Overtreatment in couples with unexplained infertility

Kersten, Fleur A M; Hermens, R; Braat, D.D.M.; Hoek, Annemieke; Mol, BW; Goddijn, Mariëtte; Nelen, W.L.D.M.; Study, Improvement

doi:10.1093/humrep/dev185

Cited by 6 publications

(6 citation statements)

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“…These spontaneously occurring pregnancies reflect the relative nature of subfertility in these cases. Although expectant management remains a valid option for couples with unexplained subfertility (27), there remains considerable pressure from patients for intervention due to lack of confidence in natural conception.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine insemination with gonadotropin stimulation or in vitro fertilization for the treatment of unexplained subfertility: a randomized controlled trial

Nandi

Bhide

Hooper³

et al. 2017

Fertility and Sterility

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Section: Discussionmentioning

confidence: 99%

Intrauterine insemination with gonadotropin stimulation or in vitro fertilization for the treatment of unexplained subfertility: a randomized controlled trial

Nandi

Bhide

Hooper³

et al. 2017

Fertility and Sterility

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“…Moreover, expectant management might not be acceptable to many couples, as further attempts of natural conception add to already existing stress and frustration . This leads to overtreatment in many of these cases …”

Section: Treatment Options For Unexplained Subfertilitymentioning

confidence: 99%

Unexplained subfertility: diagnosis and management

Nandi

Homburg

2016

The Obstetric & Gynaecologis

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Key content Unexplained subfertility is diagnosed when standard investigations (tests for ovulation, tubal patency and semen analysis) are all normal. Between 30% and 40% of subfertile couples fall into this category. In some couples, unexplained subfertility may result from subtle undetectable factors; in other couples, it may be associated with a genuine absence of any abnormality. There is currently much controversy about the selection of appropriate management options for such couples, especially following the National Institute for Health and Care Excellence (NICE) guideline published in 2013. Therefore, a clear understanding of the available evidence is essential for the management of couples with unexplained subfertility. The potential contributing factors, diagnosis and management of unexplained subfertility are discussed. Learning objectives To summarise the available recent evidence and help the reader obtain a clear understanding of the continuing debates in this field. To help clinicians in counselling couples with unexplained subfertility. Ethical issues Should couples be advised to try to conceive naturally for 2 years (regardless of their age) before they are offered treatment, even though fecundity declines with age? What does the evidence suggest should be the first line of management for couples with unexplained subfertility: intrauterine insemination or in vitro fertilisation?

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“…Our results indicate that the chance of live birth following IUI+SO or IVF is higher than that associated with expectant management. Does this mean that we should treat everyone immediately (Kamphuis et al, 2014;Kersten et al, 2015)? Clinicians must consider the absolute chances with and without treatment on an individual basis together with the cost to the health service (or patient) and the physical and emotional burden to the woman (Brandes et al, 2011).…”

Section: Interpretation and Clinical Importancementioning

confidence: 99%

Predicting the chances of having a baby with or without treatment at different time points in couples with unexplained subfertility

et al. 2019

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STUDY QUESTION Can we develop a prediction model that can estimate the chances of conception leading to live birth with and without treatment at different points in time in couples with unexplained subfertility? SUMMARY ANSWER Yes, a dynamic model was developed that predicted the probability of conceiving under expectant management and following active treatments (in vitro fertilisation (IVF), intrauterine insemination with ovarian stimulation (IUI + SO), clomiphene) at different points in time since diagnosis. WHAT IS KNOWN ALREADY Couples with no identified cause for their subfertility continue to have a realistic chance of conceiving naturally, which makes it difficult for clinicians to decide when to intervene. Previous fertility prediction models have attempted to address this by separately estimating either the chances of natural conception or the chances of conception following certain treatments. These models only make predictions at a single point in time and are therefore inadequate for informing continued decision-making at subsequent consultations. STUDY DESIGN, SIZE, DURATION A population-based study of 1316 couples with unexplained subfertility attending a regional clinic between 1998 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS A dynamic prediction model was developed that estimates the chances of conception within 6 months from the point when a diagnosis of unexplained subfertility was made. These predictions were recomputed each month to provide a dynamic assessment of the individualised chances of conception while taking account of treatment status in each month. Conception must have led to live birth and treatments included clomiphene, IUI + SO, and IVF. Predictions for natural conception were externally validated using a prospective cohort from The Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE A total of 554 (42%) couples started fertility treatment within 2 years of their first fertility consultation. The natural conception leading to live birth rate was 0.24 natural conceptions per couple per year. Active treatment had a higher chance of conception compared to those who remained under expectant management. This association ranged from weak with clomiphene to strong with IVF [clomiphene, hazard ratio (HR) = 1.42 (95% confidence interval, 1.05 to 1.91); IUI + SO, HR = 2.90 (2.06 to 4.08); IVF, HR = 5.09 (4.04 to 6.40)]. Female age and duration of subfertility were significant predictors, without clear interaction with the relative effect of treatment. LIMITATIONS, REASONS FOR CAUTION We were unable to adjust for other potentially important predictors, e.g. measures of ovarian reserve, which were not available in the linked Grampian dataset that may have made predictions more specific. This study was conducted using single centre data meaning that it may not be generalizable to other centres. However, the model performed as well as previous models in reproductive medicine when externally validated using the Dutch cohort. WIDER IMPLICATIONS OF THE FINDINGS For the first time, it is possible to estimate the chances of conception following expectant management and different fertility treatments over time in couples with unexplained subfertility. This information will help inform couples and their clinicians of their likely chances of success, which may help manage expectations, not only at diagnostic workup completion but also throughout their fertility journey. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a Chief Scientist Office postdoctoral training fellowship in health services research and health of the public research (ref PDF/12/06). B.W.M. is supported by an NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck, and Guerbet. None of the other authors declare any conflicts of interest.

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Overtreatment in couples with unexplained infertility

Cited by 6 publications

References 0 publications

Intrauterine insemination with gonadotropin stimulation or in vitro fertilization for the treatment of unexplained subfertility: a randomized controlled trial

Intrauterine insemination with gonadotropin stimulation or in vitro fertilization for the treatment of unexplained subfertility: a randomized controlled trial

Unexplained subfertility: diagnosis and management

Predicting the chances of having a baby with or without treatment at different time points in couples with unexplained subfertility

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