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Temperature issues

Sperm production

Sperm penetration

Sperm assessment

IUI

ICSI


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All About Sperm

Human sperm are an extremely interesting subject. Although biology is all about reproduction, high school curriculums continue to de-emphasize biology while the body of information constituting biology grows exponentially. It is therefore no surprise that when I talk to patients about male reproduction, the information I share with them is often completely new to them.

The cells that make sperm migrate to the developing testicles during fetal life (from the yolk sac). These cells are the ancestors of the sperm that a man produces in his adult life. They form an upper limit to the number of sperm a man produces at any one time. Another way of saying this is, if these progenitor sperm cells do not successfully migrate to the testicles from the yolk sac or if something damages these cells (radiation, trauma, intra-abdominal location), then adult sperm counts will necessarily be reduced. The testicles initially develop intra-abdominally and then move down the inguinal canal into the scrotal sac. If this doesn't happen by early childhood, then sperm production will be significantly reduced. If they stay intra-abdominal, then the boy is also at risk for developing testicular cancer (seminoma).

Temperature issues

At puberty, boys begin producing the pituitary hormones, LH and FSH, which stimulate cells in the testicles to produce both testosterone and sperm. For optimal sperm production, the testicles should be at least three degrees cooler than the rest of the body. That is why they are designed to hang away from the body and why the scrotum has several temperature regulatory mechanisms. As men age and their bodies change, it may be more difficult for the body to effectively maintain this lower testicular temperature. Also lifestyles that involve a lot of sitting or wearing clothing that traps heat near the testicles may impair sperm production. One of the potential causes of a low sperm count is a varicocele or dilated scrotal vein. Because more blood stays in the scrotum, researchers believe that it may increase the temperature of the scrotum and decrease sperm production.

Individuals and companies have invented methods to try to keep the scrotum cool. The one I am most familiar with uses evaporative cooling to reduce scrotal temperatures. We would identify candidates for this devise on the basis of a very low sperm count, lack of a varicocele, and an elevated skin scrotal temperature. The devise was a jock strap attached to a plastic tube connected to a reservoir containing water. A man needed to wear this wet jock strap under his normal clothes for at least three months. I had several highly motivated men who tried this devise. I had no patient who was able to wear the devise for a full three months. This devise was not a commercial success and is no longer available.

Sperm production

The progenitor cells, referred to above, divide to produce cells (spermatogonia) that contain the correct amount of DNA to become sperm. Unless the person has abnormal chromosomes, these pre-sperm contain the normal DNA package to potentially create a baby. On average about 10% of sperm contain an abnormal amount of DNA. Chromosomally abnormal sperm are thus uncommon. Initially pre-sperm are round in shape like normal cells. They need to be processed into the specialized cells that are functional sperm. This process occurs within the seminiferous tubes (of total length if placed end to end of 100 yards). Making sperm involves repackaging the DNA, getting rid of most of the cytoplasm, re-organizing cellular components (like mitochondria and liposomes), and creating a tail. The process takes place over about 10 weeks and requires the expression of at least 100 genes (expressed at exactly the right time and producing exactly the right amount of enzymes) to remodel these round cells into sperm. At any point in time, there are sperm in the testicles at all stages of their development. It should be no surprise that it is hard for the human body to make a good sperm.

My view is that the body makes such a large number of sperm (some men will have a billion sperm in their ejaculate), because usually it is so rare to make a good one. Most sperm produced by most men would not be able to fertilize an egg if the egg were placed directly in front of it. Aside from the basics of having a good DNA package and the motility to get to get through the female reproductive tract and find the egg, sperm must have subtle specialized features to be able to attach to and penetrate the egg.

Sperm penetration

The human egg is surrounded by a shell (zona pellucida) which is about three times as thick as a sperm's head. The sperm must get through this barrier in order to fertilize the egg. I like to visualize this as a gnat trying to fly through the peel of an orange to get to the juice. The best that a determined gnat could do is to bounce off the orange as it flies into it at a high velocity. Sperm must have specialized tools (that the gnat doesn't have) to successfully get into the egg.

The successful sperm locates the egg, attaches and tightly binds with special receptors to the zona pellucida. The sperm membrane then undergoes a number of changes which cause the sperm to change its swimming (flagella movement) pattern so that more force is directed toward the egg. Some sperm have a package of digestive enzymes (acrosome) that is a part of their heads. This package begins to leak from the head of the attached sperm and softens the proteins that make up the zona pellucida. Not all sperm have acrosomes, can bind to the zona pellucida, can undergo hyperactivation or can undergo capacitation. These are all functional features of sperm that can be tested for in research laboratories.

Sperm assessment

In clinical specialty sperm labs, a careful assessment of sperm morphology is used as a surrogate for specifically assessing for these functional properties of sperm since they strongly correlate to subtle sperm morphology. However, morphology assessments by non-specialty labs are generally useless in providing information since they are not looking for the same things. Since there are relatively few specialty sperm labs in existence, patients most commonly have semen studies in routine or general laboratories. They should not be reassured by normal sperm morphology, but should be concerned about abnormal morphology findings.

Very few sperm have a chance of getting to the egg through normal intercourse. A woman's cervix is a major barrier to the sperm (see science of infertility). Sperm with normal morphology are more likely to get through the cervix. With a decreased proportion of sperm with normal morphology, if all else is equal, it is likely to take longer for pregnancy to occur (you need to be luckier). The worse the sperm, the lower the probability of pregnancy. However, given enough time, good luck, and a highly fertile partner (which most commonly is an age issue), pregnancy may occur with a wide range of sperm quality.

IUI

Intrauterine insemination (IUI) is a commonly used pregnancy acceleration technique. The cervix is by-passed and many more sperm are placed in the uterus than would naturally have the opportunity to get there. If there is a moderate decrease in the proportion of normally shaped or functional sperm, IUI will enable many more normal sperm to get to the egg.

ICSI

When the proportion or number of normally shaped sperm is significantly decreased, IVF (in vitro fertilization) or ICSI (intracytoplasmic sperm injection) can be used to make pregnancy more likely. IVF involves placing eggs together with sperm (perhaps up to 50,000 sperm) in a small quantity of media. This process bypasses much of what sperm have to do in the female reproductive tract. However, sperm still have to get through the zona pellucida. Most programs use ICSI whenever there is major concern about the functional quality of sperm. ICSI bypasses what the sperm has to do in breaching the zona pellucida. Fertilization still requires that the sperm head (DNA package) be able to de-condense in the egg cytoplasm, contribute the centromere to direct future cell division, and provide normal DNA to supplement the DNA from the egg. ICSI can compensate for almost all sperm problems. It essentially reduces the difficulty of achieving pregnancy to female issues (primarily age).

Sometimes, failed fertilization can be the fault of the egg rather than the sperm. For example, the zona pellucida of the egg may not be able to bind to the sperm's receptors. As part of normal fertilization, after the sperm penetrates the zona pellucida and binds to the egg membrane, a substance is released which changes the zona pellucida so that no further sperm can penetrate it. This zona hardening can also occur prematurely. ICSI will also compensate for these problem.