Manual on Advanced Infertility & Assisted Reproductive Techniques Nandita Palshetkar, Kedar N Ganla, Sunita Tandulwadkar
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SECTION 1
1Intrauterine Insemination2

IUI Patient Selection &WorkupChapter 1

 
DEFINITION
The deposition of spermatozoa in the uterus at any point above the internal os is considered as intrauterine insemination (IUI).
 
RATIONALE
The rationale of IUI performed using either husband's or donor spermatozoa is to overcome the problems of
  1. Vaginal acidity
  2. Cervical mucus hostility and
  3. Deposition of a good number of highly motile and morphologically normal sperms in the uterus near the fundus at the anticipated time of ovulation.
 
INDICATIONS OF IUI
 
1. Unexplained Infertility
In this condition, there is no definite cause for infertility, even after subjecting the patient to complete workup. The complete workup includes routine lab investigations, hormonal investigations (T3, T4 TSH, Prolactin, T, DHEAS, Day 2 LH, FSH & E2 & Day 21 Progesterone) semen analysis, assessment of tubal status (HSG or Laproscopy-hysteroscopy-D&C) & assessment of Ovulation(Serial vaginal USG, BBT, daily Urinary LH or day 21 progesterone).
The avarage incidence of unexplained infertility is around 10-15%.
The pregnancy rates in these patients is as follows :
  1. Natural cycle+IUI:6%
  2. Clomiphene(CC)&/or Goandotrophins + IUI: 18-19%
    Zeyneloglu et al demonstrated that superovulation with IUI gave the best chance of pregnancy.
 
2. Cervical factor
The following are some common causes of cervical factor
  1. Insufficient mucus production
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  2. Altered quality of mucus
  3. Abnormal cervix:stenosis, injury, malformation, infection, erosion
  4. Abnormal postcoital test (the general consensus is that PCT has nonpredictive value in terms of pregnancy.)
The pregnancy rate is as follows :
  1. Natural cycle+ IUI: 14%
  2. CC&/or HMG/FSH: 17%
 
3. Male Factor
Zayed et al reported a PR of 19% per cycle in patients with mild male factor:
Mild male factor was defined as follows :
  1. Patient with only one abnormal male parameter
  2. Total motile sperm concentration of more than 5 million & morphology greater than 5%.
    Patients with severe male factor infertility should go directly for IVF/ICSI. (From a practical view point, even though patients have severe malefactor it is best to give them a trial of 2-4 IUI cycles, after counseling them about the very poor chance of pregnancy. If they still do not achieve pregnancy, one can advise them ICSI or AID)
 
4. Ejaculatory failure
Causes:
  1. Anatomical: servere hypospadias: in this the semen is collected by masturbation & IUI is performed.
  2. Neurological: Retrograde ejaculation & paraplegics. In retrograde ejaculation urine is centrifuged & then washed to isolate sperms & IUI performed. In paraplegics, the semen is collected by electroejaculation. In electroejaculation, a probe is inserted into the rectum &a stimulus is given to the seminal vesicles to bring about ejaculation. The semen is collected & IUI performed. In both these conditions the sperm quality especially its motility is hampered. Good results are obtained in whom the progressive motility is more than 20-30%.
  3. Psychological conditions: lmpotence & erectile dyfunction. In this the patient is given sex-psychotherapy. Drugs such as viagra, muse, or papaverine may be given to bring about a good erection. Some patients benefit with the use of mechanical vibrators. Very occasionally the patients may have be subjected to general anesthesia & electroejaculation. Following this IUI may be performed.
 
5. Immunological
 
6. Endometriosis
Patients with mild to moderate endometriosis have good pregnancy rates of between 7-18% with IUI. However, as the pregnancy rates (3-5%) are very low with severe endometriosis, it is best to opt for IVF / ICSI.5
 
PREREQUISITES FOR IUI:
  1. Age less than 40 years
  2. Patient capable of spontaneous or induced ovulation.
  3. At least one patent fallopian tube with good tuboovarian relationship which would not hamper the egg collection by the tubalfimbria from Pouch of Douglas.
  4. Sperm count of more than 10 million / ml prewash or a postwash count of >5 million motile sperms.
  5. Easy access to the uterine cavity via a negotiable cervical canal.
 
Intrauterine Insemination: Steps
  1. Patient Selection & workup
  2. Ovarian stimulation
  3. Semen wash
  4. Insemination
  5. Luteal Support
 
PATIENT SELECTION & WORKUP:
The patients are selected based on their tubal, hormonal & seminal status. For further details one can look up the section on indications.
 
Patient workup:
  1. Routine investigations of both Husband & wife
    Hb, CBC, ESR, VDRL, HBSAG, HIV, HCV Urine sugar, bleeding & clotting time.
  2. Investigations of the Husband
    Semen analysis after 4 days of abstinence
    Optional tests: semen culture
    Kruger sperm morphology
    Sperm antibodies: immunobead & MAR test
    Scrotal Doppler to rule out varicocele
    FSH, Testesterone, prolactin
  3. Hormonal investigations of the wife
    1. Serum FSH, LH, Estradiol on Day 3 of Cycle
      (FSH>10miu/ml & E2>60pg/ml indicates poor ovarian reserve
      LH/FSH>2/1 indicates PCOS
      Low LH, FSH, E2 indicates hypogonadotrophic hypogonadism
      FSH more than 17 miu/ml on Day 10 after CC indicates poor prognosis)
    2. In case of patients suspected to be poor responders, one can do two additional tests :
      1. Serum inhibin - B test which is >45 pg/ml in poor responders
      2. Clomiphene challenge test:
        CC 100 mg per day from Day 5 to Day 9 & FSH on Day 10. A high FSH indicates poor response & poor prognosis.
      3. AM H
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    3. Serum Prolactin &T3T4TSH
    4. In case of patients with PCOS diagnosed by USG, or symptomatology or having feature of androgenisation one can do the following tests:
      1. Fasting Serum Insulin level (>10Miu/ml is significant)
      2. Fasting & Post prandial blood sugar.
      3. DHEAS, Androstenidione & testosterone.
      4. In obese patients a follicle phase 17-OHP level (to rule out congenital adrenal hyperplasia) & dexamethasone suppresion test (to rule out Cushings syndrome) should be carried out.
      5. Rarely Serum Alanine transaminase level is done in patients who are intolerant to metformin treatment & who need to be placed on Rosig litazone
      6. In women with past history of renal disease on metformin treatment, Serum creatinine &/or 24 hr creatinine clearence may have to be done.
      7. For screening and academic purposes a C peptide assay may be performed to pick up latent diabetes.
  4. Tests to rule out Tuberculosis:
    These are especially important in developing countries.
    1. CBC
    2. ESR.
    3. Mantouxtest
    4. Serum Ig G & lgM for tuberculosis
    5. Plain X ray of chest
    6. Sputum Acid Fast Bacilli on 3 consecutive days.
    7. TMA or PCR on any tissue suspected of having tuberculosis
    8. Guinea pig inoculation & culture
  5. An USG of the abdomen & pelvis should be done. It is preferable to perform a pelvic USG
  6. Hysterosalpingography (8 days after period:)
    1. It is normally indicated in the early phase of treatment when the couple has just started trying for a pregnancy. It is a relatively simple minimally invasive test which can give us a lot of information, If HSG is normal, one can offer the couple few cycles of CC with planned relations. If that fails to achieve pregnancy, one can try few cycle of CC plus IUI before going for a thorough investigation by performing a laparoscopy, hysteroscopy & D & C. It is prudent not to subject the patient to too many CC cycles before doing Laparoscopy, as too many stimulation cycles may predispose to long term effects of increased incidence of ovarian cancer in the 6 th & 7 th decade of the patients life.
    2. It can also be performed in patients who have already undergone Laparoscopy in the past. It can be done to rule out any gross abnormalities in the uterus prior to starting IUI treatment.
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    3. It can also be done as a therapeutic procedure of Fallopian Tube Recanalisation (FTR) where the tubal blocks could be opened by guide wire under image intensifier HSG control. One of the prerequisites of this procedure is blocked tubes without having any major pathology seen on Laparoscopy.
  7. Diagnostic cum Operative Laparoscopy-Hysteroscopy-D&C-histopathalogy
  8. Tests for classifying patients ovulatory status (Ovulatory or Anovlatory)
    1. Basal body temperature
    2. Serial vaginal ulround follicular scan in spontaneous cycle
    3. Serum preogesterone on Day 21 of cycle >4ng/ml indicates ovulation & > 10ng/ml indicates adequate luteal phase.
    4. Endometrial biopsy-Secretory Premenstrual biopsy indicates ovulation.