Rates of ongoing pregnancy and live births were 10% higher among infertile women who underwent hysterosalpingography with an oil contrast agent vs those whose procedure used a water contrast agent, according to findings from a multicenter randomized trial published online May 18 in the New England Journal of Medicine.
Smaller previous studies had reported conflicting results. Therefore, Kim Dreyer, MD, PhD, from VU University Medical Center in Amsterdam, the Netherlands, and colleagues designed the H2Oil trial to resolve the issue.
The study, conducted from 2012 to 2014, enrolled 1119 women ages 18 to 39 years from 27 hospitals and randomly assigned them to hysterosalpingography with oil contrast (n = 557) or water contrast (n = 562). Both agents were made by Paris-based Guerbet: Lipiodol Ultrafluid (Ethiodol in the United States), an ethiodized poppy-seed oil, and Hystero, a water-based agent.
Within 6 months of randomization, 39.7% of the women in the oil contrast group had an ongoing pregnancy vs 29.1% of those in the water contrast group (rate ratio, 1.37; 95% confidence interval, 1.16 -1.61; P < .001). Live births were also more frequent in the oil group, at 38.8% vs 28.1% (rate ratio, 1.38; 95% confidence interval, 1.17 - 1.64; P <.001).
The 10.6% advantage in rate of pregnancy with oil contrast translates to a number needed to treat of 10, the authors note.
In terms of patient characteristics, the median age in both groups was about 33 years and the median duration of infertility was about 20 months, with about two thirds in each group having primary infertility defined as the failure to conceive an initial pregnancy after at least a year of unprotected sexual intercourse. Motile sperm counts in the fathers of both groups were similar, at about 55 million/mL.
The majority of women were found to have patent bilateral fallopian tubes in both imaging groups: 86.1% (oil) and 88.6% (water).
The study also found similar rates in both groups in the way conception was achieved. The 220 ongoing pregnancies in the oil group were conceived as follows: 73.6% naturally, 6.8% after intrauterine insemination without mild ovarian hyperstimulation, 17.7% after intrauterine insemination with mild ovarian hyperstimulation, and 1.8% after embryo transfer after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI).
In the water group, 72.7% of 161 ongoing pregnancies were naturally conceived, 9.9% were conceived after intrauterine insemination without mild ovarian hyperstimulation, 16.1% were conceived after intrauterine insemination with mild ovarian hyperstimulation, and 1.2% were conceived after embryo transfer after IVF or ICSI.
"The rates of successful pregnancy were significantly higher in the oil-based group, and after only one treatment," said coauthor Ben Mol, MD, a professor of obstetrics and gynecology at the University of Adelaide in Australia, in a university news release.
"This is an important outcome for women who would have had no other course of action other than to seek in vitro fertilization treatment. It offers new hope to infertile couples."
But S. Zev Williams, MD, PhD, chief of the Division of Reproductive Endocrinology and Infertility at Columbia University in New York City, was more cautious.
"This study provides useful information that can help guide clinical care when there's a choice of two imaging agents," he told Medscape Medical News. "But the patients who benefit from this are those who have open fallopian tubes. For those who have closed tubes, this isn't going to save them from having IVF. Still, it's nice when a diagnostic test may have some therapeutic benefit."
Nor will this study's findings greatly affect the timing of hysterosalpingography, as this test is generally performed early on in fertility investigations. As to relative expense, Dr Williams said a pending cost analysis will address this question. "If there's a difference in fertility outcome, that will dramatically affect cost as more women use the oil agent," he said.
Linda C. Giudice, MD, PhD, a professor of medicine at University of California, San Francisco, called the results "promising overall" and said they suggest that doing an oil-based hysterosalpingogram early in the fertility workup can enhance fecundity even in women with a protracted period of infertility. "It is much larger than previous studies and shows that adverse events are not more frequent with oil," she said. "Previously there had been fear of extravasation into the veins, with fat droplets traveling to the lungs and causing emboli," Dr Giudice told Medscape Medical News.
Allergic reaction has also been a concern, but the study found no indication of that complication. The underlying fertility-enhancing mechanisms of oil contrast media remain unknown. "Some studies suggest that tubal-patency testing with an oily medium will flush debris and dislodge mucus plugs from undamaged tubes," Dr Dreyer and associates write.
Once commonly used, oil-based agents gave way to water-soluble media as potentially safer and yielding images that are somewhat easier to interpret.
In the current study, the researchers also found the median time to pregnancy onset was shorter, at 2.7 months (interquartile range [IQR], 1.5 - 4.7 months) in the oil group vs 3.1 months (IQR, 1.6 - 4.8) in the water group (P = .44). Median duration of pregnancy was similar in both groups, at 39.9 weeks.
Adverse events were similar in both groups, with still birth rates of 0.7% in both groups, miscarriage rates of 5.2% in the oil group and 5.6% in the water group, and ectopic pregnancy of 0.4% in both. Although three infants from the oil group had congenital abnormalities, that was likely a result of chance and was similar to the rate found in the general population. "[W]e are unaware of other data suggesting an increased risk of congenital abnormalities with oil contrast," the authors write.
They emphasize that as the findings are based on young women at low risk for tubal disease and no known endocrinological disease, they are not generalizable to other infertile populations. They also note that new outpatient testing techniques such as foam sonography are being used, but so far there are no data on the effect of oil contrast.
The study received no financial assistance from Guerbet, the manufacturer of the contrast agents. Several study authors have disclosed financial relationships with Guerbet and/or other industry partners outside the scope of the submitted work.
N Engl J Med. Published online May 18, 2017. Full text
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Cite this: Oil-Based Hysterosalpingograms Enhance Fertility - Medscape - May 22, 2017.