This document discusses several complex cases involving intrauterine insemination (IUI). It describes patient histories, stimulation protocols, semen analysis results, and challenges that arose during IUI procedures. The panelists discuss options for each case, including risks of ovarian hyperstimulation, limitations of IUI for endometriosis patients, preventing premature ovulation, difficult insemination techniques, and using ultrasound guidance. The document provides guidance on managing risks and complications to optimize IUI success rates.

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 ???

11. Novel technique

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)

33. From which Laboratory?

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

53. Tenaculum= Decreased pregnancy rate?

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