33 Duration of the fertility enhancing effect of HSG with oil-based contrast 2 Although a previous analysis did not identify characteristics that were associated with a greater or lesser effect of oil-based contrast compared with water-based contrast, the hypothesis regarding the Fallopian tubes is supported by a recent analysis of perceived pain during HSG (20, 24). Women who reported a VAS score of 6.0 or more were found to benefit more from oil-based contrast (49.4% versus 29.6%, Relative Risk 1.7, 95% CI 1.1–2.5) (20). In the current study, there was no evidence that the effect of oil versus water contrast decreased over time for women who had a VAS score of 6 or higher. Thus, in addition to the effect of oil contrast being dependent on VAS score, this provides some evidence to support the theory of dislodging debris or mucus plugs in the Fallopian tubes, as that effect is likely to be (semi-)permanent. However, the small sample sizes for this sensitivity analysis must be acknowledged as the VAS score was not measured in all patients (n = 401) and only 152 of those scored 6 or higher. The previously mentioned second mechanism might also explain the decrease in hazard ratio that was found in the whole cohort: that there is only an effect in the group in which debris was dislodged and pain was felt, and as their chances increase, they conceive and drop out of the cohort. This secondary analysis was performed to understand the biological mechanism underlying the fertility-enhancing effect of tubal flushing and to evaluate how long it is beneficial for infertile women. However, the study emphasized the complexity of ‘unexplained infertility’ with multiple unknown aspects. All studied women were below 39 years of age, had a regular ovulatory cycle and had a low perceived risk of tubal pathology, so it is unclear what causes infertility in these women. Women who did not conceive within 2 years after HSG no longer benefited from the oil-based contrast. This may support the hypothesis that tubal flushing using oil-based contrast dislodges debris or mucus plugs from the proximal parts of the tubes and that, after 2 years, most of these women conceived. This hypothesis can be further explored by studies in which the pressure build-up of oil-based and water-based contrast during HSG, resulting in dislodgment of material such as debris and mucus plugs, is investigated. Furthermore, future studies are needed to evaluate whether HSG with oil-based contrast before IVF has an fertility-enhancing effect, and to assess whether the fertility-enhancing effect of oil-based contrast is also present in women above 39 years of age with a diminished ovarian reserve, women who have ovulation disorders or women at high risk of tubal pathology. CONCLUSION The fertility-enhancing effect of oil-based contrast versus water-based contrast after HSG in terms of the hazard ratio was highest shortly after HSG and then decreased,
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