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Infertility is a relatively common condition affecting approximately 10% of couples of reproductive age and the incidence of infertility seems to be increasing. Part of this increase is due to heightened awareness and new highly successful treatment options causing more couples to seek treatment.
The American Society of Reproductive Medicine (ASRM) defines infertility as the inability to conceive after one year of regular, unprotected intercourse. This time is shortened to six months in women over 35 because of the direct correlation between advancing female age and increased infertility.
Infertility was once considered a "female" problem. We now know that almost half of all infertile couples will have a male infertility component. This finding means that male infertility must be “ruled out” before female therapy begins. Correcting a condition, such as irregular ovulation, does little good if there are not enough “quality” sperm for fertilization.
There are many causes of infertility that are discussed in detail throughout our Web site. Quite often, there are two or more factors contributing to a couple's infertility, which is why a reproductive endocrinologist, infertility specialist will always order a complete evaluation of the female and male.
The causes of infertility can be separated into categories based upon the "organ system" that is affected. A series of “biologic events” must occur successfully for pregnancy to result. These processes include:
- The female must be capable of producing eggs that will fertilize and develop normally, and she must ovulate regularly. Ovarian factor infertility occurs when the ovaries can no longer release “healthy” eggs, which is a natural consequence of the menopause. A woman is born with a lifetime’s supply of eggs within the ovaries, a portion of which are developed during each menstrual cycle. Menopause can occur at younger ages, a condition known as premature menopause. For women, the greatest enemy of fertility is aging as there is a direct correlation between advancing age and reduced fertility. One indicator of reduced ovarian reserve is an elevated FSH level on cycle day three. When viable eggs are no longer present, the only treatment option is donor egg IVF, the use of donor embryos or adoption.
- A normal menstrual cycle culminates in ovulation of a “healthy” egg. During the first phase of the cycle, follicle stimulating hormone (FSH) directly stimulates the development of eggs within the ovarian follicles. In response to estrogen produced by the ovarian follicles, the endometrium must thicken and become more vascular to support a developing embryo. The production of progesterone after ovulation helps complete the development of an optimal endometrial lining for pregnancy during the luteal phase of the ovulatory cycle. If the endometrial lining does not develop properly to support a developing embryo infertility can result.
- The hormonal control of ovulation is referred to as the hypothalamic pituitary ovarian axis. The hypothalamus is a small gland located at the base of the brain. It produces gonadotropin-releasing hormone (GnRH) which stimulates the pituitary to produce follicle stimulating hormone (FSH). As follicles mature, they produce estrogen that stimulates endometrial development and influences FSH production. Once the eggs mature, the hypothalamus releases additional GnRH that stimulates the release of luteinizing hormone (LH) by the pituitary gland, which causes ovulation. When these processes do not occur properly anovulation (no ovulation) or oligoovulation (irregular ovulation) and infertility can occur.
- Once the eggs are ovulated from the follicles, they travel through the fallopian tubes to the site of fertilization at the distal end. If the tubes are blocked by endometriosis, scarring, or other conditions, the eggs cannot complete this journey. IVF avoids the tubes as the eggs are retrieved directly from the ovaries and fertilization takes place in the lab.
- The male must be capable of producing enough “quality” sperm to reach the egg and cause fertilization. If optimal sperm are not available (male infertility), treatment options include donor sperm, IUI, or IVF usually with intracytoplasmic sperm injection (ICSI) depending on the severity of the sperm abnormalities. ICSI often allows men with very poor sperm to father genetically related children.
- The sperm are normally ejaculated into the vagina and must travel in the cervical mucus through the cervix and into the uterus. The cervical mucus must be of the correct consistency and be free of antisperm antibodies. Antibodies seek to destroy sperm in the same manner as viruses and bacteria. If antibodies are present, IUI is often effective because the sperm are placed directly into the uterus, thus avoiding the cervical mucus. The presence of antisperm antibodies can lead to infertility.
- The lining of the uterus, the endometrium, must thicken and become more vascular to support the developing embryo. This development occurs under the influence of progesterone and estrogen. Sometimes the endometrium does not develop properly, a condition known as a luteal phase defect. In these cases, ovulation enhancing agents or progesterone can be administered to stimulate proper development.
- Once the embryo embeds in the endometrial lining, it will divide and continue its growth. The uterus must be normally shaped and free of large defects such as polyps or fibroids. An abnormally shaped uterus can sometimes be treated surgically as can polyps and fibroids.
- The developing embryo must be free of major genetic defects, such as aneuploidy (abnormal number of chromosomes) which can cause miscarriage. In some cases, embryos will be screened using preimplantation genetic diagnosis (PGD).
Infertility tests examine each of the processes above. For example, day 3 hormone evaluations can provide “clues” to egg quality. The hysteroscope is used to examine the inside of the uterus and can also be used to remove fibroids and polyps. The laparoscope is used to examine the reproductive organs and treat conditions such as endometriosis. The common fertility tests are discussed in detail in the appropriate section of our Web site.
Given the complexity of the reproductive processes, it is easy to understand why a reproductive endocrinologist / fertility specialist should always be consulted especially if the female is in her thirties. Often, these couples do not have the “biologic time” to waste on treatments, such as extended clomiphene citrate, Clomid®, therapy. A fertility specialist will rule out all known causes of infertility before beginning treatment.
Infertility Causes
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