Unexplained infertility guideline: IUI for all?

Copenhagen 2023 Bhattacharya

Published 30 June 2023

Review of a new ESHRE evidence-based guideline on unexplained infertility, which made 52 recommendations, emphasised IUI with ovarian stimulation as first-line treatment, but noted expectant management as still important when the prognosis is good.

IUI with ovarian stimulation is recommended as a first-line treatment over expectant management in unexplained infertility especially in poor prognosis couples, according to a new ESHRE guideline.(1)

Published in June, the guideline makes 52 recommendations of which the key ones were summarised by Siladitya Bhattacharya, a member of the guideline development group. He emphasised in his presentation that a prognosis-based approach to active treatment is necessary and that expectant management remained important.

Emphasising that unexplained infertility is ‘not sterility’, Bhattacharya, from the University of Aberdeen, said that some couples thus have a ‘real chance’ of natural pregnancy and that this chance of conception changes over time.

With the aid of a flowchart, Bhattacharya explained how unexplained infertility should be managed, including the role (if any) of IVF. The guideline recommends treating poor prognosis patients with IUI/OS followed by IVF after 3-6 failed cycles, but to manage good prognosis patients first with six months of expectant management before IUI/OS. Healthy diet, regular exercise, behavioural therapy and psychological support should all be part of care, he added.

Some countries including the Netherlands have developed their own prediction models for the probability of live birth from expectant management and from treatment. Bhattacharya added data from his own research group in Scotland based on estimating the chance of conception using expectant management, IVF and IUI to show how age influences outcomes.

Overall, the evidence available on the efficacy of active treatments for unexplained infertility compared with expectant management was limited and described by Bhattacharya as ‘devoid of high quality’ in some areas.

The weight of evidence strongly suggests that IUI/OS is recommended in preference to expectant management, particularly for couples with poor prognosis. However, other approaches appeared to show no benefit (over expectant management), such as clomiphene with timed intercourse without OS, and IUI in a natural cycle.

What about IVF vs expectant management? Literature on this is again scarce, but the guideline development group concluded that IVF is probably not recommended over IUI/OS, and ICSI not recommended over conventional IVF. Bhattacharya added that the decision to use IVF should be based on patient characteristics, such as age, duration of infertility, previous treatment, and previous pregnancy.

Next, Bhattacharya offered a summary of the mechanical-surgical procedures and alternative therapeutic approaches reviewed by the development group.

The guideline does not recommend endometrial scratching and hysteroscopy; and tubal flushing with an oil-soluble contrast medium is deemed preferable over water, but the risks and benefits should be discussed with patients. Psychological support for patients when needed is recommended, but the group agreed it would probably not recommend treatment with antioxidants, acupuncture and inositol.

To conclude, Bhattacharya said the guideline group had outlined three top priorities for future research, ideally in well-designed RCTs, to address the lack of evidence around UI and the low quality of the data that is available. The first is whether a predictive model can be developed, tested and validated to compare the outcomes of different management strategies for couples with unexplained infertility. The other priorities are to identify the optimal ART for UI; and to determine the value of current methods of assessing sperm DNA integrity as a means of prediction.

1. https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Unexplained-infertility


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