IMPROVING SUCCESS RATE IN IUI

1. Dr. Sunita ChandraDr. Sunita Chandra
M.DM.D..
Director, Morpheus Lucknow Fertility CentreDirector, Morpheus Lucknow Fertility Centre
Director, Rajendra Nagar Hospital & IVF CentreDirector, Rajendra Nagar Hospital & IVF Centre
Fellowship IVF,GermanyFellowship IVF,Germany

3. IMPROVING RESULTS IN
IUI

4. IUI
Involves sperm processing removing
pgs,infectious agents ,immotile
sperms,,leucocytes And placing the
processed specimen into the uterine cavity
with a catheter.

5. IUI can be very effective in :
 Infertility due to ovulation disorders
 Unexplained infertility
 Mild male factor infertility
 Mild endometriosis

6. IUI IS BEST AVOIDED IN
Blockage of both tubes
Severe male factor infertility
Severe endometriosis
Severe pelvic scarring
 Multiple aetiologies
 Multiple previous IUI failures
 AGE is an important factor to be considered.
At 30yrs – per cycle success rate is 20%
At 40yrs – per cycle success rate is 1%

7.  Non-expensive
 Non-invasive
 Simple procedure without substantial
complications &
 Can be practiced by all gynecologists at their
present facility after simple modifications in their
laboratory setup & adding a few equipments.

8. The rationale is that
increasing the density of
both eggs and sperms
near the site of
fertilization to increase
the likelihood of
pregnancy

9. Recent Data on Success rates of
IUI RCT in which 201 couples with 3-4 years unexplained
infertility were randomised to receive three cycles of IUI or
expectant management (Farquhar et al., 2017a).
 A live birth rate of 31% with IUI and 9% with expectant
management was observed, a three-fold difference in
outcome.
 In another RCT performed in the Netherlands stimulated IUI
with clomiphene turned out to be first-line therapy
compared to low dose FSH (Danhof et al., 2017).
 It’s obvious that we are over-using IVF to treat unexplained
infertility. Promoting IVF and ICSI to result in pregnancy “as
quick as possible” ignores the advantages of IUI completely
in case of unexplained and mild male factor infertility.
Willem Ombelet. Facts Views Vis Obgyn. 2017 Sep;.

10. Patient workup
 Prolactin, TSH, AMH
 Day 2- FSH,LH,E2,
 Baseline TVS/colour USG of pelvis . Assess no of antral follicles
 Pre ART hysteroscopy especially in previously failed IVF or
suspect TVS findings
 TB PCR+Bactec +histopath in suspected cases of genital TB
 Detailed semen analysis and culture

11. AMH: Advantages
Over other markers for ovarian reserve
 most sensitive predictor of ovarian response to COH
 levels appear to be relatively stable throughout the
menstrual cycle
 have the greatest reproducibility with the least
variation between cycles
 it does not suffer from the problem of large inter-
observer variations as seen in ultrasound
assessment of ovarian reserve (antral follicle count,
ovarian volume and Doppler assessment).

12. Sonography

13.  Abnormal male factor
 Oligospermia
 asthenospermia
 teratospermia
 The impossibility of vaginal
ejaculation
 psychogenic or organic
impotence
 severe hypospadias,
retrograde ejaculation
 cryopreservation of sperm
in cases of cancer
treatment.
 Unexplained infertility
 Cervical factor infertility
 Husband is away from wife
for long time (work abroad)
 Pelvic pathologies like-
endometriosis, fibroids,
infections & adhesions not
severe or have been surgically
corrected
 Hormonal-PCOD, Hyper
Prolactin, Hyper-Hypo
Thyroid, Hyper Adrenals,
Insulin Resistance & other
conditions leading to Chronic
Anovulation

14. IUI works if . . .
• If the total count is below 1 – 5 million ,success is
very unlikely
• Post-wash sample - 2-5million/ml, 70% motile
sperms
• At-least one functional fallopian tube open
• Ovulation possible
• Functional receptive uterus with endometrial
thickness of @8mm.

15. Patient Selection
Important
Highest pregnancy rates observed in patients
with cervical factor
Lowest pregnancy rates observed in patients of
Endometriosis
Male factors have also not fared well in IUI

16. Many Factors affect pregnancy rate in
IUI
 Age and Ovarian reserve
 Selection of patient (etiology)
 Ovulation induction
 Monitoring of cycle IUI - timing
- no of inseminations
- no of cycles
- luteal support

17. Age also plays a very important role
 Under 35 success 18 %
 35-37 9 %
 38-40 7 %
 41-42 4 %
 Over 42 1 %

18. Factors influencing the outcome of IUI:
AGE, clinical variables and significant
thresholds.
 The total IUI history (856 cycles) of 352 couples was
studied.
 Live-birth showed a strong negative correlation with
female age but no correlation with male age.
 AMH and AFC correlated negatively with female age, and
FSH correlated positively..
 Calculating miscarriages, showed a strong correlation with
increasing female age. Male age had no effect on rate of
pregnancy loss.
In conclusion, female age, FSH, AMH and TMC are good predictive factors for
live-birth and therefore relate to essential in vivo steps in the reproductive
process.
Speyer BE, J Obstet Gynaecol. 2013 Oct;.

19. Impact of unilateral tubal blockage
diagnosed by HSG on the success rate of treatment
with controlled ovarian stimulation and IUI.
 CPRs were similar in patients with proximal unilateral tubal
blockage and unexplained infertility
 CPR was significantly lower in patients with distal unilateral
tubal blockage than in patients with unexplained infertility
 IVF instead of IUI may be a more appropriate approach for
distal unilateral tubal blockage patients.
Berker B1
J Obstet Gynaecol. 2014 Feb;

20. Endometriosis
Minimal or Mild Endometriosis
If Laparoscopy is done for other indications, then ablate or
excise endometriotic lesions
In < 35 years woman with stage I / II endometriosis
associated fertility – expectant Mx or super ovulation with
IUI can be first line of therapy.
 35 years age, COH with IUI or IVF should be considered.
 Stage – III , IV, endometriosis – Surgical therapy alone or
followed by IVF may be effective.
ASRM practice comm guidelines. Fertil Steril 2012

21. Fibroids
 Removal of sub mucous fibroids
 Removal of intramural fibroids if size is more than
4 cm.
Meldrum in David &Gardner
In Virto Fertilization
A Practical Aproch Informa 2008.

22. Male Factor
 Incidence 50%
 30% severe male factor
 In couples suffering from infertility the efficacy of six♂
consecutive IUI cycles is comparable to one ICSI cycle
 Therefore IUI is not a single Rx but a series of successive
trials

23. The four sperm parameters most frequently examined were:
 (i) inseminating motile count after washing: cut-off value between
0.8 and 5 million;
(ii) sperm morphology using strict criteria: cut-off value >4% normal
morphology;
(iii) total motile sperm count in native sperm sample: cut-off value of
5-10 million; and
(iv) total motility in native sperm sample: threshold value of 30%.
Ombelet W. Reprod Biomed Online 2014 Mar,
Semen quality and predictor of IUI success in
male subfertility: A systematic reveiw

24. Not < 3 days & not >5 days

25. Semen sample collection
• Wide mouth sterile semen container
• Not to spill any sample- 1st drop of ejaculate has
maximum motile sperms
• Sample to be collected ideally in a room next to
laboratory
• Follow all aseptic precautions
• No water droplets on the hand or the container

26. Time before processing
 Semen sample stored at 37° C
 Start semen processing immediately after
liquification
 It is critical that the spermatozoa are separated
from the seminal plasma within 1 hour of
ejaculation, to limit any damage from products
of non-sperm cells

27. Selecting Appropriate Semen
preparation method
Based on the count and motility of the native semen
sample:
Double spin swim-up for good count & motility
Density Gradient is selected for poor count & motility
In all methods seminal plasma containing
prostaglandin should be thoroughly removed as
this may cause uterine contractions & cramping

28. Volume of IUI sample
Minimal sample (.5-.6 ml)with maximum
concentration of rapid linear progressive sperm
should be put into the uterus at the time of IUI
because capacity of uterus is only 20-30 micro-
liters.
Excess volume can inflate the uterus causing reflex
spasm
(greater volume to be injected very slowly, gently,
over longer period of time)

29. COS is an important part of IUI Rx.
Natural cycle is rarely done in IUI

30. Optimum ovarian stimulation for IUI
 2 – 3 follicles with Ø 18 – 19 mm.
 Endometrium ≥ 9 mm thick & trilaminar.
 IUI between Cycle D13 and D16, 36-40 hrs. from
HCG inj.
Cancellation :
≥ 6 follicles ≥ 15 mm & E2 level >900pg/ml

31. Monitoring ovarian stimulation
Transvaginal ultrasound scanning :
. No. & size of follicles
. Pattern & thickness of endometrium
 Estrogen blood level

32. Monitoring
• Follicular monitoring from D7
• Follicles size and numbers
• To time HCG
• Prevent OHSS
• Prevent Multiple Pregnancy
• S. estradiol levels not always done- but done
if large no. of follicles, or in cases of poor
responders, or to differentiate cyst from
functional follicle

33.  Anti oestrogens: Clomiphene Citrate, Tamoxifen
 LETROZOLE
 Gonadotrophins:
 HMG
 highly purified ur FSH
 Rec. FSH
 GnRH (pulsatile)
 GnRHa (intranasal- S.C- I.M)GnRHa (intranasal- S.C- I.M)
 GnRH ant (involved in final steps of oocyte maturation)GnRH ant (involved in final steps of oocyte maturation)
 HCGHCG
 Bromocriptine, Metformin, (PCOD) ANASTRAZOLEBromocriptine, Metformin, (PCOD) ANASTRAZOLE

34. Protocols
• CC only + HCG for 2 cycles
• CC ± FSH or ± HMG +HCG for 2 cycles
• FSH or HMG + HCG for 2 cycles
PCOD
• Gn. Standard step-up protocol
• Gn. Low dose step-up protocol
• Gn. Low dose step-up, step-down protocol
(Sequential)

35. Which drug to choose for IUI?
 Drug Cost, Drug availability and Patient acceptability
 CC is effective for young women with good prognosis
 Remaining cases hMG or FSH would be the preferable
drug
 rFSH Vs Urinary preparations: no difference in clinical
pregnancy rate
 No advantage in routinely using GnRh-a in conjunction
with gonadotrophins for ovulation stimulation
 At the moment one should use the least expensive
medication.

36. Type of Gonadotrophin
Recombinant versus urinary gonadotrophin for ovarian stimulation inRecombinant versus urinary gonadotrophin for ovarian stimulation in
ART cycles:ART cycles:
• It appearedIt appeared that all available gonadotrophins were equally effectivethat all available gonadotrophins were equally effective
and safe.and safe.
• The choice of one or the other product will depend upon theThe choice of one or the other product will depend upon the
availability of the product, the convenience of its use, and theavailability of the product, the convenience of its use, and the
associated costs.associated costs.
• Any specific differences are likely to be too small to justify furtherAny specific differences are likely to be too small to justify further
researchresearch
Farquhar C, Dec 2014
Cochrane Database of Systematic ReviewsCochrane Database of Systematic Reviews

37. GnRh Antagonist –
Indications & Uses
 Standard Protocol for IUI – 34% PR
Ragni et al Human Reprod, Jan 2004
Bakas P. Fertil Steril.2011 May;
 Elimination of LH surge
 Conversion of IUI to IVF cycles
i.e. flexibility of cycles
 Programming of IUI cycles – can avoid weekends
 Fixed or flexible protocol.

38. Complications
 Multifetal pregnancy (36%)
 Ovarian Hyper Stimulation Syndrome (14%)
More common in
Young/ lean/ low BMI/
PCOS
HCG triggering
Prev. OHSS
Pregnancy

39. Insulin sensitizing
drugs Metformin
• Oral, 1500-2000mg
• Hyperinsulinaemia, hyperandrogenaemia
• RCT- clomiphene resistant pts., use of metformin &
CC produced significant improvement
• Recent study- Myoinositol & metformin also showed
promising results
• Metaanalysis of metformin co-adm during
gonadotrophin induction in PCOS has shown
promising results
 D chiro inositol, melatonin, vit D

40. When should trigger be given?

41. Trigger
 HCG at 18-20 mm (CC+Gn cycles)
 HCG at 20-22 mm (CC cycles)
 Recombinant HCG
 Occasionally GnRha – if risk of hyperstimulation

42. Ovulation trigger
 Natural cycle- raised Oestradiol leads to LH surge
 Ov. stimulation- unpredictable
 HCG
 5000- 10,000 IU S/C
 Causes higher luteal phase conc. of progesterone.

43. Early versus late hCG administration to trigger
ovulation in mild stimulated IUI cycles: a RCT.
612 infertile women candidates for IUI received HMG 75 IU/day
from cycle days 4 to 8 and then as per ovarian response.
Ovulation was randomly triggered (hCG 5000 IU, IM) when the
leading follicle diameter ranged between either 16.0 and 16.9 mm
(Early hCG group, ) or 18.0 and 18.9 mm (Late hCG group, ) and
IUI was performed approximately 36 h later.
CONCLUSION:
HCG administered when the largest follicle size reaches 16.0-16.9 mm leads to
similar clinical and ongoing pregnancy rates as when it reaches 18.0-18.9 mm in
IUI cycles
da Silva AL, Eur J Obstet Gynecol Reprod Biol.2012 Oct

44. When do you time the IUIWhen do you time the IUI
procedure?procedure?
Single or double IUI?Single or double IUI?

45. The effects of timing of IUI in relation to
ovulation and the number of inseminations on PR.
 IUI was timed for 36 ± 2 h after HCG.. Post-ovulatory cases received single
IUI, while pre-ovulatory cases were randomized to receive either single or
double IUI.
 When ovulation was present before IUI, CPR was 11.7% compared with
6.7% when ovulation was absent.
 Comparing the CPR for double versus single IUI in pre-ovulatory cases, the
OR for all cycles was 1.9 but according to etiology, it was 4.667 in male
factor and 1.2 for non-male factors.
CONCLUSIONS:
Single IUI timed post-ovulation gives a better CPR when
compared with single pre-ovulation IUI for non-male infertility,
For male factor, pre-ovulation, double IUI gives a better CPR
when compared with single IUI.
Ghanem ME, Hum Reprod. 2011 Mar;

46. Single versus Double Intrauterine
Insemination in Controlled Ovarian
Hyperstimulation Cycles:
A Randomized Trial
Double versus single IUI did not increase the
pregnancy rate of IUI
Zahiri Sorouri Z, Arch Iran Med. 2016, July

47. Does the type of catheter matter ?

48. Soft versus firm catheters for
intrauterine insemination
There was no evidence of a significant effect difference
regarding the choice of catheter type for any of the outcomes.
van der Poel N .Cochrane Database Syst Rev.2010

49. Luteal Support
• Vaginal progestin pessaries
• 100 bd – if CC/FSH/HMG cycle
• 200 tds - if GnRhant+HMG/FSH
• Vaginal Gel
• Oral – dehydrogestone 10mg
bid or micronized sustained
release oral prog.
• HCG 2000-2500 U IM day 3
• Progesterone – IM 50-100mg
• Rationale
• Correction of abnormal
endometrium seen in COH
(50%)
• High E2 in COH – premature
luteolysis
• COH + Gn Rhant down
regulation – affects CL P4
production
• FSH instead of HMG –increase
incidence of short L.P.
• Short luteal phase in GnRha
usage for ovulation trigger

50. Efficacy of luteal phase support with vaginal
progesterone in IUI: review and meta-analysis.
Five RCT s. 1,271 patients.
 Women treated with vaginal progesterone achieved significantly higher
live birth rate (confidence interval 1.36 to 2.77,), and clinical pregnancy
rate ( CI 1.14 to 1.76)
 This beneficial effect of receiving progesterone was only observed in the
group stimulated with gonadotropins compared to the group stimulated
with CC. No differences were observed in the miscarriage and multiple
pregnancy rates.
CONCLUSIONS:
 The supplementation of luteal phase with vaginal progesterone
significantly increases live birth among women undergoing IUI when
receiving gonadotropins for ovulation induction. Women receiving CC to
induce ovulation do not seem to benefit from this treatment.
Miralpeix E, J Assist Reprod Genet. 2013 Nov

51. Clinical tips to improve success ratesClinical tips to improve success rates

52. Effect of cervical mucus aspiration before
IUI
 PR was 15% in the cervical mucus aspiration
group and 9.9% in the control group.
 Mucus aspiration led to significantly increased
pregnancy rates for women with unexplained
infertility
Int J Gynaecol Obstet. 2008 Nov;
Simsek EHaydardedeoglu

53. Efficacy of passive uterine straightening during
IUI on pregnancy rates and ease of technique.
 Interventions were IUI by passive straightening of the uterus by bladder
filling, or IUI on an empty bladder
 The PR was higher in the full bladder group than in the empty bladder
group 13.5% vs 7.4.
 The risk of undergoing difficult IUI was higher in the empty bladder group
than the full bladder group 10.0% vs 37.8%,
 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 -12.7% vs
5.5%
Conclusion:
Passive straightening of the uterus makes the procedure less
difficult and improves the clinical pregnancy rate.
Ayas S J Obstet Gynaecol Res. 2011 Nov 9.

54. Cost & IUI
• A proper USG, sr. E2 monitored IUI costs
approximately Rs. 8000/-
• Gonadotropins per cycle costs approximately Rs.
5000/-
• Maximum IUI success @27.2% per cycle
• Cumulative pregnancy rates 85% at end of 6 cycles for
unexplained infertility
• 70% pregnancy occur in first 3 cycles
IUI is a Wonderful treatment modality for
young couples upto 4 to 6 cycles.

55. How many IUI s ?

56. How many cycles of IUI
 Unexplained- 6 cycles: age < 30yrs
5 cycles: age 30-35yrs
4 cycles: age 35-40yrs
1-2 cycles: age >40yrs
 Anatomical, Hormonal, & Male factor Compromise :
2 cycles less in each of the above age groups

57. Predictive factors for pregnancy after
IUI:
The couple with the best chance of pregnancy can be described as follows:
an under 30 woman
with cervical or anovulatory infertility and
a man with a TMS >/=5 million spermatozoa.
The "ideal" stimulation cycle enables the recruitment of two follicles measuring >16
mm with an E(2) concentration >500 pg/mL on the day of hCG administration. The
best results are obtained when IUI is performed using a soft catheter.
Merviel P, Fertil Steril.2010 Jan
.

58. IUI is the 1st
Line of treatment in
sub fertility and is a simple,
effective and inexpensive procedure

59. WHY IUI FAILS
 Poor semen prep
 Poor selection of pts
 Peritubal adhesions
 Poor oocyte quality

60. LIMITATIONS OF IUI
 Hospital and lab distance
 Sperm requirement in millions
 Fertilisation can not be assured
 Quality of embryo unknown

61. CONCLUSION
 Ovarian stimulation is the fundamental tool of
subfertility treatment
 Choice depends on doctors expertise and
patients condition
 Increases the pregnancy rate
 Time the IUI
 Judicious monitoring to avoid complications
 Shifting to ART at appropriate time