Scenario: Management | Management | Infertility | CKS | NICE (2024)

From age 18 years onwards.

How should I advise a couple seeking information on infertility?

  • Involve both partners in all aspects of management.
    • Provide evidence-based information (verbal and written) to enable them to make an informed decision regarding their care and treatment.
    • Ensure the information provided is 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.
  • Give women and men general advice on the following:
    • Chance of conception
      • Advise that over 80% of couples in the general population will conceive within 1 year if the woman is aged under 40 years and they have regular (every 2–3 days) unprotected sexual intercourse. About half of those who do not conceive in the first year will do so in the second year (cumulative pregnancy rate over 90%).
      • Inform people who are using artificial insemination to conceive and are concerned about their fertility that over 50% of women under 40 years old will conceive within 6 cycles of intrauterine insemination (IUI). About half of those who do not conceive within 6 cycles of IUI will do so with a further 6 cycles (cumulative pregnancy rate over 75%).
      • Advise that fertility in women (and, to a lesser extent) fertility in men declines with age.
    • Smoking
      • Advise women that smoking (including passive smoking) will likely reduce their fertility and that maternal smoking can harm a developing baby.
      • Advise men that smoking affects semen quality (although it is unknown if this adversely affects fertility).
      • Discuss the benefits of quitting smoking to general health.
      • Offer those who smoke support to help them quit. See the CKS topic onSmoking cessation for more information.
    • Alcohol intake
      • Advise women that alcohol consumption during pregnancy is not advised as it can adversely affect the foetus.
      • Advise men that excessive alcohol consumption may affect semen quality. However, there is no evidence that drinking within recommended safe limits (no more than 14 units per week) has an adverse effect.
      • Offer those who drink excessively support to help them quit.See the CKS topic onAlcohol - problem drinkingfor more information.
    • Obesity
      • Advise women that a body mass index (BMI) of 30 kg/m2or over may increase their time to conceive.
      • Advise men that a BMI greater than 29 kg/m2 is likely to have reduced fertility.
      • Advise women with a BMI of 30 kg/m2or over who are not ovulating that losing weight is likely to increase their chance of conception.
      • Explain that women with obesity are at increased risk of infertility and developing maternal and fetal complications during pregnancy.
      • Offer those who are overweight or obese support to help them lose weight. See the CKS topic on Obesityfor more information.
    • Low body weight
      • Advise women with a BMI less than 19 kg/m2plus either amenorrhoea or irregular menstruation that gaining weight is likely to increase their chance of conception.
    • Drugs
      • Advise that some prescription, over-the-counter, and recreational drugs can interfere with fertility in women and men.
      • Offer users of illicit drugs referral to a specialist drugs and alcohol service.
    • Stress management
      • Advise 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.
      • Explain that psychological stress(for both the woman and the man) may be caused by infertility as well as the investigation and treatment.
      • Offer counselling before, during, and after investigation and treatment, irrespective of the outcome of these procedures.
    • Occupational risks
      • Advise anyone concerned about occupational risks to their health, including their fertility, to seek specialist advice from occupational health at their place of workor from theHealth and Safety Executivewebsite, which provides detailed information on occupational risks.
    • Caffeinated beverages
      • Advise that no consistent evidence exists of an association between consumption of caffeinated beverages (tea, coffee, and colas) and fertility problems.
    • Complementary therapies
      • Advise that the effectiveness of complementary therapies for fertility problems has not been adequately evaluated, so further research is needed before such interventions can be recommended.
    • Tight underwear
      • Advise men that although an elevated scrotal temperature is associated with reduced semen quality, it is uncertain whether wearing loose-fitting underwear improves semen quality.
  • Give women additional relevant pre-conception advice.
    • Folic acid
      • Dietary supplementation with folic acid before conception and up to 12 weeks of 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, a higher dose of 5 mg per day is recommended.
    • Susceptibility to rubella
      • Offer testing for rubella status.
      • 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
      • Ask about the timing and result of their most recent cervical smear test to avoid delay in fertility treatment.
      • Where applicable, offer cervical screening in accordance with the national cervical screening programme guidance.
    • See the section on Advice for all women in the CKS topic on Pre-conception - advice and management for more information on these and other pre-conception care that is applicable to all women who are planning a pregnancy.
  • Providesources of additional information and support.
    • Patient information on infertility is available on:
    • Patient support is available from the following charities:
    • The Human Fertilisation and Embryology Authority (www.hfea.gov.uk) provides information onIn vitro fertilisation(IVF), clinics, and other fertility treatments from the UK government fertility regulator.
    • The NHS website provides an information guide, trying for a baby, to explain how a woman can prepare for a pregnancy, how conception occurs, and how she and her partner can improve her chances of getting pregnant.

Basis for recommendation

These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guidelineFertility problems: assessment and treatment[NICE, 2017a]. The recommendations on obesity are also based on the American Society for Reproductive Medicine (ASRM) Practice Committee reportObesity and reproduction: a committee opinion[ASRM, 2021]. The recommendations on alcohol intake are also based on theUK Chief Medical Officers' Low Risk Drinking Guidelines 2016[DH, 2016] and on a meta-analysis of semen quality and alcohol intake[Ricci, 2017].

General lifestyle advice
  • A Cochrane systematic review assessed the safety and effectiveness of preconception lifestyle advice on fertility outcomes and lifestyle behavioural changes for people with infertility[Boedt, 2021].
    • The authors concluded that the review does not provide clear guidance for clinical practice in this area. However, it does highlight the need for high-quality RCTs to investigate preconception lifestyle advice on a combination of topics and to assess relevant effectiveness and safety outcomes in men and women with infertility.

What initial investigations should I arrange in a woman?

Investigate both partners simultaneously to categorize the cause of infertility. Start investigations in couples who have not conceived after 1 year of regular (every 2–3 days) unprotected sexual intercourse. Offer investigations earlier than 1 year to couples identified as less likely to conceive. Early investigations may be prompted by the same factors that prompt early referral.

  • Measure mid-luteal phase progesterone in all women to confirm ovulation.
    • Offer a blood test to measure serum progesterone in the mid-luteal phase of the cycle (day 21 of a 28-day cycle) even if the woman has regular menstrual cycles.
  • Screen for chlamydia.
    • Before undergoing uterine instrumentation, women should be offered screening for Chlamydia trachomatis using an appropriately sensitive technique.
    • If the result is positive, the woman and her sexual partner(s) should be referred for appropriate management with treatment and contact tracing.
    • Prophylactic antibiotics should be considered before uterine instrumentation if screening has not been done.
    • See the section onTesting to confirm the diagnosisin the CKS topic onChlamydia - uncomplicated genital for more information.
  • The following additional tests may be needed:
    • Serum progesterone (in women with prolonged irregular menstrual cycles) — depending on the timing of menstrual periods, serum progesterone may need to be measured later (for example, on day 28 of a 35-day cycle) to confirm ovulation and repeated weekly after that until the next menstrual cycle starts.
    • Gonadotrophin measurement (in women with irregular menstrual cycles) — gonadotrophin (follicle-stimulating hormone and luteinizing hormone) measurements are of value in women with anovulation or oligo-ovulation. They can be used to identify ovulation disorders.
    • Thyroid function tests (in women with symptoms of thyroid disease).
    • Prolactin measurement (in women with symptoms of an ovulatory disorder [for example, polycystic ovary syndrome], galactorrhoea, or a suspected pituitary tumour).
  • The following investigations arenotrecommended:
    • Endometrial biopsy — there is no evidence that medical treatment of luteal phase defects improves pregnancy rates.
    • Basal body temperature charts — they do not reliably predict ovulation.
    • Use of ovulation predictor kits — there is no evidence that attempts to time sexual intercourse to the menstrual cycle result in improved conception rates. Furthermore, there is evidence that the use of these kits causes stress.
    • Postcoital testing of cervical mucus — has no predictive value for pregnancy rates.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guidelineFertility problems: assessment and treatment[NICE, 2017a] and the European Association of Urology (EAU) guideline onSexual and Reproductive Health[EAU, 2023].

What initial investigations should I arrangein a man?

Investigate both partners simultaneously to categorize the cause of infertility. Start investigations in couples who have not conceived after 1 year of regular (every 2–3 days) unprotected sexual intercourse. Offer investigations earlier than 1 year to couples identified as less likely to conceive. Early investigations may be prompted by the same factors that prompt early referral.

  • Arrange for semen analysis.
    • Give clear written and verbal instructions concerning the collection of the semen sample:
      • The specimen should be collected by masturbation; ejaculated into a clean, wide-mouthed container made of plastic from a batch that has been confirmed to be non-toxic for spermatozoa; and protected from extremes of temperature (below 20°C or above 37°C).
      • The specimen should be collected after a minimum of 2 days and a maximum of 7 days of sexual abstinence.
      • Ideally, the sample should be collected in a private room near the laboratory to avoid exposure of the semen sample to fluctuations in temperature and to control the time between collection and analysis.
      • If the man, for any reason, must collect the sample at another place, the specimen container should be kept close to the body under the clothes (for example, in the armpit) during transport and should be delivered to the laboratory, preferably within 30 minutes after collection and at least no longer than 50 minutes after collection.
    • Emphasize that the semen sample needs to be complete and that the man should report any loss of any fraction of the sample.
    • The results should be interpreted using the most recent World Health Organization (WHO) reference values for human semen characteristics.
      • 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, for example, if the man is very anxious about 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), repeat the test within 2–4 weeks.
      • If the repeat test result is normal, regard the semen as normal; no further testing is required.
      • Refer men with two abnormal semen examination results to secondary care for further assessment.
  • Screen for chlamydia.
    • See the section onTesting to confirm the diagnosisin the CKS topic onChlamydia - uncomplicated genitalfor more information.
  • The following tests arenotrecommended:
    • Screening for antisperm antibodies — there is no evidence of effective treatment to improve fertility.

Basis for recommendation

These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guidelineFertility problems: assessment and treatment[NICE, 2017a],theEuropean Association of Urology (EAU) guideline onSexual and Reproductive Health[EAU, 2023], and World Health Organization (WHO) publication WHO laboratory manual for the examination and processing of human semen (Sixth Edition)[WHO, 2021].

Investigating both partners simultaneously
  • The EAU advises that parallel assessment of the fertility status should be included during the diagnosis and management of the infertile man, since this might determine decision-making in terms of timing and therapeutic strategies, for example, the choice between assisted reproductive technology or surgical intervention.

When should I refer a couplepresenting with infertility?

Referral criteria for people presenting with infertility may vary between health authorities. Refer to local guidelines.

  • In women younger than 36 years of age:
    • In general, consider referring the couple for additional investigations and management if history, examination, and investigations are normal in both partners and the couple has not conceived after 1year.
  • Consider earlier referralif the following factors are present:
    • In women:
      • Age 36 years and older (refer after 6 months).
      • Amenorrhoea or oligomenorrhoea.
      • Previous abdominal or pelvic surgery.
      • Previous pelvic inflammatory disease.
      • Previous sexually transmitted infection (STI).
      • Abnormal pelvic examination.
      • Known reason for infertility (for example, prior treatment for cancer).
    • In men:
      • Previous genital pathology.
      • Previous urogenital surgery.
      • Previous STI.
      • Varicocele.
      • Significant systemic illness.
      • Abnormal genital examination.
      • Two abnormal semen examination results.
      • Known reason for infertility (for example, prior treatment for cancer).
  • Ensure that the couple is offered counselling before, during, and after investigation and treatment regardless of the outcome of these procedures.
    • Psychological stress (for both the woman and the man) may be caused by infertility as well as the investigation and treatment.
    • 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).

Additional investigations and management

  • Following referral, additional investigations may be undertaken.
    • Investigations in women normally include tubal patency tests.
      • Women who are not known to have comorbid conditions (such as pelvic inflammatory disease, endometriosis, or previous ectopic pregnancy) are offered hysterosalpingography or hysterosalpingo-contrast ultrasonography.
      • Women thought to have comorbid conditions are offered diagnostic laparoscopy and dye so that tubal and other pelvic abnormalities can be assessed simultaneously.
    • Investigations in men mayinclude 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.
  • Fertility treatment falls into 3 main types:
    • Medical treatment to restore fertility.
      • Clomifene (an anti-oestrogen drug) is an effective treatment for anovulation and may be used in selected women.
      • Gonadotrophins may be offered to women with clomifene-resistant anovulatory infertility.They are also effective in improving fertility in men with hypogonadotropic hypogonadism.
      • Pulsatile gonadotrophin-releasing hormone and dopamine agonistsare other treatments that induce ovulation.Dopamine agonistscan be considered for women with ovulatory disorders secondary to hyperprolactinaemia.
    • Surgical treatment to restore fertility. This includes:
      • Tubal microsurgery in women with mild tubal disease—tubal catheterization or cannulation improves the chance of pregnancy in women with proximal tubal obstruction.
      • Surgical ablation, or resection of endometriosis plus laparoscopic adhesiolysis in women with endometriosis.
      • Surgical correction of epididymal blockagein men with obstructive azoospermia — this is likely to restore patency of the duct and improve fertility.
    • Assisted reproduction techniques (any treatment that deals with means of conception other than vaginal intercourse). These include:
      • Intrauterine insemination (IUI)— in this process, which is timed to coincide with ovulation, sperm is placed in the woman's uterus using a fine plastic tube. Low doses of ovary-stimulating hormones (oral anti-oestrogens or gonadotrophins) might be given (stimulated IUI) to maximize pregnancy rates.
      • In vitro fertilization (IVF) — involves retrieval of one or more ova combined with sperm and incubated for 2–3 days; the resultant embryo is then injected into the uterus via the cervix. This method is suitable for women who have blocked fallopian tubes, men with a minor degree of subfertility, and couples who have been diagnosed with unexplained infertility or have been unsuccessful with other techniques (such as ovulation induction or IUI).
      • Intracytoplasmic sperm injection (ICSI) — involves injecting an individual sperm directly into the ovum to bypass natural barriers that prevent fertilization. The embryo is then transferred into the uterus. This method is suitable when the man has a very low sperm count or problems maintaining an erection and ejaculation (such as diabetes or spinal cord injury).
      • Donor insemination—involves insemination of sperm, from a donor, into a woman via her vagina into the cervical canal or into the uterus itself (IUI). This method is considered when the man has no (or very few)sperm on testicular biopsy or surgical extraction,has had a vasectomyand reversal has failed or not been tried,or has an infectious disease (such as HIV),or where there is a high risk of transmitting a genetic disorder to the offspring. It is also considered in couples where there is no male partner.
      • Oocyte donation — involves stimulation of the donor's ovaries and collection of ova. The donated ova are then fertilized by the recipient's partner's sperm. After 2–3 days, the embryos are transferred to the uterus of the recipient via the cervix after hormonal preparation of the endometrium. This method is considered for women with ovarian failure (premature or after radiotherapy or chemotherapy); those with bilateral oophorectomy; those with gonadal dysgenesis, including Turner's syndrome; and when the risk of transmitting a genetic disorder is high. It is also used in certain cases of IVF failure. Couples who have had successful IVF or ICSI may decide to donate their spare embryos to help other infertile couples (embryo donation).
  • Further information on many aspects of infertility treatments can be found on the Human Fertilisation and Embryology Authority (HFEA) website (www.hfea.gov.uk).
    • The HFEA 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 topatients, donors, and healthcare professionalsincludes:
      • Information on potential treatments and their success rate.
      • Detailed information on allUK fertility clinics, including the services they provide and their success rates.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Fertility problems: assessment and treatment [NICE, 2017a] and The American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and The Practice Committee of the American Society for Reproductive Medicine (ACOG/ASRM) expert opinionFemale age-related fertility decline [ACOG/ASRM, 2014].

How should I manage complications that may occur after assisted conception?

  • Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of superovulation.
    • Symptoms and signs include:
      • Mild—abdominal bloating andmild abdominal pain.
      • Moderate—nausea and vomiting andincreased abdominal discomfort.
      • Severe—oliguria, generalized oedema,abdominal pain and/ordistension (caused by enlarged ovaries and acute ascites), and hydrothorax (occasionally).
      • Critical— oligo/anuria, tense ascites or large hydrothorax, thromboembolism, and acute respiratory distress syndrome.
    • If a woman presents with these symptoms and signs:
      • Consider alternative diagnoses, such as complications of an ovarian cyst (torsion, haemorrhage), pelvic infection or abscess, intra-abdominal haemorrhage, ectopic pregnancy, bowel perforation, or appendicitis.
      • If OHSS is suspected, seek urgent advice from thespecialist unit.The severity of OHSS can worsen over time, and even initially mild presentations should be kept under review.
  • Other possible complications that may occur after assisted conception include:
    • Ectopic pregnancy — see the CKS topic on Ectopic pregnancy for more information on when to suspect an ectopic pregnancy and how to manage the woman.
    • Pelvic infection — see the CKS topic on Pelvic inflammatory disease for management information.
    • Multiple pregnancy —the National Institute for Health and Care Excellence (NICE) guideline on Twin and triplet pregnancy covers the care that should be offered to women with a twin or triplet pregnancy in addition to the routine care that is offered to all women during pregnancy.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Fertility problems: assessment and treatment(full guideline)[NICE, 2017a]and theRoyal College of Obstetricians and Gynaecologists (RCOG) guideline The management of ovarianhyperstimulation syndrome [RCOG, 2016].

Scenario: Management | Management | Infertility | CKS | NICE (2024)

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