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Greetings from Bangladesh
Predictive Factors influencing
pregnancy
rate after intrauterine insemination
Dr. Rokeya Begum
Professor
USTC
Bangladesh
Intrauterine insemination (IUI) is
an assisted reproduction procedure
that involves the deposition of a
processed semen sample in the
upper uterine cavity.
This is non invasive and cost
effective first line therapy for
infertile couple.
IUI can be done easily in simple
setups.
Pre requisites for intrauterine
insemination
• At least one patent functional fallopian
tube.
• Evidence of ovulation.
• Adequate sperm count.
• Responsive endometrium.
Pregnancy rate in ART
Method
Timed intercourse
IUI
CC
CC+IUI
FSH/HMG
CC/FSH/IUI
FSH/HMG/IUI
IVF
Pregnancy rate
4%
6%
6%
8%
7.7%
9-12%
17-20%
20-maximum 40%
50-60 % donar cycle
Though the technique of IUI has remained
same but several advancement has been
developed to improve the success of IUI.
 Type of stimulation protocols.
 Wider use of Gonadotrophins.
 Sperm preparation techniques
tailored to every specimens.
 Meticulous ultrasound monitoring.
Indications of Intrauterine
Insemination
 Ovulatory dysfunction.
 Mild endometriosis.
 Mild to moderate male factor.
 Cervical stenosis/factor.
 Unexplained infertility.
 Women with patent-tubes and IVF is not
affordable.
The reported pregnancy rate per cycle range
from 8 to 22%
Rationale
Super ovulation increase the chance of
pregnancy in both IUI and IVF.
Super ovulation is associated with
OHSS and multiple pregnancy
while IVF is expansive.
Objective
To determine prognostic factor
for IUI in Bangladeshi people
 To provide important data for
planning whether proceed for IUI
of IVF.
Methodology
 Design – Prospective, observational
 Place – Surgiscope fertility centre Bangladesh
 Time – 3 months
 Number -221 couple in single cycle
Patient selection criteria
 Male factor infertility
 Unexplained infertility
 Minimum to mild endometriosis
 Ovulatory disorder/Anovulation
At least one patent fallopian tube
by HSG or laparoscopy.
Exclusion criteria
 Bilateral tubal block
 severe endometriosis
 Total motile sperm count
(Post Wash) < 1 million/ml
 At least one dominant >18mm at the day of
trigger of ovulation.
Ovulation induction
 Tablet clomiphene citrate 100mg from D3-D7
of menstrual cycle.
 Inj. rFSH (Gonal F) 75IU started from 7th day
of menstrual cycle daily and stimulation
assessed by transvaginal ultrasound on 10th
day of menstrual cycle.
Stimulation was assessed by
follicular response and
endometrial thickness.
Transvaginal scan monitoring
Easy
Reproducible
Visual image
Diameter
No of follicles
Endometrium
Aim of monitoring
1. To evaluate optimum dose.
2. To adjust – the dose
- Hypo
- Hyper
3. To find out optimal time of
ovulation trigger.
4. To select the time of IUI.
5. To avoid OHSS and multiple pregnancy.
Ovulation trigger was given
1. Anatomical maturity
a) Follicle (18-26mm)
b) Endometrial thickness (7-10mm)
2. Functional maturity
a)Follicle - ¾ of follicle
- PSV  10cm/sec
b)Endometrium- Subendometrial
blood flow.
Follicular diameter and vascularity
Endometrial thickness and vascularity
Ovulation trigger
Human chorionic gonadotrophin
(hcg) 10,000 IU
Intrauterine insemination was
performed 36-42 hours after hcG
injecton.
The male subject was instructed to
abstain from ejaculation for 2-3
days prior to IUI.
Fresh semen was collected by
masturbation into a sterile 100 ml
container carried out near to
andrology lab.
Where should IUI be
done?
• It could be done at
every where which
provide optimal
conditions
• It should be connection
with andrology lab.It
could ideally be done at
department with
andrology lab
Semen preparation was
performed
1. Double layer density gradient
centrifugation technique
2. Washing step with culture media.
Idea of Semen Preparation
 Remove seminal plasma to avoid prostaglandin
induce uterine contractions and pelvic infection.
 There is not enough to randomised controlled trail
for systematically assessment of the best sperm
preparation method.
Boomsma et al 2007
Prior to insemination verbal
consent of husband and wife
was taken.
From sperm deposition to sperm ovum
interaction.
Four steps take place in cervix ,uterus and
fallopian tubes
 Capacitation
 Acrosomal reaction
 Hyper activation
 Sperm-oocyte binding.
Technique of intrauterine
insemination
Success lies in looking into details of techniques
 Lithotomy or dorsal position.
 All aseptic precaution.
 Vagina wash with normal saline.
 Cervical mucus – aspiration
 UCL was measured by USG at the time of
baseline scan.
 Target time – 90 minute after semen collection.
 Gentle a traumatic insertion.
 Semen sample about 0.4-0.5ml inserted above
the internal 0S but below fundus.
 No need of antibiotics.
 Rest for 20-30 minutes.
Single insemination was
considered for each patient.
Luteal phase support in the from of
tablet dydrogesterone (Duphaston)
10mg twice daily orally for 10 days for
each and every patient.
Clinical pregnancy was define
by
• Positive urine pregnancy test on 21
days post IUI
• Presence of intrauterine gestational
sac by USG.
Primary outcome was measured by
clinical pregnancy rate and attempt
to from a predictive model for
success of IUI.
Pregnancy 23.98%
Clinical pregnancy per cycle for
women in different age groups.
Years Pregnancy/cycle(%)
<30yrs 160/39(24%)
31-35 yrs 50/13(26%)
36-40yrs 11/1(9%)
>40yrs nil
Assessment and treatment for people with
fertility problem
NICE guideline
• Women <40 years who have not conceived after 2 years of regular
unprotected intercourse or 12 cycles of artificial insemination (where
≥6 are by intrauterine insemination), should be offered 3 full cycles of
IVF.
• One full cycle of IVF should offered if a women is aged 40–42 years
provided they have never previously had IVF treatment, there is no
evidence of low ovarian reserve and there has been a discussion of the
implications of IVF and pregnancy at this age
• An earlier referral for specialist consultation is appropriate when the
woman is aged ≥36 years, there is a known cause of infertility, or a
history of predisposing factors. People at risk of infertility because of
planned treatment (for example, for cancer), should be offered referral
to a fertility specialist.
Harris,Fertil Steril2010
Intrauterine insemination pregnancy
rate according to duration of infertility
(years)
Infertility duration Pregnancy/cycle (%)
<5years 141/31(27%)
5-11years 83/18(21%)
>10years 24/4(16%)
FSH/IUI is better than
expectant management ?
ESHRE Capri Workshop Group
Duration of infertility less than 2-3 years’ ‘at least among patients with unexplained
infertility’, FSH/IUI (4.3%) is no better than expectant management (4.6%)
But has a modest better effect with FSH-IUI for patients, more than 3 years duration of
infertility; “12% ---3%”. There would be one additional pregnancy for every 11
cycles of FSH/IUI compared with control cycles.
Guzick 1999.Steures
2006
Duration of infertility is an important prognostic factor!!!!
Human Reproduction Update 2009
Type of infertility Pregnancies/Cycle (%)
Primary 161/41( 25%)
Secondary 59/12(20%)
Pregnancy rate in relation to
causes of IUI
Indications Pregnancies/Cycle (%)
Ovulation disorder 109/31(28%)
Male factor 22/4(18%)
Unexplained 53/10(18%)
Tubal factor 11/4(36%)
Cervical factor 7/1(14%)
Endometriosis 11/1(9%)
Fibriod 5/-
Adenomyosis 1/-
Uterine Anomaly 2/2(100%)
Number
of
follicles
Pregnanci
es per
cycle (%)
ONE
08/0%
TWO
52/11
(21%)
THREE
47/09
(19%)
FOUR OR
MORE
113/33
(29%)
Numberof maturefollicles
(18 mm in diameter ormore)
Higher pregnancy rate with three preovulatory follicles.
(Huttenen et al 1999)
Follicle number
 The presence of three or more dominant follicles (16%) is
associated with a two- three fold increase in pregnancy
rates compared with monofollicular growth(5.7%)
Huttunen SN 1999,Tominson 1996,Hughes 1998 ErdemA 2008
 Although multifollicular growth is good prognostic factor.it
is not considered as adventage due to risk of increasing
frequency of multiple pregnancy and it adopted to a cause
of cycle concellation
NICE guideline 2004
Endometrial Thickness (mm)
&
Pregnancy Rate
Endometrial thickness Pregnancies/cycle (%)
< 8mm 23/4(17%)
8-10mm 145/31(21%)
 10mm 53/18(33%)
Sperm quality necessary for successful
intrauterine insemination.
Post wash
Total mobile
fraction (million/ml)
Pregnancies/cycle (%)
< 5 10/1(10%)
5-10 20/9(45%)
10-20 -
20-25 129/32(%)
> 50 39/11(28%)
• Total Progressive Motile Sperm Count (TPMSC)
>5million/mL
• Initial total motility (TM)>30%.
• Inseminating motile count (IMC)>1million/mL
If less than 5 million counsel and do IUI
(Guven et al, 2008;Abdelkader & Yeh 2009)
Grading of Success of IUI
• Age <35years
• Duration <05 years
• Ovulationdisorder
• Folliclenumber>04
• Endometrialthickness
10mm
• UnexplainedInfertility
• Tubal factor
• Age > 35 years
• Endometriosis
• Duration >10years
• Male factor (< 05 mill/mL)
Best Outcome
Good
Outcome
Poor Outcome
Key to Success
1. Age
2. Follicular response
3. Total motile sperm count
4. Endometrial thickness
Why IUI Fails
 Poor selection of patient.
 Poor semen preparation.
 Improper egg pick up by fimbria due to
peritubal adhesion.
 Poor quality of oocyte.
 Improper technique of insertion.
Limitations of IUI
 Proper maintenance of standard of lab.
 Sperm requirement in millions.
 Fertilization cannot be assured.
 Quality of embryo unknown.
Summary
Decision of IUI should be designated by
1. Woman’s age
2. Ovarian reserve
3. Duration of infertility
4. Number of motile spermatozoa inseminated
> 05 million/mL

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Predictive Factors influencing pregnancy rate after intrauterine insemination

  • 2. Predictive Factors influencing pregnancy rate after intrauterine insemination Dr. Rokeya Begum Professor USTC Bangladesh
  • 3. Intrauterine insemination (IUI) is an assisted reproduction procedure that involves the deposition of a processed semen sample in the upper uterine cavity.
  • 4. This is non invasive and cost effective first line therapy for infertile couple. IUI can be done easily in simple setups.
  • 5. Pre requisites for intrauterine insemination • At least one patent functional fallopian tube. • Evidence of ovulation. • Adequate sperm count. • Responsive endometrium.
  • 6. Pregnancy rate in ART Method Timed intercourse IUI CC CC+IUI FSH/HMG CC/FSH/IUI FSH/HMG/IUI IVF Pregnancy rate 4% 6% 6% 8% 7.7% 9-12% 17-20% 20-maximum 40% 50-60 % donar cycle
  • 7. Though the technique of IUI has remained same but several advancement has been developed to improve the success of IUI.  Type of stimulation protocols.  Wider use of Gonadotrophins.  Sperm preparation techniques tailored to every specimens.  Meticulous ultrasound monitoring.
  • 8. Indications of Intrauterine Insemination  Ovulatory dysfunction.  Mild endometriosis.  Mild to moderate male factor.  Cervical stenosis/factor.  Unexplained infertility.  Women with patent-tubes and IVF is not affordable.
  • 9. The reported pregnancy rate per cycle range from 8 to 22%
  • 10. Rationale Super ovulation increase the chance of pregnancy in both IUI and IVF. Super ovulation is associated with OHSS and multiple pregnancy while IVF is expansive.
  • 11. Objective To determine prognostic factor for IUI in Bangladeshi people  To provide important data for planning whether proceed for IUI of IVF.
  • 12. Methodology  Design – Prospective, observational  Place – Surgiscope fertility centre Bangladesh  Time – 3 months  Number -221 couple in single cycle
  • 13. Patient selection criteria  Male factor infertility  Unexplained infertility  Minimum to mild endometriosis  Ovulatory disorder/Anovulation At least one patent fallopian tube by HSG or laparoscopy.
  • 14. Exclusion criteria  Bilateral tubal block  severe endometriosis  Total motile sperm count (Post Wash) < 1 million/ml  At least one dominant >18mm at the day of trigger of ovulation.
  • 15.
  • 16.
  • 17. Ovulation induction  Tablet clomiphene citrate 100mg from D3-D7 of menstrual cycle.  Inj. rFSH (Gonal F) 75IU started from 7th day of menstrual cycle daily and stimulation assessed by transvaginal ultrasound on 10th day of menstrual cycle.
  • 18. Stimulation was assessed by follicular response and endometrial thickness.
  • 19. Transvaginal scan monitoring Easy Reproducible Visual image Diameter No of follicles Endometrium
  • 20. Aim of monitoring 1. To evaluate optimum dose. 2. To adjust – the dose - Hypo - Hyper 3. To find out optimal time of ovulation trigger. 4. To select the time of IUI. 5. To avoid OHSS and multiple pregnancy.
  • 21. Ovulation trigger was given 1. Anatomical maturity a) Follicle (18-26mm) b) Endometrial thickness (7-10mm) 2. Functional maturity a)Follicle - ¾ of follicle - PSV  10cm/sec b)Endometrium- Subendometrial blood flow.
  • 22. Follicular diameter and vascularity
  • 24. Ovulation trigger Human chorionic gonadotrophin (hcg) 10,000 IU
  • 25. Intrauterine insemination was performed 36-42 hours after hcG injecton.
  • 26. The male subject was instructed to abstain from ejaculation for 2-3 days prior to IUI.
  • 27. Fresh semen was collected by masturbation into a sterile 100 ml container carried out near to andrology lab.
  • 28. Where should IUI be done? • It could be done at every where which provide optimal conditions • It should be connection with andrology lab.It could ideally be done at department with andrology lab
  • 29. Semen preparation was performed 1. Double layer density gradient centrifugation technique 2. Washing step with culture media.
  • 30. Idea of Semen Preparation  Remove seminal plasma to avoid prostaglandin induce uterine contractions and pelvic infection.  There is not enough to randomised controlled trail for systematically assessment of the best sperm preparation method. Boomsma et al 2007
  • 31. Prior to insemination verbal consent of husband and wife was taken.
  • 32. From sperm deposition to sperm ovum interaction. Four steps take place in cervix ,uterus and fallopian tubes  Capacitation  Acrosomal reaction  Hyper activation  Sperm-oocyte binding.
  • 33. Technique of intrauterine insemination Success lies in looking into details of techniques  Lithotomy or dorsal position.  All aseptic precaution.  Vagina wash with normal saline.  Cervical mucus – aspiration  UCL was measured by USG at the time of baseline scan.
  • 34.  Target time – 90 minute after semen collection.  Gentle a traumatic insertion.  Semen sample about 0.4-0.5ml inserted above the internal 0S but below fundus.  No need of antibiotics.  Rest for 20-30 minutes.
  • 36. Luteal phase support in the from of tablet dydrogesterone (Duphaston) 10mg twice daily orally for 10 days for each and every patient.
  • 37. Clinical pregnancy was define by • Positive urine pregnancy test on 21 days post IUI • Presence of intrauterine gestational sac by USG.
  • 38. Primary outcome was measured by clinical pregnancy rate and attempt to from a predictive model for success of IUI.
  • 40. Clinical pregnancy per cycle for women in different age groups. Years Pregnancy/cycle(%) <30yrs 160/39(24%) 31-35 yrs 50/13(26%) 36-40yrs 11/1(9%) >40yrs nil
  • 41. Assessment and treatment for people with fertility problem NICE guideline • Women <40 years who have not conceived after 2 years of regular unprotected intercourse or 12 cycles of artificial insemination (where ≥6 are by intrauterine insemination), should be offered 3 full cycles of IVF. • One full cycle of IVF should offered if a women is aged 40–42 years provided they have never previously had IVF treatment, there is no evidence of low ovarian reserve and there has been a discussion of the implications of IVF and pregnancy at this age • An earlier referral for specialist consultation is appropriate when the woman is aged ≥36 years, there is a known cause of infertility, or a history of predisposing factors. People at risk of infertility because of planned treatment (for example, for cancer), should be offered referral to a fertility specialist.
  • 43. Intrauterine insemination pregnancy rate according to duration of infertility (years) Infertility duration Pregnancy/cycle (%) <5years 141/31(27%) 5-11years 83/18(21%) >10years 24/4(16%)
  • 44. FSH/IUI is better than expectant management ? ESHRE Capri Workshop Group Duration of infertility less than 2-3 years’ ‘at least among patients with unexplained infertility’, FSH/IUI (4.3%) is no better than expectant management (4.6%) But has a modest better effect with FSH-IUI for patients, more than 3 years duration of infertility; “12% ---3%”. There would be one additional pregnancy for every 11 cycles of FSH/IUI compared with control cycles. Guzick 1999.Steures 2006 Duration of infertility is an important prognostic factor!!!! Human Reproduction Update 2009
  • 45. Type of infertility Pregnancies/Cycle (%) Primary 161/41( 25%) Secondary 59/12(20%)
  • 46. Pregnancy rate in relation to causes of IUI Indications Pregnancies/Cycle (%) Ovulation disorder 109/31(28%) Male factor 22/4(18%) Unexplained 53/10(18%) Tubal factor 11/4(36%) Cervical factor 7/1(14%) Endometriosis 11/1(9%) Fibriod 5/- Adenomyosis 1/- Uterine Anomaly 2/2(100%)
  • 47. Number of follicles Pregnanci es per cycle (%) ONE 08/0% TWO 52/11 (21%) THREE 47/09 (19%) FOUR OR MORE 113/33 (29%) Numberof maturefollicles (18 mm in diameter ormore) Higher pregnancy rate with three preovulatory follicles. (Huttenen et al 1999)
  • 48. Follicle number  The presence of three or more dominant follicles (16%) is associated with a two- three fold increase in pregnancy rates compared with monofollicular growth(5.7%) Huttunen SN 1999,Tominson 1996,Hughes 1998 ErdemA 2008  Although multifollicular growth is good prognostic factor.it is not considered as adventage due to risk of increasing frequency of multiple pregnancy and it adopted to a cause of cycle concellation NICE guideline 2004
  • 49. Endometrial Thickness (mm) & Pregnancy Rate Endometrial thickness Pregnancies/cycle (%) < 8mm 23/4(17%) 8-10mm 145/31(21%)  10mm 53/18(33%)
  • 50. Sperm quality necessary for successful intrauterine insemination. Post wash Total mobile fraction (million/ml) Pregnancies/cycle (%) < 5 10/1(10%) 5-10 20/9(45%) 10-20 - 20-25 129/32(%) > 50 39/11(28%)
  • 51. • Total Progressive Motile Sperm Count (TPMSC) >5million/mL • Initial total motility (TM)>30%. • Inseminating motile count (IMC)>1million/mL If less than 5 million counsel and do IUI (Guven et al, 2008;Abdelkader & Yeh 2009)
  • 52. Grading of Success of IUI • Age <35years • Duration <05 years • Ovulationdisorder • Folliclenumber>04 • Endometrialthickness 10mm • UnexplainedInfertility • Tubal factor • Age > 35 years • Endometriosis • Duration >10years • Male factor (< 05 mill/mL) Best Outcome Good Outcome Poor Outcome
  • 53. Key to Success 1. Age 2. Follicular response 3. Total motile sperm count 4. Endometrial thickness
  • 54. Why IUI Fails  Poor selection of patient.  Poor semen preparation.  Improper egg pick up by fimbria due to peritubal adhesion.  Poor quality of oocyte.  Improper technique of insertion.
  • 55. Limitations of IUI  Proper maintenance of standard of lab.  Sperm requirement in millions.  Fertilization cannot be assured.  Quality of embryo unknown.
  • 56. Summary Decision of IUI should be designated by 1. Woman’s age 2. Ovarian reserve 3. Duration of infertility 4. Number of motile spermatozoa inseminated > 05 million/mL