An overview of the reproductive process
The female reproductive system is a wonderfully complex system involving continuous communication between the brain centers and the ovary. Hormones secreted by the hypothalamus, the pituitary, and the ovary are the messengers which regulate the monthly cycle.
The hypothalamus is located centrally in the brain and communicates by way of an exchange of blood with the pituitary gland. Several neuroendocrine agents, or hormones, are produced by the hypothalamus. The one which is most important for reproduction is called gonadotropin releasing hormone or better known as GnRH. It is released in a pulsatile fashion every 60-120 minutes.
GnRH stimulates (or causes) the pituitary gland to produce the hormone responsible for causing the release of FSH (follicle stimulating hormone) which starts egg (oocyte) development and causes the level of estrogen (the primary female hormone) to rise. Luteinizing hormone (LH), the other pituitary hormone, aids in egg development and maturation and causes ovulation.
The main function of the ovaries is the production of eggs and hormones. At birth, the ovaries contain thousands of immature eggs. No new eggs will be developed. These eggs are constantly undergoing a process of development and loss.
Most will die without reaching maturity. This process of egg loss occurs at all times including before birth, before puberty, and while on birth control pills. It is a constant process of oocyte (egg) depletion. As the levels of FSH and LH in the blood increase with puberty, the eggs begin to mature and a collection of fluid (the follicle) begins to develop around each.
The first day of menses is identified as cycle day one. Estrogen is at a low point. Therefore, the pituitary secretes FSH and LH. These hormones in turn stimulate the growth of several ovarian follicles (each containing one egg). The number of follicles in the “cohort” of developing follicles each month is unique to each individual.
One follicle will soon begin to grow faster than others. This is called the dominant follicle. As the follicle grows, blood levels of estrogen rise significantly by cycle day seven. This increase in estrogen begins to inhibit the secretion of FSH. The fall in FSH allows the withering away of smaller follicles. They are, in effect, “starved” for FSH.
When the level of estrogen is sufficiently high, it produces a sudden release of LH, usually around day thirteen of the cycle. This LH peak (surge) triggers a complex set of events within the follicles that result in the final maturation of the egg and follicular rupture with egg extrusion. The rupture, called ovulation, takes place 28-48 hours after the onset of the LH surge and 10-12 hours after LH reaches its peak.
The cells in the ovarian follicle that are left behind after ovulation undergo a transformation and become the so-called corpus luteum. In addition to estrogen, they now produce high amounts of progesterone to prepare the lining of the uterus for pregnancy implantation.
The luteal phase, or second half of the menstrual cycle, begins with ovulation and lasts approximately 14 days (typically 12-15 days). During this period, changes occur which will support the fertilized egg (embryo) should pregnancy result. The hormone responsible for these changes is progesterone and it is manufactured by the corpus luteum.
Under the influence of progesterone, the uterus begins to change its character, creating a highly vascularized bed for a fertilized egg. The corpus luteum produces progesterone until about 10 weeks gestation, if a pregnancy occurs. Otherwise if no embryo implants, the circulating levels of hormone decline with the degeneration of the corpus luteum, the lining of the uterus (endometrium) degenerates, and bleeding results (menses).
The lining of the uterus prepares each month for the implantation of an embryo. This preparation occurs under the influence of estrogen and progesterone from the ovary. If no pregnancy develops, the endometrium is shed as a menstrual period about 14 days after ovulation.
In order for a pregnancy to occur, three steps must be accomplished: 1) the sperm must be deposited and transported to the site of fertilization, 2) ovulation must occur, and 3) union between the sperm and egg must result.
The transport of sperm is dependent upon several factors. The sperm must be capable of propelling themselves through the environment of the female vagina and cervix. This environment, which is under cyclic hormonal control, must be favorable to admit the sperm without destroying them. Finally, the sperm must possess the capability of converting to a form that can penetrate the cell membrane of the egg (capacitation).
Following ejaculation, the semen forms a gel which provides protection for the sperm from the vagina. The gel is liquified within 20-30 minutes by enzymes from the prostate gland. This liquefaction is important to free the sperm so transportation may occur. The seminal plasma is left in the vagina. The protected sperm with the greatest motility travel through the layers of cervical mucus that guard the entrance to the uterus.
During ovulation, this barrier becomes thinner and changes its acidity creating a friendlier environment for the sperm. Once the sperm have entered the uterus, contractions propel the sperm upward into the fallopian tubes. The first sperm enter the tubes minutes after ejaculation.
Egg transport begins at ovulation and ends once the egg reaches the uterus. Following ovulation, the fimbriated end of the fallopian tube sweeps over the ovary. Adhesive sites on the tube, which are located on the surface of the fimbriae, are responsible for egg pickup and movement into the tube. Transport through the tube requires about 30 hours.
Once the egg arrives at a specific portion of the tube called the ampullary-isthmic junction, it rests for another 30 hours. Then it begins rapid descent to the uterus. This period of rest in the tube appears to be necessary for full development of the fertilized egg and preparation of the uterus for receipt of the egg. Defects in the process may increase the risk of tubal (ectopic) pregnancy.
Following ovulation, the egg is capable of fertilization for approximately 24 hours. Fertilization occurs in the ampulla, or the widest segment of the fallopian tube. Contact between the egg and sperm is random. A membrane (shell) surrounding the egg, the zona pellucida, has two major functions in fertilization. First, the zona pellucida contains sperm receptors which are species specific (specific for human sperm). Second, once the membrane has been penetrated by the sperm it becomes impermeable to penetration by other sperm.
Once fertilization occurs, the embryo starts dividing into cells. There are several stages. However, once the embryo reaches the blastocyst stage (approximately 6 days after fertilization), it hatches out of its zona pellucida (shell) and begins the process of implantation. In nature, 50% of all fertilized eggs are lost before a woman’s missed menses.
So, too, in the IVF process an embryo may begin to develop but not make it to the blastocyst stage (the first stage where those cells destined to become the fetus separate from those which will become the placenta). The blastocyst may implant but not grow or the blastocyst may grow and still cease development before the two-week time at which a pregnancy can be detected. The receptivity of the uterus and the health of the embryo are important for the implantation process.