Dr.Sanjay Makwana

Vasundhara Hospital & Fertility Research Centre Jodhpur

www.vasundharafertility.com

The Fallopian tube plays an important role in the mechanical transport and physiological sustenance of the gametes and early conceptus. Complex and coordinated neuromuscular activity, cilial action and endocrine secretions are required for successful tubal function

Compromised tubal damage can occur after external or internal injury, inhibiting the normal transport of gametes. The overall prognosis for fertility depends principally on the insult and the severity of the tissue damage; hence, assessment of tubaldamage plays a major role in predicting occurrence of pregnancy and the likelihood of developing ectopic pregnancy

Functional competence of the fallopian tubes implies both tubal patency as well as integrity of the mucosal lining or the endosalphinx.

Tubal factor infertility (TFI) includes an array of disorders affecting one or more of the above components.

Transient or permanent and is manifested by peri-tubal adhesions, proximal and/or distal tubal blockage or hydrosalphinx formation.

Severe impairment of the tubal function can occur in presence of patent tube due to damage to the inner micro architecture.

Classification for scoring Tubal damage

TFI in to the three groups (Grade I : filmy adhesions;

Grade II: unilateral severe damage ; and Grade III:

bilateral severe damage) using the “Hull and

Rutherford” classification system.( BJOG 2004)

Tubal patency testing

Tubal disease is probably best diagnosed by means of

laparoscopy and chromotubation (Lap and Dye) . It can

demonstrate tubal patency as well as assess the pelvis

for the presence of endometriosis and adhesions.

(Meta analysis –Fertil Steril 1995 )

Laparoscopy also helps in staging the tubal disease into

diagnostic and Prognostic categories.

(ASRM ,Fertil Steril 1989)

Laparoscopy & Dye Test

The reference standard for tubal factor assessment

Patency, periadenxal adhesions & Endometriosis can be assessed

Additional information on uterine malformation

Advantage of correcting underlying pathology

Invasive

Expensive

General anaesthesia needed

Surgical complications (1.3-1.5%) (human reprod.1998)

Availablity of Operating facilities

Hysterosalpingography (HSG)First line most common test

(crosignani & rubin 2000.,lanzani et al 2004)Hysterosalpingography (HSG) – Which involves a pelvicX-ray following the injection of a radio opaque iodine-based dye through the cervix, is less invasive, and can be helpful in cases where laparoscopy is contraindicated or hazardous, or in women at low risk of pelvic pathology.

Its ability to identify the site of obstruction and to delineate the mucosal pattern of the endosalphinx means that, HSG has a role in assessing the extent of tubal Disease.HSG also has a therapeutic effects (Watson et al –Fertil Steril 1994., 2002.,Sing. Med. J. 2007)

HSG Relatively inexpensive OPD procedure.

As a test of tubal obstruction it has a sensitivity 0.65(95% CI 0.50 – 0.78) & a specificity of .83 (95% CI 0.77 – 0.88) compared to lap & dye.

( Meta analysis – Fertil Steril 1995)

HSG is a reliable indicator of tubal patency ,relatively poor at identifying cases of tubal occlusion .( FertilSteril 2011 )

HSG has certain limitations in diagnosing spasm from proximal tubal occlusion & pelvic pathology.

According to the fertility-guideline of the National Institute for Clinical Excellence (NICE, 2004), HSG should be offered to women who are not known to have co-morbidities (such as a history of pelvic inflammatory disease, previous ectopic pregnancy or endometriosis) to screen for tubal pathology. In women who are assumed to have co-morbidities, laparoscopy should be offered instead of HSG.

Chlamydial antibody testing (CAT) has become a popular

test because seroepidemiological studies have

demonstrated a link between serum antibodies ,

chlamydia trachomatis and TFI.

A meta analysis of 23 study reported the discriminative

capacity of CAT, comparable to HSG in diagnosing

Tubal Factor.

( Meta analysis Fertil Steril 1997) (Mol et al .,1997)

Most importantly, a positive result gives no information

on the severity of TFI and therefore, fertility prognosis.

The advantage of HSG is that it has a high specificity (Swart et al., 1995), accurate in confirming the absence of tubal pathology, with oil-soluble contrast medium has a positive effect on pregnancy rates (Luttjeboer et al., 2007).

So far, this positive effect on pregnancy rates has not been found when water-soluble contrast medium was used (Perquin et al., 2006).

The role of HSG in the fertility evaluation of low-risk patients (i.e. CAT- negative women) deserves critical reappraisal.

In CAT-positive high-risk patients, HSG should be omitted because of the 10% risk of post-HSG complications in the absence of additional value in risk assessment of tubal pathology.

S S G

Sonohysterosalpingography involves the use of ultrasound

along with injection of a sonoreflective contrast medium

through the cervix (HyCoSy)

In comparison to lap & dye test & HSG it has shown good

concordance. ( Eur J Radio 2000 )

Holz et al 97., performed a meta-analysis of the results of

three clinical studies comparing the ultrasound echo-contrast

with HSG .

Additional advantage of ultra sound assessment of pelvis & is

superior in detection of intrauterine lesions.

Campbell et al., 1994.,Heikkinen et al 1995

Salpingography

Salpingography, performed either laparoscopically of hysteroscopically, offers an opportunity to visualize the endosalphinx and diagnose intraluminal tubal damage.

The extent of tubal damage may not correspond with

that of peri-adnexal adhesions.

There are no experimental studies comparing this

approach with conventional methods of tubal evaluation.Human Reprod 1999, J A G L 2001

Routine assessment of Tubal status is debatable in situation where knowledge of tubal patency is unlikely to change the proposed management plan – such as severe male factor infertility.

Treatment of tubal factor infertility Conservative

Wu and Gocial explored cumulative conception rates in women

with untreated tubal disease, graded from 1 (mild) to 4

(extensive) based on the presence of adhesions , salpingitis , and tubal

occlusion and scored as mild, moderate , severe, or extensive.

Cumulative conception rates related to tubal disease grading, compared to normal

Fecundity was reduced in tubal infertility and up to

10% of the pregnancies in women with TFI were

ectopic.

Intrauterine pregnancies have been reported women

with tubal block diagnosed with HSG and lap and dye.

The cumulative pregnancy rate in women with tubal

disease on the waiting list for in vitro fertilization was

2.4%. ( Lancet 2002 )

Medical

Infection -as a causative factor in the genesis of TFI.

Tubal infection may persist despite repeated courses of antibiotics,

and the role of antibiotic therapy in cases of TFI secondary to

pelvic inflammatory disease is unproven.

Women with tuberculosis require chemotherapy, but this

will not reverse the damage present. After treatment, increased

ectopic and miscarriage rates are reported on a background of

decreased conception.(J.Indian med. Asso.1996,2002)

Tubal flushing with an oil-soluble contrast medium will

increase pregnancy rates compared with no intervention.

SURGERY

Surgery has a complementary role to IVF in the management of patients with TFI.

Counseling is complex and a number of factors should be taken into account before a decision is made to embark on surgery.

Effect of surgery is not limited to one or more episodes of treatment.

Risk of ectopic pregnancy has to be kept in consideration.

The evidence underpinning the decision to perform surgery as opposed to other interventions,as IVF & expectant management,is very limited.

There are few randomized trials and most of the data are from uncontrolled observational studies.

Proximal tubal obstruction

Proximal tubal obstruction (PTO) may occur in

either the intramural segment or utero-tubal

junction. It accounts for 10-25% of tubal factor

infertility. In up to 40% of women is due to spasm or transient occlusion.

(Fertil Steril 1999, Radiology 1994)

Tubal cannulation , anastomosis & IVF

Selective salpingography with tubal cannulation

Diagnostic selective salpingography differentiates true PTO from

blocks due to spasm or plugs and can delineate the exact site of

occlusion. Canalization can be done under sonography , fluroscopy

or under hysteroscopic guidance

Reocclusions, perforation, bleeding, infection

Pregnancy rates reported – 9-57%

No RCT’s or observational studies have compared with conservative

management

Hysteroscopic cannulation has much higher pregnancy rates then

salpingographic catherization. ( Fertil Steril 1999,2007 )

Tubo- Cornual anastomosis – 27-53% live birth rate (Fertil Steril 87)

( Post surgical ectopic rates are >8%) - Int.J.Fertil 1998

Distal Tubal obstruction

Distal tubal obstruction accounts for 85% of all cases of

TFI and is caused by PID, adhesions from previous

surgery, and endometriosis.

Surgery & ART

Non-randomized data suggest higher pregnancy rates in

women who were treated surgically compared with

those who were not. Surgery was more effective in

women with mild disease and the outcome was

closely linked to the severity of tubal damage.

There are no randomized trails comparing IVF with tubal surgery. In

women with mild adhesions or distal Blockage, observational data

suggest that pregnancy rates after tubal surgery are comparable to

those following IVF.

Pregnancy rates after micro surgery ranged from 5% to 40% in 36

months to 50 months & ectopic rates 23%

(Cochrane database of systemic review 2000.,CD000221.2007 CD

0006415 Fertil Steril 1986,98., human reprod. 2004 )

Surgery No Surgery

Mild disease stage I 67% 24%

Moderate disease stage II 41% 10%

Stage III 12% 3%

Stage IV 0% Surgery not

offered

In a retrospective cohort study, BJOG 2004 , explored

the live birth following tubal reconstructive surgery in

women under 40 years. Women were grouped

according to the severity of disease.

Grade I tubal damage involved Filmy adhesions,

grade II and Grade III referred to Unilateral severe

damage and bilateral severe damage, respectively.

Ectopics rates increased with severity .

Cochrane database review 2000 No difference in pregnancy rates - laser adhesiolysis or

diathermy (53% vs.52%)

Use of operating microscope vs loupe for micro tubal surgery ( 72% vs. 78% )

Laparoscopy vs. laparotomy for distal tubal surgery –overall pregnancy rates were comparable ,in severe tubal disease laparotomy was found to have higher pregnancy rates.

Cochrane database review 2000 Postoperative hydrotubation-no improvement in

pregnancy rates

Hydrotubation with steroid / antibiotics-not appears to improve the pregnancy rates.

Second look laparoscopy with adhesiolysis-falls in the same category.

Data suggest that most pregnancy resulting from tubal surgery occur between 12-14 months.

fertil steril 1982,1991,1995

In younger women with mild distal tubal occlusive disease, laparoscopic surgery may be viewed as an alternative to IVF, but when disease is severe or pregnancy does not occur during the first postoperative year, IVF is the logical choice.

For older women with any significant degree of distal tubal disease, IVF is generally the first and best option because cycle fecundability after distal tubal surgery is low (1-2 %), time is limited, and IVF is both more efficient and more effective.

Reversal of sterilization

Systemic review failed to identify any trials comparing IVF verses reversal of sterilization.

Age ,type & site of anastomosis, final length of the repaired tube and risk of ectopic must be considered.

IVF for TFI 20% of the IVF cycles in UK in 2008 were undertaken

for TFI.

Success with expectectant management is so poor for moderate and severe tubal disease that there is a little equipoise to support - a randomized trial comparing it with IVF –Human reproduction 1994 , 1999.

Hydrosalpinges affect the outcome of the IVF by lower pregnancy rates, poor implantation and early pregnancy loss . salpingectomy prior to IVF results in increase live birth rates (cochrane database 2010.)

When deciding on treatment for TFI important factors are –patient selection and number of IVF cycles available

Reserving surgery for PTO, low grade disease and reversal of clip sterilization- number of operations can be reduced , repeated attempts at conception allowed and good live birth rates achieved .

This must be balanced against the risk of OHSS , multiple pregnancies , and the fact that, at present many women have fewer cycles of IVF due to cost constrants.

Prognosis should be individualized taking into account local experience and age of the patient.

Challenges of evidence based approach to TFI

Lack of evidences

The diagnosis of TFI is influenced by the nature of the test used.

Difficulty in comparing the outcome with IVF

Maternal age

Cost effectiveness

conclusion The evidence based underpinning interventions for

the diagnosis & treatment of tubal factor infertility is limited & mainly reliant on observational data. despite the absence of data from RCTs current pregnancy & live birth rates associated with IVF suggest that this is the treatment of choice for older women with moderate to severe tubal factor infertility.

Selective salpingography or hysteroscopic cannulationof the tube is useful in confirming true PTO and may have role in treating this condition.

conclusion

Risk of ectopic pregnancy are relatively high following both IVF as well as tubal surgery.

There is need for more trials of surgery verses IVF and of alternative surgical techniques in mild tubal disease & post tubal sterilization.