FertilityTies posts tagged with maleinfertility

Sperm Meets Egg – Why Doesn’t It Work Every Time?

Fri, 18 Sep 2009 11:17:18 -0500

Why me? My wife never had an infection, surgery or any other problem? I have no difficulty ejaculating and there’s plenty to work with so why can my friends, neighbors and coworkers get pregnant and we can’t?

I hear these questions daily and appreciate the frustrations, anger and stress felt by my patients expressing these feelings through such questions. There are many reasons why couples do not conceive. An infertility workup will identify some of these. A semen analysis will pick up a male factor in 50-60% of cases and in more than half of these cases the male has the only problem. An hysterosalpingogram will locate tubal disease in about 20% of cases. Another 20-25% of women do not ovulate or ovulate dysfunctionally preventing conception.

Even when a semen analysis is normal it is possible that a post coital test may identify that the problem is that the sperm is not reaching the egg. It may not be able to swim up the cervical canal into the womb and up the tubes where it should normally find an egg to fertilize. When these tests are normal a laparoscopy may be performed to identify the 20-25% of infertile women with endometriosis. However, even when the infertility workup is normal and there is no test that logically explains the lack of success in achieving a pregnancy; an IVF procedure may both identify the cause as failure of the egg to fertilize and treat it successfully by injecting sperm microscopically into the egg by a procedure called Intracytoplasmic Sperm Injection or ICSI.

What causes male factor infertility?

There are several potential causes of male factor infertility. Hormonal causes can be caused because of problems at the hypothalamic-pituitary level or at the testicular level. Normally, the hypothalamus regulates pituitary production of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). FSH and LH drive the testis to produce sperm and testosterone. Deficiency of FSH or LH can lead to lack of ability to drive the testicular production of sperm and testosterone just as lack of gas will prevent a car from being able to run. Today, the most common reason for a man to have FSH and LH production shut off is from his use of anabolic steroids such as testosterone, hcg (human chorionic gonadotropin) and clomiphene (clomid). These all may provide negative feedback on the pituitary turning off FSH and LH production. One can also see elevated testosterone shutting down the testis with congenital adrenal hyperplasia and adrenal tumors.

Pituitary tumors, infarction, surgery, radiation and infiltrative processes can also diminish FSH and LH production. In the presence of low FSH and LH it may be useful to check for elevated prolactin levels to rule out a pituitary prolactinoma and obtain an MRI to check for other tumors or pituitary pathology.

Isolated deficiency of LH and FSH can occur (Kallmann’s syndrome) and lead to diminished testis (hypogonadism). This occurs in 1 in 10,000 men. Less common defects are seen in hypothalamic stimulation of the pituitary and are usually associated with other congenital findings.

Abnormal thyroid and glucocorticoid (prednisone) excess can result in decreased spermatogenesis through effects on the hypothalamus and LH production or conversion of androgens (male hormone) to estrogens.

Testicular causes include the presence of tumor, chromosomal abnormalities, congenital absence of germ cells, drugs and radiation that are toxic to the testes, undescended testes and varicocoele.

Ten per cent of males with a sperm count under 10 million and 20% of men with azospermia have a chromosomal abnormality. Kleinfelter’s syndrome is a genetic disorder due to the presence of an extra x chromosome in the male. This occurs in 1 out of 500 males and is often seen in the mosaic form where some cells are 46 xy and some are 47 xxy. The testes tend to be small and these men have delayed sexual maturation, azospermia and gynecomastia (enlarged male breasts). There has been some success with ICSI of biopsied immature sperm cells.

Sertoli-cell only syndrome or germinal cell aphasia may have several causes including congenital absence of the germ cells, genetic defects or androgen resistance. Testicular biopsy shows complete absence of germinal elements. Men are azospermic yet virilize normally. Testes may have normal consistency but be slightly smaller in size. Testosterone and LH levels are normal but FSH is usually elevated. Men with testicular failure secondary to mumps, cryptorchidism or radiation/chemotherapy damage have smaller testes with a non uniform histologic pattern. The testes may have severe sclerosis and hyalinization. There is no treatment for this form of azospermia.

Gonadotoxic drugs like chemotherapy or radiation can effect the germinal epithelium because it is a rapidly dividing tissue and is susceptible to the interference imposed by these toxins on cell division. At radiation exposure below 600 rads, germ cell damage is reversible. Recovered spermatogenesis may take up to 2-3 years even when exposed to low doses of radiation. Elevated FSH levels reflect the impaired spermatogenesis and return to normal once the testes recover.

Orchitis occurs in 15-25% of males who contract mumps which is unilateral in 90% of cases. Testicular atrophy may take years to develop. At least two thirds of men with bilateral orchitis remain infertile for life.

Trauma either through accident or torsion of a testis is a relatively common cause of subsequent atrophy with potential diminished fertility.

Medical conditions such as renal failure, cirrhosis of the liver and sickle cell disease can all lead to low testosterone levels and decreased spermatogenesis.

Cryptorchidism occurs in 1 in 12 males. The undescended testis becomes abnormal after age 2. Even when unilateral, cryptorchid patients have reduced fertility potential.

The varicocoele is the most common finding in infertile men. It is the result of backflow of blood due to incompetent valves in the spermatic veins. 90% occur on the left and is found in 20% of males 40% of the infertile population. 50% of men with varicocoeles are fertile. It is thought that a varicocoele can cause infertility by elevating the temperature of the testis. Varicocoelectomies however are not universally helpful and remain somewhat controversial for many cases of infertility.

Unfortunately, at least 25-40% of infertile men have idiopathic infertility for which no cause may be identified.

Other causes of azospermia include congenital absence of the vas deferens or obstruction secondary to infection or surgery. These cases may be amenable to surgical reconstruction and/or ICSI with epididymal aspiration or testicular biopsy to obtain sperm. These are the most successful cases of ICSI associated with azospermia.

Sperm antibodies may be a relative cause of infertility in about 3-7% of cases. Treatment has been successful with intrauterine insemination and with ICSI.

Infections can affect sperm motility secondary to e coli, Chlamydia, mycoplasma, ureaplasma and trichomonas. Culture and treatment for asymptomatic infertile males remains controversial.

Sexual dysfunction is a presenting cause of male infertility in about 20% of cases. Decreased sexual drive, erectile dysfunction, premature ejaculation and failure of intromission are all potentially correctable causes of infertility.

Treatment of Male Infertility

Treatment depends on diagnosis. In cases where the FSH and LH are low with a normal head MRI, clomiphene may be of benefit. Clomiphene citrate (Clomid or Serophene) is one of the most widely used drugs in male infertility. It is a weak anti-estrogen that interferes with the normal feedback of circulating estrogens and results in an increase in GnRH that stimulates gonadotropin secretion. The resulting elevation in LH and FSH increases intratesticular testosterone levels and in theory should improve spermatogenesis. Gonadotropin therapy may be used if clomphene is unsuccessful in the face of low FSH and LH.

If a pituitary tumor is found, surgery or medications to lower prolactin may restore spermatogenesis to normal.

An obstructed vas may be microsurgically reconstructed. Surgery may also be performed in the presence of a varicocoele.

Intrauterine insemination may improve delivery of sperm to an egg or in the absence of any sperm, artificial insemination with donor sperm is often successful.

Intracytoplasmic sperm injection into the egg in an IVF procedure is highly successful when sperm may be obtained through the ejaculate and even through testicular biopsy. When normal mature sperm are rare such as in testicular failure, associated with elevated FSH, ICSI is much less likely to result in fertilization and pregnancy. Immature sperm cells rarely can result in a healthy pregnancy.

Naturopathic Treatment

Naturopathic treatment for male infertility focuses on improving sperm quantity, sperm quality, and overall male reproductive health. There have been reports that sperm counts have fallen almost 50% since the 1930s. Although some dispute these findings, it is generally accepted that sperm counts are declining. The cause may be environmental and dietary and lifestyle changes may interfere with men's sperm production. If this is so, improving diet and making healthy lifestyle choices should positively impact male reproductive health.

Nutrition

The importance of a healthy diet cannot be overstated. To function properly, the reproductive system requires the proper vitamins and minerals. Nutritional deficiencies can impair hormone function, inhibit sperm production, and contribute to the production of abnormal sperm.

• Eat a natural foods diet that focuses on fresh vegetables, fruits, whole grains, fish, poultry, legumes, nuts, and seeds.

• Drink 50% of body weight in ounces of water daily (e.g., a 150 lb man would drink 75 oz of water).

• Eliminate processed and refined foods (e.g., white flour), junk food, sugars, alcohol, and caffeine.

• Avoid saturated fats and hydrogenated oils (e.g., margarine); use olive oil.

• Pumpkin seeds are naturally high in zinc and essential fatty acids which are vital to healthy functioning of the male reproductive system. Eat pumpkin seeds to help maintain a healthy reproductive system.

Supplements

The following supplements may increase sperm count and/or motility. Allow 3-4 months for the supplements to work. The following is a list of supplements with their supposed benefit.

• Arginine - Take 4 gr daily. Needed to produce sperm. If the sperm count is below 10 million per ml, arginine probably will not provide any benefit.

• Coenzyme Q10 - Take 10 mg daily. May increase sperm count and motility.

• Flaxseed oil - Take 1 tbsp daily. Is a source of essential fatty acids.

• L-carnitine - Take 3-4 grams daily. Required for normal sperm function.

• Multivitamin-mineral - Buy a high-quality product and take one serving size (differs from brand to brand).

• Selenium - Take 200 mcg daily. May improve sperm motility.

• Vitamin B-12 - Take 1000 mcg daily. A B-12 deficiency reduces sperm motility and sperm count. Even if no deficiency exists, B-12 supplementation may help men with a sperm count of less than 20 million per milliliter or a motility rate of less than 50%

• Vitamin C - Take 500 mg 2 times daily. Is an antioxidant.

• Vitamin E - Take 400 IUs 2 times daily. Is an antioxidant and may improve sperms' ability to impregnate.

• Zinc - Take 30 mg 2 times daily. Required for a healthy male reproductive system and sperm production.

Herbal Medicine

Herbal remedies usually do not have side effects when used appropriately and at suggested doses. Occasionally, an herb at the prescribed dose causes stomach upset or headache. This may reflect the purity of the preparation or added ingredients, such as synthetic binders or fillers. For this reason, it is recommended that only high-quality products be used. As with all medications, more is not better and overdosing can lead to serious illness and death.

The following herbs may be used to treat male infertility:

• Ginseng (Panax ginseng) - Known as a male tonic (an agent that improves general health) and used to increase testosterone levels and sperm count. Siberian ginseng (Eleutherococcus senticosus) may also be used.

• Astragalus (Astragalus membranaceus) – May increase sperm motility.

• Sarsaparilla (>Smilax spp.) - Known as a male (and female) tonic.

• Saw palmetto (Serenoa repens) - Used for overall male reproductive health.

Other Recommendations

• Avoid alcohol. Alcohol consumption is associated with an increased number of defective sperm.

• Consider acupuncture.

• Do not smoke, or quit smoking. There is an association between smoking and low sperm count, poor sperm motility, and abnormal sperm.

• Proxeed - is a new nutritional supplement that may improve sperm health and fertility rates. The ingredients include L-carnitine and acetylcarnitine, two vitamin-like substances synthesized naturally by the body. These chemicals are involved in cellular metabolism and are found in semen at a rate that is proportionate to the amount of healthy sperm. Proxeed is purported to improve sperm count, concentration, and motility when taken orally for about 2 months. It is reported that approximately 30% of couples using it conceive. It is available without a prescription, although couples considering it should consult their physician.

Dr. David Kreiner

male infertility and increasing sperm count

Fri, 12 Jun 2009 09:18:00 -0500

I just found out my husbands sperm count is low. The dr suggests he go on clomid or we try invetro. We got pregnant once 4 years ago when i got off birth control. Why did his sperm count drop since then and why cant we get pregnant? is there anything we can use to boost his count? His diet hasnt changed(actually he eats better and exercises a lot). what can we do to boost his count?

Ren

Who is dealing with male factor infertility?

Tue, 05 May 2009 10:58:20 -0500

My DH has 1% morphology and was diagnosed with a varicocele. In the coming months the doctor will be doing bloodwork including LH, Estradiol and Testosterone. He will also be getting an ultrasound to determine what stage varicocele is in and if he will need surgery. Finally, the doc wants DH to get SCSA test (DNA Fragmentation).

Is anyone out there currently dealing with or have you dealt with some of these issues in the past? Has your DH had any of these tests and what were the results? Have you done anything to correct these issues and did it work?

JaimeTTC#1

The Male Biological Clock

Mon, 25 Jun 2007 19:32:00 -0500

Say "biological clock" and most people immediately think "women." Female fertility, after all, strikes "midnight" with the cessation of menses. This occurs because of distinct—and dramatic—declines in estrogen production. And as women age, the genetic quality of their eggs and the efficiency with which their bodies reject genetically damaged embryos both decline, leading to an increased risk of genetic problems in their offspring. This triad of declining fertility, declining hormone levels, and increasing risk for genetic problems is what most people mean when they say "biological clock."

Until recently, that is. Although it's an idea that has not yet filtered down to the general public, we now know that men have biological clocks too. And those clocks involve the same physiological triad experienced by women. Male fertility and male sex hormones do decline with age. And the genetic quality of sperm does decline, leading to an increased risk of genetic problems in offspring above and beyond any contributed by the female. The object of this review is to describe these features of male aging and, hence, to expand the notion of "biological clock" to include both sexes.

Male Infertility

Data obtained in the past decade suggested a worldwide decline in male fertility. Although initially thought to be the result of external variables such as exposure to pollution, we now understand a real culprit: men are simply waiting longer to have children and aging is adversely affecting their fertility. It is well known that women are waiting longer to have children. Data from the Centers for Disease Control (2001) clearly demonstrate that over the last 30 years there has been a decline in the number of children to woman under the age of 30 with a corresponding increase in the number of children born to women over 30. In fact, the largest increase has been the more than doubling of the number of births to women over the age of 35. In 1970 the number of births to such women was 6 percent. That increased to 13 percent in 1999 and is undoubtedly higher now. What is less often discussed, but hardly surprising, is that there has been a parallel increase in paternal age. There was a 50 percent increase in fathers older than 35 in the past 30 years.

The increase in paternal age is both a personal problem for many couples and a public health problem because of the simple (but still largely unrecognized) fact that male fertility declines with age. Journal articles by Kidd et al. (2001) and Ford et al. (2000) demonstrate that men over the age of 35 are twice as likely to be infertile as men younger than 25. In addition, a study of couples undergoing fertility treatments with intra—uterine inseminations found that the amount of time it takes for a man to achieve a pregnancy rises significantly with age. After controlling for maternal age, men older than 35 had a 50% lower pregnancy rate than men younger than 30 (Mathieu et al 1995). Although further epidemiological research is needed to prove the point, this pattern of rising difficulty to achieve pregnancy likely holds true for the male population in general. The bottom line: current reviews of controlled studies looking at male aging show robust positive correlations between age and infertility as well as age and the time required to achieve pregnancy.

Testosterone

As with women, the levels of sex hormones in men declines with age. The drop is not as steep or as sudden as that associated with menopause, but it can be equally significant for fertility and overall well—being. In fact changes in men's hormones are just as important as changes in women's hormones. The roughly 1 percent per year decline in testosterone levels after age 30 has been termed "andropause," though this is a somewhat unfortunate choice because testosterone levels don't actually "pause" in the same way that estrogen levels do. A more technically accurate (though clumsy) term is "symptomatic hypogonadism in the aging male." Whatever you call it, declining testosterone causes problems. Rhoden and Morgentaler (2001) estimate that between 2 and 4 million men in the US alone suffer from hypogonadism (defined as serum total testosterone levels lower than 325 ng per deciliter). The same article found that only 5 percent of these men are getting treatment for their symptoms, which include decreased libido and erectile dysfunction, loss of muscle mass and strength, weight gain, and declining cognitive function. Hypogonadism is also associated with type II diabetes, insulin resistance, central obesity and the metabolic syndrome. Newer treatments for hypogonadism such as exogenous testosterone replacement and stimulation of endogenous testosterone production are gaining tremendous popularity. Sales of prescription testosterone products have soared more than 500 percent since 1993 and show no signs of leveling off (Bhasin & Buckwalter, 2001). This enormous increase is not without risks. Indiscriminate use of testosterone supplements can raise the risk for prostate problems, blood disorders, and infertility.

Genetic quality of sperm

Although increasing maternal age has long been known to be associated with increased incidence of birth defects, the age of the male as been seen as irrelevant. New data show what we should have suspected all along: the age of the male does matter and the genetic quality of sperm does decline with age. Specifically, a 2004 study by Malaspina et al., found that older men are at higher risk of fathering a child with schizophrenia. In fact men older than forty were more than twice as likely to have a child with schizophrenia as men in their twenties. A 2003 study (Fisch et al.) found a similar influence of paternal age on the risk of having a child with Down Syndrome. Paternal age was a factor in half the cases of Down Syndrome when the maternal age was over 35. And a 2002 study by Rochebrochard and Thonneau of the rate of miscarriages found similar increased risks with rising paternal age when maternal age was older than 35. These and other studies clearly show that when the mother and father are both over the age of 35 years, there is a markedly increased risk of both genetic abnormalities and miscarriage. The father's contribution to these events is increased with increasing age, similar to women. As noted above, these facts are worrisome in light of the large increases in maternal and paternal age over the past 25 years.

The Male Biological Clock is Real

This brief review demonstrates a still un—appreciated reality: men have biological clocks that affect their fertility, hormone levels, and the genetic quality of their sperm. This clock plays a role on a personal level (when couples must grapple with infertility or birth defects) and on a public health level (when society must decide policies governing, for instance, insurance coverage for advanced fertility treatments such as in vitro fertilization.) Women should no longer be viewed as solely responsible for age—related fertility and genetic problems. Infertility is not just a woman's problem and with the new awareness of a male biological clock couples and their physicians can much more accurately proceed with proper testing, diagnosis and (if needed) treatment of the male. The field of male—factor infertility is still young, and much more research is needed to fully characterize risks and to find more effective treatments. We also need to better understand the cellular and biochemical mechanisms of "gonadal" aging in order to find safe, effective ways to delay this process and, in effect, "rewind" the male biological clock. Doing so will lessen the potential for adverse genetic consequences in offspring, improve the sexual and reproductive health of aging males, and increase a woman's chance of having healthy children by correcting defects in the male reproductive machinery.

References:

2001 Assisted Reproductive Technology Success Rates. U.S. Department of Health and Human Services, Centers for Disease Control. 2003. p. 11.

Bhasin S, Buckwalter JG. Testosterone supplementation in older men: a rational idea whose time has not yet come. Journal of Andrology. 2001;22:718—731.

E. de la Rochebrochard, and P. Thonneau. Paternal age and maternal age are risk factors for miscarriage: results of a multicentre European study. Human Reproduction, 17 (6), 2002, 1649—1656.

Fisch H, Hyun G, Golden R, et al. The influence of paternal age on down syndrome. Journal of Urology 169(6), (2003):2275—2278.

Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertility and Sterility. 2001;75(2):237—248.

W. C. L. Ford, K. North, H. Taylor, et al. Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. Human Reproduction, 15 (8), 2000: 1703—1708.

Rhoden EL, Morgentaler A. Risks of testosterone—replacement therapy and recommendations for monitoring. New England Journal of Medicine 350 (2004):482—92.

Malaspina D., etal Advancing Paternal Age and the Risk of Schizophrenia Arch Gen Psychiatry.158:758, 2001

Mathieu, C., Ecochard, R.,Bied, V.,Cummulative conception rate following intrauterine artificial insemination with husband's spermatozoa:influence of husband's age. Human Reproduction 1995,10,1090—1097

Dr. Harry Fisch