Infertility: Causes, Tests and Treatments

Infertility is the inability to conceive after 12 months of unprotected sexual intercourse. It is a distressing condition that affects 1 in 6 couples in Australia. Infertility has many possible causes and requires thorough evaluation to determine the most effective treatment.

How is infertility defined?

Making the diagnosis of infertility is based on the rationale that the chances of achieving a pregnancy are a function of time; the longer a couple tries, the more likely they are to eventually conceive, and intervening too early may lead to unnecessary, and expensive, investigations. On the other hand, there is a cut-off period after which the chances become slim even with further sexual exposure.

Around 50% of couples would be expected to conceive by 6 months and around 80% after 1 year. Since only a minority of couples would not have conceived after 12 months of trying, 12 months is chosen as the cut-off period for making the diagnosis of infertility.

In patients with obvious causes for infertility such as infrequent periods (indicating a problem with ovulation), it is not necessary to wait 12 months before undertaking infertility investigations or commencing treatment. A very important group for whom unnecessary delay could be disastrous is women above 36 years who are entering a phase of accelerated fertility decline. In these women it is justifiable to investigate after 6 months of trying.

What are the requirements for natural fertility?

To understand fertility requirements, it is first important to understand how pregnancy comes about. For pregnancy to occur, sperm and egg need to come together. This will only occur if an egg has been released and if sexual intercourse occurs around the time that the egg is released. The egg is released from the surface of the ovary at ovulation and is swept up by the “fingers” or fimbriae at the end of the Fallopian tube. The sperm needs to be of good enough quality to swim from the vagina, through the neck of the womb and all the way through the womb cavity and Fallopian tube to meet the egg which waits within the end portion of the tube. Since a single sperm (or spermatozoon) is only 0.005 cm long and the distance from the neck of the womb to the outer portion of the tube is around 18 cm, sperm would need to swim a distance equivalent to 3600 times their length to get to the egg! Although over 50-100 million sperm may be present in a single ejaculate, only around 1 out of every million sperm will reach the egg at the end of the tube.

Based on the foregoing, therefore, the three fundamental requirements for falling pregnant are:

  1. Regular ovulation
  2. Healthy Fallopian tubes
  3. Good quality sperm

What is the difference between fertility requirements and fertility potential?

The three basic elements – ovulation, tubes and sperm – outlined in the section above are required for falling pregnant naturally. However, the chance of being able to have a successful pregnancy (or fertility potential) is not guaranteed by merely having these three elements in place. Pregnancy success is also heavily dependent upon the egg being of very good quality. This is because egg quality is the rate-limiting factor for determining the potential of the early pregnancy (or embryo).

Why is female age such an important determinant of fertility potential?

Since no new eggs are produced after birth, a woman’s eggs age as she ages. Eggs therefore succumb to ageing effects along with other cells in the body. For eggs, these ageing effects occur surprisingly early, around the mid-thirties. Based on the critical importance of egg quality and its close relationship to age, the most important predictor of fertility potential is therefore female age.

In contrast to women, men retain a reservoir of sperm-producing cells (known as germline stem cells) in their testes allowing them to produce new sperm throughout their lifetime. As a result, and although age does affect sperm quality to some extent, the effects of ageing are far less severe for men than for women.

To put this in perspective, a 45-year-old patient who is ovulating, has healthy tubes and whose partner has normal sperm, has all the natural fertility requirements in place but has relatively low fertility potential due to low egg quality. In contrast, a 26-year-old patient with normal tubes and normal sperm but who is not ovulating, has limited natural fertility because of not releasing an egg. However, due to her young age, her fertility potential is high so that with appropriate treatment she has a very good chance of achieving a successful pregnancy.

Professor Homer is an internationally leading expert in egg quality and the effects of ageing. He has received millions of dollars in research funding from the NHMRC to study egg quality. Using this funding, his lab is actively researching novel treatments for reversing poor egg quality. Click here to read his recent paper on the effect of ageing on egg quality published in the world’s top reproduction journal.

What are the causes of infertility?

Since sperm and eggs need to come together in the tube for pregnancy to occur, infertility can be caused by any factor that affects egg release, sperm quality or tubal health.

Anovulation:
Anovulation refers to the failure to release an egg. Over 80% of cases are due to polycystic ovarian syndrome (PCOS). For more information see my sections on Anovulation and Ovulation Induction and PCOS.

Sperm problems:
Poor quality sperm contribute to 20-40% of cases of infertility. Sperm defects vary in severity from relatively mild to the most severe form in which, sperm production is completely absent. In the latter case, there will be no sperm in the ejaculate (known as azoospermia). For more information on sperm and the conditions that can affect sperm quality, see my Section on Male Infertility and Sperm.

Tubal problems:
The main causes of tubal damage are infection, previous pelvic surgery and endometriosis.

Pelvic inflammatory disease (PID) caused by “bugs” such as chlamydia and gonorrhoea lead to scarring and blockage of the Fallopian tubes. Even if the tubes remain open, their function could be severely compromised by infection. Some of the tell-tale signs of PID include pelvic pain, fever and an abnormal vaginal discharge. In some cases, infection may remain silent and only become discovered during a workup for infertility.

Surgery in the vicinity of the Fallopian tubes can also result in tubal scarring. The appendix often sits very close to the right Fallopian tube. Consequently, surgery for removing the appendix (appendicectomy) can result in tubal damage, especially if appendicitis led to a ruptured appendix. Another form of surgery that can affect the tubes is surgery for ovarian cysts.

Deposits of endometriosis in the vicinity of the Fallopian tubes may cause inflammation and scarring that envelops the tube. For more information see my section on Endometriosis.

Unexplained infertility:
In around 20-30% of couples, no abnormality is identified with ovulation, sperm or tubes. This is referred to as unexplained infertility. It is not a very accurate term and only means that standard tests for infertility (see below) have not identified any major abnormality. However, a cause for the couple’s infertility often emerges after the couple have embarked on fertility treatment. For instance, if IVF is undertaken, it may become apparent that there is a problem with the ability of the sperm to fertilise the egg. For more information, see my section on IVF/ICSI Treatment.

What are the tests for infertility?

Investigations aim to evaluate ovulation, tubes and sperm.

Tests for ovulation:
A number of tests have been proposed for determining whether ovulation is occurring. Some, such as basal body temperature charting and cervical mucus testing, are not very reliable and not routinely used any more.

One of the most common tests used is a blood test for measuring serum progesterone. The timing of this blood test needs to take into account the length of the woman’s menstrual cycle. Progesterone levels should be tested when they are expected to be at their highest, which is usually around 1 week before the start of the next menstrual bleed. This means that for a typical 28-day cycle, the blood test needs to be performed on Day 21 (hence the reason this test is often referred to as a Day 21 Progesterone). The timing of the test will be different for other cycle lengths. For instance, for a 32-day cycle, the appropriate time for the test is Day 25; doing the test on Day 21 will give a falsely low result. Other tests for ovulation include ultrasound monitoring and LH kits for testing urine. For more information, see my section on The Menstrual Cycle and Ovulation Tracking.

Sperm tests:
A man’s sperm is tested using a test called a semen analysis. Sperm tests are used to try to predict the ability of the sperm to fertilise the egg.

To do this test, a man needs to ejaculate into a sterile plastic pot and take the sample to an accredited andrology laboratory which will determine a number of different features of the sperm. Semen analyses evaluate sperm features in the sample against stringent criteria set by the World Health Organisation (WHO 2010).

For reliable results, it is critical that semen production is performed properly:

  1. The male should abstain from ejaculation for 2-7 days prior to the test
  2. All the sample should be collected into a wide-mouth sterile plastic container
  3. The sample must be delivered to the lab within 45-60 minutes of production

A number of parameters are analysed in the semen sample. The three key ones are:

  1. Sperm concentration which should be greater than 15 million sperm/millilitre
  2. Progressive sperm motility (or the proportion swimming fast in a straight line) which should be 32% or more
  3. The proportion of normally shaped sperm (or normal morphology) which should be 4% or more

Tests for tubal patency:
Tests for tubes aim to determine whether tubes are open (or patent). It is important to stress, however, that Fallopian tubes do not simply act as passive conduits for sperm, eggs and embryos. Tubes provide the proper mix of nutrients required for sperm, eggs and embryos. Tubes also possess very fine hair-like processes on their internal surface (known as cilia) that “walk” the embryo towards the womb cavity. Therefore, a test that shows tubes are open doesn’t necessarily mean those tubes are fully functional.

HSG: One commonly used test for evaluating tubal patency is a Hysterosalpingogram (HSG). This is an X-Ray test. It is performed without an anaesthetic and involves placing a tube into the neck of the womb and injecting radio-contrast dye through the tube into the womb cavity. A series of X-Ray images are then taken in order to track the flow of dye through the womb and tubes. If the dye is seen flowing through the entire length of both tubes and entering the pelvic cavity this means that the tubes are open. If the tubes are blocked, the dye may accumulate in the swollen ends of the Fallopian tubes; a blocked and swollen tube forms what is known as a hydrosalpinx. HSG’s can also identify fibroids and polyps, which show up “filling defects” in the womb cavity. For more information see my sections of Fibroids and Miscarriage and Recurrent Miscarriage (section on “Problems with the womb”).

HyCoSy: Another approach for investigating tubal patency is called HyCoSy (for Hysterosalpingo Contrast Sonography) and involves using ultrasound. Similar to HSG, HyCoSy involves placing a tube at the neck of the womb and injecting a liquid, which can be detected using ultrasound. The ultrasound examination can also provide other important information at the same time such as identify fibroids and polyps, determine whether the womb shape is normal and estimate ovarian reserve by counting antral follicles (see below).

Laparoscopy and dye: The third way to evaluate tubal patency is via a laparoscopy and dye test. This is the most invasive and expensive approach but is also the most reliable. It requires a general anaesthetic and involves keyhole surgery to visualise the Fallopian tubes directly. Blue-coloured dye (Methylene blue) is then instilled through the neck of the womb. Using the laparoscope, blue dye will be seen coming through the end of the tubes if they are patent. This is the only approach that directly looks at the tubes and allows their condition to be carefully inspected. It also allows for any co-existing conditions like endometriosis or scarring from prior infection to be treated at the same time, and allows surgery to be performed to unblock tubes. It also allows very badly damaged and swollen tubes (hydrosalpinges) to be removed prior to embarking on IVF treatment. This is important since hydrosalpinges markedly reduce IVF success rates by around one half.

Estimating egg numbers:
Sometimes, as part of the infertility workup, a test for estimating how many eggs are left (also known as the ovarian reserve) is performed. The most commonly used one nowadays is a blood test known as Anti-Müllerian Hormone or AMH. Ovarian reserve can also be estimated using ultrasound scanning to count the numbers of small antral follicles. For more information on AMH and ovarian reserve, see my section on AMH, Ovarian Reserve and the Egg-Timer test.

What are the treatments for infertility?

For choosing the correct treatment option, careful consideration must be given to the totality of test results, information obtained from a detailed history and female age.

Ovulation induction:
For cases in which an egg is not being release, ovulation induction is appropriate, provided the tubes are open and the sperm is normal. For more information, see my section on Anovulation and Ovulation Induction.

Artificial insemination:
For mild sperm problems when tubes are patent, artificial insemination may be pursued. It is often combined with ovarian stimulation to produce more than one egg. For more information, see my section on Artificial Insemination.

IVF and ICSI:
In cases of tubal damage resulting in blocked tubes, IVF can be used to bypass the tubes. In fact, the first successful IVF treatment that led to the birth of Louise Brown was performed because of tubal damage.
IVF in combination with ICSI is ideal for cases of severe sperm problems or when sperm has to be surgically removed from the testes.
IVF is also the last line of treatment when other treatments such as artificial insemination have been successful.
For more information, see my section on IVF/ICSI Treatment.

Donor eggs:
In cases of very poor egg quality, or if a woman has no eggs (e.g. because of premature menopause), eggs donated from another woman can be used. Obtaining these eggs will require an IVF-type treatment cycle for stimulating the ovaries and retrieving eggs from the donor. For more information, see my section on Donor Treatment.

Donor sperm:
Donor sperm may be used when the male partner has either no or very poor sperm, for treating single women and female same-sex couples. The two treatment options with donor sperm are Artificial Insemination or IVF/ICSI. For more information, see my sections on Donor Treatment, Artificial Insemination and IVF/ICSI Treatment.

Who should I see to evaluate my fertility?

A doctor’s credentials provide guidance on whether that doctor has undertaken additional training to become an expert in infertility management. In Australia, these credentials are known as CREI, which stands for Certificate in Reproductive Endocrinology and Infertility. CREI is conferred by the Royal Australian and New Zealand College of Obstetricians & Gynaecologists (RANZCOG) and is proof that a doctor has undergone an extensive period (3 years and more) of sub-specialty training in IVF and all other aspects related to infertility management.

Prof Homer is one of only four CREI-accredited sub-specialists in Queensland. He is the only one who has also received REI sub-specialty accreditation from the UK’s Royal College of Obstetricians & Gynaecologists (CCSST). Hayden also has a PhD in fertility research into egg quality. He continues to undertake extensive research and directs Queensland’s first and only research lab dedicated to studying egg quality and developing new fertility treatments. Prof Homer therefore has a unique breadth of knowledge, experience and expertise required for thoroughly evaluating your fertility and for designing highly individualised and personalised management plans.