Intrauterine Insemination for Unexplained Infertility

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Intrauterine Insemination for Unexplained
Infertility

• Presented by
• Ahmed Walid Anwar Morad, M.D
• Assistant Professor of Obstetrics and Gynecology
• Banha Faculty of Medicine
• Egypt
• 2013

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OBJECTIVES

• The main objective of this presentation is to
  spotlight on the role of IUI in the treatment of
  unexplained infertility

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Unexplained Infertility
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• 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)

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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.

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

• Expectant
• Encourage
• Advice
• Inform

• Active
• IUI
• Oral stimulating agents (CC / letrozole)
• CC IUI
• Gonadotropin injections with or without IUI
• IVF/ICSI
• Alternatives
• Bromocriptine, Danazol, Tubal flushing.

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• 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)

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Suggested Protocol for Management of Unexplained
Infertility (Ray et al, 2012)
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The role of IUI in treatment of unexplained
infertility
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IUI

• Definition
• Rationale
• Other indications of IUI
• Steps
• Advantages
• Complications
• Indications of IUI in unexplained infertility
• Effectiveness of IUI in unexplained infertility

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Intrauterine Insemination

• Definition
• IUI involves the placement of processed semen
  into the uterine cavity around the time of
  ovulation (Allahbadia and Merchant,2012).

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• Rationale
• increase the rate of conception by increasing
  the chance that maximum number of healthy sperms
  reaches the site of fertilization (ESHRE,2009).

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• Indications
• I. 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)

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• 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

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Steps

• Patient selection counseling.
• Natural cycle IUI
• Stimulated cycle IUI (Ovarian stimulation)
• Monitoring of treatment
• Sperm preparation
• Insemination

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(No Transcript)
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Advantages of IUI

• Non invasive (like Pap smear).
• Bypass possible cervical mucous hostility.
• Easy performance and training
• Minimal cost and risk

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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.
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IUI Indications in Unexplained Infertility
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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 (2040)
• 50 of those in whom conventional treatments have
  failed.

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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)

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Effectiveness of IUI in treatment of unexplained
infertility
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Unexplained Infertility PR with different
treatment Options
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/ICSI 20.7
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• 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.

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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).

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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 IUISO.
• 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.

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• NICE Guidance Feb, 2013

• 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 .

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• 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)

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Favorable Predictors of IUI Outcome

• Factors related to couples
• Factors related to therapy

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• 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 rate
Primary inf. 7.9
Secondary inf. 21.4
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• 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).

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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)

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B. Therapy (Allahbadia and Merchant,2012). 1. Us
e of CC/HMG-FSH compared with CC only .
2. Follicular dynamic - AFC gt 5 (Ombelet et
al, 2003) - Preovulatory follicles 23
follicles 16 mm with uniformly high-grade
vascularity and E2 levels gt500 pg/mL on the day
of hCG administration. (Steures et al, 2004 Bhal
et al ,2001) .
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• .3. Sperm parameters generally
• Processed total motile sperm count 10 million,
  24 h survival gt 70, and normal sperm morphology
  of gt4 (according to Krugers criteria) predict
  pregnancy outcome with 94 sensitivity, 86
  specificity (Guven et al, 2008Abdelkader Yeh
  ,2009).(12.3 vs 2.8)
• Initial sperm count, motility ?

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4.Time of insemination, preferably between D13
16. 5. Endometrium adequate thickness with
trilaminar pattern (Tomlinson et al ,1996)
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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).

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• 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).

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How to improve IUI results?Measures to?
complications

• 1. Natural cycle IUI ? PR
• 2. Mild ovarian stimulation low dose GnH
• 3. Cycle cancellation gt 3 follicles 16mm or gt
  8 follicles 12mm
• 4. Selective follicular reduction. (not routine)
• 4. Conversion to IVF cycle

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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)

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• 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 ( PR25 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)

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Conclusions

• Treatment of unexplained infertility is empiric
  as no obvious abnormality was detected.
• Treatment of unexplained infertility is very much
  dependent on availability of resources and
  patients age and duration of infertility .
• OH with IUI is a simple ,cost-effective, least
  invasive first-line treatment for Unexplained
  infertility.

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Conclusions
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.
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Conclusions

• 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.

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Thank you
E.mailahwalid2004_at_yahoo.com