The recent study from Dreyer et al  (see BioNews 901) examining the chance of natural pregnancy following hysterosalpingography (HSG) has provoked a significant amount of interest in the lay press, with suggestions that this well established diagnostic fertility test could be offered therapeutically and be considered as an alternative to IVF.
Performing an HSG is a quick, outpatient procedure, which appears to be safe and relatively inexpensive. Women experiencing subfertility are often given tests to establish whether the fallopian tubes are clear, of which HSG is one of the most longstanding and popular. The procedure consists of flushing liquid contrast media through the tubes and taking repeat x-rays to delineate tubal anatomy and identify any blockages. Various liquid agents have been used for an HSG, including water-soluble contrast media and oil-soluble contrast media.
Clinicians have often noted that many women conceive shortly after tubal flushing, which has raised the question whether it could also be used as a treatment for subfertility. In the 1950s it was first reported that women who received HSG with oil based media showed double the pregnancy rates of women who received no procedure. Many reports on the therapeutic aspect of oil-soluble contrast media have since been published, most of these reports, however, did not have satisfactory control groups. There has also been debate about which contrast medium should be used (water-soluble or oil-soluble media) and their influence on pregnancy rates.
Although many studies have shown a possible fertility-enhancing effect of HSG with the use of oil-based contrast, only three randomised, controlled trials have been published between 2002 and 2009. When the data from these trials were combined, the results showed that the odds of ongoing pregnancy after HSG performed with oil contrast were three times higher compared with no intervention.
In the newest study - the H2Oil trial - which was published in a leading medical journal, the New England Journal of Medicine , participants were recruited from 27 hospitals in the Netherlands. Women were eligible to participate in the trial if they were less than 39 years of age and had been trying to conceive for at least one year. Importantly, women with known endocrine disorders (eg polycystic ovary syndrome, diabetes, thyroid disorders), a history of pelvic inflammatory disease, previous chlamydia infection, or known endometriosis were excluded from the study. In addition patients were excluded if the male partner had impaired sperm.
Among the women included, 557 were randomly assigned to HSG with the use of oil contrast and 562 were assigned to HSG with the use of water contrast. Six months later, the ongoing pregnancy rate was assessed for all the women. The researchers found the rate was significantly higher after using oil contrast compared with water contrast.
In particular the authors reported a 38 percent live birth rate after oil-based contrast HSG compared to 28 percent after water-based contrast HSG. About three-quarters of the women who conceived did so spontaneously while the remaining one quarter underwent fertility treatment, mostly intrauterine insemination.
This multicentre study included a large number of patients and was well-designed. There may be a number of theories behind the results, which highlight the potential therapeutic role of HSG.
Firstly, HSG may flush out debris from the fallopian tubes, therefore unblocking undamaged tubes. Such debris may not necessarily block the fallopian tube but may hinder conception or embryo transport along the fallopian tube.
Secondly, oil-based contrast media have been shown to alter production of chemical agents produced by peritoneal cells called macrophages. This could in theory affect the interaction with sperm. Other theories with less supporting or no evidence include 'straightening' of tortuous fallopian tubes, disruption of adhesions around the tubes and even a contrast-induced antibacterial action on mucous membranes.
However, it should be pointed out that the aim of this study was not to compare HSG with IVF. In addition, women with identified causes of infertility, such as endometriosis, polycystic ovarian syndrome, or endocrine abnormalities, or couples with male factor infertility, were not included in the study. These patients still constitute the majority of the women and couples seen in fertility clinics.
Based on data from the HFEA (Human Fertilisation and Embryology Authority) the live birth rate after IVF in the United Kingdom is 32 percent for patients less than 35 years old, 20 percent for women aged 38 to 39 and 13.6 percent for women aged 40 to 42. This age-related effect to pregnancy rates needs to be taken into consideration before infertile patients decide to postpone IVF, particularly when a known cause of infertility has been identified or when the function of the ovaries is found to be reduced.
In conclusion, the H2Oil study results indicate that a 3 to 6-month, 'watch-and wait' approach after a normal HSG may be suitable for some patients. However, it should only be considered after a careful selection process, which should take into account the individual circumstances, wishes and diagnoses of the women and couples seeking fertility treatment.