Intracytoplasmic Sperm Injection (ICSI)
ICSI is a procedure in which a single sperm is injected directly into an egg, thus sperm and egg interactions involved with normal fertilization are by-passed. ICSI technique is used together with IVF to overcome severe male infertility. ICSI is a micromanipulation technique that was introduced in the early 1990’s and has been successfully applied to the treatment of severe male infertility including suboptimal ejaculate samples, ejaculatory failure, obstructive and nonobstructive causes of azoospermia (complete absence of sperm).
Indications for ICSI:
1. Couples who have had unexplained fertilization failure in a previous IVF cycle.
2. Decreased sperm concentration, providing enough viable sperm can be recovered for injection of eggs.
3. Decreased sperm motility, including totally immotile sperm (e.g. Kartagener’s syndrome), providing sperm are viable.
4. Unusually high percentage of morphologically abnormal sperm, including round- headed sperm (globozoospermia).
5. Complete absence of sperm in the ejaculate due to an obstruction (obstructive azoospermia) caused by conditions such as congenital absence of the vas deferens (CAVD), post-inflammatory obstruction of the epididymis or vas and failed vasectomy reversal. Testicular sperm extraction (TESE) is used to retrieve sperm for ICSI.
6. Complete absence of sperm in the ejaculate due to defective sperm production (non- obstructive azoospermia). Patients who have normal sperm formation in at least some areas of the testis (identified by testicular biopsy), providing enough viable sperm can be retrieved with TESE.
7. Ejaculatory dysfunction caused by retrograde ejaculation (enough sperm are usually recovered from the urine) or paraplegia (electroejaculation or TESE).
8. Immunological factors; antisperm antibodies in female sera, follicular fluid or on sperm caused by vasectomy or genital tract infection.
9. Testicular cancer patients with semen samples frozen prior to treatment.
IVF With ICSI Success Rates and Risks
The ICSI procedure involves stripping cells from around the egg and injecting a needle into the egg. A small percentage of eggs, often the less healthy eggs, may be damaged by these procedures and degenerate (5-10%). Sometimes eggs fail to fertilize normally or arrest at an early stage of development. ICSI pregnancy rates and live birth rates are similar to those achieved with IVF. However, studies have shown that blastocyst formation is reduced compared to IVF cycles, particularly in cases of poor sperm motility and morphology. The arbitrary selection of sperm (rather than relying on the natural fertilization process) has potential for increased risks of genetically abnormal embryos and birth defects including infertility.
Despite general medical acceptance by the ART community, ICSI is still a relatively new procedure. Children born as the result of ICSI are still very young and have not yet reached an age to reproduce. There are possible unknown long-term effects including those that could occur in subsequent generations.
At this time, reports on the risk of congenital malformations associated with ICSI, compared to IVF have yielded conflicting results. A recent (2005) multi-center study based on data from 5-year-old children, suggests that ICSI is associated with a relatively small (4.2%) increased risk of certain major congenital anomalies. There also appears to be a higher prevalence of sex chromosome abnormalities in ICSI children compared to those conceived with IVF (0.2% versus 1% in ICSI offspring). Whether this is due to the ICSI procedure itself or to an increased rate of chromosome abnormalities in sperm from some infertile men is not clear. There are also some studies that report a higher incidence of a congenital malformation called hypospadias (urethra opening on underside of penis) in babies conceived through ICSI.
Because some causes of male infertility are familial, and are related to genetic defects (e.g. Y-chromosome deletions) male offspring may inherit fertility problems. Therefore, patients with non-obstructive azoospermia or severe oligospermia (low sperm counts), who are likely candidates for genetic causes of infertility, should consider genetic counseling and karyotyping prior to ICSI.
In some cases, after ICSI embryos are co-cultured with follicular cells collected from the follicles during the egg aspiration to provide extra nourishment and remove any embryo-toxic factors that may be present.
What is a Fertilization Check?
A laboratory procedure performed on the day after egg retrieval to determine which eggs have fertilized normally and can be used for embryo development and transfer.
To check for fertilization of oocytes (eggs), the fertilized oocytes must be examined 16-20 hours after insemination for the presence of two round nuclear structures, the male and female pronuclei (PN), formed by the sperm and egg. Fertilized oocytes (“zygotes”) must be distinguished from unfertilized and abnormally fertilized oocytes. Cells surrounding the eggs are carefully dissected away to allow clear visualization of the egg. Pronuclei must be scored within the appropriate time span, before they merge and are no longer visible (during a phase called “syngamy”). This ensures only normal zygotes with two pronuclei (2PN’s) are cultured for embryo transfer or cryopreserved.
Abnormally fertilized oocytes are observed when eggs undergo development without fertilization (1PN) or are fertilized by two (or more) sperm (3PN). Such abnormal oocytes cannot be used for attempting to initiate a pregnancy since they are genetically abnormal.
Embryo Grading and Selection for Transfer
What is Embryo Grading?
Assigning a grade to each embryo to identify the best quality embryos that are then selected for embryo transfer or cryopreservation.
Selection criteria or grading systems must be applied for all cleavage stages from day 2-4 to allow selection of the most viable embryos. Embryo development is evaluated approximately every 24 h. Slow dividing, nondividing (arrested) or fragmenting embryos are selected against. Compacting embryos on day 3 that have closely apposed cell membranes are selected for.
The quality of each embryo is assessed using the following grading system:
Grade A: Even, equally sized spherical cells (blastomeres) with no cellular fragmentation.
Grade B: Embryos have uneven or irregularly shaped blastomeres and less than 10% fragmentation of blastomeres.
Grade C: Embryos have up to 25% fragmentation. Blastomeres appear viable (although may be granular).
Grade D: Embryos have 25-50 % fragmentation. Blastomeres appear viable (although may be granular).
Grade E: Embryos are considered non-viable with lysed, contracted or dark blastomeres.
In selecting embryos for an embryo transfer, one normally chooses the most viable embryos, those that are rapidly (or normally) dividing with little if any fragmentation. Therefore, those embryos that have reached the most advanced developmental stage and have the least cellular fragmentation (Grades “A” and/or “B”) are selected for transfer. Blastocysts are selected for transfer based on the rate of cell division, cavity expansion and formation of the inner cell mass (the central embryonic portion).
Cytoplasmic Transfer involves the injection of a small amount of cytoplasm (the viscous semi fluid inside an egg), taken from a donor egg, directly into the patient’s eggs. The transferred cytoplasm is thought to contain components missing or abnormally functioning in the recipient egg. The aim of cytoplasmic transfer is to overcome any deficiencies that may exist in the cytoplasm of an egg while retaining the patient’s genetic material.
Early studies on cytoplasmic transfer in the monkey demonstrated that transfusion of cytoplasm from a mature egg into immature eggs conveyed developmental competence to some immature eggs. The cytoplasmic factors transferred may be specialized proteins, messenger ribonucleic acid (mRNA), or mitochondria – units that generate energy for the egg which may enhance the quality of embryos. Unlike embryos from donor eggs, the embryos produced from cytoplasmic transfer carry the mother’s genes.
This procedure is particularly suited to patients that have a history of poor embryo quality (i.e. fragmentation, slow cleavage or arrested development) and failed implantation, but who make a reasonable number of eggs. Patient’s are typically in their 30’s. The procedure is usually not recommended for women over 40 since the main cause of implantation failure at this age is a genetic abnormality (for example, a missing or extra chromosome), and the cytoplasmic transfer does not alter the genetic makeup of the egg (nucleus).
The procedure is combined with ICSI. Thus, an immobilized sperm is injected along with the donor cytoplasm. Since the amount of cytoplasm used for injection of one egg is only about 5% of the volume of the donor egg, each donor egg may be used for several recipient eggs. Excess donor eggs may be fertilized with the partnerÕs sperm and used for embryo transfer, in the event that there are not enough good embryos from the patient’s eggs, or cryopreserved (of course, these will have the egg donor’s genetic material).
The first human pregnancy following cytoplasmic transfer was reported in 1997. For this procedure, oocyte donor and patient were simultaneously stimulated. Recent success has been reported using cytoplasm from cryopreserved donor eggs eliminating the need for synchronization between donor and patient, however, further studies are needed to determine whether the transfer of frozen material is as beneficial.
View also our information in the lastest ICSI Research papers.
Our fertility specialists at The Reproductive Sciences Center, or RSC, are conveniently located in La Jolla California in San Diego County. We have worked hard to create and maintain our reputation as the first-rate San Diego fertility clinic and sciences center. RSC has become synonymous with comprehensive and successful female and male infertility treatment, egg donor programs, and surrogacy options, in vitro fertilization, ICSI and more.
While we have provided services to hundreds of patients throughout the Temecula, Murrieta, La Jolla, Riverside, San Bernardino and Encinitas areas, we also help many people from across the United States, Europe, Australia , Asia, Africa and the Americas who make us their final destination for treatment with infertility in San Diego. We lead the area as one of the leading fertility centers in the world.
Our fertility center has long been established as having one of the highest fertility success rates in the world, and with more than 75 years of combined medical training, experience, and ongoing continuing education, our fertility specialists set the bar for the industry. Our medical director and leading fertility doctor is one of the most well-respected experts in the world.
Successful fertility treatment in San Diego is only possible with the best fertility specialists and staff in OrangeCounty. We have been providing unsurpassed treatment for infertility in San Diego, including IVF (In Vitro Fertilization) and other San Diego fertility services in La Jolla for more than a decade.
Some of our successful options for fertility treatment in San Diego include natural fertility treatment, advanced fertility treatment, IUI (Intrauterine Insemination), San Diego In Vitro Fertilization (IVF), ICSI for severe male infertility, genetic testing, embryo donation, blastocyst transfers, assisted hatching, and more. We are the top professionals of fertility options for women with cancer and fertility options for men with cancer in San Diego as well.
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