Role of

intrauterine

insemination in treatment of

infertility

Prof. Aboubakr

Elnashar

Benha university Hospital,

EgyptABOUBAKR ELNASHAR

CONTENTS

1. Definition

2. Rationale

3. Advantages

4. Indications

5. Contraindications

6. Complications

7. Evidence

8. Effectiveness

1. Factors affecting success

2. NNT

3. Cost effectiveness

Conclusion

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Direct transfer of

processed semen into the uterine cavity

about the time of ovulation

1. DEFINE

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2. RATIONALE

A. Direct transfer:

1. Bypass 3 of the natural barriers

1. Vagina

2. cervical mucus, and

3. cervix

that sperm have to traverse

B. Processed semen:

1. Washing:

1. organisms,

2. prostaglandins&

3. antibodies

2. Deposition of a bolus of

concentrated,

motile,

morphologically normal sperm

2. More sperm are

placed

closer to the site of

fertilization

(fertilization occurs in

the fallopian tube).

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3. ADVANTAGES

1. Non invasive (like Pap smear).

2. Inexpensive.

3. Easy to perform

4. Training is easy

5. Risks are minimal

6. Antenatal & perinatal complications:

like pregnancies from normal S I

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4. INDICATIONS

A.Male:

I. Ejaculatory failure:Retrograde ejaculationHypospadiusImpotenceInfrequent Intercourse during fertile period.

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Semen analysis: WHO, 2010

:

:Lower reference limitParameter

1.5 ml Volume

7.2 pH

15 million/ml Concentration

39 million/ejaculate Total sperm number

40% or PR: 32%

Total motility: (PR+NP)

58% live spermatozoaVitality

4% (strict criteria).Normal forms

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II. Male infertility: Mild

Severe male infertility:

Count<5million/ml (15million/ml)

Normal morphology <2.5% (4%)or

Total Motility <10% (40%)

Not candidate for IUI but ICSI.

ICSI is more cost effective than IUI

(Van Voorhis et al,2001)

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Before processing:

1. Total Count:

PR are lower if the semen sample contains,

10 million sperm in total (40 million)(Van Voorhis et al., 2001).

2. Total sperm motility

30% before sperm preparation (40%)

(Ombelet et al 1996; Dickey et al 1999, Montanaro et al 2001, Lee et al,

2002)

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3. TMSC/ejaculate

> 5 million/ejaculate are indicated for treatment with

IUI.

can be used as the method of choice for diagnosis

and treatment of male infertility(Hajder et al, 2016)

In the absence of teratospermia

TMSC does not appear to impact PR in subfertile

couples undergoing IUI.(Hassan et al, 2017)

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After processing:

Insemination motile count (IMC) and

Sperm morphology

(Ombelet et al 2003, 2008; Duran et al , 2002. SR; Butcher et al, 2016)

Most valuable parameters to predict IUI outcome

There is a trend towards increasing conception

rates with increasing IMC

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Infertility work -up

No tubal factor

Washing procedure

IMC> 1 million

IMC< 1 million

Morphology >5%IMC< 1 million

Morphology <5%

IVF

< 30 % or no fertilization

ICSI

IUI 4x

(Ombelet et al 2008. ESHRE Monograph)

B. Female:

I. Cervical factor:

cervical mucous hostility, poor cervical mucous

significant improvement of conception for IUI compared

with TI

(Cohlen;2005, MA of RCT)

II. Endometriosis:

mild & moderate

IUI with OS, instead of EM: increases LBR(Tummon et al., 1997; ESHRE, 2009)

IUI with OS within 6 months after surgical tt,

PR are similar to those achieved in un infertility (Werbrouck et al., 2006; ESHRE, 2009)

III. Vaginismus

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C. Both:

I. Immunological:

Male antisperm antibodies

Female antisperm antibodies (cervical, serum)

II. Unexplained infertilitybasic investigations are normal

(Hajder et al, 2016)

III. While waiting for IVF

IV. Women with patent tubes and IVF is not

affordable.

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5. CONTRAINDICATIONS1. Cervical atresia

2. Cervicitis

3. Endometritis

4. Bilateral tubal obstruction

5. Most cases of amenorrhea

6. Severe oligospermia.

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6. COMPLICATIONS

1. Uterine contraction

2. Intrauterine infection

PID: rare

0.01-0.2%

3. Psychological:

Guilt, anger, loss of self esteem

Relatively low success rate /cycle.

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4. Complications of COS:

Multiple pregnancy.

increased with

age < 30

6 mature follicles

E2 > 1000 pg/ml

Gnt.

risk is much lower with CC.

MP (7-13%) (Ombelet et al 2006).

OHSS

Only observed in

Gnt cycles following administration of hCG

Rarely occurs in women treated with CC

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7. EVIDENCE

I. IUI for unexplained or male infertility

1. NICE, 2013

No IUI

Advise them to try to conceive for a total of 2y

(including up to 1y before their fertility investigations)

IVF will be considered.

Exceptions: Social, Cultural, Religious

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Criticism against NICE recommendations:

Evidence on which the recommendation was made

was low to very low quality

Survey:

<4% of fertility clinics in the UK discontinuing

IUI

(Kim et al., 2015; Nandi et al., 2015).

Many gynecologists continuing to offer IUI,

instead of IVF, as first-line treatment

IVF:

was not regarded as an established first-

line option for unexplained infertility

compared to IUI

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2. Bensdorp et al.2015

multicentre RCT

17 fertility clinics in the Netherlands.

Group I:

3 cycles of IVF with SET. (n=201)

(plus surplus cryo embryos)

Group II: (n=194)

6 cycles of IVF in a modified natural cycle.

Group III:

6 cycles of IUI with OS (n=207)

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All three methods:

comparable proportions of healthy singletons around 50%

comparable proportions of multiple pregnancies 6% (IVF-SET)

5% (IVF MNC), and

7% (IUI-OS).

No reason to abandon IUI with OS as a first line

treatment for couples with unexplained or mild male

infertility.

It is cheaper, less invasive and has no higher MPR

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3. Tjon-Kon-Fat et al, 2015

IUI: significantly less expensive

No significant difference

No evidence in support IVF as a first line between

18 and 38 y

IUI OS

should remain the treatment of first choice for

unexplained or mild male infertility

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II. IUI for unexplained infertility

1. AMIGOS Trial Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation

(National Institute of Child Health and Human Development (NICHD)New Eng.

J. of Med 2015)

– 12 clinical sited in USA.

– 900 couples with un infertility.

– Age 18-40 years old.

– Up to 4 OS cycles with IUI

LBR Cong. Anomalies

Letrozole 18.71% 3.6%

Gonadotropin 32.2% 3.1%

Clomiphene 23% 4.3%

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2. IUI Vs TI for unexplained infertility.(Veltman-Verhulst et al, 2016, Cochrane SR).

IUI Vs TI or EM both in natural cycle

no evidence of a difference in cumulative LBR

LBR

TI:16%

IUI: 15% to 34%.

IUI Vs TI or EM both in stimulated cycle

No evidence of a difference in LBR

LBR

TI: 26%

IUI: 23% to 50%.

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No conclusive evidence of a difference in

LBR or

multiple pregnancy

in most of the comparisons for couples with

unexplained infertility treated with IUI when

compared with TI, both with and without OS.

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3. IUI Vs IVF for unexplained infertility(TjonKonFat et al, 2016)

similar LBR

insufficient evidence to conclude that IUI or IVF is effective

compared to TI in un infertility.

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4. IUI Vs IVF for unexplained infertility.

Couples were randomized to receive either

3 cycles of IUI+ OS or

1 cycle of IVF (Nandi et al, 2017)

Singleton LBR:

not significantly different (24.7% vs 31.1%) with an absolute risk difference of 6.4% (95% CI

5.8% to 18.6%).

Multiple pregnancies per live birth:

No significant difference (13.8% vs 8.3%)

(relative risk, 0.6; 95% CI 0.142.4).

OHSS:

IUI: no cases

IVF: 3 cases of OHSS (3.7%)ABOUBAKR ELNASHAR

8. EFFECTIVENESS1. Factors affecting success

CPR per cycle.

1. Female and male age

2. Male smoking

3. Female BMI

4. Infertility status: primary/secondary infertility

5. Inseminating motile count (IMC)

6. Ovarian stimulation(Thijssen et al, 2017)

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Treatment PR/cycle NNT 95% CI Source

IUI 5 32 (12.-46) Guzick et al. (1999), Martinez

et al. (1990) Steures et al.

(2007)

CC/IUI 7 14 (7.-100) Deaton et al. (1990)

FSH/IUI 12 11 (9.16) Guzick et al. (1999)

IVF 31 4 (3.7) Hughes et al. (2004)

2. PR per cycle and NNT per cycle

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3. Cost Effectiveness

initially treatment with IUI

more cost-effective than IVF in most cases of

Unexplained

Mild male infertility.

(Carceau et al 2002; Ombelet et al 2005)

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CONCLUSION

IUI

least expensive

least invasive

least stressful

least hazardous.

IMC> 1 million is a good candidate for IUI

In unexplained or mild male infertility

No evidence in support of IVF as a first line

IUI OS should remain the treatment of first choice.

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You can get this lecture from:1.My scientific page on Face book:

Aboubakr Elnashar Lectures.

https://www.facebook.com/groups/2277

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2.Slide share web site

3.elnashar53@hotmail.com

4.My clinic: Elthwara St. Mansura

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