Tuboperitoneal Infertility (Tubal Factor Infertility)
1. What every clinician should know
Many factors impact fertility rates in women: tubal factor infertility has been reported in 62.7% of primary infertility patients. Risk factors include a history of pelvic inflammatory disease, septic abortion, a ruptured appendix, tubal surgery or a previous ectopic. The number of prior pelvic infections corresponds with the incidence of infertility: approximately 12% after one episode, 23% after two and 54% after three episodes. Up to 75% of women develop adhesions post-operatively involving the fallopian tubes which may affect fertility.
Ectopic pregnancy and subsequent tubal factor infertility is also a noteworthy concern as ectopic pregnancies comprise up to 2% of all pregnancies and predispose women to future tubal pregnancies as well as tubal infertility. Obstruction can occur in virtually any portion of the fallopian tube. Proximal obstruction prevents sperm transport to the more distal portions of the tube where fertilization can take place. Distal obstruction may impede fimbrial uptake of the oocyte and can range from minimal adhesions to complete obstruction and can be a result of salpingitis, endometriosis, and inflammation or adhesion formation.
Of interest there is evidence for decreased ovarian perfusion in patients with tubal factor infertility. Specifically, assessment of pulsatility index, resistance index, and endometrial thickness was evaluated. Pulsatility index at the level of the uterine artery was noted to be lower with tubal factor.
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2. Diagnostic Testing
Tubal factor infertility can be evaluated by several methods: the most common being a hysterosalpingogram or direct intra-operative observation through chromopertubation. Sonohysterography can also be utilized to assess the tubal patency via ultrasound and an infusion of saline.
Hysterosalpingography
A hysterosalpingogram (HSG) remains one of the two most traditional ways to assess tubal patency. Not only does it assess for tubal patency, but it also allows visualization of the internal structure of the fallopian tubes and uterine cavity. It is best performed within the first five days after menses and prior to ovulation. This decreases the risk of infection and allows for a more accurate assessment without disrupting the chance of conception within that cycle.
HSGs are associated with a relatively high false positive rate with proximal obstruction; over half of studies that reveal tubal obstruction are likely to be patent while the frequency of false negative results is rare. Genuine bilateral obstruction significantly impairs a women’s chance at natural conception whereas unilateral blockage only mildly decreases her chances.
While antibiotics are not necessary, they are recommended when the suspicion of tubal disease is high or distal obstruction is noted on exam. When tubal pathology is demonstrated, the risk of acute infection is approximately one in ten. While the debate continues between whether oil-soluble or water-soluble contrast media is associated with improved pregnancy outcomes, a meta-analysis of over 2600 women linked oil-based media to significantly higher pregnancy rates.
Laparoscopy
The gold standard of diagnostic testing is laparoscopic evaluation and chromopertubation. This involves the instillation of a dilute blue dye, methylene blue, with an intrauterine manipulator and observation of flow of dye through the fallopian tubes. This evaluation technique not only provides a more accurate assessment of tubal patency, but also allows for a visual appraisal of the pelvis, including the uterus, anterior cul-de-sac, posterior cul-de-sac, ovaries and ovarian fossae. The other noteworthy advantage to laparoscopy is that it allows for immediate treatment. The lysis of mild pelvic adhesive disease and ablation of minimal to mild endometriosis is within the ability of most gynecologic surgeons and can be undertaken at the time of diagnosis.
While there are several advantages to laparoscopy as a means of diagnosis, there are inherent disadvantages as well. This is a minimally invasive surgical procedure requiring general anesthesia that is associated with increased cost as well as a post-operative recovery period. A large prospective study from the Netherlands estimated the overall risk of laparoscopic complications to be 5.7 per 1,000 laparoscopies. Most of these complications involved the bowel or superficial vasculature. Therefore, both the surgeon and the patient must weigh the risks and benefits of the procedure.
Sonohysterosalpingography
Sonohysterography is a common diagnostic tool used in the evaluation of infertility and irregular vaginal bleeding. There is a high sensitivity for intrauterine pathology; sonohysterosalpingography can be utilized as an adjunctive means of assessing tubal patency at that time. Recent advances in ultrasound techniques and contrast media have allowed for physicians to use a saline-air device to track microbubbles through the fallopian tubes and create 3-D images of tubal architecture. While studies comparing sonohysterosalpingography to more traditional methods have not yielded definitive results, its sensitivity ranges from 76-97% and specificity from 79-82%. While this technique holds promise, it is far from replacing hysterosalpingography or laparoscopy at this time.
Chlamydia antibody tests
As many women have no history of a prior pelvic infection, the most common cause of pathology is that of a silent ascending infection. It is estimated that 4-5 million new cases of chlamydia occur annually, most of which are asymptomatic. Irreversible tubal damage occurs secondary to immunopathology. While Chlamydia trachomatis and Neisseria gonorrheae remain the most common etiologies, salpingitis secondary to chlamydial infection is more likely to cause tubal infertility when compared to the latter.
Chlamydia antibody tests (CAT) can screen for the presence of IgG antibodies to C. trachomatis. Recent studies have shown it to be comparable to hysterosalpingography in screening for tubal pathology and estimating the incidence of pregnancy within this population. Even in subfertile women without visible tubal pathology, a positive C. trachomatis antibody screen is associated with a 33% lower likelihood of ongoing pregnancy. While CAT is not a diagnostic test, its convenience and ease makes it a worthwhile screening test to triage women for further testing.
Anti-Müllerian hormone and salpingectomy
The effects of salpingectomy on ovarian reserve has been studied. When compared to infertility patients with and without salpingectomy, the former resulted in lower serum levels of anti-Müllerian hormone (AMH). Specifically, with salpingectomy, median levels were 16.1 with a range of 5.2-54 pmo/L vs. 23.4 with a range of 3.5-50 pmol/L for the nonsalpingectomy group.
Differential diagnosis
While several factors can predispose women to tubal factor infertility, few diseases mimic this condition. In the face of false positive screening, tests as high as 60%, it is reasonable to repeat the evaluation prior to more invasive interventions. Although rare, carcinoma of the fallopian tube can present with a pelvic mass, vaginal bleeding or profuse watery vaginal discharge. Fallopian tube cancer comprises one percent of gynecologic malignancies and is predominantly seen in postmenopausal women. However, in high-risk patients such as BRCA carriers, the incidence of fallopian tube cancer was approximately six percent. Given that pelvic pain and irregular vaginal bleeding may also overlap with conditions associated with infertility, it is essential to keep this in mind throughout the evaluation.
Appendicitis
A systematic review of observational studies noted that prior appendectomy was not associated with infertility. However, it was associated with increased risk for ectopic pregnancy. No subgroup analysis was done; however, there was distinction of “simple vs. complex” appendicitis in part based on presence or absence of complications.
3. Management
The treatment of tubal factor infertility can be approached in several different ways, ranging from radiographic methods to surgical intervention. Historically, tubal resection and reanastomosis was one of the first modes of treating tubal obstruction. As both surgical and endoscopic techniques have improved over the years, new treatment options have emerged for the office setting and operating room alike.
Fimbrioplasty
In women with mild to moderate distal adhesions, fimbrioplasty (lysis of fimbrial adhesions) can be employed with moderate success. In patients with more severe adhesions, especially along the distal portion of the tube, the risk of treatment failure and ectopic pregnancy outweigh the benefits. In-vitro fertilization, which yields success rates approaching 50% in appropriately selected women, enables us to circumvent the tubal occlusion. In older women, the combination of diminishing ovarian reserve and tubal factors also make IVF the most effective means of attaining pregnancy. A good prognosis is associated with fine filmy adhesions with minimal distal dilation i.e., < 3cm.
Hydrosalpinges
The diagnosis of a hydrosalpinx presents a unique situation within the realm of tubal factor infertility. While the tubal obstruction can be evaded with IVF, both unilateral and bilateral hydrosalpinges negatively impact both implantation and pregnancy rates. The exact mechanism for this is uncertain, but it is hypothesized that the presence of a hydrosalpinx may exert a toxic effect on the embryo, efflux fluid to flush the embryo from the uterus or impact endometrial receptivity.
In women with a known hydrosalpinx, salpingectomy or tubal occlusion prior to IVF has demonstrated pregnancy rates up to 34%, twice that of women who were not treated. A recent Cochrane study supports salpingectomy prior to IVF. With the advent of hysteroscopic tubal occlusion, early studies have shown that placement of these hysteroscopic tubal inserts in women with hydrosalpinges can yield IVF pregnancy rates of up to 67%. Patients presenting with proximal tubal obstruction have several additional treatment options available.
Tubal cannulation
Selective salpingography allows for a catheter to be placed in the tubal ostium to help differentiate between true obstruction and tubal spasm seen on HSG. Fallopian tube catheterization, a guide wire can be advanced to aid in cannulation of a proximal blockage. These procedures can be performed by an interventional radiologist and yield success rates of 71-92%. Hysteroscopic tubal catheterization can be a viable option in patients with proximal (tubal) obstruction who do not prefer IVF with a success rate of 37% in this patient population. This can be performed in conjunction with laparoscopic guidance and subsequent chromopertubation.
In the absence of proximal occlusion due to salpingitis isthmica nodosa (SIN), tubal cannulation remains a viable option. Coaxial catheter systems with fluoroscopic guidance facilitates identification and cannulation. This procedure is primarily done by Interventional Radiologists. Success rates of 85% have been reported.
Falloposcopy
Falloposcopic tuboplasty is a technique that has recently re-emerged and entails direct visualization of the fallopian tube with the falloposcope and employment of a pressurized balloon within the outer sheath to release proximal tubal occlusions. Successful recannulation was achieved in 81-94% of women with 28-30% achieving pregnancy.
Tubal sterilization reversal
With surgical sterilization being the most common form of long-term contraception within the United States and poststerilization regret as high as 26%, the question of reanastomosis has arisen. With the growth of IVF, this procedure has less popularity. However, in certain populations, this approach holds merit and should be considered. Microtubal reanastomosis can now be accomplished through mini-laparotomy and robotic-assisted laparoscopy with similar success rates.
Generally, two things should guide patient counseling: patient age and future fertility goals. In women under the age of 37, delivery rates in patients after tubal reversal were significantly higher than after IVF. In addition, couples who plan to have two or more children are likely to benefit from tubal reversal to allow natural conception in the future. As both avenues are costly to the patient, appropriate counseling is necessary.
4. Complications
While tubal factor infertility is an obstacle in and of itself, treatment of this condition still leaves the patient at an increased risk of ectopic pregnancy and its associated risks. Therefore, in patients who have undergone treatment for tuboperitoneal infertility, it is essential for the subsequent providers to remain cautious of these increased risks.
5. Prognosis and outcome
While some instances of tubal factor infertility may be ameliorated by surgery, more severe cases may not be remedied intra-operatively. In women with unilateral or bilateral hydrosalpinges, it is in the patient’s best interest to proceed with a salpingectomy of the affected tube(s) and subsequent in-vitro fertilization. In women with tuboperitoneal pathology, it is important to counsel patients regarding their fertility options.
Surgical intervention has small, but genuine, risks associated with it. In certain cases of moderate to severe adhesions, fimbriolysis or tubal cannulation may fail to restore tubal integrity. Additionally, it is difficult to assess any initial or subsequent damage to the internal structure of the tube that would otherwise impair transportation of sperm or a fertilized embryo. This unseen damage predisposes this population to, not only infertility, but tubal pregnancy as well.
Lastly, it is prudent to evaluate a couple for any other additional causes of infertility. Decreased ovarian reserve or significant male factor infertility would likely outweigh the concern of tubal factors. In these couples, the most effective treatment is in-vitro fertilization and surgical intervention is often unnecessary as IVF circumvents the fallopian tubes entirely.
6. What is the evidence for specific management and treatment recommendations?
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