Case studies
The case studies below are designed to illustrate in practice how some of the investigations mentioned already are interpreted and applied in selecting appropriate treatments. They should be read as the narrative on the left column and the explanation on the right.
CASE STUDY 1: OVULATION FAILURE
Case history
Jane is 26. She has been married for three years. For contraception, she has used an oral contraceptive (the Pill) since she was 20, until two years ago. She and her husband then decided they wanted to start a family. Since coming off the Pill, her periods have become quite irregular and unpredictable, and sometimes she has not had one for two to three months. She is happily married and has a steady job that she likes, although it is occasionally stressful. Almost two years have passed without getting pregnant, so she asked her GP to refer her to see a specialist.
While awaiting an appointment to see a specialist, Jane’s GP did some blood tests; the first in the early part of her menstrual cycle and the second about 5 to 10 days before her next period was due. These showed absence of ovulation so her GP prescribed a mild ovulation-stimulating agent, clomifene citrate. Despite taking this for three months, there was no sign of ovulation.
When the specialist saw her, an ultrasound scan of her ovaries was done. This showed an appearance of polycystic ovarian syndrome (PCOS), and was in agreement with the blood tests that had already been taken. As Jane was slightly overweight, the specialist suggested that she start a weight-reducing diet, took smaller, regular meals and started treatment with metformin.
She began taking this medication, taking one tablet a day. After three months, this was increased to two tablets a day. She had some bowel upset at this dose and it was decreased back to one tablet a day. After six months on this treatment, her cycles were quite regular. At seven months, her period was late and when she did a pregnancy text she found it was positive. As she had already been advised, she then stopped the metformin tablets.
Comments, investigations and management outlines
Stressful situations can cause cycle irregularities. These usually need to be fairly profound, e.g. recent bereavement, moving countries or beginning a new job.
• First blood tests where periods are irregular: early follicular phase follicle-stimulating hormone (FSH) and luteinising hormone (LH) and other tests for thyroid-stimulating hormone (TSH) and prolactin
• Her results were: FSH: 4.5 IU/l (normal) (IU = international unit, a measure of the hormone)
LH: 15.9 IU/l (raised) TSH and prolactin were normal
• Second tests: The main test done at this time is progesterone: it was 4 nmol/l (reduced)
These indicate failure of ovulation, which is most probably the result of polycystic ovarian syndrome (PCOS).
Metformin is a drug that reduces excess insulin, LH and testosterone concentrations in the blood. Women with PCOS who have irregular or prolonged cycles will often get a return of regular periods on this treatment. It increases the chance of ovulation and may improve the quality of the eggs that are released. At least 20 per cent of women will conceive within the first six months. Some temporary mild gastrointestinal side effects, such as nausea or diarrhoea, can sometimes occur with increased doses and the dose may need to be adjusted to take account of this.
CASE STUDY 2: TUBAL DAMAGE
Case history
Jean is 23, and has been living with her current boyfriend for 14 months. She was not concerned about getting pregnant when they started to live together and they have not used contraception. She has had several long relationships in the past with other men, and occasional one-night stands. Before meeting her current partner, she took the Pill as she didn’t trust her partners enough to rely on them for contraception.
Over the past four years, she has had several episodes of lower abdominal pain, some of which were thought to be grumbling appendicitis and she was admitted to hospital during the last episode, as the pain was so severe.
To investigate the cause of the pain, she had some swabs taken from her cervix, and some blood tests and a laparoscopy were done. As a result of these, the diagnosis of an infection with Chlamydia was made, and an antibiotic was given to treat this.
The laparoscopy showed that both her tubes were blocked at their outer (fimbrial) ends (see the diagram). She was advised that she was unlikely to conceive and that surgery would be necessary when she wanted to try to get pregnant. This need not necessarily be done straightaway and, in fact, she was advised that she should delay this until she definitely wanted to conceive, as the best chance of success would be within the first year after surgery.
Her partner was advised of his need for antibiotic treatment as well. They were both advised that, as they might possibly have other sexually transmitted diseases (in addition to Chlamydia), they should visit the sexual health clinic. As yet, they have not decided to have any surgery.
Comments, investigations and management outlines
Having several partners increases the risk of catching a sexually transmitted infection (STI). Although the Pill is effective in preventing unwanted pregnancy, it is not of any value in prevention of STIs and a condom is much more effective.
It is likely that these episodes of pain were in fact the result of Chlamydia. Each episode of infection has about a 30 per cent chance of causing structural damage to the fallopian tubes.
The swabs did not grow any bacteria – they often don’t as Chlamydia is particularly difficult to grow in the laboratory. The blood test looked at antibodies to chlamydia infection, both recent and past. These results were positive indicating considerable infection in the past and a current infection as well. An antibiotic such as ofloxacin or doxycycline is the recommended treatment and needs to be taken by both partners.
Providing there is no further damage from another infection, the chance of success (getting pregnant within a year) from surgery is no better than 50 per cent. A hysterosalpingogram (HSG) would define the chance more accurately by giving information about the health of the inner tubal lining.
Surgery should not be done until the couple are sure that they want to proceed with a pregnancy. The best chance of success is in the first year after surgery. If pregnancy hasn’t occurred by then, it is unlikely to occur at all, usually because of damage to the delicate lining of the fallopian tubes. The first attempt at tubal surgery is the one most likely to be successful. Repeat attempts at surgery are generally not worthwhile.
CASE STUDY 3: MALE INFERTILITY
Case history
Mike is a fit 32-year-old man who exercises once or twice a week. He weighs 80 kilograms and doesn’t smoke or drink alcohol. He has been married to Sue for three years, and they have been attempting to have a child for the last two years. They have decided to seek help through their GP.
His GP examined both of them, did a smear test for Sue and some blood tests, and a sperm sample examination was organised. Mike found producing the sample ‘to order’ a bit difficult but brought in his sample at the appointed time.
When the results returned, Sue’s showed that she was ovulating with no other negative features. Mike’s sperm sample seemed to suggest a problem as the sperm were clumping together. The GP felt that more specialist advice was necessary.
They were seen at the local infertility clinic six months later. The specialist reviewed the results and suggested that the next step was a postcoital test. This was done a few weeks later and then they saw the specialist again to discuss the results.
Once again, the problem of sperm clumping together was found. The specialist suggested some additional tests on a sperm sample to check whether Mike was producing antibodies against his own sperm. When the results of these tests came back, they confirmed that anti-sperm antibodies were present in Mike’s seminal fluid. The specialist told them that the likelihood of them conceiving on their own without help was low. He advised them to seek help from an assisted conception clinic, for IVF or perhaps for IUI. Mike and Sue were devastated at the thought of not being able to have a child without help. They have not decided what to do next.
Comments, investigations and management outlines
Both smoking and drinking have been found to have detrimental effects on sperm quality, lowering their ability to fertilise eggs.
Mike’s physical examination was normal. There were no hernias, and his testicles were normal in size and consistency.
The special sperm tests examined for anti-sperm antibodies. When these are present in seminal fluid, they cause the heads of the sperm (occasionally the tails) to stick together. This reduces sperm motility and severely reduces the chance of them reaching the outer ends of the woman’s fallopian tubes to fertilise an egg. Anti-sperm antibodies can also be produced by a woman in the mucus of her cervix. In Mike’s case, they were present in the seminal fluid in high concentration and sperm clumping (agglutination) was severe.
Although some doctors have advocated the use of steroids to reduce the body’s antibody response, the most effective way of achieving a pregnancy is to remove the sperm as quickly as possible from the seminal fluid, and inject the sperm into the uterus (IUI), or mix the sperm with eggs outside the body (IVF). If very high concentrations of antibody are present in the seminal fluid, ICSI is likely to offer the best chance of pregnancy.
CASE STUDY 4: UNEXPLAINED INFERTILITY
Case history
Janet and Peter have been married for five years, and stopped using contraception a year after they married when Janet was 29. As her sister had blocked tubes, they were concerned that any delay in diagnosis might make things more difficult for them. Two years ago, they asked to be referred by their GP to see a gynaecologist as Janet had not become pregnant. After six months of blood and sperm tests, an X-ray of Janet’s uterus and a laparoscopy, they were told that there was no obvious cause for their failure to get pregnant. The gynaecologist was very positive and encouraging and said that, as this was the case, they had every chance of getting pregnant by themselves. The advice was they should relax, have regular intercourse and wait for it to happen.
The couple went on a holiday to Spain, and they went away for lots of weekends, but Janet didn’t get pregnant. After a year, Janet suggested going back to see the gynaecologist. By then, they were becoming desperate. The gynaecologist went over things again, explained how everything was in good order and that no simple measures or treatment was going to help improve their chances. The only alternative to waiting for pregnancy to occur naturally was to intervene with IVF.
After giving this some thought, and working out that they could afford two cycles of treatment, they asked to be referred to the nearest IVF clinic, 40 miles away. When they went there, it seemed as if a lot of the tests were repeated again. Within a few weeks, Janet had an egg collection operation, and then the embryo transfer. Her period came two weeks later. They had a visit to the clinic to discuss the cycle and plan the next. She is going to have this soon, with no change to the treatment plan.
Comments, investigations and management outlines
Infertility does not run in families, although sperm disorders may be passed on and endometriosis and PCOS are more commonly found in other family members than in the general population.
The diagnosis was essentially ‘unexplained infertility’ although this strictly requires three years of infertility. The role of factors such as stress is poorly understood, and difficult to define. Whenever formal studies of stress levels and stress chemicals have been done, no major differences are found in the infertile population. Yet there are many anecdotes of people who give up trying, adopt and then find themselves pregnant.
At the end of two years, 95 per cent of normal fertile couples will have conceived and, in the next year, there is still a likelihood of conception, though increasingly small (table on page 18). However, after three years, the chances of natural conception are very low and, realistically, the best chances then are from treatments such as IVF.
Many IVF clinics will want to repeat some or all of the tests that are relevant. This is partly to have accurate results, partly to ensure nothing dramatic has changed since initial testing and partly because some of the tests have important predictive value for IVF outcome.
With IVF for couples with unexplained infertility, the expected success rate is about 30 per cent per cycle, compared with the one to two per cent rate per cycle that is otherwise seen after three years of trying for natural conception. With three cycles of IVF, an overall success rate of over 60 per cent should be expected if the woman is less than 40 years old.
