1. Increasing Success in IUI
Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (Obst & Gynae- Gold Medalist)
DNB (Obst & Gynae)
Consultant: Behala Balananda Brahmachary Hospital and Research Centre
Visiting Consultant: Indian Air Force
Secretary, Bulletin & Website Committee: Bengal Obstetric & Gynaecological Society (BOGS)

3. Patient Selection: Age
Steven R B et al (2008) - Maximum success, if <25 years
Marviel et al (2010) – Maximum conception, if <30 years
Badawy et al (2009)- Little success, if >35 years
Mathieu C et al (1995)- Increased age of male partner can adversely affect outcome

4. AGE :
Age
<35yrs
35-37 yrs
38-40yrs
41-42yrs
>42yrs
No. of cycles
2351
947
614
160
120
Success rate
10.1%
8.2%
6.5%
3.6% 0%
Dovey S et al,2008
*IUI seems to be a poor treatment option for women over 40 years of age

5. Patient Selection: Duration of Infertility
Mathieu C et al (1995)- Highest rate when <3 years
Nuojua-H S et al (1999)-
Duration <6 years- conception rate 20%
Duration >6 years- conception rate 10%

6. Patient Selection: Duration of Infertility
Age less than 35 (Morsedi et al 2003) with good ovarian reserve
At least one patent Fallopian tube with good tuboovarian relation
Short duration of infertility (<5 years)

7. How many cycles?
Pregnancies resulting from IUI occur during the first 3-6 treatment cycles (Morshedi et al,2003, Dickey et al 2002).
most women conceive after 4-6 cycles of IUI
cycle fecundability declines by ½ to 2/3 thereafter
(Khalil MR et al.; Acta Obstet Gynaecol Scand Jan, 80(1): 74-81)
The NICE fertility guidelines - up to 6 IUI cycles for patients with unexplained infertility, male subfertility, cervical factor and minimum to mild endometriosis
(National Institute of Clinical Excellence. Fertility: Clinical guidelines. No 11. London: Abba Litho Ltd. UK, 2004)

8. Cause of infertility
Dickey et al (2002)- maximum success for ovulatory dysfunction, followed by male subfertility
Khalil MR et al (2001)- Best results in anovulation and unexplained infertility

9. Cause of infertility (Bourn Hall clinic, 1999 ;Tay et al,2007; Wang et al,2008)
Higher PR with :
Unexplained infertility (9.2% to 22% )
Ovulatory dysfunction (19.2%)
Modest PR → Cervical factor (16.4%)
Poor PR:
Endometriosis (11.9%)
Immunological infertility (10% )
Male factor
Male factor → the best PR with ejaculatory disorders (13.3%)

10. Stimulation Protocol Natural cycle + IUI 3.3% CC + IUI 9.5%
CC + hmG + IUI %
hmG + IUI %

11. Live birth rates could not be assessed
Anti –oestrogens versus gonadotrophins combined with intrauterine insemination outcome: pregnancy rate per couple.
(Contineau AE et al, 2007)
4/15/2018

12. Number of follicles Pregnancies per cycle (%)
ONE %
TWO %
THREE %
FOUR OR MORE %
Higher pregnancy rate with three preovulatory follicles (Huttenen et al 1999)

13. Follicular Dynamics
Aim is preovulatory follicles : 2–3 follicles≥ 16 mm
(Steures et al, 2004; Bhal et al ,2001)
Endometrial Thickness- Controversial results
Abdalla HI et al. Hum Reprod 1994;9:363-5
Basil S. Ultrasound Obstet Gynecol 2001;18:258-6
Seddigheh E et al. Fertil Steril 2006;88:432-37
No pregnancy occurs when the ET is <6mm
(Tomlinson et al ,1996)

14. If more follicles?- risks of OHSS and multiples in IUI
Cycle cancellation {> 3 follicles ≥ 16mm or; > 8 follicles ≥ 12mm} OR Conversion to IVF cycle

15. TMSC and motility– cut offs
TMSC PR/CYCLE
10–20 million %
5–10 million %
<5million %
TMSC should be 5-10 million
If less than 5 million counsel and do IUI
(Guven et al, 2008;Abdelkader & Yeh)2009)

16. Initial Seminal Parameters
Haebe J et al (2002)- Higher success with
total motile sperm count >2 million
post wash motility >40%
normal sperm morphology >4%
Montanaro GM et al (2001)-
Pregnancy rates 18.2% when normal sperm morphology >10%
Pregnancy rates 4.3% when normal morphology <10%
Lee RK et al (2002)-
Best results with normal morphology >14%
Poor when fewer than 4% sperms were normal.
Shulman et al (1998)- Higher success with motility>30%

17. Cut off of IMC
IUI should be the treatment of choice in case of male subfertility, providing an insemination motile count (IMC) of more than 1 million can be obtained after sperm preparation.
Cohlen BJ et al (Cochrane Review) .

18. Best predictors
IMC after washing and sperm morphology by strict criteria are the most valuable sperm parameters to predict IUI outcome in male subfertility
Ombelet W et al Reprod Biomed Online
Duran EH et al , Syst Review. Hum. Reprod Update

20. Sperm preparation- which method?
Depends upon the semen characteristics
Swim up commonly used
DG can also be used and shows better quality
Insufficient evidence to recommend any particular technique over the other
( Boomsma CM Cochrane Rev 2007)

21. Sperm Wash-IUI interval
Exhaustion of energy sources in the sperm-washing medium by the motile spermatozoa
Premature (in vitro) capacitation of washed motile spermatozoa

22. Timing Of Insemination
Fixed protocol
Single planned insemination: hrs post hCG
Double insemination:
1st : 24 hrs. post hCG
2nd : 48 hrs. post-hCG
Variable protocol:
TVS 36 h post hCG: Ovulated  single IUI
Not Ovulated  IUI at once
 IUI 24 hrs later

23. Exact timing of IUI
(Kucuk ,2008).
Conclusion:Postponing IUI until observation of follicle rupture may yield a higher pregnancy rate.(25% Vs 8%)

24. Double vs single IUI
No difference in PR between single vs double
Cantinaeu AE Cochrane 2009, Polyzos 2010
An exception suggested is if the TMC is less than 1 million on insemination day, a second IUI can be offered within the next 24 hours

25. Mohamad E. Ghanem et al.,Human Reproduction, Vol.0, No.0 pp. 1–8, 2010
The study included a total 1146 first-stimulated cycles in infertile couples due to male factor, anovulation or unexplained infertility.
Conclusion: Single IUI timed post-ovulation gives a better CPR when compared with single pre-ovulation IUI for non-male infertility whereas for male factors, pre-ovulation, double IUI gives a better CPR when compared with single IUI.

26. Type of catheter
No significant difference in PR when using the softer Wallace catheter or the less pliable Tomcat catheter during IUI, with the standard gentle non touch technique
(Smith et al ,2002)( Van Der Poel N Cochrane 2010)
However , Merviel et al recommended soft catheter

27. Various IUI catheters used

28. Cook Soft-Pass catheter
Makler IUI cannula
Gynetics catheter
Tomcat catheter
Wallace artificial insemination catheter

29. Inseminated volume
No difference in PR when the inseminated volume varied from 0.3 to 1 mL
(Do Amaral VFJ Assist Reprod Genet 2001)

30. IUI technical aspects Should be gentle and atraumatic
Aseptic technique to avoid genital infection
Should be gentle and atraumatic
Products of local tissue reaction to injury may be hostile to spermatozoa

31. Steps of insemination Partially filled urinary bladder
Dorsal position sometimes with hip & knee flexed & hip slightly abducted
Gently and atraumatically clean the cervix with saline soaked swab
Introduce IUI catheter through cervix; no touch to fundus
Slowly inject ml of processed semen
Slowly withdraw catheter

32. IUI Procedure

33. 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

34. Why difficult Insemination ?
IO to left of EO (80%)
IO to right of EO (10%)
IO in straight line with EO (10%)

35. EXT OS FLUSHED
AV, RV UTERUS

36. Difficult IUI:How to avoid and what to do
Keep Cx centrally in vagina by speculum manipulation
External os in transverse axis of vagina
Slight traction on Cx with Allis’ tissue forceps: straightens out utero-cervical angulation
Use of forceps do not reduce pregnancy rates

37. Difficult IUI:How to avoid and what to do
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

38. Difficult IUI: what to do next contd..
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

39. Difficult IUI: what to do next
Trial 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

40. Ultrasound guided IUI? Ultrasound guided IUI has been tried
Not found to increase pregnancy rates
Ramón et al,2009; Oztekin et al,2013
Useful in difficult IUI

41. Bed rest after IUI A ten minute bed rest has a positive effect
(Saleh A Fertil Steril 2000)

42. Timed intercourse after IUI
Timed intercourse within h period: useful in IUI with low number of motile sperm inseminated
(Huang et al, 1998)

43. Luteal phase support Most centres provide luteal support
However no evidence to support
Not needed – ESHRE 2009

44. Agonists and antagonists (Barros Delgadillo JC 2010)
Antagonists are being tried in PCOS to combat the premature LH surge
An increase in PR shown but at an increased risk of multiple pregnancies

45. Agonists and antagonists
Such patients should be counselled for IVF due to risk of OHSS and multiple pregnancy in IUI cycles
No evidence to support use of agonists or anatgonists as they are not cost effective - ESHRE 2009

46. Quality control Pregnancy rate per cycle go down Check media Incubator
Difficult IUI- trial
Stimulation protocol to be changed
Base line scan before stimulation

47. To conclude… Careful selection of couples and maximum 3-6 cycles
Good understanding of physiology of COS
Use of gonadotropin in IUI but avoid multiple pregnancies and OHSS
Well timed single IUI is the best
Avoid endometrial injury
Strict sperm cut offs for IUI
If all these adhered to – cost effective before IVF in young couples with good reserve