Indications of Hysteroscopy

Invited Lecture delivered in 23rd Annual Congress of ISAR (Indian Society for Assisted Reproduction) in April 2018 at Kolkata

1. Indications of Hysteroscopy Dr Sujoy Dasgupta MBBS (Gold Medalist, Hons) MS (OBGY- Gold Medalist ) DNB (OBGY) MRCOG (London) Consultant, Genome: The Fertility Centre, Kolkata Secretary, Website and Bulletin Committee, Bengal Obstetric and Gynaecological Society (BOGS)- 2017-18 Managing Committee Member, BOGS- 2017-18 Member, Quiz Committee, FOGSI East Zone, 2018-19 Member, Food and Drug Committee, FOGSI, 2018-19 Peer Reviewer, BMJ Case Reports

2. Infertility- a big enigma?

3. Endometrium- Friendly or Hostile? Uterine factors- Found in 2-3% of the couples struggling to conceive can be present in 10-15% cases of “unexplained subfertility”

4. Hysteroscopy To confirm abnormal findings Apparently “Unexplained” Subfertility Previous IVF failure Symptomatic Patients Recurrent Pregnancy Loss Operative Intervention

5. Hysteroscopy to confirm Abnormal Diagnostic Results

6. “Abnormal” Endometrium Polyp Endometrial Hyperplasia Adhesion Myoma Fluid Congenital Anomaly

7. Endometrial Polyp

8. Diagnosis of Polyp 1. TVS -investigation of choice where available (Level B). 2. The addition of color or power Doppler improves accuracy (Level B). 3. SIS and 3-D imaging improves the diagnostic capacity (Level B). 4. Blind D/C biopsy should not be used for diagnosis of endometrial polyps (Level B ). 5. Hysteroscopy- Gold Standard , polypectomy in the same sitting AAGL Practice Guidelines for the Diagnosis and Management of Endometrial Polyps

9. Kamel HS, Darwish AM, Mohamed SA. Comparison of transvaginal ultrasonography and vaginal sonohysterography in the detection of endometrial polyps. Acta Obstet Gynecol Scand 2000; 79 :60–4 Hysteroscopy- Gold Standard , polypectomy in the same sitting Likelihood Ratio Positive result Negative result TVS 2.7 15.5 SIS 0.46 0.07

10. Polyps and Infertility can distort the endometrial cavity may have a detrimental effect on endometrial receptivity Frequently associated with obesity, diabetes, PCOS ( hyperestrogenism ) Infertile women are more likely to be diagnosed with an endometrial polyp (Level B )* *AAGL Practice Guidelines for the Diagnosis and Management of Endometrial Polyps 10

11. Fibroids

12. AAGL Practice guidelines for sub mucous myomas :Level A HSG is less sensitive and specific TVS is less sensitive and specific than SIS/ Hysteroscopy/ MRI. MRI is superior in classification and realtionship of myomas with serosa . Hysteroscopy- Gold standard for diagnosis and treatment

13. Intrauterine Adhesion

14. Diagnosis Hysteroscopy is the method of choice for diagnosis. Level B HSG and SIS can be done in absence of hysteroscopy. Level B MRI is not fully evaluated. Level C

15. ASRM Scoring for Intrauterine Adhesion Look at... Size/description Score Extent of cavity involved <1/3 1 1/3–2/3 2 >2/3 4 Type of adhesions Filmy 1 Filmy and dense 2 Dense 4 Menstrual pattern Normal Hypomenorrhoea 2 Amenorrhoea 4 Prognostic classification Stage I (mild) 1–4 Stage II (moderate) 5–8 Stage III (severe) 9–12

16. Müllerian Anomalies

17. ESHRE/ESGE consensus on diagnosis of female genital anomalies, 2015 Asymptomatic Women- Screening Gynaecological examination 2D USS Further Evaluation- 3D USS “Symptomatic” Women- 3D USS Complex Anomalies- (defined as having anatomical deviations in more than one organ of the female genital tract) MRI Hysteroscopy and laparoscopy : in special centres after thorough non-invasive evaluation and, mainly, in the context of concomitant surgical treatment of any discovered pathology.

18. Uterine Anomalies spontaneous miscarriage – Septate > Bicornuate Recurrent pregnancy loss Malpresentation Fetal growth restriction Preterm labour Dysmenorrhea Association with Subfertility Cause-effect relationship- ?

19. Septum, Infertility and Miscarriage

20. Hysteroscopy in “Normal” Endometrium

21. Hysteroscopy in Unexplained Subfertility Semen Analysis HSG/ SIS/ Laparoscopy for tubal patency D21 Progesterone Hysteroscopy should not be a part of routine evaluation NICE- Fertility problems: assessment and treatment: Clinical guideline; February 2013

22. Unexplained Subfertility Where facilities are available, SIS together with 3D ultrasound can offer a less invasive outpatient method to assess the uterine cavity with accuracy similar to that of hysteroscopy Brown SE, et al. Evaluation of outpatient hysteroscopy, saline infusion hysterosonography , and hysterosalpingography in infertile women: a prospective, randomized study. Fertil Steril 2000;74:1029–34.

23. Draz MH, El- Sabaa TM, El shorbagy SH. Saline infusion sonography versus hysteroscopy in the evaluation of uterine cavity in women with unexplained infertility. Tanta Medical Journal. 2017, 45:155–159

24. Women with unexplained infertility should be screened for possible uterine cavity abnormalities. SIS is a simple and well-tolerated procedure that can be used as an alternative technique for the evaluation of uterine cavity abnormalities when Hysteroscopy is not available. However, Hysteroscopy is still considered the gold standard to diagnose intrauterine pathology as it is more sensitive and more accurate than SIS. Draz MH, El- Sabaa TM, El shorbagy SH. Saline infusion sonography versus hysteroscopy in the evaluation of uterine cavity in women with unexplained infertility. Tanta Medical Journal. 2017, 45:155–159

25. American Society for Reproductive Medicine (ASRM) Hysteroscopy is the definitive method for the diagnosis and treatment of intrauterine pathology. Costly and invasive method for uterine cavity evaluation, it should be reserved for further evaluation and treatment of abnormalities defined by less invasive methods such as HSG and sonohysterography Fertility and Sterility, vol. 98, no. 2, pp. 302–307, 2012 25

26. Routine Hysteroscopy before IVF? INSIGHT Trial Routine hysteroscopy does not improve live birth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy. Smit JG, et al. Hysteroscopy before in-vitro fertilisation ( inSIGHT ): a multicentre, randomised controlled trial. Lancet. 2016 Jun 25;387(10038):2622-9.

27. Hysteroscopy in Previous IVF Failure

28. Bosteels J, et al. The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review. Hum Reprod Update 2010;16:1–11. Hysteroscopy in the cycle preceding a subsequent IVF attempt nearly doubles the pregnancy rate in patients with at least two failed IVF attempts compared with starting IVF immediately (RR = 1.7; 95% CI: 1.5–2.0 ).

29. 6 eligible studies comprising 4143 patients with RIF were included. OH (Office Hysteroscopy) vs No OH Hysteroscopy may potentially improve pregnancy outcomes in patients with RIF. Cao H, You D, Yuan M, Xi M. Hysteroscopy after repeated implantation failure of assisted reproductive technology: A meta-analysis. J Obstet Gynaecol Res. 2018 Mar;44(3):365-373. OH vs No OH RR 95% CI P Clinical Pregnancy Rate (CPR) 1.34 1.14-1.57 <0.05 Live Birth rate (LBR) 1.29 1.03-1.62 <0.05 CPR (OH vs No OH) RR 95% CI P Asia 1.49 1.31-1.69 <0.05 Europe 1.08 0.93-1.26 0.291 Normal OH vs Abnormal OH RR 95% CI P CPR 0.92 0.83-1.02 0.12 LBR 0.76 0.37-1.56 0.450

30. Hysteroscopy in Symptomatic Patients

31. Symptoms HMB Not controlled by pharmacological measures with normal TVS Abnormal TVS- thickness/ polyp/ myoma IMB No apparent cause found PCOS HMB with thick endometrium No withdrawal bleeding with thick endometrium

32. RCOG Green Top Guidelines : No 33, November 2014; Polycystic Ovary Syndrome, Long-term Consequences

33. Endometrial Hyperplasia RCOG Green Top Guideline: No 67, February 2016; Endometrial Hyperplasia, Management of

34. Hysteroscopy in Recurrent Pregnancy Loss

35. Anatomical Defects as a cause of RPL All women with RPL should be assessed for uterine anomaly ( ≥3 first trimester loss, ≥1 second trimester loss) Septate Uterus- RPL in 1 st TM Bicornuate / Arcuate Uterus- RPL in 2 nd TM RCOG Green Top Guidelines No 17. April 2011. The Investigation and Treatment of Couples with Recurrent First trimester and Second-trimester Miscarriage

36. Operative Hysteroscopy Enhancing Fertility Tubal Canulation Polypectomy Myomectomy Adhesiolysis Septum Resection

37. Proximal Tubal Block

38. Proximal Tubal Blockage (PTB) Accounts for approximately 15% of cases of tubal factor infertility Salpingitis isthmica nodosa (SIN) 40% Endometriosis Cornual Polyp } 10% Cornual Spasm 20% Stromal Oedema Tubal debris Intraluminal adhesions Viscid Secretion } 30% Suresh YN, Narvekar NN. TOG 2014;16:37–45.

39. Treatment of PTB IVF vs Tubal Surgery Patient’s preferences Age Associated Fertility Problems Cost, Expertise, Resources Risk of OHSS Most of the PTB Fluroscopic Selective Salpingography Hysteroscopic Tubal cannulation SIN tubal resection and anastomosis of the diseased inflammatory area- highest success compared to tubal catheterisation or expectant management irrespective of tubal patency Suresh YN, Narvekar N. Role of surgery to optimise outcome of assisted conception treatments. The Obstetrician & Gynaecologist 2013;15 91–8.

40. Recommendations For women with proximal tubal obstruction, selective salpingography plus tubal catheterisation , or hysteroscopic tubal cannulation, may be treatment options because these treatments improve the chance of pregnancy. NICE Clinical guideline Fertility problems: assessment and treatment

41. Hysteroscopic Polypectomy

42. Management algorithm for polyps Annan JJ, Aquilina J, Ball E. The management of endometrial polyps in the 21st century. The Obstetrician & Gynaecologist 2012;14:33–38.

43. Evidences 43 Bosteels J, et al. Cochrane Database Syst Rev. 2015 Feb 21;(2):CD009461. IUI the hysteroscopic removal of polyps prior to IUI increases the odds of clinical pregnancy P´erez -Medina T, et al. Hum Reprod 2005;20:1632–5 IUI Hysteroscopic polypectomy increases pregnancy rate Stamatellos I, et al. Arch Gynecol Obstet. 2008 May;277(5):395-9. IVF In women in whom the only reason for subfertility was endometrial polyps, hysteroscopic polypectomy improved the rate of spontaneous conception regardless of size or number of polyps Ben- Nagi J, et al.. Reprod Biomed Online 2009;19:737–44 IVF Polypectomy improves implantation rate

44. AAGL Practice Guidelines for the Diagnosis and Management of Endometrial Polyps Hysteroscopic Polypectomy is the Gold Standard Treatment For the infertile patient with a polyp, surgical removal is recommended to allow natural conception or ART a greater opportunity to be successful (Level A).

45. Hysteroscopic Myomectomy

46. SUB MUCOUS HYSTEROSCOPIC MYOMECTOMY SUBSEROUS AND INTRAMURAL <4CM OBSERVE 4-7CM >7CM LAP MYOMECTOMY ? Optimum Management

47. Evidences Pritts, et al. 2009 Meta-analysis Removal of submucous fibroids seems to confer benefit in terms of pregnancy rates. T. Shokeir , et al. 2010 RCT Women, with no other factors associated with infertility, undergoing hysteroscopic myomectomy had a better possibility of becoming pregnant. Irrespective of fibroid size, number, and location in both groups.

48. AAGL Practice guidelines for sub mucous myomas :Level A Removal improves fertility esp for type 0 and type 1 but remains low as compared to normal uteri Cervical preparation can reduce trauma . Pre op use of GnRHa corrects anaemia

49. Location of myomas Number of myomas Size of myomas Asymptomatic/symptomatic Associated adenomyosis/endometriosis Distortion of endometrium Previous failed IVF cycles Previous pregnancy losses Available expertise and resources Other factors affecting fertility Before decision making

50. Hysteroscopic Adhesiolysis

51. AAGL Guidelines, 2017 Hysteroscopic guidance is the method of choice with any tool. Level B No role of blind cervical probing or D/C. Level C Laparoscopy may be combined in cases of dense and lateral adhesions. Estrogens can be used to prevent recurrence. Reassessment of cavity after 2 to 3 cycles with HSG or office hysteroscopy For women with IUAs who do not wish any intervention but still want to conceive, expectant management may result in subsequent pregnancy; however, the time interval may be prolonged. Level C.

52. Prognosis Restoration of menstruation- 70-90% Pregnancy Rate- 60-90% (20-40% for severe disease and with recurrence) Term Pregnancy- 40-80% Pregnancy Complications- High Recurrence Rate- 30% Advanced reproductive Care Inc 2002

53. Hysteroscopic Metroplasty

54. Cutter vs Keeper

55. Hysteroscopic Metroplasty For Septate Uterus – A Meta-analysis Of 16 Published Series Before After Pregnancy 1062 491 Miscarriage 933 (88%) 67 (14%) Preterm Delivery 95 (9%) 29 (6%) Term Delivery 34 (3%) 395 (80%) Homer HA, Li TC, Cooke ID. The septate uterus: a review of management and reproductive outcome. Fertil Steril . 2000 Jan;73(1):1-14. Review.

56. More Evidences Mollo et al. Fertil Steril 2009 Prospective Controlled Trial women with unexplained infertility Hysteroscopic resection of the septum improves the pregnancy rate and live birth rate Ozgur et al. Reprod Biomed Online 2004 Retrospective Study Before IVF Incomplete septum removal improves pregnancy, live birth rate and lowers risk of miscarriage Ensieh Shahrokh Tehraninejad . Int J Fertil Steril . 2013 Retrospective Analysis Subfertility, RPL Hysteroscopic metroplasty improves live birth rate in both groups Dural O, et al. JSLS, 2013 Retrospective Analysis Subfertility with past H/O miscarriage Hysteroscopic metroplasty improves live birth rate, irrespective of the method used Fedele L, et al. Hum Reprod , 1996 Observational Study Hysteroscopic Metroplasty with residual septum <1 cm Does not adversely affect reproductive outcome

57. Cochrane Review, 2017 Most studies of metroplasty for a septate uterus combine women with recurrent miscarriage and infertility, and no study has been published that randomizes infertile women to treatment versus no treatment. For this reason controversy exists as to whether infertile women should undergo metroplasty C. R. Kowalik , M. Goddijn , M. H. Emanuel et al., “ Metroplasty versus expectant management for women with recurrent miscarriage and a septate uterus,” Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD008576

58. “Prophylactic” Metroplasty May not increase fecundability, but may improve live birth rate Can prevent miscarriage and obstetric complications in IVF-pregnancy To be considered before IVF, especially if no other infertility factors were present

59. Septum and RPL RCOG Green Top Guidelines No 17. April 2011. The Investigation and Treatment of Couples with Recurrent First trimester and Second-trimester Miscarriage

60. Take Home Message Routine hysteroscopy in unexplained subfertility- ? Routine hysteroscopy before 1 st IVF- yet to be justified After failed IVF- hysteroscopy is definitely beneficial Intrauterine Pathology- should be addressed by hysteroscopic diagnosis and treatment Hysteroscopic surgery increases chance of pregnancy and live birth- spontaneously/ after IUI/ IVF

61. Thank you