Sunday, December 23, 2007
Saturday, December 22, 2007
Friday, December 21, 2007
Thursday, December 20, 2007
Klinefelter's Syndrome
Klinefelter's Syndrome is a genetic disorder characterized by infertility, abnormal male breast tissue development (gynecomastia) and small, firm testes. It is the most common cause of azoospermia (no sperm production). Klinefelter's Syndrome is caused by an abnormal number of sex chromosomes. Whereas a normal male genetic make-up includes one "X" chromosome and one "Y" chromosome, in patients with Klinefelter's Syndrome, an extra "X" chromosome is present, resulting in three (XXY) sex chromosomes. Thought at one time to be hopelessly infertile, it has been found that these men can have small amounts of sperm production occuring within the testicle. Our Center has successfully recovered sperm in men with this disorder who have gone on to father normal, healthy children. It is important that all men with very low or absent sperm counts be tested for Klinefelter's Syndrome before offering IVF and ICSI.
Wednesday, December 19, 2007
Glow-in-the-dark cats can help with gene therapy in the future
Last week South Korean scientists reported that they had successfully cloned cats whose genes had been altered so that they 'glow-in-the-dark' under UV light. It is hoped that the ability to alter genes in this way may help scientists discover how to make more complicated gene changes, allowing them to artificially create animals with human genetic diseases for carrying
out research into new treatments or cures. The discovery, made by researchers at Gyeongsang National University, is
significant because - with a duo of glow-in-the-dark cats as living proof - it marks the first time that scientists have successfully altered the genetic code of cloned cats. 'This technology can be applied to cloned animals suffering from the same diseases as humans', Kong Il-keun, who led the research, told AFP. 'It will also help develop stem cell treatments', he said, noting that cats have some 250 kinds of genetic diseases that affect humans, too. The technology can also help clone endangered animals like tigers, leopards and wildcats, Kong said.
The three cats - all Turkish Angoras - were created by taking skin cells from donor female cats and using a harmless virus to insert the gene for 'Red Fluorescent Protein' (RFP) into the nucleus of each cell, thereby altering its genetic code. The nuclei of the donor female's egg cells were then removed and replaced with the gene-altered nuclei of the skin cells, to
create a cloned embryo.
To find out if they had been successful in their attempt at creating gene-altered embryos, the researchers implanted the cloned embryos back into the donor females to show that the cloned kittens did indeed glow-in-the-dark, indicating that they expressed RFP in their skin. The three cats were reportedly born by Caesarian section in January and February of this year. Although one was a stillbirth, the scientists claim that it too had expressed the RFP protein throughout its body, indicating
that their methods had worked in all three cats. The scientists hope that the ability to create animals that mimic human diseases can speed up efforts to find treatment and drugs by allowing scientists to study animals and conduct experiments that are not possible with human patients. With the current price tag of tens of thousands of dollars to clone a single cat,
glow-in-the-dark pets are unlikely to become a commercial venture in the near future.The discovery was announced last week in a press release by the government managed Korea.net news service, however peer reviewed papers and
replications of the same experiment will be eagerly awaited to prove the validity of these results.
Tuesday, December 18, 2007
UK Couple to Test Embryos for high Cholesterol disorder
UK doctors are expected to receive permission to help a couple avoid passing on a hereditary condition that causes very high blood cholesterol to their children, according to the Times. The newspaper reports that a team lead by Paul Serhal, of University College London, will be granted a license by the Human Fertilisation and Embryology Authority (HFEA) this week. This will enable them to use preimplantation genetic diagnosis (PGD) to select embryos free from the gene mutation that causes both the mild and severe forms of familial hypercholesterolaemia (FH). One in 500 people in the UK has inherited the mild form of FH, although many of those with the condition are thought to remain undiagnosed. The condition can increase the risk of a heart attack in men under fifty by ten-fold. However, if treated through diet, exercise, lifestyle changes and
- in some cases - with statin drugs, this risk can be drastically reduced. FH also increases the risk of strokes and blood vessel failure, which can lead to limb amputations. In contrast to the mild form of the condition, which affects people who inherit just one copy of the faulty gene, there is also a severe form of FH that affects children who inherit a 'double dose' of the mutation. This 'homozygous' form of the disease leads to very high levels of cholesterol from the age of around five, and can often cause death in childhood. Unlike the mild form, it does not always respond well to treatment with statins or other drugs.
The couple seeking treatment at UCL both have mild FH, which they discovered only after having a daughter with the homozygous, severe form of the disease. There is a 25 per cent risk that any subsequent child will also inherit the severe form of FH, who, unlike their first child, may not respond well to treatment. There is also a 50 per cent chance that they will
pass on the mild form of the condition to their next and subsequent child, and a 25 per cent chance that each will be unaffected.
PGD involves taking a single cell from a 2-4 day old IVF embryo, performing a genetic or chromosome test on that cell, and then returning one or two unaffected embryos to the womb. In the UK, the use of PGD is regulated by the HFEA, which licenses the procedure on a case-by-case basis. The couple approached Mr Serhal after learning that his clinic offered PGD for hereditary breast cancer. If the procedure is successful, then the couple will be able to select one or more unaffected embryos to implant. However, if there are no unaffected embryos, then the couple will have to decide whether or not to select embryos that have the milder form of FH. Mr Serhal told the Times: 'This obnoxious disease can cause cardiovascular accidents at a very young age. Ideally, we will find embryos with no FH genes, but it is possible we will not and it will be up to the patients to choose. Some people would think twice about using embryos that they know have a risky gene, and others would say you shouldn't screen out a condition that can be managed so people can live with it. It will be an awkward choice'.
- in some cases - with statin drugs, this risk can be drastically reduced. FH also increases the risk of strokes and blood vessel failure, which can lead to limb amputations. In contrast to the mild form of the condition, which affects people who inherit just one copy of the faulty gene, there is also a severe form of FH that affects children who inherit a 'double dose' of the mutation. This 'homozygous' form of the disease leads to very high levels of cholesterol from the age of around five, and can often cause death in childhood. Unlike the mild form, it does not always respond well to treatment with statins or other drugs.
The couple seeking treatment at UCL both have mild FH, which they discovered only after having a daughter with the homozygous, severe form of the disease. There is a 25 per cent risk that any subsequent child will also inherit the severe form of FH, who, unlike their first child, may not respond well to treatment. There is also a 50 per cent chance that they will
pass on the mild form of the condition to their next and subsequent child, and a 25 per cent chance that each will be unaffected.
PGD involves taking a single cell from a 2-4 day old IVF embryo, performing a genetic or chromosome test on that cell, and then returning one or two unaffected embryos to the womb. In the UK, the use of PGD is regulated by the HFEA, which licenses the procedure on a case-by-case basis. The couple approached Mr Serhal after learning that his clinic offered PGD for hereditary breast cancer. If the procedure is successful, then the couple will be able to select one or more unaffected embryos to implant. However, if there are no unaffected embryos, then the couple will have to decide whether or not to select embryos that have the milder form of FH. Mr Serhal told the Times: 'This obnoxious disease can cause cardiovascular accidents at a very young age. Ideally, we will find embryos with no FH genes, but it is possible we will not and it will be up to the patients to choose. Some people would think twice about using embryos that they know have a risky gene, and others would say you shouldn't screen out a condition that can be managed so people can live with it. It will be an awkward choice'.
Monday, December 17, 2007
Sperms & The Laboratory
Laboratories performing sperm "counts", in general, vary in the details that they provide the physician requesting the "count". A general sperm count as part of a fertility evaluation should include the total density or count (20 million per ml or above), and the motile density (8 million per ml or higher). The motile density is perhaps the most important part of the semen analysis, as it reports the total number of sperm thought capable of progressing from the site of sperm deposition to the site of fertilization. This value is essential in both allowing a determination regarding whether or not a semen analysis is "normal", as well as in providing prognostic information should advanced reproductive medical assistance be required. (Numbers in italics are what "normal" values should be.)
Definitions of "abnormal" counts:
• Polyzoospermia: Excessively high sperm concentration.
• Oligozoospermia: Sperm count less than 20 million/ml
• Hypospermia: Semen volume < 1.5 ml
• Hyperspermia: Semen volume > 5.5 ml
• Aspermia: No semen volume
• Pyospermia: Leukocytes (germ fighter cells) present in semen
• Hematospermia: Red blood cells present in semen
• Asthenozoospermia: Sperm motility < 40%
• Teratozoospermia: > 40% of sperm seen are of abnormal form
• Necrozoospermia: Nonviable ("dead") sperm
• Oligoasthenozoospermia: Motile density < 8 million sperm/ml
Sperm Morphology (Shape and Appearance)
The evaluation of sperm size, shape and appearance characteristics should be assesed by carefully observing a stained sperm sample under the microscope. The addition of colored "dyes" (stains) to the sperm allow the observer to distinguish important normal landmarks (characteristics) as well as abnormal findings. Several methods of staining sperm are used, and the method employed should be one with which the examiner is comfortable and experienced.
Several different shapes or forms of human sperm have been identified and characterized. These forms fall into one of four main categories: normal forms, abnormal head, abnormal tail and immature germ cells (IGC).
Normal forms
Normal sperm have oval head shapes, an intact central or "mid" section, and an uncoiled, single tail.
Abnormal heads
Many different sperm head abnormalities may be seen. Large heads (macrocephalic), small heads (microcephalic) and an absence of identifiable head are all seen in evaluations. Tapering sperm heads, pyriform heads (teardrop shape) and duplicate or double heads have been seen. Overall (gross) abnormalities in appearance may be termed "amorphous" changes.
Abnormal tails
Coiling and bending of the tail are sometimes seen. Broken tails of less than half normal length should be categorized abnormal. Double, triple and quadruple tails are seen and are abnormal. Cytoplasmic droplets along the tail may indicate an immature sperm.
Immature germ cells (IGC's)
White blood cells (WBC's, germ fighters) in the semen should rarely be seen. It is very difficult to distinguish between an immature germ cell and a WBC. Because the presence of WBC's in the semen (pyospermia) can be a serious concern, if a report of "many IGC's" is delivered, it becomes very important to assure that these cells are not, instead, WBC's.
Sperm "Motility" (Movement)
Sperm motility studies identify the number of motile (moving) sperm seen in an ejaculate specimen. Here again, as in many other sperm studies, many laboratories use "normal" values that are out of date and inaccurate. Many labs will assess sperm motility upon receipt of the specimen, and again at hourly time intervals for four to twenty four hours. It is well known that sperm motility is a temperature dependent sperm function, so the handling and processing of specimens is critical. It is for this reason that we, except in very rare instances, require that specimens be evaluated only in a laboratory such as our own, where we are able to tightly control laboratory conditions. We have found the repeated testing of sperm over time for motility adds little to the evaluation of motility over the initial sperm motility assessment. Sperm are known not to survive well for extended periods of time in semen, and in nature, sperm very rapidly leave the semen to enter the cervical mucus. Many laboratories consider "normal" sperm motility to be 60% or greater. Our own studies, in agreement with many others have found men with 50% or greater sperm motility to be "normal".
Asthenozoospermia
Decreased sperm motility. If found to be present, exam should be repeated to assure that laboratory conditions did not cause the problem. Frequent causes: abnormal spermatogenesis (sperm manufacture), epididymal sperm maturation problems, transport abnormalities, varicocele. These conditions should all be looked for if sperm motility is repeatedly "low".
Necrozoospermia
A total absence of moving sperm. It is vital, if sperm are seen, but are not moving, to carry out studies (vital stains) to see if the sperm seen are alive. It is possible to have sperm with normal reproductive genetics that are deficient in one or several of the factors necessary to produce motility. We have achieved several successful pregnancies employing microinjection of healthy, non motile sperm directly into the egg (ICSI).
Chemical and Biochemical Semen Characteristics
Semen acid-base balance (pH)
The pH of semen is measured using a specially treated paper blot that changes color according to the pH of the specimen that it is exposed to. The pH of normal semen is slightly alkaline ranging from 7.2 to 7.8. Prostatic secretions are acidic while the secretions of the seminal vesicles are alkaline. Therefore, alterations in pH may reflect a dysfunction of one or both of these accessory glands. The pH of semen has not been generally found to have a major influence on a man's fertility potential.
Color and Turbidity
Semen is normally translucent or whitish-gray opalescent in color. Blood found in semen (hematospermia) can color the semen pink to bright red to brownish red. The presence of blood in semen is abnormal and should be reported. The presence of particles, nonliquified streaks of mucus or debris requires further evaluation.
Liquefaction
Semen is normally produced as a coagulum. The specimen will ususally liquify within 30 minutes. The failure to liquify within one hour is abnormal. Excellent methods for correcting this problem in the laboratory are available.
Viscosity
Nonliquefaction and excessive viscosity are two separate conditions. Viscosity is measured after complete liquefaction has occured. Viscosity is considered "normal" if the liquefied specimen can be poured from a graduated beaker drop by drop with no attaching agglutinum between drops. The role of hyper (excessive) viscosity is being studied, but it seems possible that htis condition may interfere with the ability of sperm to travel from the site of deposition into the cervix or uterus.
Definitions of "abnormal" counts:
• Polyzoospermia: Excessively high sperm concentration.
• Oligozoospermia: Sperm count less than 20 million/ml
• Hypospermia: Semen volume < 1.5 ml
• Hyperspermia: Semen volume > 5.5 ml
• Aspermia: No semen volume
• Pyospermia: Leukocytes (germ fighter cells) present in semen
• Hematospermia: Red blood cells present in semen
• Asthenozoospermia: Sperm motility < 40%
• Teratozoospermia: > 40% of sperm seen are of abnormal form
• Necrozoospermia: Nonviable ("dead") sperm
• Oligoasthenozoospermia: Motile density < 8 million sperm/ml
Sperm Morphology (Shape and Appearance)
The evaluation of sperm size, shape and appearance characteristics should be assesed by carefully observing a stained sperm sample under the microscope. The addition of colored "dyes" (stains) to the sperm allow the observer to distinguish important normal landmarks (characteristics) as well as abnormal findings. Several methods of staining sperm are used, and the method employed should be one with which the examiner is comfortable and experienced.
Several different shapes or forms of human sperm have been identified and characterized. These forms fall into one of four main categories: normal forms, abnormal head, abnormal tail and immature germ cells (IGC).
Normal forms
Normal sperm have oval head shapes, an intact central or "mid" section, and an uncoiled, single tail.
Abnormal heads
Many different sperm head abnormalities may be seen. Large heads (macrocephalic), small heads (microcephalic) and an absence of identifiable head are all seen in evaluations. Tapering sperm heads, pyriform heads (teardrop shape) and duplicate or double heads have been seen. Overall (gross) abnormalities in appearance may be termed "amorphous" changes.
Abnormal tails
Coiling and bending of the tail are sometimes seen. Broken tails of less than half normal length should be categorized abnormal. Double, triple and quadruple tails are seen and are abnormal. Cytoplasmic droplets along the tail may indicate an immature sperm.
Immature germ cells (IGC's)
White blood cells (WBC's, germ fighters) in the semen should rarely be seen. It is very difficult to distinguish between an immature germ cell and a WBC. Because the presence of WBC's in the semen (pyospermia) can be a serious concern, if a report of "many IGC's" is delivered, it becomes very important to assure that these cells are not, instead, WBC's.
Sperm "Motility" (Movement)
Sperm motility studies identify the number of motile (moving) sperm seen in an ejaculate specimen. Here again, as in many other sperm studies, many laboratories use "normal" values that are out of date and inaccurate. Many labs will assess sperm motility upon receipt of the specimen, and again at hourly time intervals for four to twenty four hours. It is well known that sperm motility is a temperature dependent sperm function, so the handling and processing of specimens is critical. It is for this reason that we, except in very rare instances, require that specimens be evaluated only in a laboratory such as our own, where we are able to tightly control laboratory conditions. We have found the repeated testing of sperm over time for motility adds little to the evaluation of motility over the initial sperm motility assessment. Sperm are known not to survive well for extended periods of time in semen, and in nature, sperm very rapidly leave the semen to enter the cervical mucus. Many laboratories consider "normal" sperm motility to be 60% or greater. Our own studies, in agreement with many others have found men with 50% or greater sperm motility to be "normal".
Asthenozoospermia
Decreased sperm motility. If found to be present, exam should be repeated to assure that laboratory conditions did not cause the problem. Frequent causes: abnormal spermatogenesis (sperm manufacture), epididymal sperm maturation problems, transport abnormalities, varicocele. These conditions should all be looked for if sperm motility is repeatedly "low".
Necrozoospermia
A total absence of moving sperm. It is vital, if sperm are seen, but are not moving, to carry out studies (vital stains) to see if the sperm seen are alive. It is possible to have sperm with normal reproductive genetics that are deficient in one or several of the factors necessary to produce motility. We have achieved several successful pregnancies employing microinjection of healthy, non motile sperm directly into the egg (ICSI).
Chemical and Biochemical Semen Characteristics
Semen acid-base balance (pH)
The pH of semen is measured using a specially treated paper blot that changes color according to the pH of the specimen that it is exposed to. The pH of normal semen is slightly alkaline ranging from 7.2 to 7.8. Prostatic secretions are acidic while the secretions of the seminal vesicles are alkaline. Therefore, alterations in pH may reflect a dysfunction of one or both of these accessory glands. The pH of semen has not been generally found to have a major influence on a man's fertility potential.
Color and Turbidity
Semen is normally translucent or whitish-gray opalescent in color. Blood found in semen (hematospermia) can color the semen pink to bright red to brownish red. The presence of blood in semen is abnormal and should be reported. The presence of particles, nonliquified streaks of mucus or debris requires further evaluation.
Liquefaction
Semen is normally produced as a coagulum. The specimen will ususally liquify within 30 minutes. The failure to liquify within one hour is abnormal. Excellent methods for correcting this problem in the laboratory are available.
Viscosity
Nonliquefaction and excessive viscosity are two separate conditions. Viscosity is measured after complete liquefaction has occured. Viscosity is considered "normal" if the liquefied specimen can be poured from a graduated beaker drop by drop with no attaching agglutinum between drops. The role of hyper (excessive) viscosity is being studied, but it seems possible that htis condition may interfere with the ability of sperm to travel from the site of deposition into the cervix or uterus.
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