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Difficult Cases in IUI

Dr Sujoy Dasgupta moderated a Panel Discussion on "Difficult cases in IUI" in the Annual Conference of ISAR (Indian Society of Assisted Reproduction), Bengal held in December, 2022

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Difficult Cases in IUI
Moderator
• Dr Sujoy Dasgupta
Panelists
• Dr Sneha Tickoo
• Dr Dorothy Ghosh
• Dr Kakoli Pal
• Dr Nilanjan Paik
• Dr Siuli Chowdhury
• Dr Paromita Hazra
• Dr Sudakshina Panja
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
Case Scenario 1
• Mrs BD, 28 yr
• Trying for pregnancy for 3 yrs
• PCOS
• BMI 23 Kg/M2
• HSG and semen analysis- normal
• Tried OI with letrozole several cycles
• Decided for IUI
Cycle day Tablet
Letrozole
Injection
hMG
Right Ovary Left Ovary Endometrial
thickness
D2 2.5 mg AFC 20 AFC 18 5 mm
D3 2.5 mg
D4 2.5 mg
D5 2.5 mg
D6 2.5 mg
D7 75 IU
D8 75 IU
D9 75 IU
D10
D11 14/2
13/2
12/5
14/3
11/2
7.5 mm
IUI stimulation started for Mrs BD
What to discuss with Mrs BD?
1. Proceed for IUI and add antagonist
2. Cancel IUI cycle and ask abstinence from
intercourse
3. Conversion to IVF
Cancellation versus conversion
• Discuss pros and cons of each option- cost
implications
• Risks of OHSS/ multiples are high if
1. Serum estradiol levels >900–1,400 pg/mL
2. >4-6 follicles ≥10–14 mm
3. >3 follicles ≥15 mm (ACOG, 2017; ESHRE, 2018).
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Difficult Cases in IUI

  • 1. Difficult Cases in IUI Moderator • Dr Sujoy Dasgupta Panelists • Dr Sneha Tickoo • Dr Dorothy Ghosh • Dr Kakoli Pal • Dr Nilanjan Paik • Dr Siuli Chowdhury • Dr Paromita Hazra • Dr Sudakshina Panja
  • 2. 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
  • 3. Case Scenario 1 • Mrs BD, 28 yr • Trying for pregnancy for 3 yrs • PCOS • BMI 23 Kg/M2 • HSG and semen analysis- normal • Tried OI with letrozole several cycles • Decided for IUI
  • 4. Cycle day Tablet Letrozole Injection hMG Right Ovary Left Ovary Endometrial thickness D2 2.5 mg AFC 20 AFC 18 5 mm D3 2.5 mg D4 2.5 mg D5 2.5 mg D6 2.5 mg D7 75 IU D8 75 IU D9 75 IU D10 D11 14/2 13/2 12/5 14/3 11/2 7.5 mm IUI stimulation started for Mrs BD
  • 5. What to discuss with Mrs BD? 1. Proceed for IUI and add antagonist 2. Cancel IUI cycle and ask abstinence from intercourse 3. Conversion to IVF
  • 6. Cancellation versus conversion • Discuss pros and cons of each option- cost implications • Risks of OHSS/ multiples are high if 1. Serum estradiol levels >900–1,400 pg/mL 2. >4-6 follicles ≥10–14 mm 3. >3 follicles ≥15 mm (ACOG, 2017; ESHRE, 2018).
  • 7. Immediate advice to Mrs BD before discharge? • Analgesics • Antiemetics • Cabergoline • High protein diet • Adequate fluid intake • Contact immediately if 1. Severe nausea/ vomiting 2. Severe pain 3. Breathlessness 4. Reduced urine output 5. Unusual symptoms (s/o VTE)
  • 8. Cycle day Tablet Letrozole Injectable Right Ovary Left Ovary Endometri al thickness D2 2.5 mg AFC 20 AFC 18 5 mm D3 2.5 mg D4 2.5 mg D5 2.5 mg D6 2.5 mg D10 D11 13/1 11/1 7 mm D14 Inj hCG (5000) 18/1 16/1 8.5 mm D16 IUI (H) was planned Mrs BD cancelled that cycle, came next cycle for IUI again
  • 9. On the day of IUI • Husband of Mrs BD failed to produce semen  Can this situation be avoided?  How to tackle this situation?
  • 10. Issues in Semen Collection Prevention • Privacy • Relaxation • Bed • Partner • Washing facility • Elective Freezing of sperms Solution • Counselling • Erectile Issue- Sildenafil 50, Tadalafil 10, Verdenafil 10 • Vibroejaculator (Saleh at al., 2003; Elliott, 1993; Ibrahim et al., 2016) • Coitus interruptus • Nontoxic condom (Dias et al., 2019) • Home Collection (ASRM, 2015; WHO, 2010) • Urine (In Retrograde ejaculation) • Prostatic Massage (Fahmy et al. 1999; Arafa et al., 2007). • Electroejaculation ???
  • 12. Semen collection problem is NOT uncommon • 8.3% of the men experienced ejaculation- failure on the day of operation for ART (Li et al., 2016). • Only 59% of the men attending the fertility clinic felt comfortable in masturbation and 48% required external stimulation to collect semen (Pottinger et al., 2016).
  • 13. Case Scenario 2 • Mr PS • Medical H/O- nothing significant
  • 14. Collection Method Masturbation Abstinence 4 days Collection Complete Volume 2 ml Colour Whitish Viscosity Normal Liquefaction Time 45 minutes pH 7.6 Sperm Concentration 10 million/ ml Total Motility 20% Progressive Motility 6% Non progressive Motility 14% Immotile 70% Motile Sperm Count 2 million Normal Morphology 3 % Vitality 34% Round cells Nil
  • 15. Options? 1. Donor sperm- IUI 2. Antioxidants for 6 months, then review 3. Detailed evaluation 4. IVF-ICSI with self-sperms
  • 16. Severe Male Factor- if not left untreated ??? • Progressive decline in semen parameters
  • 17. • Overall, 16 (24.6%) of 65 patients with severe oligozoospermia developed azoospermia. • Two (3.1%)patients with moderate oligozoospermia developed azoospermia • None of the patients with mild oligozoospermia developed azoospermia.
  • 18. Male Infertility- Mild or Severe? • TMSC= Total Motile sperm count = Sperm concentration x total volume x total motility (TM) • TMSC >5/ 10/ 20 million
  • 19. IUI/ IVF/ICSI? • Assess 1. Tubal factor 2. Ovarian reserve 3. Duration of Infertility 4. Age of the female partner
  • 20. TMSC PR/CYCLE  10–20 million 18.29%  5–10 million 5.63%  <5million 2.7% Guven et al, 2008;Abdelkader & Yeh, 2009 Hamilton et al., 2015 Criteria TMSC Treatment Pre wash TMSC > 5 million IUI Pre wash TMSC 1 - 5 million IVF Pre wash TMSC <1 million ICSI IUI, IVF or ICSI?
  • 21. TMSC <5 million • “Trial IUI” • See IMSC (inseminating motile sperm count) IMSC Next action > 1 million further 3-4 cycles of IUI <1 million Morphology ≥4% further IUI can be attempted Morphology <4% ICSI
  • 22. Any other thing? • obtaining a second semen sample when the motile sperm yield of the first semen sample is 1 million to 5 million significantly increases the total motile sperm count in the final inseminate.
  • 23. Double Ejaculate often produces better quality of sperms
  • 24. Oligospermia and IUI TMSC 5-10 million Do IUI 4-6 cycles TMSC <5 mil 1. Counseling before IUI 2. Double Ejaculate 3. Post wash- IMSC 4. IMSC >1 mil → Further IUI 5. IMSC <1 mil → see Morphology 6. No role of double insemination or any special washing technique (ESHRE., 2018)
  • 25. Case Scenario 3 • Mrs AC, 30-yr • Trying for pregnancy for 2 years • c/o severe dysmenorrhoea • AMH 3.5 ng/ml • 5 cm endometrioma in Rt ovary • Semen analysis normal
  • 26. Mrs AC underwent laparoscopy • Right Ovarian 5 cm chocolate cyst removed • Severe adhesion in POD- complete adhesiolysis was done • Dye test B/L positive
  • 27. Mrs AC is now pain-free • Visited 4 doctors over the period of next 2 years. • Received different brands of letrozole for ovulation induction- total 12 cycles • She wants to do IUI • AMH now 2.2 ng/ml
  • 28. ESHRE, 2022 rASRM stage I/II endometriosis •May perform IUI with ovarian stimulation, instead of expectant management or IUI alone •IUI+OS increases pregnancy rates. rASRM stage III/IV endometriosis •The value of IUI in women with tubal patency is uncertain •IUI +OS could be considered Can IUI be done in endometriosis?
  • 29. Hughes, 1997 Meta-analysis- IUI success is halved in stage I/II endometriosis Gandhi et al., 2014 No difference between expectant management and IUI Dmowski et al., 2002 First-cycle chance of pregnancy with IVF is significantly higher than the cumulative pregnancy rate after 6 IUI cycles Van der Houwen et al., 2014; D’Hooghe et al., 2006 The risk of endometriosis recurrence appears to be increased by IUI (more than IVF) IVF, but not IUI, can be expected to overcome the detrimental effects of a pelvic inflammatory milieu. Limitations of IUI in endometriosis
  • 31. Mrs AC agreed for IUI • On the day of IUI • Husband- Mr AC collected semen • Previous semen analysis- Normozoospermia • Today- 4-5 motile sperms/hpf  Explanation?  Remedy?
  • 32. Possible reasons of sudden abnormal semen parameters • Laboratories not adhering to WHO standards (Penn et al., 2010; Keel et al., 2002) • Significant intra-individual variability (10.3-26.8% (Alvarez et al., 2003). • Testicular heat exposure 3 months back (e.g., fever) (WHO, 2010) • New insults to spermatogenesis (mumps orchitis, Covid-19 infection, TB, diabetes, drug exposure, cancer treatment) • Inadequate sexual stimulation can affect semen quality (van Roijen et al., 1993)
  • 35. Solution for husband of Mr AC? • Double ejaculate
  • 36. Case Scenario 4 • Mrs TR, 28 yrs • Trying for pregnancy for 5 yrs • PCOS- not responded to letrozole and CC • Underwent LOD, tubes patent • Partner’s semen normal • Requests for IUI
  • 37. Cycle day Injection r- FSH Right Ovary Left Ovary Endometrial thickness D2 75 IU AFC 20 AFC 18 5 mm D3 75 IU D4 75 IU D5 75 IU D6 75 IU D7 75 IU D8 75 IU D9 75 IU 10/1 11/1 7 mm D10 75 IU D11 75 IU 13/1 14/1 7.5 mm D12 75 IU D13 75 IU No DF No DF 8 mm Fluid in POD IUI stimulation started for Mrs TR
  • 38. Can we do IUI on day13 for Mrs TR?
  • 39. ESHRE, 2018 • If a HCG injection is used, single IUI can be performed any time between 24 and 40 h after HCG injection without compromising pregnancy rates. • IUI in a natural (not ovarian stimulated) cycle should be performed 1 day after LH rise.
  • 40. Prevention of premature ovulation in IUI • GnRH Antagonist?
  • 41. 20 antagonist cycles to achieve one pregnancy (Dokuzeylül N, 2009)
  • 42. Cantineau AE, Cohlen BJ, Heineman MJ. Ovarian stimulation protocols (anti- oestrogens, gonadotrophins with and without GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with subfertility. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005356. doi: 10.1002/14651858.CD005356.pub2. Update in: Cochrane Database Syst Rev. 2021 Nov 5;11:CD005356. PMID: 17443584.
  • 43. Prevention of premature LH surge ≠ Improvement in pregnancy rate
  • 44. ESHRE, 2018 • Based upon moderate quality evidence, addition of GnRH agonist or antagonist is not recommended for our draft evidence-based guideline, because there is no increase in pregnancy rate despite increased MPRs and costs
  • 45. Case 5 • Mrs SN undergoing IUI for unexplained subfertility • Satisfactory stimulation response • No significant medical/ surgical history
  • 46. Your choice of catheters
  • 48. During IUI • Catheter could not be negotiated • Is it “difficult insemination”?
  • 49. What is difficult insemination? Insemination: easy in 80%, difficult in 20% Greater resistance during catheter negotiation Harder catheter needed Cervical dilatation needed Blood in catheter
  • 50. AV, RV UTERUS EXT OS FLUSHED
  • 51. What to do first? • Full bladder • The pregnancy rate was higher in the full bladder group than in the empty bladder (control) group (P=0.03, 13.5% vs 7.4%; RR 1.95; 95% CI 1.048-3.637). • The risk of undergoing difficult IUI was higher in the empty bladder group than the full bladder group (P<0.001; 10.0% vs 37.8%, RR 0.18 for difficulty IUI; 95% CI 0.11-0.30). • The clinical pregnancy rate was also higher in the group of patients who had easy IUI than in the group of patients who had difficult IUI (P<0.05, 12.7% [42/331] vs 5.5% [6/110]); RR 2.51 for pregnancy; 95% CI 1.04-6.09) (Ayas et al., 2012)
  • 52. Still difficult? Keep Cx centrally in vagina by speculum manipulation Slight traction on Cx with Allis’ tissue forceps: straightens out utero-cervical angulations
  • 54. Use of ultrasound? Oztekin D, et al., 2013
  • 55. • Ultrasound-guided IUI significantly improved the clinical pregnancy rate when compared to the classical group (RR = 1.33, 95% CI [1.05, 1.68], p = 0.02). • No significant differences between both groups in terms of miscarriage and live birth rates. • Ultrasound-guided IUI significantly reduced the incidence of difficulty reported during the procedure (RR = 0.42, 95% CI [0.21, 0.84], p = 0.01). • The GRADEpro GDT tool showed high quality of evidence for the evaluated outcomes.
  • 57. Difficult IUI: How to avoid? Ultrasound guidance Measuring the utero-cervical angle with ultrasound before IUI and moulding the catheter accordingly increases clinical pregnancy Hysteroscopy & cervical dilatation should be done before next IUI
  • 58. Mock IUI? Enables the clinician to assess the degree of difficulty • assessment of depth and shape of uterus • selection of optimal catheter type • mapping the easiest and least traumatic entry into uterine cavity • identify cervical stenosis