Current tests
Anamnesis (medical history)	at consultation
Physical examination, e.g. gynaecological	at consultation
Hormonal profiling	blood test | in lab
Ultrasound scan lower abdomen	consultation | outpatient
Tests based on specific indications
Biopsy of the endometrium	consultation | OT
Genetic testing	blood test | in lab
Immunological blood test	blood test | in lab
Hysterosalpingogram	radiology | outpatient
HyFoSy (hysterosalpingo foam sonography)	consultation | outpatient
Diagnostic hysteroscopy (camera into uterine cavity)	image| outpatient
Diagnostic laparoscopy (camera into abdominal cavity)	image | day admission

Defects in the normal fertility status of a woman can be caused by the following:

• ripening and ovulation problems (hormonal imbalance);
• problems with transport of eggs, for example due to endometriosis or infections;
• disturbances in the (biochemical) interaction with the sperm, for instance due to the presence of antibodies, endometriosis, high level of acidity in vagina, etc.;
• problems with embryo implantation, e.g. due to uterine abnormalities.

Preliminary blood test

A preliminary blood test is taken before any ART treatment. This also applies to men.
This allows:

• a detailed hormone balance picture to be determined (hormonal information);
• the number and the structure of the chromosomes to be checked (genetic information); and
• antibodies (infection test) against hepatitis, syphilis, the HIV virus (AIDS) and sperm to be detected.

Women are also screened for Rubella, Toxoplasmosis and CMV. They can cause serious damage to the foetus during early pregnancy.

For specific examinations: see hormonal, genetic or immunological analysis.

During your first consultation appointment at the CRG you will talk to a gynaecologist who is specialised in fertility medicine. The consultation consists of

• an anamnesis, and  
• possibly a physical and gynaecological examination

Preparation for the consultation 

To efficiently facilitate your first consultation at the CRG, you will be asked 

• to complete a detailed questionnaire beforehand (download here); and
• if you have ever had previous related treatment, bring your medical file, and particularly
• any results of already performed tests and earlier attempts at assisted fertilisation.

If you prefer not to do this yourself you can also ask the CRG doctor to request your medical file.

Medical history    

The doctor attempts to gather as much relevant information as possible regarding your medical history, current physical condition and health status.
Many of the questions the doctor will ask you will be of an intimate nature. They are all aimed at identifying the reasons why you and your partner are having difficulties in conceiving.

Below are a few examples of questions you can expect:

• your age;
• whether either of you have a child from a previous relationship;
• how long you and your partner have been trying for a baby;
• whether you have regular penetrative sex with ejaculation;
• how frequently you have intercourse; at which stage of your cycle;
• whether you experience any problems whilst having sex;
• which sorts of contraception you have ever used and your experiences with them;
• whether you have ever had surgery;
• dietary habits, alcohol use and other lifestyle issues. Smoking for example is a major cause of reduced fertility;
• your family's medical history. This is to detect any possible hereditary conditions.

Questions specifically aimed at women will be associated with:

• jyour menstrual cycle: duration and regularity, plus any changes which may have occurred over the years, etc.
• your periods. how many days they last, the extent of blood loss, whether or not they are painful and if so: bad or light pain, where the pain is situated, etc.

Painful periods do not always indicate a problem: Light pain in the pelvic floor (often coupled with breast pain and mood swings) usually indicates that ovulation is taking place.
The same goes for pain in the lower abdomen in the middle of your cycle (moment of ovulation) or during the period itself.

• the form of contraception you use, for how long and which symptoms may be associated with it..
• In the case of a coil, the doctor will check during your gynaecological examination if it has been effectively removed;
• whether you have had any abdominal surgery, including D&Cs.
  Any operation within the abdomen or uterus can cause adhesions, a D&C can cause adhesions in the uterus.

Physical examination, including gynaecological      

Further to your consultation, a physical examination will also be performed, unless this has already been performed by the doctor who referred you (GP or gynaecologist).

• EA physical examination consist of: weight, blood pressure, breast examination, etc.
• The gynaecological examination will include
  • an examination of the uterus to determine position, volume shape, consistency and mobility;
  • sometimes a mucous sample is taken from the cervix to test against infection or antibodies;;
  • in preparation of fertility treatment usually a cervical smear or 'pap test' is taken to detect the early stages of cervical cancer;
  • iin certain cases, the length of the cervix will be measured by means of a fine tube, in anticipation of future inseminations or embryo transfers.

And finally, sometimes we need images for a clearer picture of the reproductive organs.
Under Imaging investigations we provide more information about ultrasound, hysterosalpingogram, hysterosalpingo-foam sonography (HyFoSy), therapeutic hysteroscopy and laparoscopy.

Indications
The ultrasound
Hysterosalpingography
Hysterosalpingo-foam sonography (HyFoSy)
Diagnostic hysteroscopy
Diagnostic laparoscopy

For the hysteroscopy and the laparoscopy we make a distinction between:

• the diagnostic variation (the imaging technique is only to diagnose); and
• the therapeutic variation: an operation immediately follows the operation.

Therapeutic hysteroscopy and laparoscopy are discussed under gynaecological procedures.

Indications     

Endoscopic methods can be used to identify abnormalities. They are used:

• if a woman fails to get pregnant after several ART treatments
• or if there are specific indications, e.g. heavy, painful periods.

An internal examination can be useful in identifying the problems. They may include:

• endometriosis, the migration of uterine mucous membrane to a place where it does not belong;
• enlarged ovaries. Under normal circumstances, the ovaries are not visible. If they are, it can be an indication of fluid build-up or some form of ovarian cyst.
• ectopic pregnancy. Occasionally, a fertilised egg implants itself in a fallopian tube instead of in the uterus and begins to grow there;
• a single or double horned uterus: sometimes a fallopian tube is attached to a horn, sometimes both are;
• abnormalities in the uterus: fibroids, myomas, polyps and septum formation. Large septums can cause a double chamber within the uterus.

Strictly speaking, these abnormalities do not interfere with fertilisation, but they do hinder or prevent implantation of the embryo and can cause miscarriage.

The ultrasound      

An ultrasound (or echo) is a painless procedure whereby ultra-high frequency sound waves are bounced off internal organs, producing an image of them on the screen.
To perform an ultrasound of the pelvic region, a small vaginal probe is inserted. The image is produced on a screen and the patient can follow the procedure as well.
Vaginal ultrasounds form the basic examination of fertility treatment of the woman:

• As a routine examination at the start of every ART treatment to detect any gynaecological problems;
• to monitor the development of follicles in the ovaries, and
• to determine the moment of ovulation.

Hysterosalpingography      

A hysterosalpingography uses a radiography to visualise the trajectory of the eggs from the ovary through the fallopian tube to the uterus. This is done by injecting a contrast medium through the cervical canal, which passes through the cavity and fallopian tubes.
An X-ray is used to record the contrast medium's route.

We no longer perform this examination at the CRG. It is replaced by the HyFoSy (see below). This is a more patient-friendly exam that provides the same information and doesn't involve radiation.

Hysterosalpingo foam sonography (HyFoSy)      

A HyFoSy echographically depicts the trajectory of eggs from the ovary through the fallopian tube ('salpingo') to the uterus ('hystero'). For this we inject a solution of microscopically small bubbles through the cervical canal: hence the 'foam'.

A HyFoSy is a rather stressless examination. It takes place ambulatory and without anaesthesia, in the CRG consultation.

• For this examination it is best to have an empty bladder.
• First we perform a routine vaginal ultrasound.
• Then the doctor carries out a gynaecological examination.
• After this is done, we insert a fine catheter into the uterus via the cervix and inject a solution of microscopic bubbles through it.
• Via a transvaginal ultrasound, we follow the route of the mixture on the screen. If the fallopian tubes are easily accessible, the product passes from the uterine cavity through the fallopian tubes to the abdominal cavity.

With a normal result, the HyFoSy may suffice. As soon as abnormalities can be seen or if there is a suspicion of problems in the abdominal cavity – on the outside of the reproductive organs – a hysteroscopy or laparoscopy is needed to map the problem. Sometimes both examinations are appropriate.

Diagnostic hysteroscopy      

A hysteroscopy enables a clear picture of the inside and the shape of the uterus to be visualised.

• An endoscope – a sort of fine telescope – is inserted through the vagina and cervix.
• Te uterus is first dilated with physiological serum to obtain a good view. You can follow what the endoscope registers on the computer screen.
• It is a simple procedure which only takes about 15 minutes. It is performed without anaesthetic.
• It is performed during the first half of the menstrual cycle, after menstruation and before ovulation.

Diagnostic laparoscopy        

A laparoscopy allows us to visualise the inside of the abdominal cavity, and therefore the outside of the uterus and ovaries. This allows us to check for endometriosis in the abdominal cavity or adhesions in the Fallopian tubes.

• Through an incision in the navel, an endoscope – a kind of telescope, less than a centimetre in diameter – is inserted partly into the abdominal cavity.
• Gas is then used to inflate the cavity, between the front abdominal wall and intestines, so that the organs are well visible and accessible.
• A diagnostic laparoscopy is usually combined with a diagnostic hysteroscopy: two procedures in one you could say, which visualise both the inside and outside of the uterus.

Hormonale stoornissen kunnen zich voordoen:

• in the brains:
  in this case the hormonal problem will automatically result in menstrual dysfunction, affecting the egg ripening process and ovulation;
• in the reproductive organs, the adrenal or the thyroid gland:

In this case problems can occur with embryo implantation.

Therefore, a hormonal screening test will be performed as standard during your first consultation at the CRG, assuming that one has not been performed elsewhere recently.

Every hormone test is a blood test for which a blood sample must be obtained (see practical).
On the other hand, not every blood test is for the analysis of hormones. Sometimes a blood sample is used for immunological or genetic tests.

Hormonal profiling

This basic test is scheduled

• at the beginning of the menstrual cycle, between days 2 and 4
• to measure the level of FSH, LH and oestradiol, in other words, the different hormones important for egg ripening or which are secreted here (oestradiol is an oestrogen produced by the ovaries);
• to determine the hormonal values of progesterone, testosterone, androsterone, etc.

The latter two are better known as male hormones, but they are also present in the woman and are produced by the ovaries and adrenal glands respectively.

Adrenal gland hormones
Hormone production in the adrenal glands can cause fertility problems. More specifically, excess male hormones lead to problems with egg ripening. That is why the blood analysis determines the levels of DHEA-sulphate, testosterone, and andosterone.

Stress hormone
Levels of prolactine are also screened, because it is known this 'stress hormone' can cause fertility problems. Levels in the body are determined by external circumstances: sudden change in weight, erratic or irregular lifestyle, stress, etc. Levels increase after eating, which is why you are required to fast for this blood test.
If prolactine levels are too high it is necessary to find out why.
Apart from the reasons already mentioned, a small tumour (a prolactinoma) in the hypophysis can sometimes be responsible for excess levels. Treatment with medication is recommended in this case.

Thyroid gland hormones
Hormonal imbalances in the thyroid gland can also cause fertility problems. Not only does it decrease the chances of pregnancy you also run more risk of miscarriage. A routine blood test also measures the Thyroid T4 levels, a hormone produced by the thyroid gland.

• Basic genetics
• Indications
• Types of tests
  • Cytogenetic tests
  • DNA screening  

A blood sample is required for genetic screening.
A blood sample is taken in the Outpatient Clinic (see practical) and sent for analysis to the Centre for Medical Genetics (CMG) in UZ Brussel. The CMG provides us with the results, which we then share with our patients at the consultation

Basic genetics      

Important to know: our reproductive cells behave differently to other cells in the body. The latter are created by normal cell division or 'mitosis', whereas reproductive cells undergo a complex reduction process during which they retain half of the chromosomes from other body cells. During this process certain divisional abnormalities can only be detected in the reproductive cells.
The human body is made up of many different kinds of tissue, which together form every component of our being. These tissues are made up of individual cells, all of which have a specific function within that tissue. To be able to function properly each cell has a set of on board instructions. This 'recipe book' is in the form of 'chromosomes', receptors which contain genes. In other words, chromosomes are the carriers of our genetic information and are made of DNA.
Most healthy people have 46 chromosomes, or 23 pairs. There are 22 'normal' pairs and one pair of sex chromosomes. The normal pairs are sorted according to size and numbered 1 to 22. The 23rd pair are the sex chromosomes: XX in females and XY in males.

Indications       

Genetic screening used to be standard in the blood analysis of patients. However, experience has taught us this is unnecessary in the majority of cases. That is why genetic tests are only performed if there is a history of hereditary defects in your family, or indeed in case of the following specific indications.

• Reduced ovarian reserve (insufficient reserve of eggs).
• Defective menstrual cycle.
• In case of egg donation, for a genetic check-up of the donor.
• After three unsuccessful IVF attempts, where fertilisation takes place, but the embryo fails to implant.
• Unexplained infertility.
• Repeated miscarriage (three consecutive pregnancies).
• Prior to genetic testing of embryo's (PGT).

In the last four cases, both the man and the woman are genetically screened.

Types of tests      

There are two specific types of genetic tests.

• The cytogenetic test examines the chromosome in its entirety.
• The molecular test concentrates on the DNA from which the chromosome is constructed.

Cytogenetic tests       

To perform this test, white blood cells (lymphocites) are placed in a culture medium. At a pre-determined stage of mitosis - hence the name cytogenetic - the genetic carriers of the lymphocites condense into visual structures, the chromosomes. At this moment we can see how many chromosomes there are and whether they appear normal.

Karyotype screening

A cytogenetic test enables Karyotype screening to be performed.
Karyotype literally means the character of the chromosomes: amount, length and genetic content. The ingredients of our genetic identity card so to speak.
Sometimes this test is performed to look for a specific abnormality. For example, in a diagnosis of anovulation (absence of ovulation) where no hormonal explanation can be found, a cytogenetic test can reveal the presence of Turner Syndrome (X0 Karyotype). People who have this condition are missing an X-chromosome, which gradually leads to premature menopause.

FISH-analysis

As previously discussed, our reproductive cells behave differently to other cells in the body. They undergo a complex reduction division process, whereby they retain half of the chromosomes from other cells in the body. During this process certain divisional abnormalities can only be detected in the reproductive cells.
For this reason, a special test was developed. FISH stands for Fluorescent in situ Hybridisation, a process which enables a restricted chromosome analysis of eggs. Three chromosomes are examined by way of sample. However, the test is not often performed and only for certain indications, such as when an abnormal number of abnormal embryos develop as a result of IVF in a couple.

DNA screening     

Molecular testing goes slightly deeper, i.e. into the DNA structure of the chromosomes to determine which chromosomes display a mutation or deletion of genes. The question here is: where is the receptor fault or where is information missing? This sort of investigation is only restricted to a small number of chromosomes and genes.

CFTR-gen (mucoviscidosis gene)

One Belgian out of twenty is a carrier of the mucoviscidosis or CFTR-gene (Cystic Fibrosis Transmembrane Regulator gene). If both partners are carriers, their baby will stand a 25% chance of developing Cystic Fibrosis, a serious lung disease where abnormally large amounts of mucous are produced.
This DNA test is therefore performed on women who have a family member with Cystic Fibrosis, or if there is any other suspicion they may be a carrier of the faulty gene.

Fragile X-test

This specialised DNA test is used in women to detect mutations affecting the X-chromosome which can cause mental retardation in boys. Particularly women who donate eggs are screened for this condition. This sort of mutation can gradually increase from generation to generation and from a pre-mutation phase, go on to develop into an actual mutation.

In compliance with an EC directive, screening for Hepatitis B and C, HIV and syphilis infection is repeated with every new IVF/ICSI attempt, to guarantee infection free cells are used in the laboratory.

• Routine blood test  
• Smear test
• Antibodies to sperm

Routine blood test      

During your initial consultation at the CRG, and in every fertility treatment case, a blood sample will be taken. Tests will not only be performed

• to obtain information regarding hormones (see infra), 
• but also to detect any infections which might be present.

Blood tests will be performed to detect the presence of antibodies to

• HIV, 
• jaundice (hepatitis B)
• hepatitis C,
• syphilis,
• CMV (cytomegla virus),
• rubella, 
• and toxoplasmosis.

The latter two can cause serious damage to the embryo during the early stages of pregnancy.
The presence of antibodies indicates that you

• at some time been infected with the disease in question, 
• or have been vaccinated against it.

It is possible to be vaccinated against rubella before starting fertility treatment, but sadly not against toxoplasmosis.

Smear test      

This test checks the elasticity of the cervical mucus.
The first consultation at the CRG will usually include a gynaecological examination, unless her own gynaecologist performed one recently.
A cervical smear or PAP-test will be performed, which involves the removal of a small amount of cervical mucus for examination.
This will be examined in the laboratory: the smear test can indicate whether you are at risk of developing cervical cancer.
The mucus is also examined for the presence of infections such as ureaplasma, mycoplasma and others. .

Antibodies to sperm        

Sometimes a woman's body makes antibodies to sperm. The body regards sperm cells as undesirable intruders and defends itself against them. Antibodies are produced by white blood cells, which attach themselves to the sperm cell, causing them to stick together. As a result, they lose their motility and are thus unable to reach the fallopian tube and egg.
Men can also produce antibodies against their own sperm: See immunological investigations for men.

Biopsy of the endometrium

During the menstrual cycle, the lining of the uterus undergoes various changes. Useful information for the follow-up or adjustment of ART treatment can be obtained by examining the endometrium.
An endometrium biopsy is performed during the gynaecological consultation:

• via the vagina and the cervix a narrow aspiration device is inserted into the uterus 
• to obtain a small biopsy of the endometrium.

The biopsy allows us to see if it has developed well.

We can also - if necessary - check to see whether there is a biological discrepancy between the stage of your cycle (the biopsy is taken on day 18) and the tissue (which, for instance corresponds with day 15).
A blood test before the biopsy is required for this:

• a hormonal analysis allows us to determine in which stage of your menstrual cycle you are;
• the endometrium tissue is then sent to the pathology lab in UZ Brussel for dating.

An endometrium biopsy is a standard test but is only performed at the CRG for specific indications:

• e.g. if the ultrasound indicates insufficient development of the endometrium; 
• or if implantation of the embryo fails after several IVF attempts.