Around one in seven couples is affected by infertility and a small proportion of these need treatment with assisted conception.  Current guidance recommends offering investigation after one year. Over 80% of couples should conceive within a year if the woman is aged under 40 and they are having regular unprotected sexual intercourse. Of those who do not conceive within a year, half will conceive within the next year (so 90% over two years).

The main causes of infertility are:

In about 40% of cases disorders are found in both the man and the woman. Uterine or endometrial factors, gamete or embryo defects, and pelvic conditions such as endometriosis may also be involved.

For further information on aetiology, prevalence and investigation see the separate Infertility – Male and Infertility – Female articles.

The couple needs support and reassurance. It can be a very difficult time for them, especially if there is pressure from parents or in-laws, that may be more prominent in some cultures but can occur in all. Pregnancy probably will occur even without intervention but they must not feel neglected or that nothing can be done. Couples often conceive whilst awaiting further investigation, as half of those who have not conceived within a year will do so during the second year. The stress of trying to conceive can adversely affect relationships, further contributing to fertility issues.

Couples who have fertility problems should be informed that they might find it helpful to contact a fertility support group. Counselling may be appropriate for some couples, as fertility problems can cause psychological stress.

General advice:

  • Folic acid: women intending to become pregnant should be informed that dietary supplementation with folic acid (0.4 mg a day) before conception and up to 12 weeks of gestation, reduces the risk of having a baby with neural tube defects. The dose should be 5 mg a day in those women who have previously had an infant with a neural tube defect or in those receiving anti-epileptic medication or who have diabetes.
  • Frequency of sexual intercourse: couples may be advised that regular intercourse every two to three days optimises the chances of conception occurring.
  • Alcohol: in men, excessive consumption may affect semen quality but there is no evidence that drinking within recommended safe limits has an adverse effect. Women should be advised that when pregnant, drinking alcohol is not advised due to the potential risk to the developing fetus.
  • Smoking: advise women that smoking can harm a developing baby; offer those who smoke support and referral to help them quit. Advise men that smoking affects semen quality (although it is not known if this adversely affects fertility) and discuss the benefits of quitting smoking to their general health and discuss risks of passive smoking to partner and potential baby.
  • Weight: advise women that having a body mass index (BMI) ≥30 may be a cause of taking longer to conceive. Being overweight may reduce fertility in men also. Being underweight with a BMI <19 may also have an adverse effect on fertility.
  • Alternative therapies: where conventional medicine offers no help, patients are often tempted by alternative therapies. However, what little evidence there is suggests that they are of no benefit and that, as they have not been properly tested, they may even be teratogenic.
  • Timed intercourse: there are insufficient data to draw conclusions about effectiveness of methods to predict ovulation so that intercourse can be concentrated in the right time of the cycle. Methods used include measuring basal temperature and urinary hormones, monitoring cervical mucus and using ultrasound scans. There may be a slight improvement in pregnancy rates but concerns remain about the side-effects of stress and the detrimental effect on relationships and sexual spontaneity.

World Health Organization (WHO) Group I ovulation disorder
This is due to hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism). These women should be advised that they can improve their chance of regular ovulation, conception and an uncomplicated pregnancy by increasing their body weight (for those with a BMI of <19) and/or moderating their exercise levels (if they undertake high levels of exercise). These women should be offered pulsatile administration of gonadotrophin-releasing hormone or gonadotrophins with luteinising hormone activity to induce ovulation.

WHO Group II ovulation disorder
This is due to hypothalamic-pituitary-ovarian dysfunction, predominately due to polycystic ovary syndrome (PCOS). Clomifene citrate (CC) – an anti-oestrogen – is an initial treatment for the majority of these. Metformin (or a combination of clomifene and metformin) can be also considered. However, those women with a BMI of >30 should be advised to lose weight before starting treatment. Women using CC treatment should be monitored by ultrasound and should not have treatment for more than six months.

Women who are known to be resistant to CC should consider one of the following second-line treatments, depending on clinical circumstances and the woman’s preference:

  • Laparoscopic ovarian drilling (by laser or by diathermy).[4]
  • Combined treatment with CC and metformin.
  • Gonadotrophins.

WHO Group III ovulation disorder
This is due to ovarian failure or hypergonadotrophic hypogonadism.

Women with ovulatory disorders due to hyperprolactinaemia should be offered treatment with dopamine agonists such as bromocriptine.

A number of other treatments may be appropriate in certain cases. These include:

  • Tubal and uterine surgery: for women with blockages or adhesions.
  • Medical or surgical treatment of endometriosis. See the separate Endometriosis article for more detail.
  • Ovarian hyperstimulation. Agents used are CC, anastrozole and letrozole. This is not advised in women with unexplained infertility.

Assisted conception broadly refers to procedures whereby treated or manipulated sperm are brought into proximity with oocytes. It includes:

  • Intrauterine insemination (IUI) with partner or donor sperm (in natural or stimulated cycles).
  • Gamete intrafallopian transfer (GIFT).
  • In vitro fertilisation and embryo transfer (IVF-ET, widely known as IVF).
  • Intracytoplasmic sperm injection (ICSI).

In certain cases donor sperm or eggs may be required for these procedures.

Success depends upon numerous factors, including the woman’s age, BMI, previous pregnancy history and lifestyle factors, as well as differences between clinic treatment populations, etc.

Intrauterine insemination (IUI)

IUI involves the introduction of prepared sperm into the uterine cavity around the time of ovulation (spontaneous or induced).

NICE guidelines advise that unstimulated IUI can be considered as a treatment option in the following groups:

  • People who are unable to, or would find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem, who are using partner or donor sperm.
  • People with conditions that require specific consideration in relation to methods of conception (for example, after sperm washing where the man is HIV-positive).
  • People in same-sex relationships.

People with unexplained infertility, mild endometriosis or ‘mild male factor infertility’, who are having regular unprotected sexual intercourse should no longer routinely be offered IUI, either with or without ovarian stimulation. They should be considered for IVF if they have not conceived after trying for two years.

Gamete intrafallopian transfer (GIFT)

NICE guidelines state there is insufficient evidence to recommend the use of GIFT or zygote intrafallopian transfer in preference to IVF in couples with unexplained fertility problems or male factor fertility problems.

In vitro fertilisation (IVF)

Around 25% of IVF treatments result in a live birth according to HFEA statistics. Around two thirds of women treated are aged 37 or under and only 2% are aged over 45. The chances of success reduce with increasing age of the woman. There is a trend of increasing demand for IVF in same-sex female couples. Ovarian stimulation is advised prior to IVF with ultrasound monitoring of the ovarian response. Progesterone is used after embryo transfer for luteal phase support.

Access criteria for IVF:

  • Women aged under 40 years should be offered three cycles.
  • Those women who reach 40 years during treatment should not be offered further cycles.
  • Women aged over 40 years should be offered one cycle of IVF as long as these women:
    • Have never had IVF in the past.
    • Have no evidence of low ovarian reserve.
    • Have had a discussion of the additional implications of IVF and pregnancy at this age.

When IVF is used and a top-quality blastocyst is available, a single embryo transfer is now recommended. This is to minimise the numbers and associated risks of a multiple pregnancy. HFEA has produced criteria for single/multiple embryo transfers and a strategy to reduce the numbers of multiple births. Reports show this has been effective, with numbers of multiple births declining.

Intracytoplasmic sperm injection (ICSI)

In ICSI, a single sperm is injected directly into an oocyte. It should be considered for those with severe deficits in semen quality, obstructive azoospermia or those with non-obstructive azoospermia. In addition, treatment by ICSI should be considered for couples in whom a previous IVF treatment cycle has resulted in failed or very poor fertilisation.

Where the indication for ICSI is a severe deficit of semen quality or non-obstructive azoospermia, the man’s karyotype should be established (after genetic counselling).

Donor insemination

Conditions where donor insemination may be considered include:

  • Azoospermia (obstructive or non-obstructive not amenable to treatment).
  • Severe deficits in semen quality in couples who do not wish to undergo ICSI.
  • Where there is a high risk of transmitting a genetic disorder to the offspring.
  • Where there is a high risk of transmitting infectious disease to the offspring or woman from the man.
  • Severe rhesus isoimmunisation.

Oocyte donation

Conditions where oocyte donation may sometimes be appropriate include:

  • Premature ovarian failure.
  • Gonadal dysgenesis (eg, Turner syndrome).
  • Bilateral oophorectomy.
  • Ovarian failure following chemotherapy or radiotherapy.
  • Some cases of IVF treatment failure.
  • Some cases where there is a high risk of transmitting a genetic disorder to the offspring.

Guidelines exist for the screening of sperm and egg (and embryo) donations.

Multiple pregnancy

Twins and multiple pregnancy are more common in some forms of infertility treatment including medication treatment – for example, with clomifene. This is because in some of the treatments using medication, the ovaries may be stimulated so that more than one egg is released and therefore more than one egg may be fertilised. Also, in some assisted conception treatments, more than one embryo is put back into the woman’s womb (uterus) and therefore more than one pregnancy can develop. This occurs less commonly now as latest guidelines advise that in most cases only one embryo is put into the womb.

Having twins or triplets may be a great thing for some couples. However, it should be explained that it does carry an increased risk of problems during a woman’s pregnancy, such as high blood pressure and diabetes. There is also a higher risk of other complications such as a having a small baby or going into premature labour.

Pregnancy in the Fallopian tube

A pregnancy which develops in the Fallopian tube (an ectopic pregnancy) MAY be a little more likely in women who are undergoing treatment for infertility. This is especially if the cause of infertility is due to a problem with the Fallopian tubes.

Stress

Going through investigations and treatment for infertility can be a very stressful thing and can put a strain on many relationships. It is important to discuss your feelings with your partner, doctor, nurse or counsellor.

Over-stimulation of the ovaries

There is a small risk that some of the medicines used to treat infertility, such as the gonadotrophin medicines, can over-stimulate the ovaries. This may lead to a condition known as ovarian hyperstimulation syndrome. In this condition, the ovaries can swell due to a number of cysts that develop on the ovaries. Symptoms can include tummy (abdominal) pain and swelling (distension), feeling sick (nausea) and being sick (vomiting). The condition can usually be treated easily and does not lead to any major problems. However, occasionally it can be more serious and can lead to liver, kidney and breathing problems or a blood clot in an artery or vein (a thrombosis).

Close monitoring using ultrasound scans is often used when women are given medicines to stimulate the production of eggs by the ovaries. The numbers and size of the sac containing an egg (the follicle) can be measured. This helps to reduce the risk of multiple pregnancy and also ovarian hyperstimulation.

Other side-effects

Some of the medicines used to treat infertility – for example, the gonadotrophins – may cause hot flushes and menopause-type symptoms.

Before deciding to go ahead with any treatment, you should have a discussion with your infertility expert on the pros and cons of the treatment proposed and the risk of problems and side-effects.