This article from a Resolve 2006 newsletter written by Dr. Werthman
Until several years ago the belief among most reproductive specialists was that if a man had live sperm then they were suitable for use with IVF / ICSI and if the female partner didn’t get pregnant or a miscarriage ensued then it was probably an egg quality issue. Several studies had implied that the conventional sperm parameters (count, motility and morphology) as measured on a routine semen analysis had no bearing on success when ICSI was used. Many couples pursued egg donation after failed IVF attempts because the husband’s semen parameters were relatively normal and yet conception hadn’t occurred. Some of these same couples were still unable to conceive even with the “better quality” donor eggs leaving both the doctors and the couples frustrated and perplexed. Some couples then went on to use both egg donors and surrogates thinking it was both an egg quality and implantation issue, again without success. The only commonality was the husband’s sperm.
About a year and a half ago a relatively new concept was introduced to clinical practice; sperm quality was dependent on the amount of damage to the sperm DNA or DNA fragmentation. Simply put, DNA is arranged in a double helix or ladder configuration with side rails and rungs. If the rungs are broken, then the ladder is unsteady and won’t function properly. What has recently been shown in several studies is very interesting and in some ways unexpected. Sperm DNA fragmentation has little or nothing to do with the parameters that we measure on the routine semen analysis. It has little to do with the shape of the sperm or whether the sperm are moving. It is a completely independent variable. Men with otherwise normal semen analyses can have a high degree of DNA damage and men with what was called very poor sperm quality can have very little DNA damage. More importantly what has also been demonstrated is that the degree of DNA fragmentation correlates very highly with the inability of the sperm to initiate a birth regardless of the technology used to fertilize the egg such as insemination, IVF or ICSI. Sperm with high DNA fragmentation may fertilize an egg and embryo development stops before implantation or may even initiate a pregnancy but there is a significantly higher likelihood that it will result in miscarriage. By testing for sperm DNA fragmentation, many cases of formally “unexplained” infertility can now be explained. Many of those couples who have been previously unable to conceive with what would be considered extreme measures have been diagnosed with high sperm DNA fragmentation and treated. It is now very clear to see that having this information about the quality of the sperm can be tremendously helpful to couples and their physicians.
There are several ways to test for sperm DNA fragmentation; the most widely used and statistically robust test is called the Sperm Chromatin Structure Assay or SCSA. The patient semen samples are frozen and shipped in a liquid nitrogen container to the SCSA reference laboratory in South Dakota. The sperm are thawed out and a stress is applied (low pH). The sperm are then labeled with a special orange colored dye that only attaches to the ends of broken DNA within the sperm cell. If the DNA is intact then no dye will attach to the sperm. A machine called a flow cytometer is used to analyze ten thousand sperm from the sample. The sperm are passed single file by a beam of light that hits the dye inside the sperm cell and reflects light at a specific wavelength causing the sperm to appear either orange (damaged) or green (normal). A computer counts the percentage of green versus orange-labeled sperm and software allows for creation of a graphic plot of the percent of damaged sperm giving an index known as the DNA fragmentation Index (DFI).
The data from thousands of patients has been analyzed and correlated with the patient’s clinical outcomes and references ranges were compiled. A normal sample has less then 15% of the sperm with DNA damage. Men with poor fertility potential have greater then 30% of their sperm damaged. A DFI Between 16% and 29% is considered good to fair fertility potential but becomes poorer as it approaches 27%. These numbers are thresholds meaning that above 30% the outcome for most couples was failure to have a birth even though only 30+ percent of the sperm were damaged. Under 15% most couples achieved success. The logical questions that arose were: what about the rest of the undamaged sperm in the sample? Why don’t those sperm work? What causes sperm DNA fragmentation? Can the DNA fragmentation be reduced and the sperm improved? If so, How?
DNA fragmentation can be thought of as a marker for other types of damage to the sperm. It is a kin to seeing the tip of the iceberg. Apparently, in semen samples with greater then 30% DNA fragmentation, other abnormalities are occurring with the non-fragmented sperm that the SCSA doesn’t measure and that is why samples used with DFIs above this level do not usually result in births.
The causes of high DNA fragmentation are those same causes of male factor infertility that we have known about for years such as chemical/toxin exposure, heat exposure, varicocele, infection, age, smoking, testicular cancer, radiation, and anything that increases the free radical levels in the semen among a list of many other things. It is very important to understand that sperm DNA fragmentation can change with time and it can be improved in many cases. The goal of a male factor evaluation is to seek out the causes of poor sperm quality and try to correct them so conception can occur naturally or to improve the sperm quality for IVF and maximize the chances of success. In situations where DFI can’t be improved there is evidence to suggest that removing the sperm directly from the testicle via biopsy and using it with ICSI may lead to better outcomes then using poor quality ejaculated sperm. Other options include counseling patients regarding the use of donor sperm either by insemination or fertilizing a portion of the eggs harvested for ICSI with donor sperm and a portion with the patient’s sperm, once again to maximize odds.
The clinical utility of the SCSA is readily apparent. All men with an abnormal semen analysis are candidates for this test as well as men with normal semen analyses who have failed IVF for unexplained reasons. Those couples using egg donors or surrogates may also benefit from screening prior to going thru the procedures because the effort and costs are so great. Men with poor DFI should have a male factor evaluation including a physical examination by a male reproductive specialist. These new concepts have a significant implication on how we practice and what we recommend to couples but we must bear in mind that this test does not have a predictive values of 100% as healthy babies have been born from men with high DFI but this is fairly uncommon.
There are herbal medicine formulas which are exceedingly high in antioxidant properties. At The Berkley Center for Reproductive Wellness we have had great success in treating this disorder.
Showing posts with label Sperm dna fragmentation. Show all posts
Showing posts with label Sperm dna fragmentation. Show all posts
Wednesday, March 16
Tuesday, June 22
Daily sex helps to reduce sperm DNA damage and improve fertility
Published: Tuesday, June 30, 2009 - 08:38 in Health & Medicine
Amsterdam, The Netherlands: Daily sex (or ejaculating daily) for seven days improves men's sperm quality by reducing the amount of DNA damage, according to an Australian study presented today (Tuesday) to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.
Until now there has been no evidence-based consensus amongst fertility specialists as to whether or not men should refrain from sex for a few days before attempting to conceive with their partner, either spontaneously or via assisted reproduction.
Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said: "All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF.
"I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range."
To investigate this hypothesis, Dr Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI). Men who had a more than 15% of their sperm (DFI >15%) damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15% DFI for excellent quality sperm, 15-24% DFI for good, 25-29% DFI for fair and more than 29% DFI for poor quality; but other laboratories can have slightly different ranges.
The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15% and 98% DFI, with an average 34% DFI when measured after three days' abstinence. When the men's sperm was re-assessed on the seventh day, Dr Greening found that 96 men (81%) had an average 12% decrease in their sperm DNA damage, while 22 men (19%) and an average increase in damage of nearly 10%. The average for the whole group dropped to 26% DFI.
Dr Greening said: "Although the mean average was 26% which is in the 'fair' range for sperm quality, this included 18% of men whose sperm DNA damage increased as well as those whose DNA damage decreased. Amongst the men whose damage decreased, their average dropped by 12% to just under 23% DFI, which puts them in the 'good' range. Also, more men moved into the 'good' range and out of the 'poor' or 'fair' range. These changes were substantial and statistically highly significant.
"In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.
"Further research is required to see whether the improvement in these men's sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates.
"The optimal number of days of ejaculation might be more or less than seven days, but a week appears manageable and favourable. It seems safe to conclude that couples with relatively normal semen parameters should have sex daily for up to a week before the ovulation date. In the context of assisted reproduction, this simple treatment may assist in improving sperm quality and ultimately achieving a pregnancy. In addition, these results may mean that men play a greater role in infertility than previously suspected, and that ejaculatory frequency is important for improving sperm quality, especially as men age and during assisted reproduction cycles."
Dr Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species – very small molecules, high levels of which can damage cells. "The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage," he concluded.
Source: European Society for Human Reproduction and Embryology
Amsterdam, The Netherlands: Daily sex (or ejaculating daily) for seven days improves men's sperm quality by reducing the amount of DNA damage, according to an Australian study presented today (Tuesday) to the 25th annual meeting of the European Society of Human Reproduction and Embryology in Amsterdam.
Until now there has been no evidence-based consensus amongst fertility specialists as to whether or not men should refrain from sex for a few days before attempting to conceive with their partner, either spontaneously or via assisted reproduction.
Dr David Greening, an obstetrician and gynaecologist with sub specialist training in reproductive endocrinology and infertility at Sydney IVF, Wollongong, Australia, said: "All that we knew was that intercourse on the day of ovulation offered the highest chance of pregnancy, but we did not know what was the best advice for the period leading up to ovulation or egg retrieval for IVF.
"I thought that frequent ejaculation might be a physiological mechanism to improve sperm DNA damage, while maintaining semen levels within the normal, fertile range."
To investigate this hypothesis, Dr Greening studied 118 men who had higher than normal sperm DNA damage as indicated by a DNA Fragmentation Index (DFI). Men who had a more than 15% of their sperm (DFI >15%) damaged were eligible for the trial. At Sydney IVF, sperm DNA damage is defined as less than 15% DFI for excellent quality sperm, 15-24% DFI for good, 25-29% DFI for fair and more than 29% DFI for poor quality; but other laboratories can have slightly different ranges.
The men were instructed to ejaculate daily for seven days, and no other treatment or lifestyle changes were suggested. Before they started, levels of DNA damage ranged between 15% and 98% DFI, with an average 34% DFI when measured after three days' abstinence. When the men's sperm was re-assessed on the seventh day, Dr Greening found that 96 men (81%) had an average 12% decrease in their sperm DNA damage, while 22 men (19%) and an average increase in damage of nearly 10%. The average for the whole group dropped to 26% DFI.
Dr Greening said: "Although the mean average was 26% which is in the 'fair' range for sperm quality, this included 18% of men whose sperm DNA damage increased as well as those whose DNA damage decreased. Amongst the men whose damage decreased, their average dropped by 12% to just under 23% DFI, which puts them in the 'good' range. Also, more men moved into the 'good' range and out of the 'poor' or 'fair' range. These changes were substantial and statistically highly significant.
"In addition, we found that although frequent ejaculation decreased semen volume and sperm concentrations, it did not compromise sperm motility and, in fact, this rose slightly but significantly.
"Further research is required to see whether the improvement in these men's sperm quality translates into better pregnancy rates, but other, previous studies have shown the relationship between sperm DNA damage and pregnancy rates.
"The optimal number of days of ejaculation might be more or less than seven days, but a week appears manageable and favourable. It seems safe to conclude that couples with relatively normal semen parameters should have sex daily for up to a week before the ovulation date. In the context of assisted reproduction, this simple treatment may assist in improving sperm quality and ultimately achieving a pregnancy. In addition, these results may mean that men play a greater role in infertility than previously suspected, and that ejaculatory frequency is important for improving sperm quality, especially as men age and during assisted reproduction cycles."
Dr Greening said he thought the reason why sperm quality improved with frequent ejaculation was because the sperm had a shorter exposure in the testicular ducts and epididymis to reactive oxygen species – very small molecules, high levels of which can damage cells. "The remainder of the men who had an increase in DFI might have a different explanation for their sperm DNA damage," he concluded.
Source: European Society for Human Reproduction and Embryology
Monday, June 21
Male Infertility
The integrity of sperm DNA is essential for the transmission of the father’s gene contribution.
Tests which show an increased fraction of sperm DNA fragmentation often correlates to other sperm pathologies such as poor motility, count and morphology. Most reproductive endocrinology clinics do not test for sperm DNA fragmentation even when the patient presents with poor sperm parameters.
As in all areas of medicine, there is internecine battling going on between physicians as to the meaning and the effect of sperm DNA fragmentation on male fertility.
Some doctors completely disagree with its relevancy as a contributor to male infertility; some physicians accept its contribution but don’t know what to do with the findings; others think that the only real detriment to the quality of sperm rendered by DNA fragmentation is the sperms inability to penetrate the egg and they think that injecting the sperm into the egg (ICSI) effectively deals with the problem. It does not.
Sperm DNA fragmentation has a far reaching effect on fertility and surpasses the mere diminished ability of sperm to penetrate egg.
Some studies show that with higher percentages of sperm DNA fragmentation, there are increased correlations in spontaneous abortions. The proportion of patients with abnormal sperm DNA integrity is higher in couples with spontaneous miscarriage. This is not surprising as a good embryo is nothing other than the combination of a good egg with a good sperm and sperm with DNA fragmentation is not good sperm.
In sperm without DNA fragmentation the DNA is protected from damage while being transported through both the male and female reproductive tracts; if there is damage to the DNA then impaired fertility is an obvious consequence.
Causes of DNA fragmentation are many and varied ranging from genetic anomalies to reactive oxygen species due to white blood cell (leukocyte) infiltration), as well as vericoceles.
As DNA repair systems are less active in the later stages of sperm production, sperm with fragmented DNA can readily reach the ejaculate.
Men that have sperm DNA fragmentation greater than 30% are typically infertile.
Treatment options
Antioxidant therapy
Antioxidants ‘scavenge’ reactive oxygen species and can, in some instances, reduce sperm DNA fragmentation percentages. A n anti oxidant compound which has been shown to be effective in some instances is composed of lycopene 6mg, vitamin E 400IU, vitamin C 100mg, zinc 25mg, selenium 26 mg, folate .5 mg and garlic (available in pill form)1000 mg. This should be taken once daily.
Acupuncture and Herbs
Acupuncture with its ability to stimulate blood which transports oxygen and nutrients to the testes, while carrying debris away from the testes may also be an effective treatment.
Many herbal medicines also have high antioxidant properties and should be included in the treatment regimen.
Combining antioxidant therapy as described above with acupuncture and herbal medicine can potentially reduce sperm DNA fragmentation and increase fertility outcomes in men with high percentages of DNA fragmentation.
Smoking cigarettes and marijuana have been shown to contribute to sperm DNA fragmentation. Elimination of these mitigators may also reduce sperm DNA fragmentation percentages.
Mike Berkley, L.Ac.
Tests which show an increased fraction of sperm DNA fragmentation often correlates to other sperm pathologies such as poor motility, count and morphology. Most reproductive endocrinology clinics do not test for sperm DNA fragmentation even when the patient presents with poor sperm parameters.
As in all areas of medicine, there is internecine battling going on between physicians as to the meaning and the effect of sperm DNA fragmentation on male fertility.
Some doctors completely disagree with its relevancy as a contributor to male infertility; some physicians accept its contribution but don’t know what to do with the findings; others think that the only real detriment to the quality of sperm rendered by DNA fragmentation is the sperms inability to penetrate the egg and they think that injecting the sperm into the egg (ICSI) effectively deals with the problem. It does not.
Sperm DNA fragmentation has a far reaching effect on fertility and surpasses the mere diminished ability of sperm to penetrate egg.
Some studies show that with higher percentages of sperm DNA fragmentation, there are increased correlations in spontaneous abortions. The proportion of patients with abnormal sperm DNA integrity is higher in couples with spontaneous miscarriage. This is not surprising as a good embryo is nothing other than the combination of a good egg with a good sperm and sperm with DNA fragmentation is not good sperm.
In sperm without DNA fragmentation the DNA is protected from damage while being transported through both the male and female reproductive tracts; if there is damage to the DNA then impaired fertility is an obvious consequence.
Causes of DNA fragmentation are many and varied ranging from genetic anomalies to reactive oxygen species due to white blood cell (leukocyte) infiltration), as well as vericoceles.
As DNA repair systems are less active in the later stages of sperm production, sperm with fragmented DNA can readily reach the ejaculate.
Men that have sperm DNA fragmentation greater than 30% are typically infertile.
Treatment options
Antioxidant therapy
Antioxidants ‘scavenge’ reactive oxygen species and can, in some instances, reduce sperm DNA fragmentation percentages. A n anti oxidant compound which has been shown to be effective in some instances is composed of lycopene 6mg, vitamin E 400IU, vitamin C 100mg, zinc 25mg, selenium 26 mg, folate .5 mg and garlic (available in pill form)1000 mg. This should be taken once daily.
Acupuncture and Herbs
Acupuncture with its ability to stimulate blood which transports oxygen and nutrients to the testes, while carrying debris away from the testes may also be an effective treatment.
Many herbal medicines also have high antioxidant properties and should be included in the treatment regimen.
Combining antioxidant therapy as described above with acupuncture and herbal medicine can potentially reduce sperm DNA fragmentation and increase fertility outcomes in men with high percentages of DNA fragmentation.
Smoking cigarettes and marijuana have been shown to contribute to sperm DNA fragmentation. Elimination of these mitigators may also reduce sperm DNA fragmentation percentages.
Mike Berkley, L.Ac.
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