Evaluating Lipiodol Efficacy in Proximal Tubal Occlusion Treatment: Single-Center Experience and Literature Review

Infertility is described as a medical condition referring to the inability to become clinically pregnant after 1 year of consistent unprotected sexual intercourse in women under the age of 35 years, or after 6 months in women aged 35 years and older [ 1 ]. Infertility is a widespread problem affecting around 186 million people worldwide and 8% to 12% of couples of reproductive age [ 2 , 3 ]. Although in 30% of infertile couples it is impossible to determine the exact cause of infertility, most cases are successfully diagnosed, and appropriate treatment can be initiated. Among the causes of female infertility, the most common are ovarian dysfunction and tubal disease [ 1 ]. Tubal infertility accounts for up to 67% of infertility diagnoses, of which proximal tubal occlusion is estimated to range from 10% to 25% [ 4 ]. The blockage of the fallopian tubes impairs the processes of oocyte retrieval, fertilization, and transport of the fertilized egg, ultimately leading to infertility [ 5 ]. This condition can result from various factors, including infection and subsequent inflammation, endometriosis, polyps, or salpingitis isthmica [ 1 ]. Laparoscopy with chromopertubation is routinely performed in the diagnosis of fallopian tube obstruction. Despite the significant advantages of this type of diagnosis and the possibility of an accurate assessment of the pelvic anatomy, the use of minimally invasive methods, such as hysterosalpingography and contrast-enhanced hysterosalpingo-sonography, are considered the preferred methods, as they allow simultaneous selective salpingography and recanalization if a proximal fallopian tube obstruction is identified [ 6 ]. The treatment of fallopian tube obstruction is also achieved through methods such as microsurgical procedures, radiological treatments, hormonal therapies, and in vitro fertilization (IVF) techniques. Recanalization is an effective and minimally invasive treatment for proximal obstructions and is considered an excellent alternative to extensive surgery [ 4 ]. A large, multicenter, and randomized study by van Rijswijk et al showed a significant advantage of using oil-soluble contrast over water-soluble contrast when performing hysterosalpingography, as it was associated with higher pregnancy rates and was a cost-effective strategy, compared with hysterosalpingography with water-based contrast for infertile, ovulating women, with a low risk of fallopian tube pathology [ 7 ]. Lipiodol is the most commonly used oil-soluble contrast under fluoroscopy and ultrasonographic guidance, with a relatively high clinical success rate and low complication rate [ 8 ]. Therefore, this single-center study aimed to evaluate the experience of outcomes from the use of Lipiodol (ethiodized oil) in 96 women with infertility caused by fallopian tube occlusion.

The final study cohort included 96 women diagnosed with tubal infertility. Average age on admission was 33±4.1 years (range 26–45 years). In most cases (79%, 76/96) infertility was primary, and the most common diagnostic tool used prior to the procedure was hysterosalpingography and/or hysterosalpingo-sonography (66%), laparoscopy and hysterosalpingography (19%), and laparoscopy (15%). As far as the pre-procedural treatments for infertility were concerned, 35 couples (36%) tried ovulation induction, 6 (6%) tried IVF, 5 (5%) tried intrauterine insemination, and 23 (24%) tried other methods. The average duration of infertility was 2.8 years (range 1–11 years). The most common comorbidities were endocrinopathies (21%, 20/96) and endometriosis (8%, 8/96). Six patients (6%) had a history of gynecological operation that resulted in unilateral oophorectomy. Additionally, in 2 patients, bicornuate uterus was diagnosed. In terms of male partner fertility status, 26% (25/96) reported oligospermia, and 5% (5/96) had a diagnosis of varicoceles. As for procedural results, complete patency was achieved in 96% of patients (92/96 patients). In 4 patients (4%), distal occlusion of one of the ovaries was observed, resulting in partial procedural success. In most cases (67/96, 70%), selective salpingography was sufficient to restore tubal patency. Tubal catheterization was needed in 29 patients (30%). Once the tubal patency was obtained, Lipiodol was injected until spill into the peritoneal cavity was observed. No procedural complications were noted. The average radiation dose was 37.5±40.8 mGy (range 4–229 mGy). After the procedure, minor vaginal bleeding, uterine cramping, and pain were frequent symptoms. Nonetheless, no serious adverse events were noted. All patients were discharged in good clinical condition a few hours after the procedure. Reproductive outcomes at a minimum of 6 months (follow-up ranging from 6 to 18 months) after the treatment were collected by a telephone survey. One patient was lost to follow-up and therefore excluded from further analysis. From the remaining 95 women who answered the survey, 34 conceived, resulting in a 35.8% overall pregnancy rate. From this group, in 74% (24/34) of patients, selective salpingography was performed, and 26% (10/34) required tubal catheterization. Miscarriage was noted in 5 patients, and tubal ectopic pregnancy in 1 patient. No long-term complications were reported. Demographic data, clinical data, procedural details, and outcomes are presented in Table 1 .

In our center, in 2023, we introduced oil-based contrast medium for selective salpingography and tubal catheterization, and we aimed to present our preliminary results with nearly 100 patients and 1 year of experience and review currently available literature. Early results described in this paper show promising results of a very high rate of procedural success, with a 96% recanalization rate, with minimal complications risk (no major complications were noted), and a high rate of clinical success, with 35.8% of women reporting pregnancy within the follow-up period. Our findings remain in line with results presented by authors of other studies on larger groups of patients. Van Rijswijk et al, who compared oil-based vs water-based contrast media for hysterosalpingography, achieved an even higher pregnancy rate, of 39.7%, in the Lipiodol group, and Peart et al observed that Lipiodol is a safe contrast medium for tubal patency evaluation and restoration [ 7 , 8 ]. Tubal pathologies are common causes of infertility and account for up to 67% of female infertility diagnoses [ 3 ]. From this group, tubal obstruction is an important and potentially curable factor [ 9 ]. In terms of diagnostic tools, hysterosalpingography, contrast-enhanced ultrasound hysterosalpingo-sonography, and laparoscopic chromopertubation can be considered in case of suspected fallopian tube obstruction [ 10 ]. Hysterosalpingography is the most commonly used method, and its most important advantages are low cost and non-invasiveness, combined with relatively high sensitivity and specificity [ 11 ]. Its only disadvantage is X-ray radiation; however, there are studies that suggest it may enhance the potential of oocytes rather than have an adverse effect on female reproductive organs [ 12 ]. As far as hysterosalpingo-sonography is concerned, there is an ongoing debate on its effectiveness, and that is why it is not as commonly performed as is hysterosalpingography [ 13 ]. Laparoscopic evaluation provides reliable information on tubal patency and might be performed for curative purposes during the same procedure; however, it is an invasive and more expensive method compared than hysterosalpingography and hysterosalpingo-sonography [ 14 ]. Regarding therapeutic management, tuboplasty, laparoscopic tubal cannulation, IVF, and tubal catheterization are available for patients with tubal infertility [ 9 ]. Tuboplasty and laparoscopic cannulation are important therapeutic methods for treatment of tubal occlusion, not only proximal, with comparable clinical outcomes to IVF [ 15 ]. Nonetheless, the invasive nature of the procedures and relatively high costs of hospitalization, anesthesia, and surgical equipment remain the main drawbacks of these methods [ 16 ]. IVF is traditionally used for irreparable tubal disease, and its high efficacy has been confirmed in many studies [ 17 ]. However, it is an expensive therapy, and there are several concerns regarding its ethical justification [ 18 ]. Considering all of the above, tubal catheterization seems an interesting alternative to surgical therapies, with its low costs and minimally invasive character, and IVF, with no ethical issues. First described in 1985 by Platia and Krudy, the procedure of transvaginal X-ray-guided tubal recanalization with a guidewire placed through the catheter positioned against the tubal ostium, followed by contrast media injection, demonstrated a technical success rate ranging from 70% to 100% [ 1 , 19 – 21 ]. The average pregnancy rate following the procedure is 30% and occurs more commonly within the first 6 months after treatment [ 22 ]. In our center, we have been performing selective salpingography and tubal catheterization for over a decade, with a relatively high rate of subsequent pregnancies [ 23 ]. Lipiodol, which is an oil-based contrast medium, has been in use for hysterosalpingography examination since the 1970s [ 24 ]. It was reported as an effective treatment for tubal infertility in several studies, especially in patients with endometriosis [ 25 – 27 ]. In 2017, Dreyer et al published results of a randomized and multi-center trial that aimed to compare the therapeutic effects of water-based vs oil-based contrast for hysterosalpingography in women with infertility [ 28 ]. The authors observed higher pregnancy rates and live birth rates among women who underwent hysterosalpingography with oil contrast than in those with water contrast (39.7% vs 29.1%). On the other hand, oil-soluble contrast media are associated with several disadvantages, including poorer visualization due to its high density, higher costs than water-soluble contrast media, and higher rate of intravasation [ 6 , 29 ]. In addition, a recent prospective study by Zeng et al investigated the pregnancy outcomes among women with recurrent implantation failure undergoing IVF or intracytoplasmic sperm injection; the women were divided into 2 groups: the first group received Lipiodol flush, and the second did not receive it [ 30 ]. The authors observed a significantly lower incidence of biochemical pregnancies and live birth rates in the first group, which challenges the value of Lipiodol use in clinical practice for the treatment of recurrent implantation failure. It is important to note that we used Lipiodol as a therapeutic agent rather than diagnostic medium, and it was injected once the tubal patency was achieved, either with diagnostic hysterosalpingography or fallopian tube catheterization. As far as the technical success rate was concerned, the achieved rate of 96% of recanalization was comparable to percentages reported in other studies [ 19 – 21 , 31 ]. However, it is worth mentioning that in the remaining 4% of patients, partial success, defined as unilateral recanalization, was achieved. Although no ongoing pregnancy was reported in this group of patients during follow-up, it is still possible to become pregnant with a single patent fallopian tube. In terms of procedural complications, no serious adverse events were noted in the present study. Nonetheless, mild pain and discomfort were frequent symptoms. Painful sensations occurred most commonly during initial contrast agent injection, with simultaneous traction of the cervix, and during guidewire maneuvers, while we attempted to recanalize the occluded fallopian tubes. To minimize pain, all patients received intravenous analgesic treatment with ketoprofen and/or paracetamol during the procedure. All patients were discharged in good clinical condition a few hours after intervention. In the telephone survey, all patients were asked about late complications, including pelvic infections and abnormal bleeding, but no such event was reported. A concern with any intervention involving the reproductive system in women is the potential effect on future fertility, especially in cases of radiological interventions. Our approach to image-guided radiation dose reduction is described in the Material and Methods section. On average, 37.5 mGy were required in our cohort, which is comparable with results achieved by other authors [ 22 , 32 , 33 ]. As for clinical outcomes in the literature, the pregnancy rate following the procedure ranges from 20% to 60% in selected groups of patients, with an average rate of 30% [ 1 , 19 ]. In our study, we noted a comparably high rate of successful pregnancy following the tubal recanalization with Lipiodol, at 35.8%. Most common factors favoring achieving a pregnancy after tubal recanalization include age <35 years, shorter duration of infertility (<5 years), secondary infertility, and lack of tubal disease [ 21 ]. In our cohort, the average patient age was 33 years, average duration of infertility was 2.8 years, and no tubal disorders other than occlusion were noted, which may explain the higher than average success rate. Occurrence of tubal ectopic pregnancy following selective salpingography and tubal catheterization are reported to be around 3% [ 34 ]. In our study group, 1 case was noted, resulting in a rate of 3%, which corresponds to data available in the literature. Our study had several limitations. First, our sample size was relatively small, and subgroup analysis was not possible. That is why the significance of our results and of the conclusions requires further validation in future studies. We are planning to continue to investigate the outcomes of tubal recanalization with oil-based contrast in our institution and will provide more date in the future. Second, our study lacked a control arm including patients treated with other methods, especially laparoscopic methods. Nonetheless, despite potentially wide opportunities for surgical methods in the treatment of proximal tubal occlusion, less invasive radiological methods are preferred in many centers, including ours. Finally, we did not provide a very long-term follow-up, which might increase the overall pregnancy rate, hence the potential bias of the study. However, it has been reported by several authors mentioned in our paper that most pregnancies occur within the first 6 months after the procedure.

In summary, the results of our center’s 1-year experience with oil-based contrast medium for selective salpingography and tubal catheterization show that it is a safe and effective treatment with a relatively high pregnancy rate and acceptably low complication rate. Further studies with subgroup analysis, including comorbidities, primary vs secondary infertility, and partner’s fertility status, are required to fully discover the potential benefits of this method.

All individuals gave their informed consent for the study. All procedures were conducted in accordance with the Declaration of Helsinki. The local ethics committee approved this study. This was a retrospective and single-center study that included 96 consecutively enrolled female patients with infertility caused by tubal obstruction who underwent selective salpingography and tubal catheterization followed by Lipiodol injection from January to December 2023. Prior to the treatment, medical history of the patient and her male partner was collected. Inclusion criteria included (1) primary or secondary female infertility of at least 12 months, and (2) tubal occlusion confirmed prior to the treatment, either with hysterosalpingography, hysterosalpingo-sonography, or laparoscopy. The following exclusion criteria were applied: (1) history of tubal ectopic pregnancy, (2) known iodine and/or Lipiodol allergy, and (3) lack of informed consent for participation in the study. All patients received a course of antibiotics with doxycicline 100 mg orally 2 times a day for a period of 5 days starting 2 days before the procedure. Additionally, treatment with ketoprofen and/or paracetamol was routinely administered intravenously during the procedure. All procedures were performed in the follicular phase of the menstrual cycle by an experienced gynecologist and radiologist. In a sterile condition, a balloon catheter ranging from 5 to 12 Fr was inserted into the uterine cavity and inflated to block internal os. Afterward, the contrast media (iodixanol, Visipaque 320, Amersham Health, UK) was injected into the inner fallopian tube ostia via a catheter (5 Fr Kumpe catheter, Cook, Bloomington, IN, USA). In case of proximal visible tubal occlusion, catheterization with 0.035″ guidewire (Terumo, Tokyo, Japan) was performed. Once the tubal patency was obtained (defined as bilateral spill into the peritoneal cavity), repeated contrast injection was performed. Finally, 10 mL of Lipiodol (Guerbet Pharmaceuticals, Paris, France) was instilled as a therapeutic agent. In our institution, all measures are taken to reduce the radiation dose in case of interventions involving female patients in childbearing age, according to the “as low as reasonably achievable principle”. Therefore, all procedures were performed with short fluoroscopy pulses and tight collimation. After the procedure, all patients remained at the Gynecological Department and were discharged in the afternoon if no complaints were reported. A typical procedure of selective salpingography followed by tubal catheterization is presented in Figure 1 . Information regarding the reproductive outcome at a minimum of 6 months following the treatment was collected either by a telephone survey or direct contact with the patient. The measurement data are expressed as mean±standard deviation, and ranges are provided.