ASSISTED REPRODUCTION

Assisted Reproduction facilitates sperm-egg interaction and, therefore, improves the likelihood of fertilization and pregnancy in infertile couples

 

Assisted Reproduction Techniques

 

Intrauterine insemination.

IUI alone is not an effective treatment for male factor infertility. Recent techniques of ovarian stimulation with conjunction with IUI, however, significantly improved success rate of IUI in patients with male factor infertility. Since greater number of oocytes present after ovarian stimulation, the chances of sperm-egg interaction are higher.

IUI is most effective in couples with " cervical factor infertility" indicated with poor postcoital tests. In general, men are considered candidates for IUI if all male factors have been corrected or unexplained infertility is suspected. Severe abnormalities in semen parameters indicated low success rates for IUI. Worse prognosis for IUI correlated with poor sperm motility. Although IUI has been attempted with sperm count as low as 190.000 motile seprm, the most IUI pregnancies were documented with more than 1x10motile sperm in the specimen. No more than 6 cycles of IUI are recommended since no pregnancies are usually achieved beyond 4-5 cycles of IUI.

Ovarian hyperstimulation is achieved using Clomiphene citrate, Pergonal or Metrodin (by increasing FSH) with subsequent production of large number of oocytes. Semen specimen, collected by masturbation, washed from seminal fluid and processed with Percoll gradient or swim-up technique. Motile sperm are collected and inserted into the uterine cavity via cervical canal under direct vision using a fine "Tomcat" catheter.

In some cases, preliminary sperm function tests may be considered to assess sperm-egg interaction in vitro. If results of these tests are poor, the couple should be advised of other methods of Assisted Reproduction.


In -Vitro Fertilization.

Although male factor infertility was considered a contraindication to IVF, fertilization and live births are possible with abnormal sperm. The rates of fertilization with poor quality sperm are significantly lower than sperm from otherwise healthy men, even when sperm are placed directly with oocytes in culture. In addition, the needed concentration of 100000 sperm/oocyte cannot be easily obtained from patients with male factor infertility.

The technique of IVF includes down regulation of women's pituitary function with GnRH agonists during the preceding luteal phase followed by controlled ovarian hyperstimulation using FSH. After follicles development confirmed by transvaginal ultrasound and serial measurement  of serum estrogen and progesterone levels, final oocytes maturation is induced with IM injection of hCG. Transvaginal oocyte retrieval is performed under ultrasound guidance.

Processed and washed free of seminal fluid sperm in concentration, preferably, 100000 or more per oocyte are used to inseminate oocyte. In case of successful fertilization embryo are incubated in vitro for 2-3 days to divide up to 8-cell stage and, then, transfer back to the uterus. Usually up to 4 embryos may be transferred.


IVF with micromanipulation.

Micromanipulation involves mechanical alteration of the oocyte in vitro to increase the chance of fertilization of the oocyte by sperm.

  1. PZD- partial zona dissection, consists of piercing of zona pellucida, an acellular layer surrounding the oocyte which serves as a major barrier to sperm penetration. Then regular IVF procedure is performed.
  2. SuZI- subzonal injection, involves direct placement of sperm into the perivitelline space between zona pellucida and oocyte, completely bypassing the zona pellucida.

Intracytoplasmic sperm injection with superior fertilization and pregnancy rates completely replaced PZD and SuZI for the treatment of male factor infertility. This is the most aggressive mechanical micromanipulation technique which involves direct microinjection of a single sperm into the cytoplasm of the oocyte. ICSI surmounts the last barrier of the oocyte, the oolemma. Since first successful ICS procedure performed by Palermo et al. in 1993, this technique has gained the worldwide acceptance because it almost completely bypasses the male factor infertility. The procedure requires only 1 viable sperm per oocyte for injection and basically independent of sperm quality. Refinement and widespread use of sperm retrieval techniques enables use ejaculated as well as epididymal and testicular sperm from patients with severe male factor infertility and azoospermia. Fertilization rates were shown to be independent from female factors, but implantation and pregnancy rates are significantly lower in couples with maternal age above 34 ( 49%, 23% and 6% respectively at <34, 35-39 and >40 years)

ICSI can cause significant mechanical damage to oocyte. Rates of oocyte loss reported to be 7-14%.

Indications for ICSI (Schlegel PN, Girardi SK, 1997) include but not limited to:

  1. sperm concentration less than 2 x106 sperm/cc
  2. sperm motility <5%
  3. Strict criteria normal morphology <4%
  4. Only surgically retrieved spermatozoa available
  5. Previous IVF cycles are unsuccessful

 

Technique of ICSI:

Ovarian stimulation for oocyte retrieval is performed according to the protocol of IVF. Thirty-six hours after induction of ovulation with 10000I.U hCG, oocytes are retrieved by ultrasound-guided puncture of follicles. Only mature oocytes of metaphase II are used for the injection. Metaphase II oocytes are identified by the presence of extruding of the first polar body. The microinjection performed with an injection pipette under the microscope equipped with micromanipulator, after oocyte is stabilized with holding micropipette. The single sperm is injected head first after the micropipette is pushed through zona pellucida and oolemma at the 3 o'clock position.

 

 

Risk of Assisted Reproduction

  1. Ovarian hyperstimulation syndrome- 3-4% (0.1-0.2% in severe form)
  2. massive ovarian enlargement, ovarian torsion, ascitis, peritoneal irritation with follicular

    rupture, oliguria, hypercoagulability and, sometimes death

  3. Bleeding, intestinal perforation, pelvic infection from the retrieval procedure-0.3-3%
  4. Spontaneous abortion-25% ( 10-16% for ICSI cycle)
  5. Ectopic pregnancies- 3-5.5%
  6. Multiple gestations- 22% with IVF, 44-46% with ICSI

Present data do not suggest increased risk of genetically transmitted diseases in children born after ICSI. Major malformations were found in a range of 2.4%, which is comparable to figures known from children born after IVF or natural conception. Nevertheless, patients need to be counseled before any treatment on the basis of the available data about the risk of transmitted chromosomal defects, de-novo chromosomal aberrations and fertility problems to the offspring.

 

Results (average clinical pregnancy rates)* 

IUI**

  

IVF

  

ICSI

  
  

5-20%

 

14-20%

  

25-30%

 

  • *Results depend on IVF center. Each center's results must be available to the couple before procedure.
  • ** With ovarian hyperstimulation

 

 Selected Bibliography

  

 

 

  1. Schlegel PN., Girardi SK. In vitro fertilization for male factor infertility. J Clin Endocr Metab. 1997;82:709-716
  2. Foresta C., Rosato M., Garolla A., Ferlin A. Male Infertility and ICSI: are there limits? Hum Reprod 1996;11:2347-2348
  3. Kupker W., Al-Hasani S., Diedrich K. Assisted Fertilization-treatment of severe male subfertility Andrologia 1996;28( suppl 1):37-42
  4. Silber SJ., Nagy ZP., Liu J., Godoy H., Devroey P, Van Steirteghem AC. Conventional in-vitro fertilization versus intracytoplasmic sperm injection for patients requiring microsurgical sperm aspiration. Hum Reprod 1994;9:1705-1709
  5. Palermo G., Joris H., Devroey et al. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992;340:17
  6. Palermo GD., Cohen J., Alikani M., Adler A., Rozenwaks Z. Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility. Fertil Steril 1995; 63:1231-1240.
  7. Palermo GD, Colombero LT, Schattman GL, Davis OK, Rozenwaks Z. Evolution of pregnancies and initial follow-up of newborn delivered after intracytoplasmic sperm injection. JAMA 1996; 276:1893-1897
  8. Centola GM. Successful treatment of Severe Oligospermia with Sperm Washing and intrauterine Insemination. J Androl 1997;18:448-453
  9. Hamberger L. Lundin K. Sjogren A. Soderlund B. Indications for intracytoplasmic sperm injection. HumanReproduction. 1998;.Vol 13(SUPPL. 1): 128-133.

 

     

 

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