Normal Human Reproduction and Infertility

Normal Human Reproduction	Determination of Ovulation & Female Testing	Advanced Reproductive Techniques (ART)
Female Reproduction	LH Surge	Super Ovulation
The Menstrual Cycle	Progesterone	In Vitro Fertilization (IVF)
Fertilization	Basal Body Temperature	Intracytoplasmic Sperm Injection (ICSI)
Male Reproductive System	Hysterosalpingogram	Zona Hatching
Semen	Cervical Mucus / Sperm Compatibility	Embryo Freezing
Fertility	Laparoscopy
The Emotional Response to Infertility
Infertility Evaluation		A Healthy Lifestyle & Reproduction
Evaluating the female		Summary

Normal Human Reproduction

Female Reproduction System
The female reproduction system is primarily internal. The external genitalia are known as the vulva. The vagina is the internal passage or canal, which leads to the cervix, the opening to the uterus. The uterus is a muscular organ about the size of a pear. Its lining is the endometrium. The fallopian tubes extend from the top of the uterus and reach back and downward toward the ovaries where the oocytes (eggs) are kept. The outer-most ends of the tubes are flared and have fringed "fingers" named fimbria that move to draw the egg into the tube immediately after ovulation. Along with producing mature eggs, the ovaries produce the female hormones, estrogen and progesterone, which are necessary for preparing the uterus for the implantation of the embryo, and for the maintenance of the growing embryo and fetus.

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The Menstrual Cycle
The typical menstrual cycle averages about 28 days. Day one of the cycle is the first day of menstruation, when the endometrium from the previous cycle is shed. Follicle stimulating hormone or FSH stimulates the development of the follicle that contains the maturing egg. The developing follicle is drawn from a limited pool of primordial follicles present at the time of birth. The maturing follicle produces increasing amounts of estradiol, which can be monitored by a blood test to assess the maturity of the egg(s). Near the middle of the cycle, when there is an increase in the release of luteininzing hormone or LH from the pituitary, ovulation occurs. The fimbria of the tube sweep over the ovary and collect the egg into the tube. Meanwhile, the follicle that contained the egg becomes a functioning gland given the appelliation of the corpus luteum, which produces progesterone and estrogen to stimulate the uterus into forming the lining necessary for embryo implantation.??

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Fertilization
After sexual intercourse, the egg and sperm meet in the end of the fallopian tube where conception may (or may not) occur. The fertilized egg travels down through the tube toward the uterus with the help of tiny hair-like projections termed cilia, which sweep the egg along. Once inside the uterus, the embryo implants into the uterine lining on or around the 21st day of the cycle. The corpus luteum will continue to produce progesterone, which preserves the uterine lining and therefore the pregnancy. If fertilization does not occur, the egg passes through the uterus and the corpus luteum will cease to function 12 days post ovulation. This causes the uterine lining to break down and be shed, causing the menstrual period. Pregnancy can be detected by measuring the level of a hormone identified as Human Chorionic Gonadotropin (hCG), which is produced by the developing embryo. The corpus luteum senses the pregnancy through a delicate feedback of hormones from the developing conceptus (fertilized egg).

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Male Reproductive System
Most of the male reproductive system is located outside of the body cavity. The testes are located in the scrotal sac and produce the male hormone testosterone. They also produce spermatozoa (mature sperm). Sperm are produced by repeated cellular division small coiled tubes referred to as seminiferous tubules located within the testes where sperm may be produced at a rate of up to 100 million sperm cells a day. Unlike the female’s oocytes or eggs, the precursor cells for sperm can be renewed throughout life. Sperm production is a lengthy process that lasts nearly three months from the beginning of the division of the precursor cells to the maturation of spermatozoa in ejaculate. After leaving the testicle, the sperm spend about 10-14 days passing through the epididymis (a coiled tube), during which time they mature and become capable of swimming and fertilizing the egg.

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Semen
Semen is composed of sperm and seminal fluid. The volume of seminal fluid from the testes and epididymis is less that 5 percent of the ejaculate. About 65 percent comes from the seminal vesicles and 25 percent from the prostate gland. The average semen volume for healthy men ejaculating every two to three days is two to three milliliters, or about one teaspoon. There is a wide range in the average of sperm concentration from 20 million to 100 million sperm per milliliter of semen.

Upon ejaculation during sexual intercourse the fluid and sperm are discharged into the women’s vagina where the sperm are either lost within the vagina or they travel to the cervix to pass through the cervical mucus into the uterus. Sperm may become lost in the mucus, the uterus or the fallopian tubes and never reach the egg. Fertility may be reduced by a number of factors that decrease the number of sperm that reach the egg. Sperm must undergo a wide range of biochemical events collectively labeled "capacitation" while traveling through the female reproductive tract. Sperm capacitation allows the sperm that reach the egg to undergo the acrosome reaction, a precursor to normal fertilization. Sperm cannot undergo normal fertilization without these processes, and even a large quantity of sperm reaching the egg would not result in conception without them.

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The Emotional Response to Infertility
The emotional response to infertility may touch a person or family in ways the physiological aspects cannot. Learning to understand how emotional reactions may affect a person is as important as knowing about the physical processes involved. The emotional experience of infertility may have short and long term effects, from manageable stress to crisis stage depression. The frustration associated with infertility may be exacerbated by the social stigmas that accompany any kind of inability. This may make it even more difficult to discuss feelings with those who might help.

Infertility is multi-layered and unique to every person challenged with it. There is no "right" or predictable way to feel when emotionally dealing with infertility.   
An impact of infertility could be the change in the focus of intimate relations. Instead of viewing intimacy as a pleasurable expression of love, it may become a clinical procedure to conceive a child. There is hope, keep in mind that the treatments for infertility are changing rapidly. Couples who were told as recently as two years ago that they would never have children can now be treated successfully. There are also many other aspects of life that should continue to be fulfilling: relationships with family and friends, work, hobbies, service given to church and charities. There should be a balance between realistic hope and striving for progression regardless of whether or not treatment options become available.

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Infertility Evaluation

Evaluating the female
The evaluation will consist of a review of the woman’s fertility history (including previously performed fertility tests), medical and surgical events, current health status, occupation, lifestyle, and history of sexual development, use of birth control and information about previous pregnancies. The physical examination will consist of a general health exam and a more detailed pelvic examination; this will help to provide information about the size, shape and position of the reproductive organs. A routine Pap smear may be done to rule out cervical cancer. A sample of cervical secretions may be taken to test for infection and all women not previously immunized for Rubella (German measles) should be immunized before proceeding with the fertility treatment. A complete female infertility evaluation can be provided by a Gynecologist who specializes in Reproductive Endocrinology and Infertility.

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Determination of Ovulation & Female Testing

LH Surge
One way of pinpointing the time of ovulation may be done by identifying the "LH surge." LH is a hormone produced by the pituitary and acts upon the ovaries to prompt ovulation. About 36 hours before ovulation the level of LH will greatly increase in the blood and subsequently the urine. This increase in LH is called the "LH surge" and may be detected by testing the urine twice daily, once in the morning and once in the early afternoon. Patients are asked to use home-testing kits to monitor this hormone level.

Testing should be done carefully as several factors may cause inaccurate readings. The excessive drinking of liquids and/or extreme physical activity may affect the concentration of LH in the urine. Avoid these activities while testing. It is not unusual for the tests to be difficult to interpret. Any questions should be directed to a primary care provider or the Andrology laboratory.

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Progesterone
Another method of determining ovulation is measuring the levels of progesterone which is secreted by the follicle in which ovulation has occurred. Peak levels will be obtained seven days following ovulation. By measuring the serum progesterone level about seven days later, the time of ovulation may be estimated.

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Basal Body Temperature
Though more inaccurate, the monitoring of Basal Body Temperature (BBT) is less expensive and invasive than other tests. Because the menstrual cycle effects body temperature due to hormonal changes, a sensitive oral thermometer may be used to take a temperature every morning before the woman gets out of bed. Changes in the temperature may be indicative of ovulation. This technique tends to be rarely used due to the fact that illness or activity may easily induce false readings.

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Hysterosalpingogram
The uterine cavity may be examined by means of Hysterosalpingogram (HSG), which is a special dye that appears white on an X-ray. This test is performed after menstruation, but before ovulation. Done in the Radiology department, a small tube is inserted into the vagina and cervix, after which the dye (HSG) is injected slowly into the uterine cavity. The dye may be seen on a TV screen and a permanent record is kept by taking X-rays. During the injection of the dye the woman may feel cramping that may last for several hours. After the test there may be a discharge of contrast fluid (HSG), which is being expelled from the uterus. The body absorbs whatever fluid remains in the pelvic cavity safely with no adverse side effects. The incidence of conception is sometimes elevated after this procedure indicating that there may be some therapeutic benefits to it.

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Cervical Mucus / Sperm Compatibility
The post-coital or Huhner’s test is an evaluation of sperm survival in periovulatory cervical mucus. A few hours before a scheduled office visit, sexual intercourse takes place. A physician removes and observes cervical mucus under a microscope to examine the sperm’s motility and concentration. It would be expected to see five to ten sperm per high-powered field moving well. If the timing has been incorrect, or if the cervical mucus will not allow penetration or support sperm function, this test (done a couple of times) may reveal important information.??A more accurate and informative test to assess sperm/cervical mucus interaction requires that ovulatory cervical mucus be collected on the day of ovulation and evaluated for quality. A drop of the husband’s sperm is placed on a microscope slide on one side of the cervical mucus and the sperm of a donor who has been tested for fertility is placed on the other side. The ability of the sperm to penetrate and survive the cervical mucus is evaluated every 30 minutes for about one and a half to two hours. If both sperm samples have reacted poorly with the cervical mucus, the woman should be examined for anti-sperm anti-bodies. If the donor’s sperm penetrates and survives, but the husband’s does not intrauterine insemination may be beneficial to overcoming the sperm’s inability to navigate through the cervical mucus to fertilize the egg.

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Laparoscopy
Though more invasive than other procedures, laparocopy is generally used when preliminary tests have failed to provide information as to the cause of the infertility. It is done under general anesthesia on an outpatient basis. It will occasionally identify problems that need treatment by additional surgical procedures. It may also be used to ascertain the extent of a condition such as endometriosis.

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Advanced Reproductive Techniques (ART)

Super Ovulation
As the name implies, super ovulation is a strategy to increase the number of maturing eggs. The female is given a hormone stimulant with the aim of preparing 2 to 5 eggs for ovulation. If there are more eggs than one there should be a greater chance of pregnancy by virtue of having more chances of fertilization. No more than five eggs are desirable because of the possibility of multiple births. Theoretically all five eggs could become fertilized and implanted. The maturity of the eggs may be monitored by ultrasound and by estrogen levels. When the time is right the female is given an injection of hCG to allow the eggs to undergo the final stage of maturation and then ovulation may occur. A day after the injection a density gradient insemination is performed and the sperm are placed into the uterus. The pregnancy rate for this procedure is between 15 and 20 percent per insemination.

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In Vitro Fertilization (IVF)
This procedure requires that the female be administered a hormone which promotes multiple egg maturation. Estrogen levels and ultrasound readings measure the growth of the eggs and when the eggs are sufficiently mature the female is given an hGC injection. About 36 hours after this injection the eggs are obtained by ultrasound-directed aspiration. The eggs are allowed to incubate for three to six hours in a laboratory incubator before they are exposed to 150,000 to 375,000 motile, density gradient prepared, sperm (per egg). The number of sperm per egg depends upon the quality of the sperm as determined by a SPA. The eggs are then evaluated the next day to see if they have been fertilized. They are given two more days and then two to four of the highest quality embryos are placed into the uterus with a small plastic catheter. The embryo transfer is completed without anesthesia. Usually the female does not experience discomfort. The overall chance of a viable pregnancy from IVF is greater than 40 percent.

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Intracytoplasmic Sperm Injection (ICSI)
Micromanipulation used in connection with in vitro fertilization allows a single sperm cell to be injected directly into an egg. When the sperm count is extremely low or of poor quality, or if the sperm must be taken from the epididymis or testicle, this technique can be very useful. It has broadened the use of IVF, especially to men who, only a short time ago, had little or no chance of contributing to a pregnancy. The pregnancy rates with this ICSI are about the same as conventional IVF.

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Zona Hatching
The Zona Pellucida is a membrane or outer shell that the embryo must hatch out of before implantation. In some women, particularly those over 37, this membrane may become hard or too thick and difficult to hatch out of. During in vitro fertilization this shell may be measured and if it is too thick, a small hole may be drilled in the outer membrane to make implantation more probable.

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Embryo Freezing
IVF may produce extra embryos that can be frozen and stored in liquid nitrogen for later embryo transfers. However, only 5 to 10 percent of patients undergoing IVF have sufficient numbers of embryos with high enough quality to allow the cryopreservation of the embryos. The pregnancy rate of transfers of cryopreserved embryos is about half that of non-cryopreserved embryo transfers.

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A Healthy Lifestyle & Reproduction

Lifestyle can play an important role for both men and women in relation to fertility. Accurate as well as inaccurate information on this subject is abundant. Experience has shown that most lifestyle choices will not take a person from normal fertility to complete infertility. Instead, certain choices may subtly contribute to a couple’s infertility. A rule of thumb to remember is this; if a lifestyle choice is detrimental to a person’s general health it is going to be harmful to a person’s reproductive health.

Smoking has been linked to heart disease, cancer and it is also detrimental to sperm production, motility, morphology and possibly its ability to fertilize. In women, smoking has also been linked to severe developmental defects in the egg and embryo. Among the lifestyle choices currently under investigation, smoking has been definitively proven to have severely harmful effects. Studies that deal with the consumption of alcohol are less conclusive. Infrequent and moderate levels of alcohol will probably not have a significant effect on fertility, but excessive consumption can have a harmful effect on sperm production and sexual function. Other drugs such as marijuana, cocaine and heroin have been shown to adversely affect sperm function and fertility in general.

Most people would not consider stress a lifestyle choice or a possible contributor to infertility, but it can be. Stress is a part of life, but it should not last for extended periods of time, nor should a person experience extreme stress. A person may also experience a loss of fertility when experiencing physically induced stress, which is often caused by a strenuous work out or exercise session.

It is recommended that a person get six to eight hours of sleep each night. Exercise should be regular and moderate. Vitamins should be taken as supplements to a well balanced diet. New vitamins or drugs may appear on the market that promise to deliver health, wealth and happiness based upon this or that clinical study. Remember that it usually takes many studies to establish a fact about a drug or vitamin. A good multivitamin with vitamin C has been established as beneficial to good health.

Environmental pollutants in the form of industrial chemicals and waste are being studied for their effects upon fertility. Environmental estrogens that are found in some insecticides and industrial waste have been shown to have severe fertility and developmental effects upon animals. It is likely that these environmental estrogens are harmful to human fertility. If exposed to chemicals in the workplace or elsewhere, speak with a physician about the issue. Some, but not all, common industrial chemicals that have been shown to affect fertility include: lead, carbon disulthide, benzine, mercury, and DBCP. The effects of many medications on fertility is not known, but some which have been shown to have detrimental effects on fertility include:

• Spironolactone-used as part of many anti-hypertensive regimes
• Sulfasalazine-used in the treatment of inflammatory bowel disease
• Colchicine-used in the treatment of acute and chronic control of gout and the suppression of familial Mediterranean fever.
• Allopurinol-alters uric acid metabolism
• Anabolic Steriods-used by weight lifters and body builders
• Cyclosporine-A component of immunosupperessive regimes used in renal and liver transplant recipients.
• Chemotherapeutic Agents-used for the treatment of malignant or cancerous conditions
• Calcium Channel Blockers-in antihypertensive or cardiac medication

Because sperm production occurs at a lower temperature than body temperature the testicles are located in the scrotum. It can relax or contract according to changes in its environment’s temperature. Increased heat to the testicles has been shown to be harmful to sperm production. In order to maintain the highest level of fertility men should avoid: hot baths, hot tubs, whirlpools and occupational environments that expose them to long lasting heat.

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Summary

The treatment of infertility is one of the fastest advancing fields in medical science. Providing an accurate, complete diagnosis increases the chances of finding an appropriate treatment for infertility. Please call and let us know if there is anything we can do to be of assistance, it is our desire to provide the best possible professional care.

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