Inseminations (IUIs)


Ovarian Hyperstimulation


In Vitro Fertilization
  • Indications for IVF
  • Patient Selection

  • Patient Preparation
  • Cost
  • Medication Protocols
  • Egg Retrieval

  • IVF Versus GIFT
  • Hatching of Embryos
  • In Vitro Maturation of

  • Genetic Concerns with

  • Embryo Co-Culture

  • Transfer Cellular

  • Implantation

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Men who were previously incapable of reproduction may now be able to produce children using the assisted fertilization technique called Intracytoplasmic Sperm Injection (ICSI). The success of this technique appears to be largely independent of the quality of the sperm used (as long as the sperm is alive) since virtually any living sperm placed into the egg’s cytoplasm will initiate (induce) oocyte (egg) activation and the formation of (male and female) pronuclei.

Pregnancies with ICSI have been reported using mature ejaculated sperm that is otherwise fertilization incapable, epididymal sperm aspirated during MESA (microscopic epididymal sperm aspiration) or PESA (percutaneous epididymal sperm aspiration), and testicular sperm (that may have a variety of spermatogenic or chromosomal abnormalities) obtained by direct tissue biopsy of the testis. At the best IVF centers in the USA, there does not appear to be a significant difference in the pregnancy rates when comparing couples that undergo ICSI with ejaculated sperm versus retrieved sperm.

There is an association between severe oligospermia (including azoospermia) and either Y chromosome genetic defects (microdeletions and anomalies) or other significant chromosomal or genetic abnormalities. ICSI has the ability to dramatically improve the chances for these genetic mutations (defects) to survive within the overall human gene pool. Therefore, it is necessary to address the clinical importance of these genetic abnormalities (that are being helped to survive) within the population.

It is my current recommendation that all men offered IVF with ICSI specifically to treat a severe male factor abnormality have a chromosome analysis performed. Also, if there is a congenital obstruction within the outflow tract I recommend cystic fibrosis mutation screening (of cellular DNA).

Men requiring ICSI for assisted fertilization have a greater than normal chance of carrying a significant chromosomal abnormality and (if an abnormality is identified) this can be addressed with a genetic counselor prior to bearing children. Types of genetic abnormalities (that might be identified) and counseling (suggestions that may be offered) include:

(1) Balanced autosomal (non sex chromosome) structural abnormalities (such as a translocation, inversion, or deletion):

Couples should be informed that with balanced structural abnormalities there is an increased chance of miscarriage (although clinically miscarriage occurs less frequently than theoretically suggested by the genetic principle of independent assortment of chromosomes) and possibly also a reduced chance of pregnancy. A liveborn may carry the same abnormality (which may also result in reduced reproductive potential for these offspring), no abnormality (genetically normal) or a more serious chromosomal imbalance (possibly resulting in reduced life expectancy, mental retardation, or birth defects for a liveborn).

(2) Structural abnormality (such as a translocation, inversion or deletion) of (one of) the sex chromosomes

Azoospermic or severely oligospermic men may have an associated abnormality of the Y chromosome, including (micro-) deletions of the distal portion of the long arm (often starting at Yq11), which is thought to contain the genes regulating spermatogenesis (including the “azoospermia factors” = AZF and “deleted in azoospermia” genes = DAZ).

Couples should be informed that there is a chance of transmitting the abnormality to a liveborn, which can then result in (eventual) reduced reproductive potential for that child or possibly birth defects (possibly anomalies that are not affecting the father).

(3) Abnormal number (aneuploidy) of the sex chromosomes

47 XXY (an extra X chromosome) results in Klinefelter’s syndrome, which often results in degenerate (atrophic and hyalinized) testes that have few or no sperm cells (germ cells). Sperm retrieved directly from testes tissue specimens (of Klinerfelter’s syndrome patients) have been used with ICSI (with generally a reduced fertilization rate compared to control sperm) to achieve pregnancies.

Couples should be informed that preimplantation genetic diagnosis of the fertilized eggs (preimplantation embryos) is technically possible (and has been done) for some genetic (chromosomal) abnormalities but is not universally available. If not performed, there is a significant chance of transmitting this sex chromosome abnormality to the offspring.

(4) Autosomal (non sex chromosome) gene abnormalities

Cystic fibrosis is one of the most common (autosomal recessive) genetic diseases in the Caucasian population, with a carrier frequency of 1 in 25 (disease frequency of 1 in 2500). More than 600 gene mutations have been associated with this disorder. Cystic fibrosis gene mutations (in men who are either affected or carriers) are strongly associated with obstructive azoospermia (usually as a result of bilateral congenital absence of the vas deferens = CAVD). The literature suggests that 66% (2 of 3) men with obstructive azoospermia due to CAVD will carry one or more cystic fibrosis gene mutations.

Couples should be informed that cystic fibrosis testing is strongly suggested for men with CAVD (or obstructive azoospermia) and if a mutation is identified then testing the female partner and expert genetic counseling is advised.

I strongly suggest that either chromosome analysis and cystic fibrosis gene mutation screening (depending on the particular situation) be recommended for men with severe male factors (prior to ICSI). Having said this, it should also be noted that the available literature (in 2001) concerning obstetric outcomes of pregnancies resulting from IVF with ICSI is reassuring. In about 1,450 pregnancies after ICSI the miscarriage rate ranged from about 25 to 33% (for pregnancies using ejaculated, epididymal and testicular sperm) and no differences were observed in the incidence of birth defects (congenital abnormalities) comparing these children with controls (the baseline rate of birth defects in the general population). Also, there were no differences in observed birth defects that depended upon the source of the sperm that was used (ejaculated, epididymal or testicular).

Men with a normal 46,XY karyotype and a severe male factor requiring ICSI should be counseled that they may carry a micro-deletion in AZF (on the long arm of the Y chromosome) that is identifiable using DNA screening (of blood cells) and that if this genetic abnormality is passed on (as it is to all sons) it probably will result in a similar insult to (the son’s) fertility.

The available literature on pregnancies resulting from IVF and ICSI also suggests that there is a greater chance of “new” (de novo) sex chromosome aneuploidies (abnormal number of sex chromosomes) in these fetuses. These “new” abnormalities would therefore not be able to be identified with chromosome analysis of the biological parents. The overall increase in incidence (frequency rate) is thought to increase from about .15% (general population) to about .85% (ICSI couples), with both (therefore) occuring in less than 1 in 100 couples. Because of this suggested increase, routine prenatal diagnosis of all ICSI pregnancies should be considered. When we have more information on this concern, routine prenatal diagnosis may become recommended.

All children born from parents with a known chromosomal or genetic abnormality should be screened for that same abnormality. Also, screening all ICSI children with at least a chromosome analysis is a good idea, primarily to add important data to the (overall) genetic information available on these offspring.

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