Male fertility and infertility
How are sperm produced?
Sperm are produced in the testicles in tiny, coiled tubes called seminiferous tubules. Stem cells for sperm are found in the walls of the semeniferous tubules. when the cells divide, they go through a process called meiosis which gives the sperm the correct number of chromosomes and another process which gives the sperm it characteristic appearance. during the final changes of cell division, the nearly mature sperm call is deposited into the lumen of the semeniferous tubule.
The semeniferous tubules merge together and will move the sperm toward these larger tubes. Eventually, all of the tubules will have merged into one main, large tube called the epididymis. It takes a few months for the sperm to get to this point. Sperm in the epididymis are still not mature enough to move on their own. They are pushed through the epididymis by contraction in the muscle in the wall of the tube. The epididymis is tightly coiled. If the epididymis were stretched out, it would measure about 20 feet long. During their passage through the epidiymis, the sperm will continue to mature and develop. It takes about two weeks for the sperm to move all the way through the epididymis.
From the epididymis, the now mature sperm move into a tube called the vas deferens. Sperm are stored in the vas deferens until ejaculation. The vas deferens also contains muscle in the wall which contracts during the male orgasm and expels the sperm out through the penis. Most men can restore their sperm counts in less than 24 hours following ejaculation. It may take longer in older men or men with sperm production problems. The entire process of sperm production takes 70 to 90 days with at least 17 stages of sperm that can be identified before reaching the vas deferens.
Fluid is added to the sperm in the vas deferens. This seminal fluid is largely due to a gland called the seminal vesicle. An average man will produce from 1-5 milliliters of fluid during ejaculation. During a vasectomy, the vas deferens is cut to block the escape of sperm into the ejaculate. Fluid from the seminal vesicle will still come out and so men who have had a vasectomy will still see fluid emerge from the penis during orgasm.
At the time of ejaculation, the fluid is thick like a gel. On average it takes about 30 minutes for the fluid to liquefy. This liquefaction allows the sperm to swim more easily.
Unlike women, who have all the eggs they are ever going to have in their life before they are born, men produce sperm continuously all during their lives.
Several hormones are necessary to maintain the process of sperm production. FSH is a hormone from the pituitary gland which stimulates the semeniferous tubules to produce sperm. In order to produce sperm, testosterone production form other cells in the testicles is needed. LH is a second hormone from the pituitary gland which stimulates the testicles to produce testosterone.
Sperm delivery to the egg
During intercourse, the sperm are released into the vagina. The vagina is very acidic and most sperm will be killed. It is thought that one of the functions of the seminal vesicle is to provide fluid that is “basic” (the opposite of acidic) to protect the sperm while in the vagina. It is possible that men with low semen volume may lack this protection.
The sperm will travel under their own power through the vagina until they reach the cervix. The cervix is the small opening to the uterus. The cervix produces mucous which limits what can enter the uterus. During the early portion of the female menstrual cycle, the cervical mucous is thick and few sperm can get into the uterus. As ovulation approaches, the female makes increasing amounts of estrogen which causes the cervical mucous to become thinner and more watery. This allows more sperm into the uterus.
The cervix also contains deep channels. Together with the mucous, the sperm will get caught in these channels. Nutrients in the cervical mucous can keep the sperm alive for several days. It is for this reason that pregnancy is possible even if a couple has intercourse several days before ovulation occurs.
Once the sperm passes the cervical canal, there are few obstacles to reaching the egg. The sperm passes through the uterus and eventually into the fallopian tubes where the egg is met.
Even though tens of millions of sperm are released into the vagina, only a few sperm reach the egg in the fallopian tube.
Does lowering the frequency of intercourse improve sperm concentration?
No. At some point, the number of sperm made daily begins to equal the amount which die while being stored. In addition, the movement of the sperm (motility) starts to decrease with increasing length of time stored.
Overview of male infertility
It has been stated that male issues alone can be the cause of a couple’s infertility in 40% of cases and a part of the problem in another 20% of cases. These numbers, however, are essentially meaningless. They will vary greatly depending on the patient population and how intently infertility causes are searched for.
Male infertility is due to the complete absence of sperm in the ejaculate and is relatively uncommon. Male subfertility can be due to low numbers of sperm, a low percentage of sperm with effective progressive movement or abnormalities in the sperm’s ability to fertilize an egg. Finally, male subfertility may be due to the inability to produce an embryo which is capable of normal development and implantation.
Azoospermia — no sperm are present in the ejaculate
The complete absence of sperm in the ejaculate can be due to two different causes: obstruction in the pathway between the testicles and the outside or the failure of production of the sperm in the testicles.
Obstruction as a cause for male infertility with no sperm
At the top of this article, we learned that there is a continuous channel that runs from the cells in the testicle all the way to the tip of the penis. Blockage of this channel anywhere along is course can prevent sperm from getting out. An obvious example is when a man has a vasectomy. The vas deferens are tied and this prevents sperm from reaching the penis.
A natural cause for obstruction is the absence of the vas deferens. Men can be born without a vas deferens. This problems is often referred to as Congenital Bilateral Absence of the Vas Deferens (CBAVD). Normally, the vas deferens can be felt during a physical exam of the scrotum. In addition, almost all men with CBAVD will have a low volume of ejaculated fluid. The pH of the fluid will be more acidic than normal.
Almost all men with cystic fibrosis will have CBAVD. It is important therefore, if a man has no sperm in his ejaculate, to perform a blood test to look for the gene mutation which causes cystic fibrosis. Even men without cystic fibrosis who carry a single gene mutation in the cystic fibrosis gene will sometimes suffer from CBAVD.
Another common cause of obstruction can be infection in the prostate gland or urinary tract. Infection may lead to swelling which causes temporary obstruction or scarring which may cause permanent obstruction.
In some cases, obstruction can be treated with surgery to remove the blocked portion of the male tubing. In other cases, sperm can be aspirated from the testicle, epididymus, or vas deferens prior to the obstruction and then used for IVF. If a man plans to have surgery to fix a blockage on the vas deferens, he should insist that his urologist aspirate sperm during the surgery to be frozen for future use in case the surgery fails to remove the obstruction.
Failure of sperm production as a cause for male infertility with no sperm
In some cases, a man can be born without the cells that generate sperm. They still have the cells which produce hormones however so the testicle may appear to be normal to the eye. This is called Sertoli Cell Only. This diagnosis can be made by performing a biopsy of the testes and looking at the tissue under the microscope. Occasionally, men may have only a few tiny spots were sperm producing cells are present. It can be difficult or impossible to determine whether a man has no sperm producing cells or very few sperm producing cells.
Why is this so important to determine? One reason is that if a few sperm producing cells can be found in a testicular biopsy, it may be possible to freeze these sperm and use them later for IVF. If no sperm producing cells are found then using donor sperm is the only option.
The sperm producing cells in the testicle can also be damaged or destroyed. In the past, a common cause for azoospermia was infection with the mumps. The virus which causes the mumps can attack the testicles resulting in a condition called mumps orchiitis (inflammation of the testicles) which often resulted in sterility. In the United States, most children are vaccinated against the mumps so that this cause for male sterility is rare.
Men with damaged testicles or who were born without sperm producing cells can be identified by blood testing of hormones. In many cases, this enables doctors to distinguish between failure of sperm production and obstruction.
In some cases, genetic or chromosomal abnormalities can be the cause for absent sperm production. One problem, known as Klinefelter’s syndrome, is caused by men having an extra chromosome. Instead of having two copies of every chromosome for a total of 46, men with Klinefleter’s syndrome have 47 chromosomes due to an extra “X” chromsome. As a result, men with Klinefelter’s syndrome have three sex chromosomes, two “X” chromosomes and one “Y” chromosome. The presence of this extra sex chromosome interferes with normal sperm production. In some men with Klinefelter’s Syndrome, small spots of sperm production have been identified with testicular biopsy and these sperm have been used with IVF to produce childdren. Chromosome testing of the embryos (PGD ) is used to avoid passing the problem on to sons.
The “Y” chromosome is where most of the genes responsible for sperm production are located. Men with azoospermia have been found to have portions of the “Y” chromosome missing or altered. Some of these gene “deletions” can be identified with genetic testing using a sample of tissue obtained from a cheek swab.
Male hormone problems can result in the complete absence of sperm or low numbers of sperm. In order to function properly, the testicles must be stimulated by the presence of certain hormones. Hormones from the pituitary gland are required to simulate sperm production . Blood testing for these hormones (FSH and LH) can determine whether there is inadequate stimulation to produce sperm. In this condition, testosterone levels are also usually low. Treatment can be attempted with either oral medications to stimulate the pituitary gland to produce more hormones (clomiphene citrate) or with injections that take the place of the hormones (human chorionic gonadotropin or hCG). Occasonally, overproduction of another pituitary hormone called prolactin can interfere with the production of the hormones FSH and LH and result in poor sperm production. This can also be detected by a simple blood test. There are a few types of oral medications that can treat this condition (Parlodel, Dostinex). Imbalance in thyroid hormone production is yet another cause of sperm production failure. The thryoid gland can over produce hormone (hyperthyroidism) or under produce (hypothyroidism). Both conditions can be detected by blood tests and both can be treated with medication.
A few years ago, fertility doctors from New York discovered a new type of hormonal imbalance that causes inadequate production of sperm. In these men, who are often overweight, the levels of specific hormones are all in the normal range. However, the ratio of two hormones testosterone and estradiol is out of balance. Bascially, the amount of testosterone is too low relative to the amount of estradiol. Fortunately, oral medications are available that will correct the ratio and in many men this will result in improved sperm production.