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Your Fertility Journey 2019

Tubal flushing during HSG with oil contrast: from diagnostics to fertility enhancement

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Professor Dr V. Mijatovic

Department of Reproductive Medicine, Amsterdam University Medical Center, on behalf of the H2Oil study group

Hysterosalpingography (HSG) was initially introduced as a diagnostic test, to evaluate the patency of the fallopian tubes in the fertility work-up patients presenting with infertility.

Debates on the therapeutic effects of tubal flushing during HSG started over six decades ago. Summarising the available evidence, the 2015 Cochrane systematic review showed a non-significant higher amount of ongoing pregnancies in favour of tubal flushing with oil-based contrast in infertile women (Mohiyiddeen et al., 2015).

The H2Oil study

In order to clarify the uncertainty around the use of oil- or water-based contrast for HSG, the H2Oil study, a large randomised trial, in which 1,119 infertile women participated, was conducted in the Netherlands. This landmark study, published in the New England Journal of Medicine, showed significantly 10% more ongoing pregnancies as well as live births in the first six months following HSG with oil-based contrast, as compared to HSG with water-based contrast (Dreyer et al, 2017). Publication of the study generated a worldwide renewed interest in tubal flushing and the use of oil-based contrast for fertility enhancement. Two recent and updated systematic reviews confirmed these findings (Fang, et al, 2018, Wang, et al, 2019).

Flushing debris and mucus from the fallopian tubes

The principal theory is that tubal flushing with oil-based contrast flushes accumulated debris and mucous plugs from undamaged tubes, which will enhance tubal patency (openness). Several safety concerns on oil-based contrast have been raised. Firstly, venous intravasation occurs in approximately 2-7% of the cases in HSG, and occurs more frequently when using oil contrast. While intravasation can potentially result in pulmonary embolism, no cases of embolism were reported in the published trials, which is reassuring. Pelvic infection is another potential safety concern. However, data from the available trials are also reassuring showing that it is a rare event.

The cost-effectiveness of tubal-flushing

An economic analysis based on the data of the H2Oil study and 2017 US prices (using consumer price index data and considering a cost difference between oil-based and water-based contrast in the United States being globally the highest) showed a cost-effectiveness ratio for oil-based contrast compared to water-based contrast of $8,198 for an additional ongoing pregnancy (Rijswijk van et al., 2018). This is less than the cost of one IVF treatment (US$11,500). Moreover, it is less time consuming and burdensome for women. Thus, there is a strong argument to incorporate tubal flushing with oil-based contrast during HSG in clinical practice.

Limitations in older or higher-risk women

However, the data from the H2Oil study are limited to infertile women at a low risk of tubal pathology, who were younger than 39 years and without ovulation disorders. Therefore, a clear knowledge gap exists with respect to women who were not evaluated in the H2Oil study, i.e. women with ovulation disorders, women who are at high risk for tubal pathology, or women who are above 38 years of age, in whom infertility is driven by decreased ovarian reserve. Since the mechanism of infertility in these women is completely different, it is unknown if tubal flushing with oil-based contrast increases fertility chances in these women.

What’s next?

In 2019, two randomised trials started. The first trial will test the hypothesis that HSG with oil-based contrast will increase the pregnancy – and live birth rate as compared to HSG with water-based contrast in the above mentioned groups of infertile patients – and the second one will investigate cost-effectiveness of direct versus delayed (six months after fertility work-up) tubal flushing during HSG with oil contrast in infertile women. The hypothesis is that direct tubal flushing will lead to a shorter time to pregnancy and thus reduce the need for IVF and therefore also reduce the costs.

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