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Risks and benefits of assisted conception

New ways of helping childless couples have exciting potential but limited effectiveness ­

Dr Chandra Kailasam and

Dr Julian Jenkins explain

Since the birth of Louise Brown in 1978, assisted conception has seen amazing developments both in terms of new treatments and increasing uptake. Assisted conception includes IVF, donor gametes and embryos, surrogate uteri and the cryopreservation of both gametes and embryos. More than a million babies worldwide have been born following IVF; more than one in 100 babies born in the UK today are conceived by IVF.

Treatment by IVF or intracytoplasmic sperm injection (ICSI) involves the following cycle.

 · Ovaries are hyperstimulated with follicle stimulating hormone (FSH), to increase egg numbers and provide a greater choice of embryos for replacement.

 · Progestogens or the combined pill may be given before commencing a gonadotrophin-releasing hormone agonist (or antagonist) administered nasally or by subcutaneous injection to synchronise the onset of menstruation and reduce the risk of ovarian cyst formation and to prevent premature release of oocytes.

 · Ovarian stimulation is monitored by serial transvaginal ultrasound with serum oestradiol used in selected cases.

 · Once follicular development is optimal, final maturation of the oocyte is initiated by an injection of human chorionic gonadotrophin.

 · Transvaginal ultrasound-guided oocyte collection is performed under deep sedation 36 hours later.

 · The eggs are fertilised in the laboratory and after two or three days the resultant embryos are transferred to the uterus transcervically using a specialised embryo transfer catheter.

 · Surplus suitable embryos beyond the two that are normally replaced may be frozen for subsequent treatment.

 · Progesterone supplementation is usually given for two weeks after embryo transfer, generally in the form of vaginal pessaries to help implantation.

Effectiveness of treatment

The majority of patients who persevere with IVF treatment will ultimately have at least one child. The chance of a live birth is more than 25 per cent per treatment cycle below 35 years of age, but falls to less than 10 per cent beyond 40 years of age.

The chance of success is greatest in the first few cycles then gradually declines. Overall around 90 per cent of IVF pregnancies occur in the first four attempts; prognostic features are shown in the table above.

Risks of treatment

The greatest risk of assisted conception is multiple pregnancy in view of problems later in the pregnancy, particularly prematurity. This is why the Human Fertilisation and Embryology Authority limits IVF treatment to the replacement of no more than two embryos other than in exceptional circumstances.

Patients can be reassured that limiting the number of embryos replaced in high-quality centres reduces multiple pregnancy significantly without making a major impact on pregnancy rates. There is an increasing move in the profession to transfer just single embryos in suitable patients, although patients who are paying for treatment are understandably reluctant to accept this option.

Ovarian hyperstimulation syndrome (OHSS) is the most clinically significant short-term morbidity following treatment with gonadotrophins. OHSS occurs in about one in 20 IVF cycles but presents a serious problem in only a small number of cases.

Patients may present with lower abdominal discomfort, bloating and nausea that may progress to vomiting and, in severe cases, ascites, pleural effusion and even thromboembolic disease.

The pathophysiology of OHSS is poorly understood and management

is mainly supportive. It is difficult to predict when this will occur, although it is more common in conjunction with conditions such as polycystic ovarian syndrome. Improved management of gonadotrophin stimulation appears to have reduced OHSS, but vigilance remains important with referral for expert advice when suspected.

Although the vast majority of children conceived by assisted conception appear normal in all respects, a slightly higher proportion has abnormalities when compared with natural conceptions. This is mainly due to the increased age of infertile patients presenting for treatment, increased risks with multiple pregnancies, subtle gene defects in either partner or poor reproductive function in general, but

a treatment effect cannot be excluded. Patients should be counselled appropriately, particularly with regard to the advantages of limiting the number of embryos replaced.

Although there have been theoretical concerns that controlled ovarian hyperstimulation with gonadotrophins may increase the risk of malignancy, the overwhelming balance of evidence is reassuring that this treatment does not increase the lifetime risk of either gynaecological or breast cancer.

Future developments

Already the success of assisted conception exceeds natural conception, but human conception is relatively poor compared with other animals so there is room for improvement.

Research constantly strives to do this, but it is important to be cautious in our enthusiasm for new treatments until there is adequate proof of effectiveness, which may take time. For instance, only very recently has a detailed meta-analysis of techniques used to assist the hatching of embryos provided convincing evidence that these increase pregnancy rates following recurrent unexplained failures of IVF and ICSI.

NICE guidelines on infertility treatment are due out early this year. The draft guidelines recommend that IVF is an effective treatment that should be provided on the NHS ­

it will be interesting to see the final recommendations.

Chandra Kailasam is associate specialist and Julian Jenkins is clinical director, Centre for Reproductive Medicine, University of Bristol

Further information

Centre for Reproductive Medicine, Bristol: www.ReproMED.co.uk

Human Fertilisation and Embryology Authority: www.hfea.gov.uk

British Fertility Society: www.fertility.org.uk

Nice guidance: www.nice.org.uk/cat.asp?c=20092

Braude P and Taylor A. ABC of Subfertility. London: BMJ Books, 2004

Factors affecting outcome

of IVF treatment

Good prognosis

 · Aged under 38

 · Previous pregnancy

 · Previous successful fertility treatment

Poor prognosis

 · Aged over 38

 · Long duration of infertility

 · Previous failed fertility treatment

 · Obesity (BMI >30)

 · Smoking (active and passive)

 · Untreated hydrosalpinx

 · Basal serum FSH levels >10iu

 · Poor response to ovarian stimulation

Pregnancy rate according to age

Age group Pregnancy rate*

<35 years="" 36="">

35-36 years 26 %

37-38 years 21 %

39-40 years 20 %

>40 years <10>

*Clinical pregnancy rates at CRM Bristol in 2001/3 per started IVF/ICSI cycle

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