Do fertility treatments work?

Behind the Headlines

Friday August 8 2008

Representation of an egg being fertilised

Extensive news coverage has been given to research saying that two fertility treatments commonly recommended to couples are of little help. The study has found that women who were given the fertility pill clomid, or who had intrauterine insemination (IUI), had no greater chance of having a baby. The study leader, Professor Siladitya Bhattacharya, was quoted saying “neither [of the treatments] is significantly more effective than telling the couple to just go home and get on with it” (The Guardian). He is also quoted as saying that the costs of such treatments would be better spent on in vitro fertilisation (IVF).

The findings of this well-conducted study suggest that for couples with unexplained infertility, IUI and Clomid have little effect compared to no intervention. However, no assumptions should be made about the effectiveness of these treatments for infertility with identified causes, such as in women with ovulatory problems. In addition, no assumptions should be made about the effectiveness of IVF, which is normally considered once other options have been tried. The results may lead to a rethink of how treatment for couples with unexplained infertility is managed.


Where did the story come from?

Professor Siladitya Bhattacharya from the University of Aberdeen and colleagues from the University of Oxford, Royal Infirmary of Edinburgh, Ninewells Hospital, Dundee, Falkirk and the District Royal Infirmary and Royal Infirmary, Glasgow, carried out the research. The study was funded by the Chief Scientist Office, Scotland. The study was published in the (peer-reviewed) British Medical Journal.


What kind of scientific study was this?

This was a randomised controlled trial designed to compare the effectiveness of artificial insemination and clomifene citrate with expectant management in unexplained fertility.

The researchers recruited couples who had failed to conceive naturally after two years and who had no explained cause for infertility from five hospitals in Scotland. Women had normal ovulatory menstrual cycle, normal hormone levels, and patent (open) fallopian tubes (confirmed through a surgical laparoscopy), and all measured variables in the male sperm were normal. Women with ‘mild’ endometriosis and men with mild sperm motility problems were eligible for inclusion; however, they constituted less than 10% of those included.

A total of 580 women were randomly allocated to one of three groups for six months. The first group (194 women) received clomifene citrate and were told to take it using the normal product recommendations. They also had their progesterone levels monitored, and were given advice about timing of intercourse and appropriate action was taken if there was overstimulation of the ovaries with too many egg follicles developing. The second group (193 women) were given insemination, which involved a single introduction of prepared semen via a catheter into the uterus after ovulation had been indicated by a surge in hormone levels. The third group (193 women) received expectant management, in which the couples were advised to have regular intercourse, but were given no other medical care (such as visits to the clinic), and no other advice (such as measuring temperature).

All couples in the three groups were balanced for the duration of their fertility trouble, age, woman’s BMI, and number of previous children. Pregnancy tests were performed two weeks after artificial insemination, and in the other two groups at day 28 of their menstrual cycle (unless their period had already started). If a test was positive, it was confirmed by ultrasound.

The main outcome that the researchers looked at was the live birth rate. Other outcomes were pregnancy rate per woman, multiple pregnancy rate, acceptability of the treatment, adverse effects, and anxiety or depression.

What were the results of the study?

All but four participants were included in the analysis. In the group assigned to clomifene, 48% of women received six completed cycles of treatment and 9% received none (reasons not given). In the group assigned intrauterine insemination, 19% of women received the full six inseminations, and 13% received none (reasons not given).

Live birth rates in the three groups were 14% in the clomifene group, 23% in the insemination group, and 17% in the expectant management group. There was no significant difference in chance of a live birth or time to pregnancy with either clomifene or insemination compared to expectant management.

When looking at secondary outcomes, the researchers found that pregnancy rates, miscarriage rates and multiple birth rates were all similar between the groups. Adverse effects of abdominal pain, nausea, headaches and hot flushes were more frequent in the clomifene group. Women receiving either clomifene or insemination found the process of treatment significantly more acceptable to them than those in the expectant management group, however, rates of anxiety or depression did not differ between the three groups.

What interpretations did the researchers draw from these results?

The researchers concluded that clomifene citrate and intrauterine insemination appear to offer no benefit over expectant management in couples with unexplained infertility.

What does the NHS Knowledge Service make of this study?


This carefully designed and well-conducted study demonstrated that for couples who have no clear cause for their infertility, active treatments such as clomifene or insemination do not appear to be any more beneficial than expectant management. However, it is worth noting that after six months, rates of pregnancy resulting in a live birth were low in all groups. It is not possible to say whether the outcomes would have been different after a longer period of time (for example one year of treatment). Additionally, the acceptability of waiting with no fertility assistance was much lower for the expectant management group compared to the couples receiving some form of treatment. The benefits in terms of causing less distress to the couple may need to be considered, even if the outcomes are not significantly different.

It is very important that the interpretation of these reports are given in the right context. This was a comparison of expectant management, intrauterine insemination and the drug clomifene in couples who had failed to get pregnant naturally after two years, but had no explained reason for infertility. That is, the woman had a normal ovulatory menstrual cycle, normal hormone levels, and patent fallopian tubes, while all measured variables in the male sperm were normal. Although they did include women with mild endometriosis and men with mild sperm motility problems, they made up a very small proportion of the total. However, there may have been other causes for fertility problems that could have been identified by more extensive testing (depending on resources at the care centres).

At the current time, no assumptions should be made about the use of infertility treatment in people with identified causes for infertility. Additionally no assumptions should be made from this research about the effectiveness of IVF, which would normally be considered once other options have failed. Further research would be needed on pregnancy outcomes following different treatment options both in more couples with unexplained infertility, and in couples with identified fertility problems. These would need to gain a better understanding of the treatments (or treatment combinations) that are most beneficial and to whom they are best suited.


Sir Muir Gray adds...

This emphasises again that the most important service is unbiased information that is clearly presented.


Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Two fertility drugs recommended for childless couples are virtually useless, says study. Daily Mail, August 08 2008

Fertility study scorns frontline treatments. The Guardian, August 08 2008

Fertility treatments 'no benefit'. BBC News, August 08 2008

Common fertility treatments 'do not aid conception'. The Daily Telegraph, August 08 2008

Common fertility treatments are 'no better than nature', study finds. The Times, August 08 2008

Two fertility therapies found to be 'worthless'. The Independent, August 08 2008

Would you conceive it? Daily Mirror, August 08 2008

Futility drug. The Sun, August 08 2008

Fertility aids ‘a waste of time’. Metro, August 08 2008

Links to the science

Bhattacharya S, Harrild K, Mollison J, et al. Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial. BMJ 2008; 337: a716

El-Toukhy TA, Khalaf Y. Treatment of unexplained infertility. BMJ 2008; 337: a772

Further reading

Hughes E, Brown J, Collins J, Vandekerckhove P. Clomiphene citrate for unexplained subfertility in women. Cochrane Database Syst Rev 2000, Issue 1

Verhulst SM, Cohlen BJ, Hughes E, te Velde E, Heineman MJ. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev 2006, Issue 4

Pandian Z, Bhattacharya S, Vale L, Templeton A. In vitro fertilisation for unexplained subfertility. Cochrane Database of Syst Rev 2005, Issue 2


How helpful is this page?

Average rating

Based on 0 ratings

All ratings

0  ratings
0  ratings
0  ratings
0  ratings
0  ratings

Add your rating