Process and Effects
The process of conception begins with the act of intercourse. When the male’s penis is inserted into the female’s vagina, the stimulation of the penis by movement within the vagina triggers a reflex resulting in the ejaculation of sperm. During ejaculation, involuntary muscles in many of the male reproductive organs contract, causing semen, a mixture of sperm and fluid, to move from its sites of storage out through the urethra within the penis.
The average volume of semen in a typical human ejaculation is only 3.5 milliliters, but this small volume normally contains two hundred million to four hundred million sperm. Other constituents of semen include prostaglandins, which cause contractions of involuntary muscles in both the male and the female; the sugar fructose, which provides energy to the sperm; chemicals that adjust the activity of the semen; and a number of enzymes and other chemicals.
In a typical act of intercourse, the semen is deposited high up in the woman’s vagina. Within a minute after ejaculation, the semen begins to coagulate, or form a clot, because of the activation of chemicals within the semen. Sperm are not able to leave the vagina until the semen becomes liquid again, which occurs spontaneously fifteen to twenty minutes after ejaculation.
Once the semen liquefies, sperm begin moving through the female system. The path to the ovum (if one is present) lies through the cervix, then through the hollow cavity of the uterus, and up through the oviduct, where fertilization normally occurs. The sperm are propelled through the fluid within these organs by the swimming movements of their tails called flagella, as well as by female organ contractions that are stimulated by the act of intercourse and by prostaglandins contained in the semen. The contractions allow sperm to reach the oviduct within five minutes after leaving the vagina, a rate of movement that far exceeds their own swimming abilities.
Although some sperm can reach the oviduct quite rapidly, others never enter the oviduct at all. Of the two hundred million to four hundred million sperm deposited in the vagina, it is estimated that only one hundred to one thousand enter the oviducts. Some of the other millions of sperm may be defective, lacking the proper swimming ability. Other apparently normal sperm may become lost within the female’s organs, possibly trapped in clefts between cells in the organ linings. The damaged and lost sperm will eventually be destroyed by white blood cells produced by the female.
Sperm movement through the female system is enhanced around the time of ovulation. For example, at the time of ovulation, the hormones associated with ovulation cause changes in the cervical mucus that aid sperm transport. The mucus at that time is extremely liquid and contains fibers that align themselves into channels, which are thought to be used by the sperm to ease their passage through the cervix. The hormones present at the time of ovulation also increase the contractions produced by the uterus and oviduct, and thus sperm transport through the structures is enhanced as well.
During transport through the female system, sperm undergo a number of important chemical changes, collectively called capacitation, that enable them to fertilize the ovum successfully. Freshly ejaculated sperm are not capable of penetrating the layers surrounding the ovum, a fact that was uncovered when scientists first began to experiment with in vitro fertilization (the joining of sperm and ovum outside the body). Capacitation apparently occurs during transport of the sperm through the uterus and possibly the oviduct, and it is presumably triggered by some secretion of the female reproductive system. With in vitro fertilization, capacitation is achieved by adding female blood serum to the dish that contains the sperm and ovum. Capacitation is not instantaneous; it has been estimated that this process requires an hour or more in humans. Even though the first sperm may arrive in the vicinity of the ovum within twenty minutes after ejaculation, fertilization cannot take place
until capacitation is completed. In 2003, scientists discovered that sperm has a type of chemical sensor that causes the sperm to swim vigorously toward concentrations of a chemical attractant. While researchers long have known that chemical signals are an important component of conception, the 2003 findings were the first to demonstrate that sperm will respond in a predictable and controllable way, a fact promising for future contraception and fertility research.
The site where ovum and sperm typically come together is within the oviduct. At the time of ovulation, an ovum is released from the surface of the ovary and drawn into the upper end of the oviduct. Once within the oviduct, the ovum is propelled by contractions of the oviduct and possibly by wavelike motions of cilia, hairlike projections that line the inner surface of the oviduct. It takes about three days for the ovum to travel the entire length of the oviduct to the uterus, and since the ovum only remains fertilizable for twelve to twenty-four hours, successful fertilization must occur in the oviduct.
Upon reaching the ovum, the sperm must first penetrate two layers surrounding it. The outermost layer, called the corona radiata, consists of cells that break away from the ovary with the ovum during ovulation; the innermost layer, the zona pellucida, is a clear, jellylike substance that lies just outside the ovum cell membrane. Penetration of these two layers is accomplished by the release of enzymes carried by the sperm. Once through the zona pellucida, the sperm are ready to fertilize the ovum.
Fertilization occurs when a sperm fuses its membrane with the membrane of the ovum. This act triggers a protective change in the zona pellucida that prevents any additional sperm from reaching the ovum and providing it with extra chromosomes. Following fusion of the fertilizing sperm and ovum, the chromosomes of each become mingled and pair up; the resulting one-celled zygote contains a complete set of chromosomes, half contributed by the mother and half by the father.
It is at the moment of fertilization that the sex of the new child is decided. Genetic sex is determined by a pair of chromosomes denoted X and Y. Female body cells contain two Xs, and each ovum produced contains only one X. Male body cells contain an X and a Y chromosome, but each sperm contains either an X or a Y chromosome. Men usually produce equal numbers of X- and Y-type sperm. The sex of the new individual is determined by which type of sperm fertilizes the ovum: If it is a Y-bearing sperm, the new individual will be male, and if it is an X-bearing sperm, the new individual will be female. Since entry of more than one sperm is prohibited, the first sperm to reach the ovum is the one that will fertilize it.
Following fertilization, the zygote or early embryo begins a series of cell divisions while it travels down the oviduct. When it arrives at the uterus about three days after ovulation, the zygote will be in the form of a hollow ball of cells called a blastocyte. Initially, this ball of cells floats in the fluid-filled cavity of the uterus, but two or three days after its arrival in the uterus (five to six days after ovulation), it will attach to the uterine lining. In 2003, researchers made an exciting discovery when they identified how embryos stop and burrow into the lining of a woman’s uterus. A protein, called L-selectin, on the surface of the embryo acts like a puzzle piece when it touches and quickly locks into carbohydrate molecules found on the uterine surface. This implantation process must occur in exact synchrony during a very short time in a woman’s cycle. (If it occurs outside the uterus, usually in one of the Fallopian tubes, then the result is an ectopic pregnancy, which is often a medical emergency.) In the weeks following conception, the cells of the zygote will form the fetus and the placenta, which surrounds and provides nutrients to the fetus. Over the next nine months, the fetus will increasingly take on a human form, developing muscle tissue, bone, organs, and skin. Pregnancy typically lasts for forty weeks from conception until childbirth. .
Complications and Disorders
Three factors limit the time frame in which conception is possible: the fertilizable lifetime of the ovulated ovum, estimated to be between twelve and twenty-four hours; the fertilizable lifetime of ejaculated sperm in the female tract, usually assumed to be about forty-eight hours; and the time required for sperm capacitation, which is one hour or more. The combination of these factors determines the length of the fertile period, the time during which intercourse must occur if conception is to be achieved. Taking the three factors into account, the fertile period is said to extend from forty-eight hours prior to ovulation until perhaps twenty-four hours after ovulation. For example, if intercourse occurs forty-eight hours before ovulation, the sperm will be capacitated in the first few hours and will still be within their fertilizable lifetime when ovulation occurs. On the other hand, if intercourse occurs twenty-four hours after ovulation, the sperm will still require time for capacitation, but the ovum will be near the end of its viable period. Thus the later limit of the fertile period is equal to the fertilizable lifetime of the ovum, minus the time required for capacitation.
Obviously, a critical factor in conception is the timing of ovulation. In a typical twenty-eight-day menstrual cycle, ovulation occurs about halfway through the cycle, or fourteen days after the first day of menstrual bleeding. In actuality, cycle length varies widely from month to month. It appears that generally the first half of the cycle is more variable in length, with the second half more stable. Thus, no matter how long the entire menstrual cycle is, ovulation usually occurs fourteen days prior to the first day of the next episode of menstrual bleeding. Therefore, it is relatively easy to determine when ovulation occurred by counting backward, but difficult to predict the time of ovulation in advance.
Assessment of ovulation time in women is notoriously difficult. There is no easily observable outward sign of ovulation. Some women do detect slight abdominal pain about the time of ovulation; this is referred to as Mittelschmerz, which means, literally, pain in the middle of the cycle. This slight pain may be localized on either side of the abdomen and is thought to be caused by irritation of the abdominal organs by fluid released from the ovary during ovulation. Other signs of ovulation are an increased volume of the cervical mucus and flexibility of the cervix and a characteristic fernlike pattern of the mucus when it is dried on a glass slide. There is also a slight rise in body temperature after ovulation, which again makes it easier to determine the time of ovulation after the fact rather than in advance. It is also possible to measure the amount of luteinizing hormone (LH) in urine or blood; this hormone shows a marked increase about sixteen hours prior to ovulation. Home test kits to detect LH levels are available for urine samples. There are additional signs of the time of ovulation, such as a slight opening of the cervix and a change in the cells lining the vagina, that can be used by physicians to determine the timing and occurrence of ovulation.
Since ovulation time is so difficult to detect in most women on an ongoing basis, most physicians would counsel that, to achieve a pregnancy, couples should plan on having
intercourse every two days. This frequency will ensure that sperm capable of fertilization are always present, so that the exact time of ovulation becomes unimportant. A greater frequency of intercourse is not advised, since sperm numbers are reduced when ejaculation occurs often. Approximately 85 to 90 percent of couples will achieve pregnancy within a year when intercourse occurs about three times a week.
Couples often wonder if it is possible to predetermine the sex of their child by some action taken in conjunction with intercourse. Scientists have found no consistent effect of diet, position assumed during intercourse, timing of intercourse within the menstrual cycle, or liquids that are introduced into the vagina to kill one type of sperm selectively. In the laboratory, it is possible to achieve partial separation of sperm in a semen sample by subjecting the semen to an electric current or other procedure due to the physical difference of X- and Y-containing sperm. The separated sperm can then be used for artificial insemination (the introduction of semen through a tube into the uterus). This method is not 100 percent successful in producing offspring of the desired sex and so is available only on an experimental basis.
Some couples have difficulty in conceiving a child, in a few cases as a result of some problem associated with intercourse. For example, the male may have difficulty in achieving erection or ejaculation. The vast majority of these cases are caused by psychological factors such as stress and tension rather than any physiological problem. Fortunately, therapists can teach couples how to overcome these psychological problems.
About 10 to 15 percent of couples suffer from some type of biological infertility—that is, infertility that persists for more than one year when intercourse occurs successfully. In about 10 to 20 percent of the cases of infertility, doctors are unable to establish a cause. About one-third of infertility cases are caused by the female partner's problems, while another one-third of infertility cases are caused by the male partner's problems. The remaining cases of infertility are caused by both male and female problems or are unexplained..
In men, the most commonly diagnosed cause of infertility is low sperm count. Sometimes low sperm count is caused by a treatable imbalance of hormones. If not treatable, this problem can sometimes be circumvented by the use of pooled semen samples in artificial insemination or through in vitro fertilization. In vitro fertilization may also be a solution for men who produce normal numbers of sperm but whose sperm lack swimming ability. Another cause of male infertility is blockage of the tubes that carry the semen from the body, which may be caused by a previous infection. Surgery is sometimes successful in removing such a blockage. Another problem, called varicocele, occurs when the veins on the testicle are too large or do not properly circulate blood. This causes the testicles to overheat, which may affect the number or the viability of the sperm. Varicocelectomy, the surgical correction of this problem, may be performed on an outpatient basis.
In women, a common cause of infertility is a hormonal problem that interferes with ovulation. Polycystic ovarian syndrome (PCOS) is a hormone imbalance that affects normal ovulation and is the most common cause of female infertility. Women with PCOS typically have high levels of androgens and many ovarian cysts. Treatment with one of a number of so-called fertility drugs may be successful in promoting ovulation. Clomiphene, a selective estrogen receptor modulator (SERM), is the most commonly prescribed fertility medication. Fertility drugs, however, have some disadvantages: They have a tendency to cause ovulation of more than one ovum, thus raising the possibility of multiple pregnancy, which is considered risky; and they may alter the environment of the uterus, making implantation of a resulting embryo less likely. Therefore, other causes of infertility, both male and female, should be ruled out before fertility drugs are used.
Another common cause of female infertility is blockage of the oviducts or the fallopian tubes resulting from scar tissue formation in the aftermath of some type of infection or prior surgery. Because surgery is not always successful, this condition may require the use of in vitro fertilization or the new technique of surgically introducing ova and sperm directly into the oviduct at a point below the blockage. Another cause of female infertility is an abnormally shaped uterus, which may interfere with the fertilized egg's ability to attach to the uterine wall. Uterine fibroids, noncancerous growths in the uterus, are very common among women and most often cause no symptoms; however, in certain cases, uterine fibroids can make it difficult for the fertilized egg to attach to the uterine wall. Surgery may be performed to shrink or remove the fibroids.
Finally, some cases of infertility result from biological incompatibility between the man and the woman. It may be that the sperm are unable to penetrate the cervical mucus, or perhaps that the woman’s immune system treats the sperm cells as foreign, destroying them before they can reach the ovum. Techniques such as artificial insemination and in vitro fertilization offer hope for couples experiencing these problems.
Perspective and Prospects
For most of history, the events surrounding conception were poorly understood. For example, microscopic identification of sperm did not occur until 1677, and the ovum was not identified until 1827 (although the follicle in which the ovum develops was recognized in the seventeenth century). Prior to these discoveries, people held the belief espoused by early writers such as Aristotle and Galen that conception resulted from the mixing of male and female fluids during intercourse.
There was also confusion about the timing of the fertile period. Some early doctors thought that menstrual blood was involved in conception and therefore believed that the fertile period coincided with menstruation. Others recognized that menstrual bleeding was a sign that pregnancy had not occurred; they assumed that the most likely time for conception to result was immediately after the menstrual flow ceased. It was not until the 1930s that the first scientific studies on the timing of ovulation were completed.
Since there was little scientific understanding of the processes involved in conception, medical practice for most of human history was little different from magic, revolving around the use of rituals and herbal treatments to aid or prevent conception. Gradually, people rejected these practices, often because of religious teachings. By the twentieth century, conception had been established as an area of intense privacy, thought by physicians and the general public to be unsuitable for medical intervention.
In the early part of the twentieth century, the role of physicians in aiding conception was mostly limited to educating and advising couples finding difficulty in conceiving. There were few techniques, other than artificial insemination and fertility drug treatment, available to assist in conception at that time.
The situation changed with the first successful in vitro fertilization in 1978. This event ushered in an era of intense medical and public interest in assisting conception. Other methods to aid conception were soon introduced, including embryo transfer, frozen storage of embryos, and surgical placement of ova and sperm directly into the oviduct.
Paralleling the development of these techniques has been demand on the part of society for medicine to apply them. In most developed countries, infertility rates have been gradually increasing. One reason for increased infertility has been the increasing age at which couples decide to start a family, since the fertility of women appears to undergo a decline past the age of thirty-five. Another factor affecting fertility rates of both men and women has been an increased incidence of various sexually transmitted diseases, which can result in chronic inflammation of the reproductive organs and infertility caused by scar tissue formation.
People’s attitudes toward medical intervention in conception have also changed. The earlier taboos against interference in conception have been somewhat relaxed, although some individuals still do not approve of certain methods of fertility management. Although there remain ethical issues to be resolved, the general public seems to have accepted the idea that medicine should provide assistance to those who wish to, but cannot, conceive children.
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