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

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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 my patients feel 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 percent 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 percent of cases. Another 20–25 percent of women do not ovulate or ovulate dysfunctionally, preventing conception.

Even when a semen analysis is normal, it is possible that a postcoital 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 percent 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 percent 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 percent of males who contract mumps which is unilateral in 90 percent 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 percent occur on the left and is found in 20 percent of males 40 percent of the infertile population. 50 percent 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 percent 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 percent 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 percent 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.

This article was written by Dr. Kreiner a reproductive medicine and Medical Director of East Coast Fertility. Dr. Kreiner has helped thousands of families achieve their dreams of having babies.


Originally published on FertilityTies

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