intra uterine insemination for unexplained infertility

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Intrauterine Insemination for Unexplained Infertility Presented by Presented by Ahmed Walid Anwar Morad, M.D Ahmed Walid Anwar Morad, M.D Assistant Professor of Obstetrics and Gynecology Assistant Professor of Obstetrics and Gynecology Banha Faculty of Medicine Banha Faculty of Medicine Egypt Egypt 2013 2013

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Page 1: Intra uterine insemination for unexplained infertility

Intrauterine Insemination for

Unexplained InfertilityPresented byPresented by

Ahmed Walid Anwar Morad, M.DAhmed Walid Anwar Morad, M.D

Assistant Professor of Obstetrics and Gynecology Assistant Professor of Obstetrics and Gynecology

Banha Faculty of MedicineBanha Faculty of Medicine

EgyptEgypt

20132013

Page 2: Intra uterine insemination for unexplained infertility

OBJECTIVES

The main objective of this

presentation is to spotlight on the

role of IUI in the treatment of

unexplained infertility

Page 3: Intra uterine insemination for unexplained infertility

Unexplained Infertility

Page 4: Intra uterine insemination for unexplained infertility

Definition

Unexplained infertility means that ,couple does not conceived after 1 year of unprotected vaginal sexual intercourse, with basic infertility evaluation shows no obvious abnormality

(RCOG guidelines,1998; Randolph,2000; ASRM,2006).

Incidence

15% to 30% of infertile couples (ASRM,2006)

Page 5: Intra uterine insemination for unexplained infertility

Basic investigations for diagnosis of Unexplained infertility

Normal basic semen analysis according to

WHO criteria (WHO ,2010).

Patent fallopian tube confirmed by HSG.

Ovulation confirmed by mid-luteal serum

progesterone level.

Page 6: Intra uterine insemination for unexplained infertility

In unexplained infertility: the cause is not defined ,so the treatment is empirical (ASRM, 2006).

Expectant Encourage Advice Inform

Active IUIIUI Oral stimulating agents (CC / Oral stimulating agents (CC /

letrozole)letrozole) CC+ CC+ IUIIUI Gonadotropin injections with or Gonadotropin injections with or

without without IUIIUI IVF/ICSIIVF/ICSI Alternatives:Alternatives:

Bromocriptine, Danazol, Tubal flushing.

Page 7: Intra uterine insemination for unexplained infertility

Treatment

Dependent on:

○ Availability of resources ,

○ Patients’ age ,

○ Duration of infertility.

The standard protocol is to:

○ Progress from simple to complex treatment options,

○ Balance the effectiveness against the cost and side effects. (Ray et al,2012)

Page 8: Intra uterine insemination for unexplained infertility

Suggested Protocol for Management of Unexplained Infertility (Ray et al, 2012)

Page 9: Intra uterine insemination for unexplained infertility

The role of IUI in treatment of unexplained infertility

Page 10: Intra uterine insemination for unexplained infertility

IUI Definition

Rationale

Other indications of IUI

Steps

Advantages

Complications

Indications of IUI in unexplained infertility

Effectiveness of IUI in unexplained infertility

Page 11: Intra uterine insemination for unexplained infertility

Intrauterine Insemination

Definition

IUI involves the placement of

processed semen into the

uterine cavity around the time

of ovulation (Allahbadia and Merchant,2012).

Page 12: Intra uterine insemination for unexplained infertility

Rationale

increase the rate of

conception by

increasing the chance

that maximum number

of healthy sperms

reaches the site of

fertilization (ESHRE,2009).

Page 13: Intra uterine insemination for unexplained infertility

IndicationsI. Male:

1. Ejaculatory failure: ( sever hypospadius ;retrograde

ejaculation; impotence)

2. Male factor infertility (mild ;moderate)

3. Sperm cryopreservation prior to treatment of

husband cancer.

4. Processed semen of HIV + husband for HIV

negative women (NICE, 2013)

Page 14: Intra uterine insemination for unexplained infertility

II. Female:

1.Cervical factor infertility

2. Endometriosis

3. Ovulatory dysfunction

4. Combined non-tubal

infertility factors

III. Combined:

1. Unexplained infertility

2. Immunological infertility

Page 15: Intra uterine insemination for unexplained infertility

Steps

Patient selection & counseling.

Natural cycle IUI

Stimulated cycle IUI (Ovarian stimulation)

Monitoring of treatment

Sperm preparation

Insemination

Page 16: Intra uterine insemination for unexplained infertility
Page 17: Intra uterine insemination for unexplained infertility

Advantages of IUI

• Non invasive (like Pap smear).

• Bypass possible cervical mucous

hostility.

• Easy: performance and training

• Minimal: cost and risk

Page 18: Intra uterine insemination for unexplained infertility

IUI Complications

Of the procedure

Infection Pain Psychological (guilt,

anger, loss of self esteem)

Of COH Multiple

pregnancy

OHSS

Antenatal & perinatal

As pregnancies from sexual intercourse.

Page 19: Intra uterine insemination for unexplained infertility

IUI Indications in Unexplained Infertility

Page 20: Intra uterine insemination for unexplained infertility

ESHRE Capri Workshop Group (2009)

IUI or stimulated ovary/IUI is indicated as

empiric treatment for all categories of

unexplained infertility

20% of couples after initial work-up.

Couples with mild male subfertility (20–40%)

50% of those in whom conventional

treatments have failed.

Page 21: Intra uterine insemination for unexplained infertility

NICE Guidance Feb, 2013

In the treatment of unexplained infertility

The evidence does not support the use of IUI as

an alternative to expectant management .

IUI (with or without stimulation) should not be

routinely offered (exceptions e.g. when people

have social, cultural or religious objections to IVF)

Page 22: Intra uterine insemination for unexplained infertility

Effectiveness of IUI in treatment of unexplained infertility

Page 23: Intra uterine insemination for unexplained infertility

(Guzick et al. 1998.)

Conclusions (Cochrane, 2012 ): In stimulated cycles PR was higher with IUI compared to timed intercourse

Treatment % preg

Expectant (No treatment ) 1.3%

Natural cycle IUI 3.8%

Clomiphene 5.6%

Clomiphene+ IUI 8.3%

Gonadotropins 7.7%

Gonadotropins+ IUI 17.1%

IVF/ICSIIVF/ICSI 20.7%20.7%

Unexplained Infertility :PR with different treatment Options

Page 24: Intra uterine insemination for unexplained infertility

NICE Guidance Feb, 2004 ; For unexplained infertility

ovarian stimulation should not be offered, even though

it is associated with higher pregnancy rates than

unstimulated IUI, because it carries a risk of multiple

pregnancy.

Cochrane, 2012 ; risks and alternative treatment options

of stimulated IUI should be discussed.

NICE Guidance Feb, 2013 ; Do not offer oral ovarian

stimulation agents (such as clomifene citrate,

anastrozole or letrozole) to women with unexplained

infertility.

Page 25: Intra uterine insemination for unexplained infertility

IUI versus alternative insemination techniques

1 } Fallopian Tube Sperm Perfusion (FSP) :

Past : FSP is superior to IUI (Trout & Kemmann,1999) .

Later: a meta-analysis reported no clear benefit (Cantineau et

al, 2009)

2} No difference between IUI and Intraperitoneal

insemination (IPI) (Noci et al,2007)

3} Intrauterine tuboperitoneal insemination (IUTPI) is

superior to IUI &FSP (CPR/cycle 29.4% ) (Mamas, 2006)

4} IUI is superior to Intracervical insemination ICI (Besselink et al,2008).

Page 26: Intra uterine insemination for unexplained infertility

IUI Vs. IVF for unexplained infertility

Starting treatment with IUI rather than IVF was

either cheaper or more cost-effective than IVF in

unexplained infertility (Goverde et al., 2000).

Cochrane, 2012 (Pandian et al, 2012)

IVF may be more effective than IUI+SO.

Due to lack of data from RCTs the effectiveness of

IVF for unexplained infertility relative to

expectant management, clomiphene citrate and IUI

alone remains unproven.

Page 27: Intra uterine insemination for unexplained infertility

For people with:

○ unexplained infertility,

○ mild endometriosis or

○ mild male factor infertility,

who are having regular unprotected sexual intercourse:

advise them to try to conceive for a total of 2

years before IVF will be considered .

NICE Guidance Feb, 2013

Page 28: Intra uterine insemination for unexplained infertility

IUI in stimulated cycles may be considered while

waiting for IVF or when in women with patent tubes,

IVF is not affordable (ESHRE Capri Workshop Group, 2009)

Page 29: Intra uterine insemination for unexplained infertility

Favorable Predictors of IUI Outcome

Factors related to couples

Factors related to therapy

Page 30: Intra uterine insemination for unexplained infertility

A.Couple:

1.Female age ≤ 35y (Morshedi et al, 2003 )

2.Shorter duration of infertility .

3. Type of infertility (Guven et al,2008)

Type of infertility Pregnancy ratePrimary inf. 7.9%

Secondary inf. 21.4

Page 31: Intra uterine insemination for unexplained infertility

A.Couple:

4. First treatment cycles (≤ 4). Pregnancies resulting from IUI occur during the first 3-4

treatment cycles (88-95.5%; respectively) (Morshedi et al,2003).

Aboulghar et al, 2001, suggested a maximum of 3

COH/IUI cycles for treatment of unexplained infertility

However ,others recommended up to 6 cycles

(Dickey et al, 2002; Morshedi et al,2003; Ray et al, 2012).

Page 32: Intra uterine insemination for unexplained infertility

5. Cause of infertility: (Bourn Hall clinic, 1999 ;Tay et al,2007; Wang et al,2008).

Overall CPRs/cycle 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% )

♂ factor → the best PR with ejaculatory disorders (13.3%)

Page 33: Intra uterine insemination for unexplained infertility

B. Therapy: (Allahbadia and Merchant,2012).

1 .Use of CC/HMG-FSH compared with CC only .

2 .Follicular dynamic:

- AFC > 5 (Ombelet et al, 2003)

- Preovulatory follicles : 2–3 follicles≥ 16 mm with

uniformly high-grade vascularity and E2 levels >500

pg/mL on the day of hCG administration. (Steures et al, 2004;

Bhal et al ,2001).

Page 34: Intra uterine insemination for unexplained infertility

.3 .Sperm parameters: generally

• Processed total motile sperm count ≥ 10 million, 24 h

survival > 70%, and normal sperm morphology of >4%

(according to Kruger’s criteria) predict pregnancy

outcome with 94% sensitivity, 86% specificity (Guven et al,

2008;Abdelkader & Yeh ,2009).(12.3 vs 2.8%)

• Initial sperm count, motility ?

Page 35: Intra uterine insemination for unexplained infertility

4.Time of insemination ,

preferably between D13 &16.

5 .Endometrium:

adequate thickness with trilaminar pattern(Tomlinson et al ,1996)

Page 36: Intra uterine insemination for unexplained infertility

Measures does not affect IUI results

1. US monitoring & HCG induction of ovulation

versus urinary LH monitoring of ovulation.

HCG allow final follicular maturation (Kosmas et al, 2007)

2. GnRH agonist and antagonist. ↑complications (Allahbadia and Merchant,2012).

3. Double IUI versus single IUI (Polyzos et al,2009).

Page 37: Intra uterine insemination for unexplained infertility

4. Type of catheter: 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).

However , Merviel et al ,2010 recommended soft catheter.

5 . Luteal phase support do not appear major

requirements in IUI cycles (ESHRE ,2009)

6. Sperm preparation technique (ESHRE,2009).

Page 38: Intra uterine insemination for unexplained infertility

How to improve IUI results?Measures to↓ complications:

1. Natural cycle IUI: ↓ PR

2. Mild ovarian stimulation : low dose GnH

3. Cycle cancellation {> 3 follicles ≥ 16mm or; > 8

follicles ≥ 12mm}

4. Selective follicular reduction. (not routine)

4. Conversion to IVF cycle

Page 39: Intra uterine insemination for unexplained infertility

How to improve IUI results?Measures to↑ PR:

1. COH: all except sever male factor ( Risks???)(Cohlen ,2002).

2. Vaginal misoprostol.???? (Brown et al,2001; Barroso et al,2001).

3. 10 -15minutes bed rest after IUI (Saleh et al,2000 ; Custers et al, 2009 )

4. Cervical mucous aspiration before IUI (Paasch et al, 2007)

Page 40: Intra uterine insemination for unexplained infertility

5. Timed intercourse within 12 -18 h period: useful in IUI with low

number of motile sperm inseminated (Huang et al, 1998).

6. Postponing IUI until the observation of follicle rupture by TV

sonography ( PR;25% vs 8.8%) (Kucuk ,2008).

7. US guidance in IUI

(Ramón et al,2009; Oztekin et al,2013)

8. Pre-insemination hydrotubation

(Edelstam et al, 2008; Aboulghar et al, 2010 ; Morad & Abdelhamid , 2012)

Page 41: Intra uterine insemination for unexplained infertility

1. Treatment of unexplained infertility is empiric as no obvious abnormality was detected.

2. Treatment of unexplained infertility is very much dependent on availability of resources and patients’ age and duration of infertility .

3. OH with IUI is a simple ,cost-effective, least invasive first-line treatment for Unexplained infertility.

Page 42: Intra uterine insemination for unexplained infertility

4.Couples should be fully informed about the risks of IUI and COH as well as alternative treatment options.

5. In unexplained infertility OH with IUI may be considered while waiting for IVF or when IVF is not affordable.

6. The pregnancy rates of FSP & Standard IUI are similar.

Page 43: Intra uterine insemination for unexplained infertility

7.Pre-insemination hydrotubation, US guided IUI , cervical mucous aspiration, post-insemination bed rest for 10 min and vaginal misopristol may improve IUI outcome .

8. In unexplained infertility, up to 6 cycles of IUI should be considered before shifting to IVF.

Page 44: Intra uterine insemination for unexplained infertility

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