Intra-Uterine Insemination (IUI)

Intrauterine Insemination (IUI) is the least invasive, effective, relatively simple, cheap, first line assisted conception treatment method for infertility couples wherein the washed semen with good sperm quality are inseminated into the uterine cavity of the female partner at the time of ovulation. The goal is to place as many active, well-formed sperms as close to the ovulated eggs as possible, thereby increasing their chances of Fertilization.

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A pre-IUI workup for any couple being considered for IUI should include:

  • Thorough clinical history of both partners.
  • Thorough physical examination of both partners.
  • Semen sample of male partner for semen analyses.
  • MAR test to check for presence or absence to anti-sperm antibodies.
  • Confirmation of ovulation in the female partner by:
    •  Follicular USG study.
    •  Day 21 P2 assay.
  • Confirmation of tubal patency by:
    • HSG
    • Laparoscopic chromopertubation
    • Hysterosalpingo- contrast-sonography (HyCoSy)
  • Ruling out uterine anomalies/cavity abnormalities

Careful selection of patients for IUI is a cornerstone for achieving success rate. As an inappropriate application of these treatments to the whole of the infertile population will obscure its efficacy, patient selection is very important IUI with Husband’s Semen- Indications:

  • Ejaculatory failure
  • Cervical factor.
  • Male Subfertility.
  • Immunological
  • Idiopathic infertility
  • Combined Infertility
  • Anatomical defects
  • Viscous/ frozen semen
  • PCO
  • HIV discordant couple.
  • Bilateral tubal block/tubal infection.
  • Severe pelvic inflammatory.
  • Severe oligoasthenoteratozoospermia.
  • Resent pelvic surgery or irradiation.

As per the proposed guideline for ART in India, an IUI center has reach level 2 facility which must have the infrastructure for further in-depth investigation and advanced treatment of infertility except where oocytes are handled outside the body. The IUI center must have the following facilities:

For Investigation:

  • Immunological test for infertility.
  • Sperm function test.
  • Assessment of TVS/follicular growth
  • Hysteroscopy/Laparoscopy/TV scan

For Treatment:

  • Facilities for semen preparation and IUI.
  • Provision for semen collection on men with a vibrator or electro ejaculation.
  • Conservatives surgery either through a hysteroscopy,

List of equipment:

  • Laminar air unit
  • Sperm counting chambers
  • Microscopy
  • Incubator
  • Centrifuge

       Optional:

  • Semen analysis
  • Semen Freezer
  • Semen Storage container
  • Warmer
  1. Ovarian Stimulation
  2. Follicular/ET monitoring
  3. Times of Insemination
  4.  Ovarian Stimulation1. Ovarian Stimulation –

1. Ovarian Stimulation – 

• All can be performed either in an unstimulated natural cycle or in a stimulated cycle.
• There is evidence that IUI with ovarian stimulation result in higher success rate than  IUIonly
• The benefit of increased pregnancy rate and live birth rate achieved with ovarian mutation must be balanced against the monitoring and poetical complications such as multiple pregnancies and ovarian hyperstimulation syndrome.

2. Follicular/ET monitoring – 

  • Monitoring of the cycle is essential in the stimulated cycle to rule out the possibility of OHSS/  high order multiple pregnancies.
  • If more than 4 mature follicles develop, most Infertility clinics prefer to withhold HCG  injection or abandon the cycle or abstain from intercourse, Alternatively, the treatments cycle or treatments cycle can be converted to IVFor GIFT as appropriate.
  • Ultrasound scans hence do monitoring of follicular development and endometrium with or without blood hormones test.
  • As the dominant follicle reaches > 18 min diameter and endometrium is well-developed HCG injection is given to time insemination.

 

3. Times of Insemination

  • The precise timing of insemination is very tent to fetch a higher success rate.
  • IUI is done either when ovulation is imminent or just after.
  • The method useful to time insemination in a natural cycle are:
  •  Ultrasound scans (Most reliable).
    o Detection of LH sugar in urine/blood (most accurate).
    o Cervical mucus assessment (Not very reliable)
    o Basal body temperature (Least accurate)
  • Insemination is usually performed at 24 to 48 hours after urine LH sugar.
  • For stimulated cycles, insemination is usually performed about 40 hours after HCG  injection.

4. Sperm washing and preparation

  • Male partner produces semen by masturbation or frozen thawed is used.
  • In cases of retrograde ejaculation, sperm is collected from voided urine by centrifugation.
  • Only washed and prepared sperm are used for IUI because near semen may cause several uterine contractions/pains/cramps and even collapse sometime.
  • The aim of washing and preparing sperm:
    o Separate sperm from preparing sperm.
    o Remove bacteria, other debris, and chemical that may infection and irritation.
    o To improve sperm capacitation.

 

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  • Most common.
  • Convenient method
  • Separate good motile Sperms by allowing them to swim up to a large layer of sterile culture medium
  • Procedure involves layering sterile culture medium over Liquefied semen.
  • Sperm swim up into culture medium, Upper part of layered culture medium is removed and centrifuged and pellet is responded in a clean sterile medium.

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Density Gradient Technique:

  • Separate normal Live sperm from seminal plasma and other cells and debris.
  • Procedure Involves pipe ting semen sample on top a density gradient column ( a layer of fluid containing particles that act as filter) and then centrifuged
  • Normal sperm becomes concentrated at the bottom of layer and can then be removed and washed by centrifugation and resuspenstion in clean medium.

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Wash and Centrifugation

  • The procedure involves diluting semen sample with a sterile culture medium and centrifuge. Following which the pellet is resuspended in culture medium and incubated.
  • As per the Cochrane database there is no evidence that technology is superior to other although the trend suggest density gradient is the best.
  • Presence of one million motile sperms after preparation seems to provide a realistic cutoff below which pregnancy rate are decreased.
  • Morphology of sperm is also important and if the preparation of normal sperm falls below 4 present, pregnancy is rarely achieved.
  • “Processed total motile sperm count correlate with pregnancy outcome after IUI” – Ohl DA, Miller DC, University of Michigan school of medicine.
  • The result of the study has demonstrated that the PTMS count independently predicts success with IUI. Alternatives to IUI should be considered for the couple when PTMS count is less than 10 million.

The success rate of Insemination varies considerably between infertility clinics and insane clinic between different couples. Success rate between 5 to 30 present and depend on
many factors like
:

  • Cause of infertility.
  • Endometriosis: Patient with severe endometriosis is not suitable for IUI because of meager success.
  • Male factor infertility: Unstipulated IUI increases pregnancy rate by 2- fold.
  • Stimulated IUI: Increase pregnancy rate by 5- fold.
  • Unexplained infertility
  • Tubal /ovulation factor
  • Female parterre’s age
  • Duration of infertility
  • Sperm quality/ quantity
  • Cycle rank

Complication of IUI:

  • Failure of treatment.
  • The possibility of using wrong semen sample.
  • Infection/bleeding/trauma/Pain
  • No infective salpingitis/allergic reactions
  • Anti-sperm antibodies
  • Multiple pregnancies
  • Abortion/ectopic pregnancy
  • OHSS

Indications for use of Donor Semen for IUI

  • Severe oligo-/astheno-/teratozoospermia (in those not willing for IVF / ICSI)
  • Azoospermia
  • Genetic disorders
  • These are now relative indications as the newer developments in the field of male infertility such as MESA/TESA/TESE male with opportunity for biological parenthood.
  • Donor screening
  • AIM:
    • To prevent disease transmission
    • To increase the chances of pregnancy by selecting appropriate semen parameters.
  • Hence, complete medical and family history or complete physical examination/ appropriate investigations like blood group or typing, urine test, semen analysis (parameters to be judged as per WHO’s recent criteria) is important to rule out transmittable diseases, genetically inherited disorders.
  • In case of attempted sperm banking, the sperm should be checked for good post-thaw recovers and prospective donors should be provided with relevant information and guidelines so that they understand moral/legal implications.

Instructions to Perspective Sperm Donor

  • Not to supply more than 2 samples per week.
  • Semen should be collected on site for it to be fresh at laboratory.

  • They understand the moral/legal implications sample is allowed to liquefy at room temperature.
  • The required volume of freezing medium in thawing.
  • An equal volume of freezing medium is added and mixed slowly drop-wise.
  • The mixture should be placed at 300C for 10 minutes.
  • The tube is kept in the refrigerator at 40C for 90 minutes.
  • Prepared sample is loaded into the cryovial.
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  • The cryovial is identified and removed from the goblet.
  • Identification details on the removed cryovial are confirmed.
  • Vials are placed in the water bath at 370C.
  • Vials are swirled gently for 10 minutes.
  • Complete liquefaction of the sample is confirmed.
  • Contents are transferred into a round-bottomed tube.
  • A quick count and motility study is performed.
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  • As per the study by Cleveland clinical center for advance research in human reproduction, the DI-SQ score (donor nsemination semen quality) Was an effective predictor of pregnancy and live birth outcomes in IUI patients who underwent AI with anonymous DISQ could also be used by sperm banks to help or select donors.

  • Soon after identification of ovulation by TV scan assessment, male partner is instructed to collect semen.
  • After collection semen sample is allowed to liquefy.
  • Rapid semen analysis done to check count and motility.
  • Sperm wash/preparation done by appropriate technique.
  • Patient is given a good pre-procedure counseling about the procedure steps
  • Patient is asked to void urine
  • Placed on an examination table in dorsal or lithotomy position.
  • It is preferable to elevate the foot end of the table.
  • Physician should maintain asepsis throughout the procedure.
  • Vulva and vagina cleaned with warm normal saline.
  • Cuscos bivalved speculum is inserted into the vagina to expose the cervix.
  • Vaginal discharge/cervical mucus should be cleaned with cotton swabs.
  • Prepared and loaded sperm sample is checked for identity.
  • Sperm loaded tuberculin syringe is attached to insemination cannula after removing air carefully.
  • Loaded cannula is inserted into uterine cavity.
  • Sperm gently pushed into the uterine cavity.
  • Pushing air into the uterine cavity should be avoided .
  • Cannula is removed after keeping it in position for 2 to 3 minutes. In foot end elevated position, patient is advised to rest for 10 to 15 minutes

1 DAY VS 2 DAY IUI TREATMENT CYCLES

Two day IUI treatment cycles are more successful than one day IUI cycles when using frozen thawed donor sperm – Matilsky, Geslevich Y, Haernek medical center, Israel. Such studies support the use of two day treatment cycles when using frozen thawed donor sperm while Cochrane database review does not support the difference in pregnancy rates with 1 day vs 2 day IUI treatment cycle especially with fresh semen samples.

With improved treatment options for HIV patients and the increase in their life expectancy, it is not surprising that many HIV patients desire to have children and discuss the available fertility options. Serodiscordant couples have limited options if they wish to have natural conception as sexual intercourse carries a risk of 1 in 500 times of transmitting the virus in semen to the female partner.

The only wholly safe option available to HIV discordant couples is adoption or in case of HIV positive males-sperm donation. Nevertheless, many couples desire genetically related offspring.

IUI forms one of the treatment options to serodiscordant couples willing for conception without seroconversion of uninfected partners.

In a serodiscordant couple, when female partner HIV positive IUI will suffice to prevent horizontal infection transmission. However, when the male partner is positive, sperm washing technique is used to minimize the infection of the healthy partner.

The absence of detectable HIV is verified before insemination using PCR-nucleic acid based sequence amplification assay.

Thus far, worldwide there are >3000 such cycles and 497 pregnancies with over 300 deliveries and no infection of the female partner or infant.

Pregnancy rate per insemination is 14% based on a European experience of more than 2000 insemination. Though current data from European programs suggest sperm washing to be a safety risk reduction option for heterosexual couples wishing to bear a child, CDC in the USA has recommended against insemination of women with semen from men infected from HIV.

“Safety of sperm washing and art outcome in HIV-1 serodiscordant couples”- Italian study in 2007 concluded sperm washing with a program of reproductive counseling was proved to be safe in a large series of 741 serodiscordant couples. The overall pregnancy rate of about 70.3% independent of the procedure used (IUI or IVF) justifies the effort of the medical team in setting up and implementing dedicated centers and individual patient in seeking a safe pregnancy.