Deciphering Tubal Tales: Comparative Analysis of Tubal Patency Tests

Invited lecture by Dr Sujoy dasgupta in the "Basic Subfertility" Workshop at AICOG (All India Congress of Onstetrics and Gynaecology), 2023 at Kolkata

1. Dr Sujoy Dasgupta MBBS (Gold Medalist, Hons ) MS (OBGY- Gold Medalist) DNB (New Delhi) MRCOG (London) Advanced ART Course for Clinicians (NUHS, Singapore ) M Sc, Sexual and Reproductive Medicine (South Wales, UK) Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata Managing Committee Member, BOGS, 2022-23 Executive Committee Member, ISAR Bengal, 2022-24 Clinical Examiner, MRCOG Part 3 Examination Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019 Tubal Tales Deciphered: A C omparative Analysis of Tubal Patency Tests

2. Tubal Factors Tubal factor- 35-40% cases of infertility (Klein et al., 2022)

3. Tubal Patency Tests HSG SSG HyCoSy HyFoSy MRI- HSG Laparoscopy and Chromopertubation Fertiloscopy Hydrolaparoscopy Salpingoscopy Falloposcopy Chlamydia antibody testing

4. Tubal investigations (NICE, 2013) Women NOT known to have comorbidities ( e.g , PID , previous ectopic pregnancy or endometriosis) hysterosalpingography ( HSG ) to screen for tubal occlusion reliable test for ruling out tubal occlusion, less invasive makes more efficient use of resources than laparoscopy Where appropriate expertise is available screening for tubal occlusion using hysterosalpingo -contrast- ultrasonography should be considered effective alternative to HSG for women Women thought to have comorbidities Offer- L aparoscopy and dye test

5. Hysterosalpingogram ( HSG ) Most commonly used , commonly available Easy to perform Cheaper, noninvasive Oil-based contrast medium, may have some therapeutic benefit (Suresh and Narvekar , 2014 ; Saunders et al., 2011; Wang, et al. 2019) Specificity- 87%- negative test correctly identifies patent tubes in 87% cases. A good screening test in diagnosing tubal patency ( Suresh and Narvekar , 2014 Verhoeve , 2010; Mol et al., 2010; Den Hartog et al., 2008; Bosteels et al., 2007) Sensitivity- 53%- positive test correctly identifies blocked tubes in 53% cases (Suresh and Narvekar , 2014; Papaioannou et al., 2007)

6. Drawbacks of HSG Radiation exposure and infection (1-3%) Spasm of the smooth muscles of the tube → “false” impression of “fallopian tube block” (Suresh and Narvekar , 2014) In 40-60% cases of B/L tube block diagnosed in HSG , at least one tube may be found open on further investigations (repeat HSG , SSG , laparoscopy) ( Hajishafiha et al., 2009; Verhoeve et al., 2010; Foroozanfard and Sadat, 2013)

7. Sonosalpingography ( SSG ) Relatively simple procedure Avoids radiation exposure and iodine allergy ( Saunders, 2011; Suresh and Naverkar , 2014, Maheux-Lacroix , 2014) Can assess tubal patency, uterine cavity, myometrium and the ovaries in the same sitting Sensitivity- 93%, Specificity- 89% ( Papaioannou et al., 2007 Suresh and Narvekar , 2014) Can be combined with 3-D scan to evaluate the cavity and tubes ( Exacoustos , 2009; Sladkevicius , 2000) 3-D does not have any significant benefit over the 2-D. ( Maheux-Lacroix et al, 2014)

8. HSG vs SSG Fair agreement between HSG and SSG for tubal patency (k= 0.61 to 0.66) ( Izhar , 2019; Luca, 2017) Oil-based media for tubal flushing in HSG vs saline in SSG (Wang, 2019; Luttjeboer , 2007) In women with PCOS - similar pregnancy rates between HSG and SSG (Christianson et al., 2018) Meta-analysis- comparable sensitivity (95% vs 94%) and specificity (93% vs 92%) between SSG and HSG for diagnosing tubal block, compared with Laparoscopy ( Maheux-Lacroix , 2014) The likelihood ratios in diagnosing tubal occlusion, of HSG and SSG were similar, especially as the experience of the operator increased ( Dijkman , 2000)

9. Can SSG be used as a first test? SSG should be considered as “initial” test ( Izhar , 2019; Rogerson et al., 2002; Maheux-Lacroix , 2014) Recommendated by NICE Some studies even found better accuracy of SSG than HSG (Ali et al., 2005; Chan et al., 2005)

10. “ SSG cannot tell the site of block” Unilateral tube block ( UTB )- the fertility potential remained as same as in case of bilateral tubal patency ( Lavy et al., 2004; Coppus et al., 2007) Success rate of IUI in UTB = unexplained subfertility ( Farhi et al., 2007;. Tan et al., 2018; Yetkin et al., 2017; Berker et al., 2013, Selcuk et al., 2016) Distal tube block had significantly lower chance of pregnancy in IUI ( Farhi et al., 2007;. Tan et al., 2018; Berker et al., 2013) Issue of proximal versus distal UTB yet remains unresolved. (Tan, 2018)

11. Hysterosalpingo -Contrast Sonography ( HyCoSy ) Delineates exact site of block and peritubal adhesion ( Luciano et al., 2011) Meta-analysis- HyCoSy NOT superior to SSG ( Maheux-Lacroix , 2014) Expensive, not easily available, not licensed- Echovist ! (Schering AG, Berlin) and SonoVue ! ( Bracco , Milan) ( Exalto and Emanuel, 2019)

12. Hysterosalpingo -Foam Sonography ( HyFoSy ) Foam is created by rigorously mixing 5ml ExEm gel (containing hydroxyethyl cellulose and glycerol) with a viscosity of 270 cc and containing 94.12 % water Sufficiently stable to show echogenicity for at least 5 minutes, Better accuracy than HyCoSy ( Exalto and Emanuel, 2019) Needs further studies Not yet FDA-aproved

13. Commonly advised as a confirmatory test ( Hajishafiha , et al., 2009) Additional pathologies in the ovaries and peritoneum can be diagnosed Treatment can be done in the same sitting Subtle changes in tubes/ fimbria / peritoneum Functional potential of the fimbria to pick-up the ova ( Sarkar , et al. 2008; Approbato et al., 2020; Elstein et al., 2008) Laparoscopy may be better predictor of fertility than HSG ( Mol et al.,1999; Verhoeve et al., 2010) Laparoscopy with chromopertubation

14. Laparoscopy- as first line test? NICE guideline (2013)- laparoscopy as the initial tool for checking tubal patency ONLY in those with risk factors for tubal block Diagnostic error still can happen in laparoscopy ( Broeze et al., 2010; Saunders et al., 2011; Luca et al., 2017; ASRM , 2015 Invasive nature- Iatrogenic injury and anaesthetic risks Cannot be offered as the primary test in all women (Saunders et al., 2011; Tan et al., 2018 “Gold standard” ???? (Tan et al., 2018; Saunders et al., 2011; Lim et al., 2011; Suresh and Narvekar , 2014)

15. Transvaginal Hydrolaparoscopy ( THL ), Salpingoscopy , Falloposcopy , Fertiloscopy Insufflation of the pelvis with 0.4–0.6 litres of a fluid medium through an insufflating needle inserted into the posterior fornix Followed by the introduction of a small diameter rigid angled endoscope to visualise the POD, pelvic side-walls, adnexa and tubal patency (the dye injected transcervically ) Complication rate higher than Laparoscopy ( Suresh and Narvekar , 2014 )

16. Need of 2 nd test after B/L tube block in HSG Further diagnostic tests Repeat HSG SSG / HyCoSy Laparoscopy- dye test Treatment Fluoroscopic catheterization Hysteroscopic cannulation Tubal microsurgery IVF directly

17. Repeat HSG After premedication with antispasmodics 60% cases initially “blocked” tubes were found open ( Dessole et al., 2000) can reduce the number of women referred for laparoscopy ( Dessole et al., 2000) Increased risk of radiation exposure and hypothyroidism ( Hart et al., 2009)

18. Can SSG affects the treatment decision? In 70-80% at least one tube is found open by SSG ( Hajishafiha , 2009; Lanzani , 2009) Can avoid both laparoscopy and IVF Offer SSG for B/L proximal tube block diagnosed in HSG before laparoscopy/ IVF ( Hajishafiha , 2009) If both HSG and SSG showing b/l block 80% cases B/L block seen in laparoscopy ( Hajishafiha , 2009) Cost-effective- Directly going for IVF without laparoscopy (unless there is any other indication for laparoscopy) (Swart et al., 1995)

19. Age of the woman- ART act Ovarian reserve Sperm parameters Number of children desired Patient’s preferences Site and extent of the tubal disease Risk of ectopic pregnancy vs risk of OHSS Success rates of IVF programme Financial burden- “two consecutive medical procedures to achieve parenthood” Findings of pathology in diagnostic laparoscopy would NOT affect the success rate of IVF Expertise of the surgeon (Suresh and Narvekar , 2014; ASRM , 2015; Sandra et al., 2003) ASRM , 2015 Laparoscopy or IVF ?

20. Our Data on B/L tube block in HSG (2018-2021)

21. Anything to do in Unilateral Tube Block? Most cases, laparoscopy would not change the management. ( Lavy et al., 2004; Mol et al., 1999) 64% chance of spontaneous subsequent pregnancy after unilateral salpingectomy for ectopic pregnancy (Fernandez et al., 2013) Treat like unexplained subfertility ( Farhi et al., 2007;. Tan et al., 2018; Yetkin et al., 2017; Berker et al., 2013, Selcuk et al., 2016)

22. Meta-Analysis Success rate of IVF - ∼25% (NNT- 4) *European IVF-Monitoring Consortium (EIM) for ESHRE, 2016 Jacobson et al., 2010 Duffy et al., 2014 OR for ongoing pregnancy (95% CI) 1.64 (1.05– 2.57) 1.94 (1.20–3.16) The number of infertile women that should undergo destruction of superficial peritoneal endometriosis 12 8 The prevalence of grade I/ II endometriosis among women with unexplained infertility ≤50% NNT 24 16 Laparoscopy if tubes are open

23. Routine or selective use of tubal patency test? Suresh and Narvekar , 2014 Overall scenario In low-risk treatment-naive women undergoing OI or IUI , we do NOT advocate the routine use of a tubal patency test prior to initiating treatment. Only women keen to proceed with >3 OI or IUI treatment are offered a tubal patency test NICE, 2013 Women with a history s/o tubal damage - tubal assessment before IUI Women with no risk factors in their history- tubal assessment ONLY after 3 cycles of failed IUI

24. Non-invasive screening test? Chlamydia antibody test (CAT) Chlamydia trachomatis is the single largest cause of acquired tubal pathology Can avoid unnecessary invasive testing. The optimal cut-off value of CAT ??? (Suresh and Narvekar , 2014)

25. Tubal Patency Tests (Suresh and Narvekar , 2014)

26. “Are the fallopian tubes OK”? Tubal patency ≠ normal function of the tube ( Approbato et al., 2020; Tan et al., 2018; Luca et al., 2017) Synchronized and intricate peristalsis and ciliary motion to allow fertilization and intrauterine implantation. Confirmation of tubal patency even at laparoscopy does not necessarily mean normal function of the tube ( Approbato et al., 2020; Tan et al., 2018; Luca, et al. 2017; Elstein et al., 2008)

27. Acknowledgement Dr Biswajyoti Guha Secretary, BOGS

28. Take Home Messages Check overall scenario before advising tubal patency test HSG / SSG / HyCoSy should be the first line of investigation Laparoscopy is useful in selected cases

29. Thank you