Diagnosis

Diagnostics for women

The traditional tests for female infertility are the blood test, ultrasound and tubal patency tests.

Blood test : tests FSH, LH, oestrogen, progesterone and androgen levels.

Ultrasound :  gives the specialist a view of the womb and ovaries.

Tubal patency test :  reveals whether the tubes are working or not.

Tubal Patency Test

Measured against these criteria, the type of infertility and the standard treatment required can be assessed.

Definition	Condition	Treatment Options
Low late cycle progesterone	AMENORRHOEA OLIGOMENORRHOEA	FSH injections
High LH levels compared with FSH. High androgen levels	POLYCYSTIC OVARIES	FSH injections May require use of LHRH antagonist to reduce LH and androgen levels before FSH.
Blocked tubes	TUBAL DISEASE	Tubal surgery or IVF
Detection of bleeding tissue on ovaries or in abdomen (at time of laparoscopy)	ENDOMETRIOSIS	Laser treatment. Long term use of LHRH antagonist. IVF
High FSH levels	EARLY MENOPAUSE	Egg donation. Surrogacy. Adoption.
No abnormality detected	UNEXPLAINED INFERTILITY	Currently very little can be done beyond diagnosis. Treatment with FSH injections, IUI and IVF all done. No proof these needed!
Low levels of FSH & LH	HYPOGONADIC INFERTILITY	Treatable by hormone injections.  May still need IVF or ICSI
Production of antibodies to the sperm is not ever normal	ANTISPERM ANTIBODIES	Sometimes treatable with intrauterine insemination, IVF although sometimes intracytoplasmic injection is required.

Physical examination is the first port of call, as well as an ultrasound scan to ensure that the gross anatomy is as it should be. Following a detailed history, an arrangement for a “day 21” blood test will be made. In the case of anovulation, a blood sample may be taken at any time. Hormone levels to be tested will be FSH, LH, Progesterone, Prolactin and sometimes, testosterone. These tests will reveal reasons for anovulation or provide information on the endocrinal state of the female patient.

Further tests will follow at different times depending on the age, duration of infertility and the urgency of the couple. Tubal patency should be proven as a matter of priority. There is some controversy though as to the timing of such tests. An early test avoiding surgery is the use of X ray. This test is called hysterosalpingography. Dye is passed into the womb and its passage is monitored by X ray. A new method of this is being developed. Instead of X ray, ultrasound is used.

Laparoscopy reveals more information, since a visual inspection of the anatomy of the pelvis is also carried out at the same time as the tubal patency test (dye spill).

At least two blood tests should be carried out initially (three month gap). Thereafter, after initial diagnosis and treatment, blood and tubal patency tests should be carried out after every 12-24 months.

HSG (X-ray)

Diagnostics for Men

Definition (World Health Organisation)	Condition	Treatment Options
Poor sperm count & motility (ie. below 20 million per ml)	OLIGOZOOSPERMIA	If below 10 million sperm per ml, requires intracytoplasmic sperm injection (ICSI)
Normal sperm count, but motility below 40%	ASTHENOZOOSPERMIA	If below 20% requires ICSI
Normal count & motility, but over 60% abnormal sperm	TERATOZOOSPERMIA	If over 85% requires ICSI
Poor count, poor motility & high abnormality.Fewer than 4.8 million motile normal sperm per ml	OAT (OUGOSTHENOTERATOZOOSPERMA)	OAT Below 4.8 million motile sperm per ml needs ICSI
No sperm in ejaculate	AZOOSPERMIA	Requires further investigation by a specialist (the surgical andrologist)
No sperm in ejaculate as a result of abnormal chromosome arrangement	KLINEFELTERS	Currently very little can be done beyond diagnosis.Treatment is by adoption or donor insemination (DI)
Low levels of FSH & LH (the hormones producing sperm and testosterone)	KALLMANNS	Treatable by hormone injections. May still need IVF or ICSI
Problem in sperm tails often associated with poor lung function	KARTAGENERS	Requires ICSI
Production of antibodies to the sperm is not ever normal	ANTISPERM ANTIBODIES	Sometimes treatable with intrauterine insemination, although sometimes intracytoplasmic injection is required.

The first test to be done in order to assess male infertility is the traditional semen analysis, commonly known as the sperm count. This consists of estimating count, motility, progression and the rate of abnormality. Although this is not adequate on its own, it is a good place to start. Low count <20 million per ml  does not indicate sub-fertility per se, but the probability of subfertility is increased.  It is important to obtain at least 3 samples, since semen samples can vary a great deal from sample to sample.

Once the sperm count has been done, if it is okay, no further action is required. If the sperm count is poor, the next step is a physical examination and a blood test. In most cases no abnormality is detectable in the man’s “plumbing”. This is usually checked by a physical examination, followed by an x-ray test using radio-opaque dye (vasogram). When the vasogram reveals a blockage, the problems are just the same as in blocked tubes in the female. The treatment is also similar; either surgery to repair the block, or IVF where the sperm used for ICSI have to be surgically retrieved as the eggs are, when the female partner has blocked tubes. If no blockage is detected, there is no surgical intervention which will be of value.

Diagnosis is not complete until testicular function has been tested, The best non-surgical method is to take a sample of the male partners blood and to measure the LH (luteinising hormone or interstitial cell stimulating hormone-this acts on the Leydig cells in the testes, which make testosterone), FSH (follicle stimulating hormone-acts on Sertoli cells of the testes which have an intimate relationship with sperm) and testosterone (promotes sperm development) levels.  Low LH or FSH levels indicates hypogonadic function, which is sometimes associated with a low sperm count.

What is a normal sperm count?

Guidelines from the WHO suggest that normal count is about 50-150 million per ml.  Motility 50-80%.

Progression is a subjective parameter, which is scored 0-3. Normal  is scored 2 or better, which indicates that the motile sperm move with vigour. Feeble moving motile sperms would be scored 0 or 1. Generally only donor samples score progression of 3. The WHO fertile abnormality rate would be 25-40%.

The WHO suggests that the following values indicate infertility. Count less than 20 million per ml, motility less than 40%, progression less than 2, abnormality rate in excess of 40%.

Treatments

Simple fertility drug treatment options

For anovulation or oligomenorrhoea, treatment is simple and usually effective.  Patients with low luteinising hormone (LH) and follicle stimulating hormone(FSH) will benefit from injections of LH and FSH preparations. This therapy is effective for 70-90% of patients.  For patients with normal FSH, LH and oestrogen, but low progesterone, follicular tracking and human chorionic gonadotrophin (hCG) administration at the appropriate time should be successful in the vast majority of cases.

Patients with polycystic ovarian syndrome (PCO) will benefit from FSH only injections. Severe cases of PCO will benefit from downregulation first. A gonadotrophin releasing hormone (GnRH) is administered, usually by nasal spray. After 21-30 days, injections of LH and FSH may be given. Success with PCO patients is about 55-70% of all treated cases. In all resistant cases of anovulation, downregulation may be offered. Failure with this treatment means progression to superovulation, intra uterine insemination (IUI), gamete intrafallopian transfer (GIFT) or in vitro fertilisation (IVF).

In the old days, clomiphene or tamoxifen or rehibin, were given to the above patients for up to six cycles. In the days when blood tests and ultrasound were not used routinely, this empirical therapy was useful for up to half of those receiving the treatment. In others the treatment was either ineffective or made matters worse.  Today, because of the routine use of ultrasound, an argument may be made for the use of gonadotrophins (LH:FSH) because of the high efficacy of the combination of follicular tracking , gonadotrophins and timing of ovulation by hCG administration. Some practitioners continue to use clomiphene etc,  for cost  and sometimes resource reasons.

Superovulation

The majority of patients with anovulation will success with ovulation induction with gonadotrophins. Those that fail may benefit from superovulation. Ovulation induction is the pursuit of one or two functional follicles. In superovulation, we are looking to develop between three and eight follicles depending on the treatment option.

  Ultrasound - superovulation treatment
  (Showing 2 follicles on the left hand side)

In empirical superovulation, we look to improve the couples natural chances of success by simply producing more follicles, which should contain more eggs. We have learnt from IVF that more embryos = more likelihood of success. This maxim goes for eggs too. With empirical superovulation (ES) we must take care to avoid multiple pregnancies. Even a triplet would = failure. The use of ES is particularly suited to failures of  ovulation induction and for unexplained infertility. Three mature follicles is ideal with ES. Patients with endometriosis might also benefit from ES.

IUI with ES

This is most suitable for male factor infertility, although the therapy is not yet proven (neither is GIFT nor IVF!). Joint presence of male and female factors should also be suitable for IUI and ES so long as tubal patency is demonstrated. This treatment is also suitable for idiopathics (unexplained) who are not having sex or who are not achieving penetration during sex.

Patients failing ES

Many will find themselves offered GIFT or IVF. More commonly, these days IVF. In my opinion, IVF is for tubals only. If there is tubal patency, ES alone should be sufficient, so long as male factors are absent. Thus GIFT should only be considered after ES failure
(at least 6 cycles). In some circumstances, where sperm or egg quality is suspected, a diagnostic IVF cycle may be useful before trying GIFT.

IVF

IVF is the first port of call for patients with tubal disease, if they are unsuitable for tubal surgery or choose not to consider it. It may also be suitable for some of the other categories of female infertility, after prolonged treatment with less stressful and invasive options.

The blastocyst 

During natural conception, this stage is reached on day 5 after fertilization. At this point, the blastocyst will have finished migrating down the Fallopian tube to reach the cavity of the womb, where, if the embryo is viable, it will begin the process of implantation into the lining.

With traditional IVF, the early embryo (usually just 4-cells) is artificially and prematurely placed into the womb, where it will have to wait prior to implantation.

More recently, especially in the USA, blastocyst culture has become commonplace. Some units claim high success rates. In the UK, most clinics do not routinely grow blastocysts, because it is argued that fewer couples will have an embryo replacement, because of higher rates of embryo wastage. Moreover, blastocyst culture is much more labour intensive and requires increased incubator facilities.

By reaching the blastocyst stage an embryo has passed some of the hurdles that indicate poor viability, which is why blastocyst transfer may produce 70% success rates.

For male factors of any type, sperm microinjection
(ICSI) is the treatment of choice.

ICSI (INTRA CYTOPLASMIC SPERM

 INJECTION)

Injected Egg (ICSI)	ICSI Equipment

ICSI is a relatively new technique whereby a single sperm is injected directly into an egg to aid the creation of an embryo. Up to three embryos created in this way may be transferred to the womb during any one treatment cycle in the same way as with
conventional IVF.

ICSI may be appropriate where the male partner has very few sperm or where the sperm have poor or no motility. It is often necessary, for example, when the sperm sample is relatively small or sperm has to be extracted surgically. In some cases ICSI may be successful where conventional IVF fails to produce viable embryos because of a low fertilisation rate.

As the success of ICSI treatments is dependent to a very high degree on the skills and experience of its practitioners, the HFEA has introduced special competency assessment and licensing for them.

Chances of success

The success rate for ICSI has increased rapidly in the last few years, and in 1997-8, 8394 fresh embryo, stimulated cycles involving the patient`s own eggs reached embryo transfer, resulting in 1850 births – a live birth rate of 22% per embryo transfer. However, your chances of success will very much depend on your own individual circumstances.

Risks of ICSI

Concern has been expressed about the potential side effects of ICSI treatment, mainly because of the risk of injecting an abnormal sperm.

Whilst there are few serious doubts about the ICSI technique itself, it is possible that genetic disorders which led to the low sperm count or reduced motility in the father`s sperm may be passed on to a son. So far there is mixed evidence about an increased risk of birth defects as a result of this treatment.

Whilst the ICSI procedure itself is unlikely to change, it remains a relatively new technique and further information concerning possible risk and safety issues is regularly produced. If appropriate, a clinic licensed to perform ICSI will be able to provide a couple with up-to-date information and discuss the potential risks with prospective patients. The HFEA also recommends that men undergoing ICSI receive genetic counselling.