how to improve success rate of iui

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