Infertility

• What is Infertility?
• Statistics
• Risk Factors
• Progression
• Symptoms
• Clinical Examination
• How is it Diagnosed
• Treatment
• References

What is Infertility?

Infertility is a condition in which a couple are unable to conceive, after frequent sexual intercourse, for 12 months or more. It is sometimes also known as infecundity, as fertility tends to imply the number of offspring one has produced (e.g. the total fertility rate for a country refers to the average number of babies born per woman), whereas fecundity implies the physiological ability to produce offspring.

Infertility can be primary (occurring in couples who have not previously had a child) or secondary (occurring in couples who have conceived in the past) and can stem from factors related to the male partner, the female partner, or both. It should be distinguished from sterility, which is an individual’s complete inability to conceive).

Infertility is a significant public health problem with emotional, financial and demographic consequences. Finding out one is infertile is often tragic for a couple who wish to conceive, and accessing treatment to enhance fertility can be an expensive, stressful and sometimes futile endeavour.

At a population level, infertility can have a significant impact on total fertility rates. Decisions regarding the provision of fertility treatments therefore have national implications. In developed countries, treatment for infertility is usually regulated and included in medical benefits schemes (e.g. in Australia, couples using assisted reproductive technology (ART) are eligible for a Medicare rebate).

Statistics

The incidence of infertility varies around the world. Overall, some 84% of couples are estimated to conceive naturally within a year of attempting pregnancy, when having frequent sexual intercourse. Some 92% of all couples conceive naturally within a two year period. The remaining 8% are considered infertile.

In Australia, the results of the 2006 National Fertility Survey showed that, across all age groups, 1 in 6 couples fail to achieve pregnancy after a year of trying. The likelihood of being infertile varies depending on a range of factors, such as the age of the partners trying to conceive.

Women

The incidence of infertility in women varies primarily by age. As the proportion of Australian women having their first child before 30 years of age has decreased dramatically in recent years (from 92% in 1976 to 27% in 2006), the number of women experiencing difficulty conceiving has increased. Estimates from England suggest that 94% of women aged 35 will conceive naturally after three years of trying. Just 77% of those aged 38 will do so, and the proportion who conceive naturally declines rapidly in women 39 years or older.

Men

Approximately 1 in 20 Australian men are affected by infertility. Male infertility accounts for about half of all infertility problems, and some 40% of infertility treatments provided in Australia are targeted at male factors. Significant declines in male fertility (and concurrent increases in testicular cancer) have been reported in a number of countries in the past several decades, and are thought to be a result of changing environmental conditions.

While no decline in fertility amongst Australian men has occurred, the rate of testicular cancer is increasing, suggesting that environmental factors with the potential to threaten male fertility may be present.

Male fertility also decreases with age. A man aged 35 years has only half the chance of conceiving compared to a 25-year-old man. Once men reach 55 years, their fertility declines dramatically and there is a significantly increased risk of conceiving a child with congenital abnormalities.

Risk Factors

There are a range of factors which predispose individuals and couples to infertility.

Predisposing factors in both men and women

Age

In both men and women, the risk of infertility increases naturally with age. Declining fertility commences at a younger age in women than in men. Women are born with a finite number of eggs and do not produce any new eggs throughout their lifetime. As a woman ages, so do her eggs. The total number of available eggs gradually reduces as they are lost through ovulation, and the quality of remaining eggs diminishes (i.e. the remaining eggs are less likely to be fertilised and are more likely to result in infants with genetic abnormalities if they do become fertilised). Men constantly produce sperm throughout their lives. The quality and quantity of sperm decreases with age, reducing the chance of conception.

History of cancer treatment

Both chemotherapy and radiotherapy commonly lead to irreversible infertility. For that reason, some people choose to cryopreserve sperm or eggs for future use before undergoing cancer treatment. In men, chemotherapy and radiology damage the production of sperm, resulting in sperm with less ability to move and and fertilise an egg. In women, chemotherapy and radiotherapy commonly cause immediate sterilisation or early menopause.

History of sexually transmitted and other pelvic infections

Sexually transmitted infections (particularly chlamydia) are often associated with infection, inflammation and scarring. In women, this can lead to scarring and abnormalities in the fallopian tubes, a higher risk of endometriosis, and other conditions which increase the risk of infertility. Men may develop partial obstruction of the testicular tubes or tubal infections which will affect fertility.

Obesity

Fertility gradually declines as weight increases above normal levels (i.e. BMI > 30). In males, this is believed to be related to the increased levels of oestrogen and reduced levels of testosterone associated with male obesity. Imbalances in these hormones affect male reproductive function, including sperm production. In women, obesity is also commonly associated with hormonal imbalance (i.e. increased testosterone), anovulation and PCOS.

Exposure to pesticides

Men and women who are exposed to pesticides on a daily or weekly basis have a higher risk of lower fertility than non-exposed men and women.

Couples who have sex infrequently

Couples who are busy with work and other activities, or separated for periods of time, are less likely to conceive.

Predisposing factors in women

Endometriosis

Endometriosis is a condition characterised by the growth of endometrial tissues outside the uterus (most commonly in the pelvic region). Surrounding tissues become inflamed, which reduces the chance of an embryo implanting in the fallopian tubes.

Fibroids

Women with uterine fibroids are more likely to be infertile than women without uterine fibroids. Surgically removing the fibroids increases natural conception rates and success in IVF treatment.

Polycystic ovarian syndrome (PCOS)

PCOS is a condition characterised by the growth of ovarian cysts. It commonly leads to anovulation and infertility.

Smoking

Women who smoke are almost twice as likely to be infertile as women who do not smoke.

Predisposing factors in men

Father with Y chromosome abnormality

Men who were conceived using assisted reproduction techniques because their fathers had abnormal Y chromosomes (e.g. deletions) inherit this condition (i.e. male babies inherit the genetic make up of the father’s Y chromosome). Female babies do not inherit paternal Y chromosomes, so it is common to select only female embryos from IVF for implantation in cases where the male partner has Y chromosome abnormalities.

Cryptorchidism

Cryptorchidism (the failure of the testes to descend into the scrotum) affects around 3% of males at birth and 1% at one year of age (after which spontaneous descent is unlikely and surgical correction is recommended). It leads to a change in testicular tissues and is associated with an increased risk of infertility.

Heat exposure

Testicular function is dependent on temperature. Exposure to high temperatures can lead to abnormalities in sperm.

Alcohol

Excessive alcohol intake (e.g. from binge drinking) reduces sperm quality.

Drugs

Some drugs reduce sperm quality, including anabolic steroids used by athletes; recreational drugs including marijuana, nicotine, heroin and cocaine; and antidepressants.

Symptoms

Many couples who find themselves infertile after 12 months of trying to conceive will go on to conceive naturally. About half of the 16% of couples who fail to conceive after one year, conceive within the next two years. For the remaining 8% of couples who fail to conceive naturally within three years, there is a good chance of conception using ART. Some two-thirds of all couples using IVF – the most common ART treatment for infertility – successfully conceive within six treatment cycles.

Fertility naturally declines with age. Despite scientific advances in ART, the chance of successful outcome (either through natural or assisted techniques) declines with age, particularly in relation to the age of the female partner. After age 35, female fertility declines significantly, and the likelihood of conception is very slim in women over 40 years.

Clinical Examination

Couples who present to a doctor with infertility problems are likely to undergo a full physical examination, including an assessment of their BMI.

Women

Women should expect to have their pelvis examined, as the doctor will need to assess whether or not there are any pelvic infections or inflammation which may be causing the couple’s infertility.

Men

Men should expect the doctor to inspect their testicles using an orchidometer. A doctor is also likely to inspect the penis and scrotum for any abnormalities or signs of infection.

How is it Diagnosed

Infertility will be diagnosed if the couple has failed to conceive after 12 months of frequent unprotected sex. It is also necessary to diagnose the underlying causes of infertility.

In the initial phase of assessment, couples will usually be asked a range of questions about their sexual and reproductive activity (past and present), their history of sexually transmitted and/or other reproductive tract infections, and their relationship problems and lifestyle habits (especially alcohol, tobacco and recreational drug use).

Women will be asked about the regularity of their menstrual cycles. Men will be asked whether they ever have difficulty maintaining an erection or ejaculating. A doctor is also likely to perform a physical examination of both partners, including an assessment of their BMI, physical examination of the genital area, and assessment of abnormal hair growth (which indicates hormonal imbalance).

Diagnosis in women

There are a number of tests which are performed to assess the causes underlying infertility in women:

• Assessment of ovulation: A blood test to measure progesterone levels can be performed on day 21 of a 28 day menstrual cycle, or day 28 of a 35 day cycle. Women with irregular cycles may also be offered a blood test for gonadotrophins, high levels of which suggest reduced fertility;
• Testosterone levels are assessed in women with symptoms of PCOS. These symptoms usually indicate high levels of testosterone;
• Screening: For chlamydia, cervical cancer and other pelvic infections;
• Assessing tubal damage: Signs of damage are particularly common in women with a history of pelvic infection. Where the woman’s pelvis shows no signs of infection or inflammation, x-rays are usually used. In women with known or suspected comorbidities (e.g. endometriosis, PID) laparoscopy is usually used.
• Ovarian reserve testing: Measures the quality and quantity of oocytes in a woman’s ovary and the potential for achieving pregnancy based on that;
• Rubella immunity should be confirmed, as rubella can seriously damage a developing foetus.

Diagnosis in men

There are a range of conditions that can cause male infertility. Determining the specific nature of each person’s condition is important in deciding on the most appropriate treatment strategy. In some 60% of men, there is no identifiable cause of reduced sperm count or quality. Common tests which are performed to diagnose the cause of male infertility include:

• Semen analysis test: Assesses the quantity and quality of a male’s sperm.
• Assessment of tubal patency: A doctor will locate the male reproductive tubes in the scrotum and feel for abnormalities which may be causing infertility (e.g. cysts or inflammation of the tubes). The doctor will assess the penis for any signs of disease or infection.
• Testicular size and volume: Usually assessed using an orchidometer.

Treatment

There are three types of treatment available for infertility, as well as numerous lifestyle modifications which can be made by couples who wish to continue to try and conceive naturally. The most suitable type of treatment will depend on the factors underlying the couple’s infertility. Whatever the underlying factors, couples should be treated together, and are entitled to accurate and objective information to let them make an informed decision regarding their fertility treatment options. In addition, all couples should be offered counselling and psychosocial support or psychoeducation before, during and after infertility treatment.

As first line treatment, there are a range of lifestyle changes which couples should make to increase their chance of conception. Surgical treatment may be provided for specific conditions, and surgical procedures can also be used to retrieve eggs or sperm for IVF or cryopreservation. Pharmacological treatments can be used in conjunction with normal, frequent intercourse or assisted reproductive technologies (ARTs). ART may be started after pharmacological treatment alone fails, or where the conditions underlying infertility indicate its necessity.

Lifestyle treatments

Many couples who fail to conceive after 12 or 24 months will conceive naturally after a longer period of time. When diagnostic tests do not identify any reproductive abnormalities which may be causing infertility, continuing attempts to conceive naturally are just as likely to result in conception as pharmacological treatment and intrauterine insemination.

There are a number of lifestyle factors which influence fertility:

• Frequency of coitus: Couples attempting to conceive should have sex every 2–3 days to maximise the chance of conception;
• Alcohol consumption: Men should not become intoxicated, as this will reduce sperm quality. Women should also avoid intoxication and limit alcohol consumption to once or twice per week (zero alcohol is ideal);
• Body mass index: Women with a BMI > 29 will take longer than average to conceive and should attempt to lose weight. Women with a BMI < 19 should gain weight to increase the chance of conception. Men with a BMI of > 29 are less fertile;
• Underwear: Men should not wear tight underwear as this increases heat to the testicles and can inhibit sperm production;
• Hot baths: Men should not take hot baths as this increases heat to the testicles and can inhibit sperm production;
• Smoking: Cigarette smoking should be avoided by both men and women trying to conceive;
• Regular exercise: 20–30 minutes of exercise per day will help maintain normal BMI and fertility;
• Folic acid supplements: Taken by women.

Surgical treatment

Surgical treatments for women

The following surgical procedures are recommended for the following infertility-related conditions:

• Laparoscopic ablation and drainage: Treats endometriosis. Deposits of endometrial tissue are drained and removed from a woman’s reproductive organs. Laparoscopic drainage and ablation increases fertility in women with endometriosis;
• Tubal surgery: To reverse prior tubal sterilisation or repair damaged tubes (e.g. resulting from PID). Tubal surgery can also be used to repair tubal obstructions;
• Ovarian drilling: Second line treatment for women with PCOS who fail to respond to clomiphene citrate. Ovarian drilling also increases pregnancy rates in women with PCOS and may be used as an alternative to clomiphene citrate to avoid the risk of multiple pregnancy, but is less effective;
• Surgical oocyte retreival: To retrieve eggs from a woman’s ovaries for use in ART treatments.

Surgical treatments for men

The following surgical treatments for the following male infertility factors have been demonstrated to be effective:

• Surgical correction of epididymal blockage: To restore damage to one of the tubes connecting the testicles to the urethral opening. It can be used as an alternative to surgical sperm removal and IVF;
• Testicular biopsy: The testicle is cut open to retrieve sperm directly from a man’s testicles, where men are unable to ejaculate or have no motile sperm in their ejaculate.

Pharmacological treatment

Pharmacological treatments for women

Pharmacological treatment is indicated in women with the following conditions:

• Hypothalamic pituitary dysfunctions (WHO Group II ovarian disorders) including polycystic ovarian disorder:
  Clomiphene citrate or tamoxifen is the usual first line treatment and can be prescribed for up to twelve months in order to induce ovulation. Clomiphene citrate increases the risk of multiple pregnancy (around 11% of pregnancies following clomiphene citrate treatment are multiple). Women who do not respond to this therapy may be offered gonadotrophin therapy;
• Polycystic ovarian syndrome and overweight or obesity:
  Women who are overweight or obese, are not experiencing menstrual cycles and have polycystic ovaries may be offered combined metformin (an insulin sensitising agent) treatment if first line treatment with clomiphene citrate fails. This drug has numerous side effects including nausea, vomiting and gastrointestinal disorders, and may be no more effective than treatment with clomiphene citrate alone.

Pharmacological treatments for men

The following pharmacological treatments for the following male infertility factors have been demonstrated to be effective:

• Hypogonadotrophic hypogonadism (abnormally small testicles resulting from hormone imbalance): Gonadotrophin drugs;
• Erectile dysfunction: PDE5 inhibitors;
• Deficiency of pituitary gonadotrophins (i.e. hormones secreted by the pituitary): A rare condition (affecting some 1% of infertile men) generally responsive to gonadotrophin therapy.

Assisted reproductive technology (ART)

Assisted reproduction refers to all procedures other than sexual intercourse which are performed with the aim of conception. There are a range of ARTs for the treatment of infertility, varying considerably in terms of complexity, cost and invasiveness.

The most appropriate treatment is determined by the factors affecting fertility, the couple’s cultural beliefs, personal preferences and financial circumstances.

ART can be a lengthy, costly and emotionally draining process that does not always result in conception or live birth. This should not discourage couples seeking treatment, but they should have realistic expectations regarding their likely treatment outcomes. At a minimum, all couples will be informed of:

• The likelihood of achieving pregnancy and live birth through natural conception and ART;
• The risks involved in ART, including long and short term risks for the conceiving couple and best available information regarding the risk of health problems in the individuals born through ART;
• The options for gamete retrieval and storage;
• The cost of various procedures;
• How confidentiality and privacy will be ensured and the potential need for future follow up.

ARTs for women

• Induced ovulation and hyperovarian stimulation
  Induced ovulation is the pharmacological stimulation of the ovaries. It can be used to induce a normal menstrual cycle (i.e. the release of a single mature oocyte) or to induce hyperovulation (the release of multiple mature oocytes in one cycle) with a view to oocyte retrieval. Such pharmacological treatment can also be provided independently of ART (e.g. induction of normal ovulation can be combined with frequent sexual intercourse). As part of ART, it is used either in conjunction with oocyte retrieval or timed intrauterine insemination.
• Oocyte retreival
  Oocyte retreival is the practice of retrieving mature oocytes from a woman’s ovaries and is generally performed following induced hyperovulation. Oocytes are usually retrieved for IVF and other ART techniques (e.g. gamete intrafallopian transfer). In some cases (e.g. before sterilising chemotherapy) oocytes may be collected for cryopreservation (freezing) with a view to future use. Oocytes collected in one treatment cycle are also commonly cryopreserved for use in future treatment cycles, either fresh, or as embryos following IVF.
• In vitro fertilisation and embryo transfer
  In vitro fertilisation refers to the process of fertilising a human embryo in a test tube (the resulting babies are known colloquially as test tube babies). The gametes are first removed from the potential parents, then combined to achieve fertilisation. The resulting human embryo is grown in a culture of uterine tissue for about five days before being transferred into the woman’s fallopian tubes. If the treatment is successful, the transferred embryo will implant into the endometrial lining and develop to a full term pregnancy.
• Donor IVF
  Donor IVF refers to IVF which is performed using donor oocytes, sperm or both. The medical procedure is the same, except that donors undergo oocyte or sperm retrieval rather than the couple intending to be the social parents. The process begins with finding suitable gamete donor/s, who may be relatives, friends or strangers.There are many moral, legal and ethical questions surrounding donor IVF which must be considered. Counselling for both the donors and recipients, to encourage full consideration of the potential psychological and social implications of donor IVF, is mandatory before the procedure can begin. Success rates are high, but donor IVF has not yet achieved the efficacy of IVF using the carrier’s gametes.
• Gestational surrogacy IVF
  Gestational surrogacy occurs when one women (known as the surrogate mother) acts as a surrogate mother for the period of gestation (i.e. she carries and bears a child) for another woman who is unable to carry and bear her own child. This treatment is highly restricted in Australia due to the many, often controversial issues that it raises with regard to the rights of surrogate mothers, the wellbeing of the individual conceived and the potential for confusion regarding parentage.

ARTs for men

• Sperm retrieval
  Sperm retrieval is the process of removing sperm from a man’s testicles for use in ARTs. For most men, sperm can be retrieved simply, through masturbation. For men with tubal blockage, there are now surgical and electro-stimulation techniques which enable sperm to be retrieved.
• Intrauterine insemination
  Intrauterine insemination (IUI) is the process of injecting retrieved sperm into a woman’s uterus. It can be used in conjunction with ovarian hyperstimulation or with natural ovarian cycles. The injection process is painless and takes less than half an hour, after which normal activities can be resumed.
• Intracytoplasmic sperm injection
  Intracytoplasmic sperm injection is a procedure through which a single sperm is injected directly into an ovum to induce fertilisation. It is used to overcome male infertility which prevent otherwise viable sperm from penetrating the zona-pellucida of the ovum. It is the most common IVF procedure for overcoming male infertility, and is carried out under a microscope.
• Donor insemination
  Donor insemination refers to intrauterine insemination performed using donor sperm. The procedure is exactly the same, except that sperm is collected from a donor, rather than the male partner of the couple trying to conceive.

Preimplantation genetic testing

Preimplantation genetic testing is the process of testing an embryo created in vitro for genetic traits which may lead to serious health conditions in the individuals born through IVF. Such tests are performed with a view to selecting embryos for implantation which appear healthy and do not contain DNA predisposing to serious health conditions (e.g. Y chromosome deletions). Preimplantation genetic tests are commonly performed on embryos created in vitro, particularly for couples over 35 years of age. The issue of preimplantation testing is controversial and there are numerous perspectives, legal and ethical considerations surrounding the use of these tests and the process of selecting embryos for implantation.

Counselling and psychoeducation in conjunction with infertility treatments

Infertility in a couple can be stressful and cause problems in the relationship and the individuals. The process of being treated and awaiting the results of treatment can also be extremely draining. Treatment is often drawn out, time consuming and costly. Treatment failure can result in grief, anger and depression. Counselling and psychoeducation is therefore recommended for couples who appear distressed about their infertility, or who wish to further discuss their treatment options. For couples who decide to use ART in Australia, counselling is mandatory before starting treatment.

Counselling should be considered by couples at all stages of ART treatment. Even if a couple are not considering using ART, counselling or psychoeducation may help them cope with emotional or relationship problems associated with their infertility. Counselling will:

• Emphasise the failure rate of treatment and encourage couples to consider other options should their treatment fail (e.g. ART if pharmacological treatment fails, adoption if ART fails);
• For men, reinforce the difference between infertility and virility to attempt to overcome male perceptions that their masculinity is threatened;
• Make couples aware of support groups which exist in all Australian states and territories.

More information

For more information on infertility, including investigations and treatments, as well as some useful animations, see Infertility.

References

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