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

Introduction

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.

Material and Methods

ETHICAL STATEMENT:

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.

STUDY DESIGN:

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 AND EXCLUSION CRITERIA:

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.

FALLOPIAN TUBE RECANALIZATION PROCEDURE:

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.

FOLLOW-UP PROTOCOL:

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.

STATISTICAL ANALYSIS:

The measurement data are expressed as mean±standard deviation, and ranges are provided.

Results

DEMOGRAPHIC FINDINGS:

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%).

INFERTILITY DETAILS:

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).

COMORBIDITIES:

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.

PARTNER’S FERTILITY STATUS:

In terms of male partner fertility status, 26% (25/96) reported oligospermia, and 5% (5/96) had a diagnosis of varicoceles.

PROCEDURAL OUTCOME:

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).

POST-PROCEDURAL DETAILS:

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:

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.

Discussion

STUDY LIMITATIONS:

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.

Conclusions

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.