how to improve success rate of iui
TRANSCRIPT
Dr Sujoy DasguptaMBBS (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)- 2015-16
Patient Selection:Age
Steven R B et al (2008) - Maximum success, if <25 yearsMarviel et al (2010) – Maximum conception, if <30 yearsBadawy et al (2009)- Little success, if >35 yearsMathieu C et al (1995)- Increased age of male partner
can adversely affect outcome
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%
*IUI seems to be a poor treatment option for women over 40 years of age
AGE :
Dovey S et al,2008
Mathieu C et al (1995)- Highest rate when <3 yearsNuojua-H S et al (1999)-
Duration <6 years- conception rate 20%Duration >6 years- conception rate 10%
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)
Patient Selection:Duration of Infertility
How many cycles?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 most women conceive after 4-6 cycles 4-6 cycles of IUIof IUI cycle fecundability declines by cycle fecundability declines by ½ to ½ to 22//33 thereafter thereafter
(Khalil MR et al.; Acta Obstet Gynaecol Scand. 2001 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)
Cause of infertilityCause of infertilityDickey et al (2002)- maximum success for ovulatory
dysfunction, followed by male subfertilityKhalil MR et al (2001)- Best results in anovulation and
unexplained infertility
Cause of infertilityCause of infertility(Bourn Hall clinic, 1999 ;Tay et al,2007; Wang et al,2008)(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%)
Stimulation ProtocolStimulation Protocol
05/01/23 11
Live birth rates could not be assessedAnti –oestrogens versus gonadotrophins combined with intrauterine insemination outcome: pregnancy rate per couple.
(Contineau AE et al, 2007)
Number Of FolliclesNumber Of Follicles
Higher pregnancy rate with three preovulatory follicles (Huttenen et al 1999)
Follicular Dynamics
Aim is preovulatory follicles : 2–3 follicles≥
16 mm)Steures et al, 2004; Bhal et al ,2001(
Endometrial Thickness- Controversial results1. Abdalla HI et al. Hum Reprod 1994;9:363-52. Basil S. Ultrasound Obstet Gynecol 2001;18:258-63. Seddigheh E et al. Fertil Steril 2006;88:432-37
No pregnancy occurs when the ET is <6mm (Tomlinson et al ,1996)
If more follicles?- risks of OHSS and multiples in IUI
Cycle cancellation {> 3 follicles ≥ 16mm or; > 8 follicles ≥ 12mm}
OR
Conversion to IVF cycle
TMSC and motility– cut offsTMSC PR/CYCLE10–20 million 18.29%5–10 million 5.63%<5million 2.7%
TMSC should be 5-10 million If less than 5 million counsel and do IUI
(Guven et al, 2008;Abdelkader & Yeh)2009)
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 2000. (Cochrane Review) .
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 2003. Reprod Biomed Online-Duran EH et al , 2002. Syst Review. Hum. Reprod Update
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)
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
Timing Of Insemination Fixed protocolSingle planned insemination: 36-38 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
Exact timing of IUI
Conclusion:Postponing IUI until observation of follicle rupture may yield a higher pregnancy rate.(25% Vs 8%)
(Kucuk ,2008).
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
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.
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 2010 recommended soft catheter
Various IUI catheters used
Makler IUI cannula
Gynetics catheter
Cook Soft-Pass catheter
Wallace artificial insemination catheter
Tomcat catheter
No difference in PR when the inseminated volume varied from 0.3 to 1 mL
(Do Amaral VFJ Assist Reprod Genet 2001)
IUI technical aspects
Aseptic technique to avoid genital infection
Should be gentle and atraumatic
Products of local tissue reaction to injury may be hostile to spermatozoa
Steps of inseminationPartially 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 0.3-0.5 ml of processed semen
Slowly withdraw catheter
IUI Procedure
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
Why difficult Insemination ?
IO to left of EO (80%)
IO to right of EO (10%)
IO in straight line with EO (10%)
AV, RV UTERUS
EXT OS FLUSHED
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
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
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
Difficult IUI: what to do next
Trial IUI enables the clinician to assess thedegree 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
Ultrasound guided IUI has been tried
Not found to increase pregnancy rates
Ramón et al,2009; Oztekin et al,2013
Useful in difficult IUI
A ten minute bed rest has a positive effect (Saleh A Fertil Steril 2000)
Timed intercourse within 12 -18 h period: useful in IUI with
low number of motile sperm inseminated
(Huang et al, 1998)
Most centres provide luteal supportHowever no evidence to support
Not needed – ESHRE 2009
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
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
Quality controlPregnancy rate per cycle go downCheck mediaIncubatorDifficult IUI- trial Stimulation protocol to be changedBase line scan before stimulation
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