Evaluation and selection of patients for Intra uterine insemination (IUI)

Dr. Rana Choudhary
(MBBS, DNB, DGO, DFP, DCR, FCPS, FICMCH, FICOG, MNAMS)

Masters in Reproductive Medicine & IVF (UK)

Consultant Obstetrician & Gynaecologist
Reproductive Medicine (Fertility) Specialist

Certified Personal Counsellor

Introduction

IUI is a procedure to treat infertility in which washed and prepared sperms are introduced into the woman’s uterus, with timed ovulation, with the aim of getting the maximum number and most motile sperms nearer to the ovum and achieving pregnancy. The history of intrauterine insemination (IUI) goes back to the 18th century when Scottish surgeon John Hunter performed an effective procedure with the use of the husband’s sperm. In 1884, after William Pankhurst from Philadelphia in the United States applied the donor’s sperm, live birth was reported. ESHRE data indicate that the pregnancy rate per cycle (PR per cycle) after IUI-H is 12.4% compared with 28.9% after IVF and the results have not changed over the last few years.

History taking:

Various important point during history taking are summarized in the table below

Table 1: Important points to be considered during history taking of a couple presenting with infertility

 Sr.   No.FactorSpecific findings/ questions  Importance
  1Name  For identification of the patientBetter rapport
  2Age, Duration of infertilityTo decide the approachMore the age and duration of infertility, more aggressive is the approach as chances of conception goes on decreasing
  3OccupationShift duties etcDecrease in frequency of intercourse
  4Sexual history  Vaginusmus, Sexual satisfaction etcDecrease in frequency of intercourse
  5Obstetric historyH/o previous abortions, RPL, D & CEndometrium may be defective
  6Medical historyh/o DM, HT, Kochs, Thyroid problemsPregnancy may be high risk
  7Surgical historyH/o surgeries in pelvis and abdomenAdhesions leading to altered tubo-ovarian anatomy

Other aspects :

  • Both partners should be seen together
  • Privacy & sufficient clinical time

Positive predictive factors for IUI success           

  • Age of female partner < 35 years {should we consider a lower age (33years) for Indian women as their ovarian reserve gets depleted earlier?}
  • Duration of infertility < 5 years
  • At least one functional normal fallopian tube and no uterine factor leading to infertility
  • Adequate ovarian reserve (based on Sr. AMH, Antral follicular count, Day 2 FSH)
  • Good semen parameters

Variables affecting IUI success

Treatment with ovulation induction and IUI is more successful in an-ovulatory women. Various factors affect the success rate of IUI.

  1. Age of female -As age advances the chances of pregnancy after ovulation induction and assisted reproductive procedures (ART) procedures like IUI decreases.
  2. Unexplained Infertility – Addition of IUI to super ovulation produces better results than super ovulation and timed intercourse (11.37%) especially in cases of unexplained infertility.
  3. Endometriosis – Mild or minimal endometriosis may benefit from IUI (pregnancy rates 7% to 18%), however in severe cases it is not advisable (4.5%).
  4. Cervical Factor – Conception rate in natural cycle is 14% and in IUI plus Gonadotrophins is 17%.
  5. Male factor infertility –Total motile sperm count (TMSC) >5 million/ml and sperm morphology are most valuable sperm parameters to predict IUI outcome.

When To Start Investigations & Treatment?

Table 2: When to start investigations in of a couple presenting with infertility

 Sr.   No.Parameters When to start investigation
   1<35 Years1 Year
  2>35 Years6 Months
  340 Years & aboveAt the earliest
  4OligomenorrhoeaAt the earliest
  5AmenorrhoeaAt the earliest
  6Abnormal pelvic ultrasonographyAt the earliest
  7History suggestive of ↓ ovarian reserveAt the earliest
  8H/o previous surgeries eg salpingectomy or disease such as Kochs abdomenAt the earliest

Ideal Body Weight (IBW)

Studies have shown that increased body weight / obesity interferes with ovulation & causes infertility

Calculate IBW using Brocas index

Males: (wt in kg) = Height (in cm) – 100

Females: (wt in kg) = Height (in cm) – 105

Table 4: Classification of obesity

Sr. NoBody weightType of obesity
   120% > Ideal body weight (IBW)Obese
   2Body weight > 200 lbs Morbidly obese 
   3 > 2 x Ideal body weight (IBW)Morbidly obese 

Table 5: Evaluation of Female Partner for infertility

 Sr.   No.Evaluation of  TestImportance
  1Ovulatory functionTSH, Prolactin, AMH, TVSDistinguish between ovulatory & non ovulatory women   AMH – To know ovarian reserve
  2Pelvic StructureDetailed transvaginal ultrasoundDetect structural abnormalities like poly, fibroid, cysts etc
  3Tubal patency testing  HSG/ Laparoscopy / HysteroscopyExtremely important before IUI

Flowchart 1: Management of thyroid abnormalities

https://drranachoudhary.com/wp-content/uploads/2020/03/Untitled.png 

Direct beneficial effect of TSH on follicular recruitment warrants investigation of serum thyroid levels and thyroxin supplementation in infertile women with Sr. TSH  ≥2.5 units in attempts to improve recruitment.

Table 6: Insulin resistance and infertility

  Insulin resistance (IR) 
  Measurement of Insulin resistanceFasting glucose (mmol/L) ÷ Fasting Insulin (micro IU/ml)
  IR Ratio < 4.5Indicates Insulin resistance (IR)
  For eg.  FBS = 100   &   Fasting   Insulin is 45 Ratio = 100 ÷ 45 = 2.22Indicates  Increased Insulin Resistance  

Anti Mullerian Hormone (AMH) test :

  • Produced by Preantral & small antral stage (< 4 mm)
  • No AMH is secreted by follicles > 8 mm
  • Can be measured on any day of cycle but better on day 2/3
  • Measurement of AMH = Biological Body Clock Test
  • Predicting live birth outcome, ovarian response & OHSS
  • May reflect fertility potential more accurately than conventional markers like FSH, inhibin B or estradiol levels
  • Should be done from a GOOD STANDARDISED LABORATORY as lab to lab variation is marked !
  • Relatively poor predictor for Pregnancy outcomes
  • Low AMH levels in isolation do not represent an appropriate marker for withholding treatment

Table 7: Importance of Anti Mullerian Hormone (AMH) test

  Sr. No.Sr. AMH levelsSignificance
   1< 0.3  ng/mlFew eggs remaining    
   2>2.5 ng/mL Probably normal reserve 
   3> 3.6 ng/mLIncreased risk OHSS  

Ovarian reserve markers / tests

Age related decline in female fertility  well recognised. It starts at 30 years with rapid decline after 37 years. Commonly used ovarian reserve tests are :
D2 antral follicle count (<5 ,Poor outcome)

  • AMH of 2 to 6 (<1 Poor ovarian reserve, >6 PCO)
  • D2 FSH   > 10  IU/l  poor response to ART
  • No evidence for ovarian volume, ovarian blood flow, inhibin B, estradiol (E2)

Table 8: Possible factors suggestive of Poor Ovarian Reserve OR  Pre mature ovarian aging

  • Short follicular phase
  • Past h/o of surgeries – Endometriosis, ovarian cysts, adhesions
  • AFC less
  • Low AMH
  • P/h/o poor response to treatment

Table 9: Investigations to evaluate tubal patency

 Sr.   No.InvestigationAdvantagesDisadvantages
  1HSGScreening testNot very specific
  Ideal cost effectiveFalse positivity rate is high
  Non-invasive 
  Pre-operative help in counseling 
 LaparoscopyGold standardCost
  High specificity & sensitivity  Invasive

Conclusion:

  • Adequate & Compassionate Counseling
  • Do not bombard with investigations as it further increases stress in patients
  • Each patient is different, hence blanket treatment is not justified
  • Keep a watch on couples age …especially ovarian aging as chances of pregnancy decreases exponentially, as age of the female partner advances
  • Give patients an idea about real expectations/ results so that they can prepare themselves
  • Timely referral
  • Individualization is the key to success

Male  Factor Evaluation

  • Detailed history – Exposure to high temperature ,environmental toxins etc
  • Thorough clinical evaluation – esp in relation to any local genital / scrotal swelling eg. Varicocoele, Hydrocoele etc
  • Lab investigations

Fig 1 : Adverse Effects Of Obesity on Semen parameters  

  Excess peripheral adipose tissue (High aromatase activity) Testosterone → Estradiol Androstenedione → Estrone   Excess of suprapubic & inner thigh fat ­ scrotal temperatures   All these can cause ↓sperm count as well as motility  

Table 10: Physical Examination in males with infertility

 Sr   No.FactorImportance
  1General examination Stature, Height ,Weight , BMI, BP 
  2Increased BMIR/o DM
  3TPR / BPR/o HT
  4GynecomastiaHormonal imbalance
  5Hair distribution & amountSubvirilization
  6Genital –  Spermatic cord, Scrotum, Testis (mobility, consistency), Abnormal shapes of penis, urethral meatusOnly in indicated cases with abnormal semen analysis
  7Azoospermia                                                                                           Rectal exam to exclude ejaculatory duct obstruction  

Table 11: Investigation of Male Partner for infertility 

 Sr   No.FactorImportance
  1Detailed Semen Analysis-  Count, Motility and    Morphology  Treatment depends primarily on this report
  2Viral markers –  HBsAg , HIV, HCV  Required for IUI
  3Semen cultureIf semen analysis shows leucospermia
  4Sperm Function Test    If semen analysis shows moderate to severe Oligoasthenozooteratospermia (OATS)
  5Sr. FSH  If semen analysis shows moderate to severe Oligoasthenozooteratospermia (OATS)   To differentiate cause of AZOOSPERMIA –                 Obstructive   versus  Non Obstructive   Low in hypogonadotrophic hypogonadism  
  6Sr. LHLow in hypogonadotrophic hypogonadism
  7Sr. Testosterone  If semen analysis shows moderate to severe Oligoasthenozooteratospermia (OATS)  
  8Sr ProlactinErectile dysfunction
  9Blood Sugar  DM
  10Colour DopplerClincial examination s/o  Varicocoele   If semen analysis shows moderate to severe Oligoasthenozooteratospermia (OATS)
  11Karyotype  If semen analysis shows moderate to severe Oligoasthenozooteratospermia (OATS)
  12Y chromosome MicrodeletionIf semen analysis shows moderate to severe Oligoasthenozooteratospermia (OATS)   H/o repeated implantation failure / abortions in first trimester

Semen Analysis

  • Cornerstone’ of  lab evaluation (although it is not a sperm function test)
  • Gives information – Functional status  of seminiferous tubules, epididymides & accessory sexual glands
  • Prostatic gland fluid (0.5ml – zinc, citric acid, acid phosphatase & proteases)- assures liquefaction
  • Seminal vesicle fluid (1.5-2ml -prostaglandins & fructose)
  • Semen sample must be collected after min 3 days & max 7 days of abstinence
  • Semen analysis – In Clinical Practice, male factor infertility is identified by ABNORMAL SEMEN PARAMETERS
  • Interpretation of semen analysis report
  • Only from a standardised laboratory
  • Any abnormal report must be confirmed by at least two reports, atleast  4 weeks apart
  • Judge  response to  treatments  after  3 months of therapy as one  spermatogenic   cycle (testicular)  lasts from 63  –  72 days 

Table 12: WHO (2010) guidelines for normal semen reporting

  Semen parametersNormal value
  Semen volume1.5 ml
  Total sperm in the ejaculate39 million
  Sperm per ml15 million/ml
  Vitality58% live
  Progressive motility32 %
  Total motility40 %
  Morphologically normal4 %

Ref: World Health Organization. NICE guideline CG156, recommendation 1.3.1.1. Oct 2014

  Success of   IUI – Total  Motile Sperm Count (TMC)  & Morphology TMSC = Count x Volume x % Motility   eg   (10 million x 4 ml x 50) ÷  100  = TMC 20 million  

 

Table 13: Semen parameters and treatment required

  Sr. No.Semen parametersTreatment required
   15 Million (Pre wash count)IUI
   21 million (Postwash)IUI
   3Pre wash 1-5 millionIVF
   4Pre wash <1 millionICSI

  • Success in IUI is highest with ≥ 14 % sperms with normal morphology, Intermediate  with  4 – 14 % and poor  with < 4 %

  Poor sperm count doesn’t rule out any pregnancy possibility Normal count doesn’t guarantee   fertilization/pregnancy

Table 14: Sperm Function Tests

 Sr.   No.Test Importance
  1Hypo-osmotic swelling (HOS) testIntegrity & behavior of the cell membrane of the sperm tail
  Helps to distinguish between immotile alive  & dead sperms
  2Sperm DNA  Fragmentation Test  Sperm quality is dependent on  the amount of damage to the sperm DNA or DNA fragmentation

   Indication for Sperm Function Tests –

  • All men with abnormal semen analysis  
  • Advanced age
  • Infection
  • Normal semen analysis but failed IVF for unexplained reasons
  • May help predict success of a procedure

Table 15: Management tips during evaluation for Varicoele

 Sr.   no.Test ImportanceManagement
  1Grade 1 & 2 VaricoeleNo surgery is requiredA trail of medical therapy can be given, followed by IUI
  2Grade 3Surgical managementSurgery
  3Positive Predictive factors of varicocelectomy in grade 3 varicocoeleLack of testicular atrophy   Normal FSH   Total sperm count more than 5 million   

Table 16: Golden Rules For Investigations

  Clinically relevant and effectiveShould impact the line of treatmentEasy to interpretFeasible – cost,     convenienceInvestigations are seldom more important than the treatment or the res    

References:

  1. Diagnostic evaluation of infertile female: a committee opinion. The Practice Committee of the American Society for Reproductive Medicine. Fertility & Sterility,  Aug 2012.
  2. What affects functional ovarian reserve, thyroid function or thyroid autoimmunity? Reprod Biol Endocrinol. 2016 May.
  3. Med Pregl. 2016 Jan-Feb;69(1-2):25-30.
  4. What affects functional ovarian reserve, thyroid function or thyroid autoimmunity? Reprod Biol Endocrinol. 2016 May
  5. Evaluating the performance of serum antimullerian hormone concentration in predicting the live birth rate of controlled ovarian stimulation and intrauterine insemination. Fertil Steril. 2010 Nov
  6. World Health Organization. NICE guideline CG156, recommendation 1.3.1.1. Oct 2014

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