Oil-based contrast medium use in hysterosalpingography is associated with higher pregnancy rates compared with water-based contrast
Dreyer K, van Rijswijk J, Mijatovic V, et al. Oil-based or water-based contrast for hysterosalpingography in infertile women. N Engl J Med. 2017;376(21):2043-2052.
Hysterosalpingography (HSG) to assess tubal patency has been a mainstay of infertility diagnosis for decades. Some, but not all, studies also have suggested that pregnancy rates are higher after this tubal flushing procedure, especially if performed with oil contrast.7,8 A recent multicenter, randomized, controlled trial by Dreyer and colleagues that compared ongoing pregnancy rates and other outcomes among women who had HSG with oil contrast versus with water contrast provides additional valuable information.9
Trial details
In this study, 1,294 infertile women in 27 academic, teaching and nonteaching hospitals were screened for trial eligibility; 1,119 women provided written informed consent. Of these, 557 women were randomly assigned to HSG with oil contrast and 562 to water contrast. The women had spontaneous menstrual cycles, had been attempting pregnancy for at least 1 year, and had indications for HSG.
Exclusion criteria were known endocrine disorders, fewer than 8 menstrual cycles per year, a high risk of tubal disease, iodine allergy, and a total motile sperm count after sperm wash of less than 3 million/mL in the male partner (or a total motile sperm count of less than 1 million/mL when an analysis after sperm wash was not performed).
Just prior to undergoing HSG, the women were randomly assigned to receive either oil contrast or water contrast medium. (The trial was not blinded to participants or caregivers.) HSG was performed according to local protocols using cervical vacuum cup, metal cannula (hysterophore), or balloon catheter and approximately 5 to 10 mL of contrast medium.
After HSG, couples received expectant management when the predicted likelihood of pregnancy within 12 months, based on the prognostic model of Hunault, was 30% or greater.10 IUI was offered for pregnancy likelihood less than 30%, mild male infertility, or failure after a period of expectant management. IUI with or without mild ovarian stimulation (2-3 follicles) with clomiphene or gonadotropins was initiated after a minimum of 2 months of expectant management after HSG.
The primary outcome measure was ongoing pregnancy, defined as a positive fetal heartbeat on ultrasonographic examination after 12 weeks of gestation, with the first day of the last menstrual cycle for the pregnancy within 6 months after randomization. Secondary outcome measures were clinical pregnancy, live birth, miscarriage, ectopic pregnancy, time to pregnancy, and pain scores after HSG. All data were analyzed according to intention-to-treat.
Pregnancy rates increased with oil-contrast HSG
The baseline characteristics of the 2 groups were similar. HSG showed bilateral tubal patency in 477 of 554 women (86.1%) in the oil contrast group and in 491 of 554 women (88.6%) who received the water contrast (rate ratio, 0.97; 95% confidence interval [CI], 0.93-1.02). Bilateral tubal occlusion occurred in 9 women in the oil group (1.6%) and in 13 in the water group (2.3%) (relative risk, 0.69; 95% CI, 0.30-1.61).
A total of 58.3% of the women assigned to oil contrast and 57.2% of those assigned to water contrast received expectant management. Similar percentages of women in the oil group and in the water group underwent IUI (39.7% and 41.0%, respectively), IVF or intracytoplasmic sperm injection (ICSI) (2.3% and 2.2%), laparoscopy (6.2% in each group), and hysteroscopy (4.4% and 4.2%).
Ongoing pregnancy occurred in 220 of 554 women (39.7%) in the oil contrast group and in 161 of 554 women (29.1%) in the water contrast group (rate ratio, 1.37; 95% CI, 1.16-1.61; P<.001). The median time to the onset of pregnancy in the oil group was 2.7 months (interquartile range, 1.5-4.7) (FIGURE 2), while in the water group it was 3.1 months (interquartile range, 1.6-4.8) (P = .44).
While the proportion of women getting pregnant with or without the different interventions was similar in both groups, the live birth rate was 38.8% in the oil group versus 28.1% in the water group (rate ratio, 1.38; 95% CI, 1.17-1.64; P<.001). Three of 554 women (0.5%) assigned to oil contrast and 4 of 554 women (0.7%) in the water contrast group had an adverse event during the trial period. Three women (1.4%), all in the oil group, delivered a child with a congenital anomaly.
Why this study is important
This is the largest and best methodologic study on this clinical issue. It showed higher pregnancy and live birth rates within 6 months of HSG performed with oil compared with water. Although the study was not blinded, the group similarities and objective outcomes support minimal bias. Importantly, these results can be generalized only to women with similar inclusion characteristics.
It is unclear why oil HSG might enhance fertility. Suggested mechanisms include flushing of debris and/or mucous plugs or an effect on peritoneal macrophages or endometrial receptivity. Since HSG is minimally invasive and inexpensive, and the 10% increase in pregnancy rates corresponds to an NNT of 10, it is reasonable to consider, although formal cost-effectiveness data are lacking.
Concerns include the rare theoretical risk of intravasation with subsequent allergic reaction or fat embolism. Three infants in the oil group and none in the water group had congenital anomalies. This is likely due to chance, since this rate is not higher than that in the general population and no other data suggest an increased risk. Comparison of these results with other new techniques, such as sonohysterography (saline infusion sonogram), awaits further studies.
Recommendation
HSG with oil contrast should be considered a potential therapeutic as well as diagnostic intervention in selected patients.
WHAT THIS EVIDENCE MEANS FOR PRACTICE
HSG is an important diagnostic test for most infertility patients. The fact that a therapeutic benefit probably also is associated with oil-based HSG increases the clinical indications for this test.
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