Low body weight

• Women who have a BMI of less than 19 and who have irregular menstruation or are not menstruating should be advised that increasing body weight is likely to improve their chance of conception

Fertility: assessment and treatment for people with fertility problems continued

Tight underwear

• Men should be informed that there is an association between elevated scrotal temperature and reduced semen quality, but that it is uncertain whether wearing loose-fitting underwear improves fertility

Occupation

• Some occupations involve exposure to hazards that can reduce male or female fertility and therefore a specific enquiry about occupation should be made to people who are concerned about their fertility and appropriate advice should be offered

Prescribed, over-the-counter and recreational drug use

• A number of prescription, over-the-counter and recreational drugs interfere with male and female fertility, and therefore a specific enquiry about these should be made to people who are concerned about their fertility and appropriate advice should be offered

Complementary therapy

• People who are concerned about their fertility should be informed that the effectiveness of complementary therapies for fertility problems has not been properly evaluated and that further research is needed before such interventions can be recommended

Folic acid supplementation

• Women intending to become pregnant should be informed that dietary supplementation with folic acid before conception and up to 12 weeks' gestation reduces the risk of having a baby with neural tube defects. The recommended dose is 0.4 mg per day. For women who have previously had an infant with a neural tube defect or who are receiving anti-epileptic medication or who have diabetes (see Diabetes in pregnancy, NICE clinical guideline 63), a higher dose of 5 mg per day is recommended

Defining infertility

• People who are concerned about delays in conception should be offered an initial assessment. A specific enquiry about lifestyle and sexual history should be taken to identify people who are less likely to conceive
• Offer an initial consultation to discuss the options for attempting conception to people who are unable to, or would find it very difficult to, have vaginal intercourse
• The environment in which investigation of fertility problems takes place should enable people to discuss sensitive issues such as sexual abuse
• Healthcare professionals should define infertility in practice as the period of time people have been trying to conceive without success after which formal investigation is justified and possible treatment implemented
• A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner
• A woman of reproductive age who is using artificial insemination to conceive (with either partner or donor sperm) should be offered further clinical assessment and investigation if she has not conceived after 6 cycles of treatment, in the absence of any known cause of infertility. Where this is using partner sperm, the referral for clinical assessment and investigation should include her partner
• Offer an earlier referral for specialist consultation to discuss the options for attempting conception, further assessment and appropriate treatment where:
  • the woman is aged 36 years or over
  • there is a known clinical cause of infertility or a history of predisposing factors for infertility
• Where treatment is planned that may result in infertility (such as treatment for cancer), early fertility specialist referral should be offered
• People who are concerned about their fertility and who are known to have chronic viral infections such as hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) should be referred to centres that have appropriate expertise and facilities to provide safe risk-reduction investigation and treatment

Fertility: assessment and treatment for people with fertility problems continued

Investigation of fertility problems and management strategies

Semen analysis

• The results of semen analysis conducted as part of an initial assessment should be compared with the following WHO reference values:*
  • semen volume: 1.5 ml or more
  • pH: 7.2 or more
  • sperm concentration: 15 million spermatozoa per ml or more
  • total sperm number: 39 million spermatozoa per ejaculate or more
  • total motility (percentage of progressive motility and non-progressive motility): 40% or more motile or 32% or more with progressive motility
  • vitality: 58% or more live spermatozoa
  • sperm morphology (percentage of normal forms): 4% or more

* Please note the reference ranges are only valid for the semen analysis tests outlined by the WHO.

• Screening for antisperm antibodies should not be offered because there is no evidence of effective treatment to improve fertility
• If the result of the first semen analysis is abnormal, a repeat confirmatory test should be offered
• Repeat confirmatory tests should ideally be undertaken 3 months after the initial analysis to allow time for the cycle of spermatozoa formation to be completed. However, if a gross spermatozoa deficiency (azoospermia or severe oligozoospermia) has been detected the repeat test should be undertaken as soon as possible

Post-coital testing of cervical mucus

• The routine use of post-coital testing of cervical mucus in the investigation of fertility problems is not recommended because it has no predictive value on pregnancy rate

Ovarian reserve testing

• Use a woman's age as an initial predictor of her overall chance of success through natural conception or with in vitro fertilisation (IVF)
• Use one of the following measures to predict the likely ovarian response to gonadotrophin stimulation in IVF:
  • total antral follicle count of less than or equal to 4 for a low response and greater than 16 for a high response
  • anti-Müllerian hormone of less than or equal to 5.4 pmol/l for a low response and greater than or equal to 25.0 pmol/l for a high response
  • follicle-stimulating hormone greater than 8.9 IU/l for a low response and less than 4 IU/l for a high response
• Do not use any of the following tests individually to predict any outcome of fertility treatment:
  • ovarian volume
  • ovarian blood flow
  • inhibin B
  • oestradiol (E2)

Fertility: assessment and treatment for people with fertility problems continued

Regularity of menstrual cycles

• Women who are concerned about their fertility should be asked about the frequency and regularity of their menstrual cycles. Women with regular monthly menstrual cycles should be informed that they are likely to be ovulating
• Women who are undergoing investigations for infertility should be offered a blood test to measure serum progesterone in the mid-luteal phase of their cycle (day 21 of a 28-day cycle) to confirm ovulation even if they have regular menstrual cycles
• Women with prolonged irregular menstrual cycles should be offered a blood test to measure serum progesterone. Depending upon the timing of menstrual periods, this test may need to be conducted later in the cycle (for example day 28 of a 35-day cycle) and repeated weekly thereafter until the next menstrual cycle starts
• The use of basal body temperature charts to confirm ovulation does not reliably predict ovulation and is not recommended
• Women with irregular menstrual cycles should be offered a blood test to measure serum gonadotrophins (follicle-stimulating hormone and luteinising hormone)

Prolactin measurement

• Women who are concerned about their fertility should not be offered a blood test to measure prolactin. This test should only be offered to women who have an ovulatory disorder, galactorrhoea or a pituitary tumour

Thyroid function tests

• Women with possible fertility problems are no more likely than the general population to have thyroid disease and the routine measurement of thyroid function should not be offered. Estimation of thyroid function should be confined to women with symptoms of thyroid disease

Endometrial biopsy

• Women should not be offered an endometrial biopsy to evaluate the luteal phase as part of the investigation of fertility problems because there is no evidence that medical treatment of luteal phase defect improves pregnancy rates

Investigation of suspected tubal and uterine abnormalities

• Women who are not known to have comorbidities (such as pelvic inflammatory disease, previous ectopic pregnancy or endometriosis) should be offered hysterosalpingography (HSG) to screen for tubal occlusion because this is a reliable test for ruling out tubal occlusion, and it is less invasive and makes more efficient use of resources than laparoscopy
• Where appropriate expertise is available, screening for tubal occlusion using hysterosalpingo-contrast-ultrasonography should be considered because it is an effective alternative to HSG for women who are not known to have comorbidities
• Women who are thought to have comorbidities should be offered laparoscopy and dye so that tubal and other pelvic pathology can be assessed at the same time
• Women should not be offered hysteroscopy on its own as part of the initial investigation unless clinically indicated because the effectiveness of surgical treatment of uterine abnormalities on improving pregnancy rates has not been established

Testing for viral status

• People undergoing IVF treatment should be offered testing for HIV, hepatitis B and hepatitis C
• 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

Fertility: assessment and treatment for people with fertility problems continued

Viral transmission

• For couples where the man is HIV positive, any decision about fertility management should be the result of discussions between the couple, a fertility specialist and an HIV specialist
• Advise couples where the man is HIV positive that the risk of HIV transmission to the female partner is negligible through unprotected sexual intercourse when all of the following criteria are met:
  • the man is compliant with highly active antiretroviral therapy (HAART)
  • the man has had a plasma viral load of less than 50 copies/ml for more than 6 months
  • there are no other infections present
  • unprotected intercourse is limited to the time of ovulation
• Advise couples that if all the criteria above are met, sperm washing may not further reduce the risk of infection and may reduce the likelihood of pregnancy
• For couples where the man is HIV positive and either he is not compliant with HAART or his plasma viral load is 50 copies/ml or greater, offer sperm washing
• Inform couples that sperm washing reduces, but does not eliminate, the risk of HIV transmission
• If couples who meet all the criteria above still perceive an unacceptable risk of HIV transmission after discussion with their HIV specialist, consider sperm washing
• Inform couples that there is insufficient evidence to recommend that HIV negative women use pre-exposure prophylaxis, when all the criteria above are met
• For partners of people with hepatitis B, offer vaccination before starting fertility treatment
• Do not offer sperm washing as part of fertility treatment for men with hepatitis B
• For couples where the man has hepatitis C, any decision about fertility management should be the result of discussions between the couple, a fertility specialist and a hepatitis specialist
• Advise couples who want to conceive and where the man has hepatitis C that the risk of transmission through unprotected sexual intercourse is thought to be low
• Men with hepatitis C should discuss treatment options to eradicate the hepatitis C with their appropriate specialist before conception is considered

Susceptibility to rubella

• Women who are concerned about their fertility should be offered testing for their rubella status so that those who are susceptible to rubella can be offered vaccination. Women who are susceptible to rubella should be offered vaccination and advised not to become pregnant for at least 1 month following vaccination

Cervical cancer screening

• To avoid delay in fertility treatment a specific enquiry about the timing and result of the most recent cervical smear test should be made to women who are concerned about their fertility. Cervical screening should be offered in accordance with the national cervical screening programme guidance

Screening for Chlamydia trachomatis

• Before undergoing uterine instrumentation women should be offered screening for Chlamydia trachomatis using an appropriately sensitive technique
• If the result of a test for Chlamydia trachomatis is positive, women and their sexual partners should be referred for appropriate management with treatment and contact tracing
• Prophylactic antibiotics should be considered before uterine instrumentation if screening has not been carried out

Fertility: assessment and treatment for people with fertility problems continued

Medical and surgical management of male factor fertility problems

Medical management (male factor infertility)

• Men with hypogonadotrophic hypogonadism should be offered gonadotrophin drugs because these are effective in improving fertility
• Men with idiopathic semen abnormalities should not be offered anti-oestrogens, gonadotrophins, androgens, bromocriptine or kinin-enhancing drugs because they have not been shown to be effective
• Men should be informed that the significance of antisperm antibodies is unclear and the effectiveness of systemic corticosteroids is uncertain
• Men with leucocytes in their semen should not be offered antibiotic treatment unless there is an identified infection because there is no evidence that this improves pregnancy rates

Surgical management (male factor infertility)

• Where appropriate expertise is available, men with obstructive azoospermia should be offered surgical correction of epididymal blockage because it is likely to restore patency of the duct and improve fertility. Surgical correction should be considered as an alternative to surgical sperm recovery and IVF
• Men should not be offered surgery for varicoceles as a form of fertility treatment because it does not improve pregnancy rates

Management of ejaculatory failure

• Treatment of ejaculatory failure can restore fertility without the need for invasive methods of sperm retrieval or the use of assisted reproduction procedures. However, further evaluation of different treatment options is needed

Unexplained infertility

Ovarian stimulation for unexplained infertility

• Do not offer oral ovarian stimulation agents (such as clomifene citrate, anastrozole or letrozole) to women with unexplained infertility
• Inform women with unexplained infertility that clomifene citrate as a stand-alone treatment does not increase the chances of a pregnancy or a live birth
• Advise women with unexplained infertility who are having regular unprotected sexual intercourse to try to conceive for a total of 2 years (this can include up to 1 year before their fertility investigations) before IVF will be considered
• Offer IVF treatment to women with unexplained infertility who have not conceived after 2 years (this can include up to 1 year before their fertility investigations) of regular unprotected sexual intercourse

full guideline available from…
National Institute for Health and Care Excellence, Level 1A, City Tower, Piccadilly Plaza, Manchester, M1 4BT
guidance.nice.org.uk/CG156

National Institute for Health and Care Excellence. Fertility: assessment and treatment for people with fertility problems. February 2013

First included online: February 2013.