With approximately 15% of all couples now reportedly experiencing difficulty getting pregnant (1) its no surprise that there is generally a bit of a wait to see a fertility specialist. You may want answers straight away but if a fertility specialist can fit you in tomorrow I’d be wondering why.   Before you see a fertility specialist you will need a referral from your GP.  GP’s will generally advise you to be trying for 12 months if you are under 35 and have no obvious reason why you are having difficulty conceiving or six months if aged over 35.

So, you’ve got your referral, googled the success rates of different clinics in your area and waited out the couple of months before your first appointment.  Although each clinic will vary, here is what to expect:

Questionnaire

You will most likely be sent out a questionnaire to complete prior to your first appointment. This will ask you all sorts of details and will be reviewed by your specialist with you and your partner as part of your initial appointment. It will include queries regarding:

• past medical history (bring any blood tests or other pertinent information you have had collected in the past year)
• your cycles (length of cycle and length and heaviness of bleed – it may be useful to write down the dates of your last six months of periods)
• how long you have been trying to conceive including how many times a week you have sex and if you experience any pain or discomfort (no such thing as privacy from here on in!)
• any past investigations
• any past pregnancies, miscarriages and terminations
• Your partners past medical history and any previous children
• Any past sexually transmitted diseases. Everything you answer matters, for example, although it may have been treated long ago, chlamydia can cause pelvic inflammatory disease which is infection in your cervix, uterus and fallopian tubes. This can potentially block your fallopian tubes meaning that the eggs will not be fertilised by the sperm and can also cause difficulty with implantation. It is also associated with ectopic pregnancy, so obviously you want to make sure that the fertility specialist has all the information straight up.

It may seem a little invasive, and yes, it is!, but it is your first step forward to getting ‘things’ sorted.

Internal Exam

The internal exam will be done by the doctor and will generally have a nurse in the room. You will need to completely undress from the waist down and is a quick and generally painless digital examination looking for signs of any structural abnormalities or endometriosis (for example, pain when pressing in a particular spot).

If the men are even suspected of having any difficulties they will also be assessed, but again it is quick and painless and nothing to worry about.

Blood Tests

Although these probably wont be done in the actual appointment, they will most likely form part of your initial work up. They include, but definitely aren’t limited to the following:

1. AMH – antemullarian hormone. At its most simplest, AMH is the hormone that dictates your ovarian reserve and measures how loudly the ‘biological clock is ticking’. AMH is a hormone that is excreted by the immature, or antral and preantral, follicles that are in your ovaries waiting to become ‘lead’ follicles. The result of this test can be useful to determine the amount of eggs, or ovarian reserve, that you have left with generally a higher number indicating a higher amount of eggs that can be retrieved. It is also useful in helping to diagnose polycystic ovaries as ladies with PCOS will generally have more antral follicles and hence higher levels of AMH.

Interpretation (women under age 35)	AMH Blood Level
High (often PCOS)	Over 4.0 ng/ml
Normal	1.5 – 4.0 ng/ml
Low Normal Range	1.0 – 1.5 ng/ml
Low	0.5 – 1.0 ng/ml
Very Low	Less than 0.5 ng/ml

Source: advancedfertility.com (2)

I have included the levels above just because some of the more obsessive of us like to know our results and compare against the ‘normal’. Be very careful though, as advancedfertility.com highlights all these figures are on a sliding scale and you should NOT be disappointed if you happen to be categorised as ‘low’ as opposed to ‘low normal’. The clinical difference is very small, though has been categorised for the purposes of putting it in a nice chart. Also, normal or expected AMH levels are highly dependent on your age, so it is best to speak to your specialist about your particular levels.

2. Prolactin – for this test you will be required to sit for around 20 minutes before the blood being taken and because prolactin levels can vary throughout the day it is usually preferred to take it within a couple of hours of waking and in a fasting state (3). Prolactin is important to measure as if your prolactin level is high it can inhibit the action of the follicle stimulating hormone (FSH) and gonadotropin releasing hormone (GnRH) which are needed for a lead follicle to mature and hence ovulate. If these levels are low then ovulation may not occur or may cause a shortened luteal phase (7).  The normal range for women is 85 – 500 mIU/L (7) Women who are breastfeeding tend to have higher levels of prolactin which is why some people consider breastfeeding as a form of contraception (its not!). If your levels are high (and significantly high, not just marginally high) these get be treated with medications such as bromocriptine and cabergoline (4,6), but there can be other reasons for high prolactin such as any other medications, stress or if you have PCOS (5). If your male partner has low sperm count it may also be worth checking his prolactin levels as it can be associated with low sperm count, low testosterone and erectile dysfunction (3). The normal range for men is 150 – 500 mIU/L (7)

3. Leutinizing Hormone (LH). LH is the hormone that in your regular cycle will experience a sharp rise just prior to ovulation, roughly 24- 48hours. It is this ‘surge’ of LH that ovulation predictor kits often rely on to predict ovulation and hence indicate to you to have sex. LH also helps develop the corpus leuteum which is important in manufacturing progesterone after ovulation to support a pregnancy and also to limit the follicle stimulating hormone.

Luteinizing hormone in blood
Menstruating women
Follicular phase:	1.68–15 international units per liter (IU/L)
Midcycle peak:	21.9–56.6 IU/L
Luteal phase:	0.61–16.3 IU/L

Source: http://www.webmd.com/women/luteinizing-hormone?page=3 (6)

Again, I have included the above chart, but remember to take all measurements with a pinch of salt and units can alter depending on what country you are in.  Some consider a normal range to be below 7 when taken on day 2 to 3 of the menstrual cycle (7)

4. FSH. In the normal cycle FSH is responsible for recruiting and growing to maturity follicles which hopefully contain healthy, viable eggs. Many ladies who have undergone IUI’s or IVF’s will be familiar with FSH in its pharmaceutical form of Gonal-F or Purgeon, to name two, and it is what is injected on a pretty much daily basis until ‘trigger’ and ovulation.  FSH should be tested on day 2- 3 of your menstrual cycle and a normal range is typically between 2 – 20 U/L with a level under 6 being excellent and the ratio with LH should be as close as possible to 1:1 (7)

5. Thyroid tests.  The thyroid produces T3 and T4 which controls growth, metabolism and energy level. The thyroid itself is influenced by thyroid stimulating hormone or TSH.  Thyroid problems are common in women and can be a cause of infertility and having either an over or an under active thyroid can result in infertility though the risk is greater for those with an underactive thyroid (7) The accepted levels of TSH varies but for women wishing to conceive it is optimal for levels to be between .3 and 2mIU/L, though ‘normal’ levels has been altered from 5mIU/L to 2.5mIU/L.  It would also be beneficial to test for thyroid antibodies as the presence of these may indicate that your antibodies are attacking your thyroid gland and hence impacting its normal functioning (7).  Women with thyroid antibodies may also have elevated levels of NK cells which are associated with infertility and recurrent miscarriage as well as other autoimmune conditions (8)

6. Oestradiol (E2) is the main oestrogen in your body and FSH stimulates the ovaries to make oestradiol.  The normal range at day 2 or 3 is 100 -200 pmol/L (7).

7. Progesterone is measured after ovulation has occurred and a reading of progesterone greater then 25nmol/L often confirms ovulation (7).  Progesterone is important for preparing your lining to accept an embryo for implantation and also to lower the immune system to accept and support a pregnancy.

8. Free testosterone and androgen. This is useful in assisting in the diagnosis of polycystic ovarian syndrome (PCOS) and women with PCOS typically have higher levels.  Free testosterone should typically be below 4pmol/L and free androgen index between 1 and 8 percent (7).

9. Autoimmune tests.  The impact of the immune system infertility is not always appreciated by all fertility specialists at the beginning of your ‘journey’.  Some specialists may not even test for these before three miscarriages or failed cycles.  If your doctor does not test for these and especially if autoimmune conditions such as rheumatoid arthritis or type 1 diabetes is present in your family it may be worth discussing this.

Tests within this group include anti-nuclear antibodies, anti-DNA/ histone antibodies, antiphospholipid antipodies, antisperm antibodies, natural killer assay, cardiolipin antibodies.  As I said, some believe that the presence of these markers are not directly relevant to fertility.  There are many women on various forums and boards however who have had success only after the investigation and treatment of various autoimmune conditions.

If you have ‘unexplained’ infertility or feel immunology might be playing a part in your medical history you may want to look at Dr Alan Beer’s book, Is Your Body Baby-Friendly, which discusses immune issues in detail.  Beware though! If you are just starting your fertility journey this book can be quite detailed and may be a little overwhelming.  That is why if you are concerned about your autoimmune response, as a first line of investigation discuss it with your doctor and see how it relates to your specific clinical presentation.

10. Sexually Transmitted Diseases and Infection.  These tests are usually done by either blood or urine test and include:

• chlamydia
• gonorrhoea
• syphilis
• rubella

Please note that while comprehensive, it is not an exhaustive list of blood tests and your clinic or treating doctor may have other tests they wish to complete depending on your clinical presentation.  Conversely, and again depending on your clinical presentation and past medical history, you doctor may not feel all of the above tests are necessary.

Tracking Cycle

The tracking cycle takes place after your initial appointment but is part of the initial work up when starting fertility treatments.  A tracking cycle involves you attending your clinic throughout your cycle, starting on Day 2 or 3, Day 1 being the first day of your proper bleed.  You usually need to attend the clinic early in the morning when nurses and phlebotomists take the blood.  There are often many women attending at the same time as you so sometimes it may take up to an hour depending on the efficiency of your clinic and how many women are waiting.  Once the blood is taken the clinics laboratory will measure your blood for hormones such as oestrodial, progesterone and luteinising hormone.  This will enable your doctor to compare your cycle with a ‘typical’ cycle and aid in the diagnostic process.  You will need to visit the clinic several times throughout the cycle, however, the nurses will tell you when you need to attend depending on your previous blood result.

During the tracking cycle you will also need to have an ultrasound completed to see how many follicles you are producing, the size of these follicles as well as the thickness and quality of the lining in your uterus.   This is a transvaginal ultrasound where, as the name suggests, the probe is placed inside of you.

Hysterosalpingogram … or HSG for short

This will likely to be done at a radiography clinic. It involves injection of a dye into your vagina and cervix which fills up the uterine cavity and fallopian tubes.  Several xrays are taken and the dye allows for any blockages, fibroids or structural abnormalities can be seen. There are certainly more pleasant experiences to be had then a HSG so some women may be advised to take pain relief prior to attending.  Additionally, there may also be the risk of infection so an antibiotic may also be provided for you to use as a preventative measure. HSG’s should be done in the follicular phase of the cycle (before ovulation) and are definitely NOT indicated for women who might be pregnant (as if!). On a positive note, there is some suggestion that women are able to successfully get pregnant in the cycles immediately after a HSG, the exact cause and success rates for this is unknown, it may just be injecting the dye into your reproductive system ‘cleans it out’ so to speak allowing for the released (and hopefully fertilised egg) to make its journey into the uterus easier.

Laparoscopy

This one will involve you being admitted for day surgery at your local hospital.  Depending on the doctor, approximately three small incisions are made in your abdomen area – one in your belly button which you wont see, one under your pubic line and one to the side of your abdomen.  These incisions enable the doctor to insert a camera to investigate from the inside, and most frequently, to see endometriosis.  If endometriosis is seen, depending on the severity of the endomentriosis your doctor may remove it then and there or otherwise, make a time for you to come back.

Below are two photos from an laparoscopy (apologies, they are a little graphic…).  The one on the left, shows severe endometriosis which is the black areas you can see.  You can see the ovary to the right of the picture.  The one on the right  is the same person six years before with only mild endometriosis as indicated by the small black dots.  The ovary is seen in the bottom right segment.

 

 

 

 

 

 

 

 

MALE TESTS

Sperm Analysis Test

This information is pretty easy to find else where by asking Dr Google so I’ll keep it brief.  It is the one where it involves the man producing a ‘sample’.  Depending on how far you live from your local clinic though he may be able to produce this at home and drive it in to the clinic, which is obviously a bit more stress free.  Also, these are best completed by laboratory technicians specialising in reproductive medicine, such as the lab attached to your fertility clinic. If your GP asks for a sample before making the referral and you are required to  take it to a regular pathology laboratory they often lack the expertise to accurately complete a proper count, so therefore take any results with a pinch of salt.

When getting results from a sperm analysis test results will include numbers on

• count – overall number
• morphology – the shape of the sperm, for example, checking they don’t have two tails etc
• motility – how they are moving? are they moving in a straight line? speed, for example
• ‘marine sperm’ – this might only be how my Dr described it but my clinic does really report on the above as all that all really matters is how many of the best of the best are there?

DNA Fragmentation Test

At its very most basic level this test is evaluating whether or not the DNA contained in sperm is healthy or intact.  Even men with seemingly healthy sperm in the sperm analysis test may have DNA fragmentation and one study suggests in 80% of couples with ‘unexplained’ infertility with further investigation, the reason for the infertility was high amounts of DNA fragmentation (10)  The clinical threshold for DNA fragmentation is 30%, that is if 30% or greater of sperm is damaged this is associated with lower fertilisation, implantation and pregnancy rates.  Although high amounts of DNA fragmentation is associated with poor outcomes, if using ICSI then this may not necessarily be the case due to the ability to ‘pick out’ sperm with DNA strands intact using particular tests and techniques.  Additionally, depending on the quality of the oocycte, damaged DNA may also be able to be repaired resulting in a positive result (9)

Blood Tests

1. Testosterone levels in men are generally within normal ranges even if there are significant sperm production difficulties (7).  The normal range of total testosterone is 8 – 27 nmol/L with free testosterone being 170 -510.

2. Luteinising hormone stimulates testosterone production and the normal range is 2 – 10U/L.

3. Follicle Stimulating Hormone.  Similar to FSH stimulating maturation of ooyctes in women, in men FSH stimulates sperm production.  THe normal range in men is 1 – 5 U/L.

Ultrasound

Men may also be required to have a testicular ultrasound done to investigate structural abnormalities in the testes and scrotum.

Done!

Phew!  That was a lot, but hopefully it gives you a better idea as to what kind of tests you may expect when visiting a fertility specialist for the first time.  As I mentioned the above is not exhaustive and conversely your doctor may not think it necessary to complete all of the above investigations.  If you have any questions or disagree with any of the above, please let me know.

References

1. https://www.nichd.nih.gov/health/topics/infertility/conditioninfo/Pages/common.aspx

2. http://www.advancedfertility.com/amh-fertility-test.htm

3. http://www.drmalpani.com/knowledge-center/articles/prolactin

4. http://www.labtestsonline.org.au/learning/test-index/prolactin#tab-index=2

5. http://www.advancedfertility.com/bromocriptine-prolactin-ovulation.ht

6.http://www.webmd.com/women/luteinizing-hormone?page=3

7. Cabot, S. & Jasinska, M. (2011) Infertility: The Hidden Causes. WHAS Pty Ltd

8. Beer, A., Kantecki, J & Reed, J. (2006) Is your body baby-friendly? Ajr Publishing.

9. Sakkas, D. & Alvarez, J. (2010) Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis.  Fertility & Sterility, 93 (4) 1027 – 1036.

10. Lewis, S.  (2013) The place of sperm DNA fragmentation testing in current day fertility management.  Middle East Fertility Society Journal. 18 (2) 78 -82