Getting Pregnant Naturally

How to Get Pregnant
by Sherman J. Silber, M.D., F.A.C.S.

For any couple having difficulty conceiving, for any reason, How to Get Pregnant lays out in straightforward, simple terms the basic information that will help them understand their situation and achieve their goal-a happy, healthy baby. Dr. Silber starts with the essential facts of getting pregnant, including normal variations in how long it can take for a couple to conceive and the most common problems that arise. He discusses in detail how age affects fertility-including tests that allow women to determine how many years of fertility they have remaining.

And for every situation, no matter how complicated, he explains the procedures that can help even the most frustrated couples become pregnant.

From the most basic issues of timing to hormone supplements and medical procedures that can help solve once-insurmountable fertility problems, Dr. Silber offers clear answers, practical advice, and compassionate support. He also explains what you can do to help ensure that your baby is healthy and explains how you can help preserve your fertility for the future.

Whether you have just begun to consider parenthood or have been trying for some time to have a baby, Dr. Silber's How to Get Pregnant is the one and only book you will need.

Chapter 1

Getting pregnant is not an easy task, but understanding the essential physiology of the process is the best place to start. In this chapter I will describe the arduous journey that sperm must make through the female genitals to reach the egg, as well as the simultaneous adventure of the egg during which it matures to become genetically ready for fertilization, erupts from the ovary, and gets grabbed by the fallopian tube, fertilized, and then hustled along into the womb at exactly the right moment to implant. Failure of the sperm or egg to make an important connection anywhere along this complicated itinerary will prevent pregnancy from occurring.

A Brief Review of Female Anatomy

The vagina is an elastic canal, about four to five inches long. At the end of this canal, in the deepest recess of the vagina, is a structure called the cervix, which is the entrance to the womb, or uterus. The uterus is a hard, muscular, pear-shaped structure with a narrow, triangular cavity inside, so small that it would barely hold a teaspoonful of fluid. Yet this is where the fertilized egg must implant itself and grow during the next nine months into a full-size baby. The uterus has a remarkable capacity to expand to allow room for the developing baby, pushing aside and squashing all the other organs of the mother's abdomen.When the baby is ready to be born, the muscles of the uterus contract during labor to squeeze the baby out into the world.

Far back in the corners of the uterus, on each side, are microscopic canals through which the sperm must squeeze in order to reach the fallopian tube, where it may encounter an unfertilized egg. Once the egg has been fertilized, it will pass through the canal in the opposite direction to reach the uterus. These microscopic canals leading from the uterus into the fallopian tubes are only about one-seventieth of an inch in diameter (the size of a pinpoint). The fallopian tubes are four inches long and hang freely in the abdomen. They widen at the ends into large, flowerlike openings called fimbriae.

The ovaries are the organs that make the female's eggs and sex hormones. They lie outside of the uterus and fallopian tubes.When an egg is extruded every month from the surface of one of the ovaries (ovulation), it is released freely into the abdominal cavity rather than directly into the tube. The fimbria then comes to life like an octopus tentacle and actively grasps the egg, pulling it into the fallopian tube. The tube swallows the egg, nourishes it before and during fertilization for three days, and then transports it into the uterus.

While the male produces billions of sperm every week, the female matures only one of her existing eggs for ovulation each month. The ovaries mature and release about four hundred such eggs during the course of a woman's lifetime. Generally, the most fertile eggs are released earlier in life, and of her limited supply of four hundred thousand, about one thousand eggs will die inexorably every month. Thus with advancing years, though a woman may still be able to get pregnant, she is much less fertile than she was in her youth.

How Do the Egg and the Sperm Reach the Fallopian Tube?

The journey of the egg, or ovum, through the fallopian tube and finally into the uterus after fertilization is extraordinarily hazardous. The woman's tube is not simply a passive channel through which the egg is transferred; many events must work in precise synchrony for successful pregnancy to occur.

There are, on the surface of the fimbria, microscopic hairs called cilia, which constantly beat in the direction of the uterus at a fantastically rapid speed and create a kind of conveyor-belt effect for moving the egg into the tube and toward the uterus. The cilia work this magic by digging into the sticky gel, called the cumulus oophorus, that surrounds the egg, and they transport this whole sticky, gooey mass. The egg itself is invisible to the naked eye, but the gel that envelops it is easily visible. If this sticky substance were not present, and the egg were placed bare upon the surface of the fimbria, the beating of the cilia would never move the egg along. The cilia are only able to dig in and transport the egg with this sticky, gooey material encasing it.

The process of grasping the egg and moving it into the interior of the tube requires only about fifteen to twenty seconds. Once the egg is safely within the tube, it is transported quickly toward the narrower region of the tube, the ampullary-isthmic junction, located two-thirds of the way toward the uterus. Here, the egg must wait for a successful sperm coming from the opposite direction to fight its way into the egg's tough outer membrane, the zona pellucida, score a direct hit, and thereby establish pregnancy. While the egg is held in this location by the tight resistance of the narrow region of the tube, the much tinier sperm nonetheless must struggle through this area of resistance to arrive from the opposite direction. Once it is fertilized, the egg must be nourished for several days in the ampulla of the tube before it can be allowed to pass into the uterus. If it is transferred into the uterus too soon, it will not be ready to implant, and it will die. If the transfer of the egg into the uterus is delayed too long, a tubal, or ectopic, pregnancy will occur (the fertilized egg will implant in the tube rather than the womb). Once the egg has been allowed to develop in the tube for three or more days, the isthmus suddenly opens up and the early embryo passes quickly into the uterus. Because the journey of the egg from the ovary to the site of fertilization, its nourishment in the tube, and the precise synchrony of the continuation of its journey into the womb are so intricate, problems with this egg and embryo transport process are frequently responsible for female infertility.

If the egg is not penetrated by sperm soon after ovulation, it becomes overripe and dies. After the egg is released from the ovary, it is only capable of fertilization for about twelve, or possibly at most twenty-four, hours. The likelihood of intercourse taking place during such a specific interval in any month is rather slight. So nature must provide some mechanism for providing a continuous flow of healthy sperm to the site of fertilization. That way, if intercourse is perhaps one or two days off schedule, some sperm can still arrive at the site of fertilization at the right time. For this reason, complicated barriers to sperm transport are necessary.

The success of IVF demonstrates that if eggs can be recovered at precisely the right time, they can be fertilized in the laboratory with only a small number of sperm. Then the complicated barrier mechanisms provided by nature to allow a slow, continuing flow of a small number of sperm at any moment is not necessary and the large numbers of sperm normally required for fertilization through intercourse are not needed.

Ejaculation into the Vagina

Most of the spermatozoa in the ejaculate are contained in the very first portion of fluid that squirts out of the penis and enters the vagina. The remaining squirts usually contain very little sperm. Thus, at the first moment of ejaculation the female's cervix (the opening leading into her uterus) is bathed by a high concentration of sperm. Within just a few minutes after ejaculation, sperm begin to invade a very thick fluid (called cervical mucus) that is pouring out of the cervix. The sperm must be able to invade the cervix via the cervical mucus by virtue of their own swimming ability. Nothing about the sexual act will help those sperm get into the cervix. They simply have to swim into the mucus on their own, and this requires a great deal of coordinated, cooperative activity on their part.

Ejaculation is a challenging moment for the sperm, as the vagina presents a very harsh, acidic environment, which would normally immobilize them quickly. The alkalinity of the semen (the fluid that contains the sperm), as well as the alkalinity of the cervical mucus, allows the sperm to survive in this difficult vaginal milieu. Any acidity at all quickly kills sperm.

Yet even the semen is a potentially dangerous milieu for the sperm; any sperm that remain in the semen for more than two hours are likely to deteriorate. In order to survive long enough to get to the egg and fertilize it, the sperm must gain rapid access to the cervical mucus. Any sperm that have not penetrated the cervical mucus within a half hour after orgasm will not be able to do so later on, because by then they will have lost their ability to swim into the more friendly environment of the cervix.

Sperm Invasion

Spermatozoa can be seen invading the cervical mucus within seconds after ejaculation, but most will not make it. Of some 200 million sperm deposited into the vagina near the cervix in a typical ejaculation, only 100,000 ever get into the womb. Thus, over 99.9 percent of the sperm never have a chance of getting beyond the vagina.

Once the sperm enter the canal of the cervix, they are capable of fertilizing the egg for as long as forty-eight to seventy-two hours, though they may actually live for up to six days. Remember, since the egg is only fertilizable for about twelve hours after ovulation, it is important to have a continuing flow of sperm across the tube so that whenever the egg appears, there will be sperm available. In this sense, the canal of the cervix can be looked upon as a receptacle through which platoons of spermatozoa migrate and in which some are detained in order to ensure a continuous supply of smaller numbers, over a prolonged period of time, to the deeper recesses of the female where fertilization takes place. Of course, these delaying mechanisms can do more harm than good in infertile couples if events do not allow the invasion of sperm to be mounted successfully.

To understand how this invasion of sperm gets launched effectively, we must first understand the remarkable liquid that covers the opening of the womb-the cervical mucus. The cervical mucus presents a very effective barrier to bacteria and thus protects the womb against infection. It is a selective filter, which favors normally active sperm and excludes other objects (including poor-quality sperm) from access. But it doesn't even permit access to normal sperm except during a specific period at midcycle when ovulation is imminent and fertilization is possible. Cervical mucus resembles a thick, clear liquid that can be poured from one container into another. However, in a technical sense, it is not a liquid. As it is being poured, it can actually be cut with scissors; therefore, although it seems to behave as a thick liquid, it also has the characteristics of a very pliable, transparent plastic.

Cervical mucus is absent or very scanty during most of the monthly cycle, gradually becoming more abundant around the middle of the cycle, under the influence of increasing estrogen levels,when ovulation is about to occur. Just prior to ovulation it becomes almost optically clear, although it is translucent at other times. At the moment when fertilization is possible, near the time of ovulation, the mucus can be stretched out into a very thin strand; at other times in the cycle it is more sticky, and if stretched it will break. All of these changes in the cervical mucus, which occur around the time prior to ovulation, are designed to help sperm gain access to the uterus. The more liquidlike character, the greater transparency, and the greater stretchability (called Spinnbarkheit) are all characteristics that favor the successful invasion of an army of sperm. When the mucus is sticky and thick, not as abundant, and translucent rather than transparent, it is difficult if not impossible for any sperm to gain access.

Microscopically, the cervical mucus consists of a dense mesh that, during most of the monthly cycle, represents a solid barrier to invasion. Just prior to ovulation, under the effect of the female hormone estrogen, mucus production rises tenfold, and the water content of the mucus increases. The otherwise impenetrable mesh opens up and allows a successful invasion of sperm.When semen first reaches the cervical mucus after ejaculation, a clear barrier line can be seen separating the two different fluids. Semen does not "mix"with cervical mucus. Soon, however, phalanges of sperm begin to penetrate the mucus, forming branching structures that invade it.

Observing the sperm's penetration of the cervical mucus under the microscope is an exciting event. Sperm at first seem to bounce against the cervical mucus without any evidence that they will ever be able to gain access. Their movements while in the ejaculate are haphazard and not specifically aimed toward the mucus. However, within a matter of minutes, one or two spermatozoa begin to make an indentation in the line separating the cervical mucus from the ejaculate. Once one sperm has been able to initiate the penetration of the mucus, other sperm then quickly follow at that same point of entry. Sperm then continue to invade the cervical mucus at that point much like a single-file line of army ants. Only one or two spermatozoa at a time can pass through this entrance.

The sperm swim in a straightforward direction along parallel rows of the invisible microscopic molecular structure of the mucus. Once this invasion of the cervical mucus has been established, sperm can reach the fallopian tubes in about thirty minutes.

Pregnancy would not be likely if all the sperm got into the fallopian tubes at one time, because they would soon pass on into the abdominal cavity, and not be available to fertilize the egg except during a very brief, lucky interval. If they were not lucky enough to pass through the fallopian tube at exactly the moment of ovulation (or within twelve hours of ovulation), they would be long gone by the time the egg arrived. Thus, nature had to invent some mechanism for allowing a continuous entry to the site of fertilization by a smaller number of sperm. To accomplish this, the cervix and the cervical mucus act as a reservoir from which spermatozoa are slowly released into the uterus and up to the fallopian tubes over a period of several days.

Capacitation of Sperm

During the course of their odyssey toward the site of fertilization, the sperm undergo capacitation, a process that was not fully understood before the advent of IVF. It used to be thought that unless sperm resided for a certain period of time outside the male reproductive tract and in the specific fluids of the female reproductive tract, they would not be capable of fertilization, even though in every other respect they looked normal. It was thought that this process of capacitation could occur only in the fluids of the female reproductive tract while the sperm migrated toward the egg. However, in vitro fertilization has demonstrated that capacitation of sperm (once considered one of the greatest problems in successfully achieving test-tube babies) can occur in relatively simple, nonspecific fluids available in any laboratory.

All that is necessary to start the capacitation process going is to remove the sperm from the semen by "washing" it. Removing the sperm from semen and placing them in any laboratory "culture media" fluid results in a dramatic tripling of their swimming velocity, so that even though they are mere human sperm, they begin to swim more like the sperm of horses or bulls. Thus, sperm seem to have a natural tendency toward developing capacitation for fertilization on their own and simply require a period of several hours outside the semen. In nature this happens when they leave the semen and enter the cervical mucus. In the IVF laboratory it happens when sperm are separated from the semen by virtually any washing technique.

Ovulation

Before egg and sperm can ever meet up in the fallopian tube, the egg must be matured and extruded from the ovary in a process called ovulation. Since many women who seem unable to have children owe their problems to a disturbance in ovulation, and since part of the IVF procedure involves stimulating the ovaries to prepare many eggs for fertilization, we should understand how the repeatable, monthly series of changes leading to ovulation occurs naturally in the ovary. Later we will unravel the hormonal events of the menstrual cycle, which regulate the clocklike orderliness of ovulation.

All of the hormonal events taking place during the month between menstrual periods are directed at preparing the egg to be genetically ready for fertilization, and preparing the uterus (womb) and the cervix for the moment of ovulation, so that the sperm and the egg have the best opportunity for joining up to form an embryo, which can then implant in a properly prepared uterus and result in successful pregnancy.

Formation of the Follicle

Each month, from the time of sexual maturity on, about one thousand undeveloped eggs, or oocytes, leave their prolonged resting phase and start to mature. This initiation of development is a continuous process, in marked contrast to ovulation, which occurs only once a month. Once the egg starts to develop, it proceeds inexorably and no longer has the choice of returning to being quiescent. It either wins the race to ovulate or must degenerate and die.

The most striking feature of the egg's development is the growth of its surrounding fluid-filled compartment, called the follicle. The growth of this follicle is stimulated by the hormone FSH (follicle-stimulating hormone), which is produced by the pituitary gland in the early phase of the monthly cycle. The time required for the egg to develop the proper follicle necessary for ovulation is about fourteen days. Although the FSH stimulates all of the developing eggs during the month to form follicles, one of the eggs always gets a head start over the others, and once it obtains that lead it never relinquishes it. The other eggs developing that month then degenerate. However, if large doses of FSH were to be given to a woman at the beginning of the cycle, far in excess of what her pituitary would normally secrete, she would develop many follicles instead of just one.

The mature follicle is a spherical, bubblelike structure that bulges up from the surface of the ovary, and contains the egg. The egg (which is only 1/200 of an inch in diameter) is surrounded and protected by a mass of sticky, gelatinous fluid called the cumulus oophorus and hangs on a stalk attached to the inside of the follicle wall. The rest of the fluid in the follicle is clear yellow, and the follicle itself is fairly large (four- fifths of an inch in diameter). Occasionally two follicles successfully reach maturity and are both ovulated. In that circumstance the woman may have fraternal, or nonidentical, twins. Indeed, the drugs used to stimulate ovulation in women who would not otherwise ovulate usually cause the development of more than one follicle. Therefore, multiple births are common in women who require medical treatment to help them ovulate.

Two or three days prior to midcycle, when the follicle has reached its maximum size (usually two centimeters, or four-fifths of an inch), it produces an enormous amount of the hormone estrogen. This increased level of estrogen before ovulation stimulates the cervix to make more (and clearer) cervical mucus in order to allow sperm invasion. This dramatic increase in estrogen production by the follicle then stimulates the pituitary gland to release another hormone, different from FSH, called LH (luteinizing hormone). The sudden release of LH is what triggers ovulation (see fig. 1.6). The increase in estrogen indicates to the pituitary that the follicle is ripe, and this beautifully times the release of the LH hormone. Ovulation then occurs normally thirtyeight to forty-eight hours after the beginning of this LH surge.

Release of the Egg

Under the influence of the midcycle LH surge, the wall of the follicle weakens and deteriorates, and a specific site on its surface ruptures. The contents of the bulging follicle are then extruded from the surface of the ovary through this ruptured area. Observed under a microscope, ovulation appears similar to the eruption of a volcano. Occasionally women actually feel several hours of discomfort in their lower abdomen during ovulation; this discomfort is called Mittelschmerz. In women who require hormone treatment to stimulate ovulation, so many follicles may grow so large that when ovulation occurs it causes strong cramps, and a woman may even become sick enough to require several days of rest in the hospital. However, this sort of complication is not very likely with modern dosage monitoring. It is mentioned only to underscore what a dramatic intra-abdominal event ovulation is.

Production of Progesterone

The ruptured, empty follicle then undergoes another dramatic change, called luteinization. Luteinization is the process by which the follicle becomes able to make progesterone in addition to estrogen. Prior to ovulation, the follicle could produce only estrogen; after ovulation it can produce the other female hormone, progesterone, as well. Because it is impossible for the follicle to make progesterone before ovulation, the production of progesterone implies that ovulation has occurred. In the past, the presence of progesterone used to be the basis for all clinical methods of evaluating ovulation. The production of progesterone by the transformed follicle after ovulation is necessary for the successful implantation of the embryo in the womb during the second two weeks of the cycle.

The cystlike structure that forms monthly from the ruptured follicle is called the corpus luteum. This is Latin for "yellow body" and simply signifies that the follicle turns yellow as it changes its identity. As soon as the ruptured follicle begins to produce progesterone, the cervical mucus (which had become maximally receptive to sperm invasion just prior to ovulation) is suddenly caused to become sticky and totally impermeable to the invasion of sperm. In addition, progesterone causes the entrance of the cervix to close dramatically, even though just prior to ovulation it had been gaping in readiness for the entry of sperm. In the first half of the cycle, before ovulation, estrogen stimulates the buildup of a thick, hard layer of tissue called the endometrium to line the uterus, but this lining does not become receptive to the fertilized egg until after ovulation, when the secretion of progesterone causes it to soften. If the uterine lining is not softened by progesterone after ovulation (i.e., transformed from proliferative to secretory), implantation of the embryo cannot occur.

The corpus luteum manufactures this progesterone over a very limited time. If no pregnancy develops, the corpus luteum ceases to produce progesterone by ten to fourteen days after ovulation, and subsequently disappears.With this cessation of progesterone production by the ovary, the soft lining that was built up in the womb to prepare for the nourishment of the fertilized egg is shed and the woman menstruates. The decrease in progesterone (and estrogen) levels during menstruation then stimulates a renewed increase in FSH. A new follicle then develops, estrogen production resumes, and the cycle begins again.

A Review of the Hormones That Control Ovulation
and the Menstrual Cycle

The reproductive cycle that animals go through is called the estrous cycle. Only humans and the apes have menstrual cycles. In a menstrual cycle the buildup of the lining of the womb is so lush, and the drop in hormone level supporting that lining so abrupt, that at the end of the cycle the lining actually sheds and the woman bleeds for four to five days in what is commonly known as her period. In all other animals, however, this shedding does not occur, and the thick lining of the womb merely returns to the thinned-out condition, marking the beginning of the next cycle. Furthermore, when animals are about to ovulate in their estrous cycle, they go into heat, or "estrus,"and know it is time to copulate. Since most woman are unaware of when they ovulate, they must try to understand the events of their menstrual cycle more fully, because unlike other animals,we do not automatically copulate at the right time. We will arbitrarily call the first day of the menstrual cycle "day one," which is the day that bleeding commences. Bleeding usually ceases by day four or five and in most cases resumes after day twenty-eight of the cycle. Although the first day of menstruation represents a shedding of the lining of the uterus (womb) from the previous month's cycle, it is actually the beginning (day one) of the next cycle.

On the first day of menstruation the pituitary hormone FSH is already stimulating development of a follicle that will take precedence over all other follicles that month. Interestingly, FSH, which in females causes the follicle to develop, is the exact same hormone that in males helps to stimulate sperm production. Estrogen from the developing ovarian follicle then inhibits further pituitary production of FSH. This is a "negative feedback" mechanism whereby the very estrogen that FSH causes to be produced by the ovary inhibits the pituitary from making more FSH.

By day twelve to fourteen of the menstrual cycle, the follicle appears on the surface of the ovary as a fluid-filled bubble ready to burst. In the meantime, the estrogen that has been produced by the follicle during this first half of the cycle has stimulated the uterus to prepare a thick "proliferative" lining. This thick, proliferative uterine lining is not ready to receive the egg until it is "softened" by progesterone in the second half of the cycle.

The final effect of estrogen (in high quantities at midcycle) is to trigger the release of a different pituitary hormone, LH. This enormous surge of LH from the pituitary is what causes the follicle to burst and then ovulate. But LH does more than simply cause ovulation (release of the egg from the ovary). LH triggers the chromosomes of the egg to separate and thereby prepares the egg genetically for fertilization.

Copyright © 2005 by Dr. Sherman Silber

About the Author

Sherman J. Silber, M.D., F.A.C.S., is an internationally known pioneer in infertility treatment, and is medical director of the Infertility Center of St. Louis at St. Luke's Hospital in St. Louis, Missouri. Infertile couples come from all areas of the world for treatment at his center. Dr. Silber invented the microsurgical vasectomy reversal, testicle and ovarian transplantation, and he developed the sperm aspiration and ICSI techniques for previously hopeless cases of male sterility. He is the author of four medical textbooks, more than 180 scientific papers on human fertility and reproduction, and the bestseller How to Get Pregnant, and How to Get Pregnant with the New Technology. A popular guest speaker, he has appeared numerous times on Donahue, Oprah, Joan Rivers, The Today Show, and Good Morning America.