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. 2023 May 6;23(1):233.
doi: 10.1186/s12905-023-02385-1.

The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial

D Kamphuis  1   2 , K Rosielle  3   4 , N van Welie  3   4   5 , I Roest  3   4   6   7 , A J C M van Dongen  8 , E A Brinkhuis  9 , P Bourdrez  10 , A Mozes  11 , H R Verhoeve  5 , D P van der Ham  12 , F P J M Vrouenraets  13 , J J Risseeuw  14 , T van de Laar  15 , F Janse  16 , J E den Hartog  17 , M de Hundt  18 , A B Hooker  19 , A G Huppelschoten  20 , Q D Pieterse  21 , M Y Bongers  6   7 , J Stoker  22 , C A M Koks  6 , C B Lambalk  3   4 , A Hemingway  23 , W Li  24 , B W J Mol  24   25 , K Dreyer  3   4 , V Mijatovic  3   4
Affiliations

The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial

D Kamphuis et al. BMC Womens Health. .

Erratum in

Abstract

Background: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study.

Methods: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated.

Discussion: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice.

Trial registration number: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).

Keywords: Cost-effectiveness; Fallopian tubes; Fertility work-up; Hysterosalpingography (HSG); Infertility; Live birth; Oil-based contrast medium; Pregnancy; Randomized controlled trial; Tubal flushing.

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Conflict of interest statement

DK, NvW, IR, AJCMvD, EAB, PB, AM, HRV, DPvdH, FPJMV, JJR, TvdL, JEdH, MdH, AGH, QDP, MYB, and CAMK have nothing to declare. KR and FJ reports receiving a travel grant from Merck. ABH reports receiving a travel –and speaker’s fee from Merck and speakers fee from Nordic Pharma. JS has a research agreement with Takeda not related to this topic. CBL reports receiving research grants from Merck, Ferring and Guerbet. AH reports receiving travel and speaker’s fees from Guerbet and reports past consultancy for Guerbet. WL reports receiving research grants from the NHMRC Centre for Research Excellence in Women’s Health in Reproductive Life and Norman Beischer Medical Research Foundation not related to this study. BWM is supported by a NHMRC investigator grant (GNT1176437) and reports consultancy for ObsEva and Merck and travel support from Merck. KD reports receiving travel and speaker’s fees from Guerbet and research grants from Guerbet. VM reports receiving travel -and speaker’s fees from Guerbet as well as research grants from Guerbet, Merck and Ferring.

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