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Monday, February 9, 2009

Fertility Basics

The Egg
A woman is born with approximately two million non-renewable eggs in her ovaries. Each egg is housed in a sac, and together the egg and sac are referred to as a follicle. Once a month, several of these follicles begin to mature under the influence of follicle stimulating hormone (FSH). FSH is produced by the pituitary gland and travels in the bloodstream. As the follicles grow, they in turn produce two hormones called estradiol and inhibin. These two hormones travel in the blood to the pituitary gland where they turn off the FSH production. Only the most mature egg follicle can continue to grow once FSH production drops. This process prevents too many egg follicles from developing and is important as humans are not litter-bearing and the womb should ideally carry only one baby at a time.

Approximately fourteen days after the start of the menstrual period, a second hormone, called luteinizing hormone (LH) is produced by the pituitary gland. This hormone travels in the bloodstream to the mature egg follicle and causes it to rupture in a process called ovulation. Once the follicle sac ruptures, the egg is released from the ovary and swept into the end of the fallopian tube. The remainder of the ruptured follicle remains in the ovary and continues to produce hormones including progesterone, which only appears after ovulation.

Men produce millions of sperm each day. Following sexual intercourse, sperm swim rapidly through the cervical mucus up into the fallopian tube where they attempt to fertilize the egg. Although sperm can survive for 2-3 days in the cervical mucus, the egg only lives for twenty-four hours. For this reason, the timing of intercourse is very important.

If fertilization is successful, the fertilized egg, now called an embryo, begins to divide as it travels down the fallopian tube toward the uterus. Approximately seven days after fertilization (twenty-one days from the last menstrual period), the embryo reaches the uterus and implants in the uterine wall. Approximately seven days later (twenty-eight days after the last menstrual period), the pregnancy hormone human chorionic gonadotropin (hCG) can be detected in the blood or urine. Approximately two percent of the time, the embryo does not make it to the uterus, but gets stuck in the fallopian tube. This is referred to as an ectopic pregnancy and is not viable.

Early Pregnancy
The pregnancy can be visualized using an ultrasound machine approximately three weeks after conception. At this point, a gestational sac can be seen in the uterus. One week later, the fetal heartbeat can be visualized. The fetus develops rapidly during the first eight weeks of pregnancy. If it is genetically abnormal, it usually dies and is miscarried at this time.

Evaluation and Testing
Infertility is defined as one year of unprotected intercourse without pregnancy. However, women over thirty-five or those with male partners over forty-five may wish to seek an earlier infertility evaluation.

The four basic components of the infertility work-up include determination of the following:

Normal sperm
Open fallopian tubes and normal uterine cavity
Healthy eggs
The release of the egg is a necessary component for pregnancy. In general, regular, predictable menses indicate that ovulation is occurring. The menstrual cycle is divided into two parts: the proliferative phase and the luteal phase. The luteal phase is the second half of the menstrual cycle following ovulation and typically lasts 13-14 days in most women. For example, if a woman has a 28-day cycle, she usually ovulates on day fourteen; a woman with a 32-day cycle would typically ovulate on day eighteen. Ovulation can also be presumed by testing the blood for progesterone level or if a monitor or kit indicates the presence of high levels of LH. There are many reasons for ovulatory disturbance including pituitary hormone imbalance, polycystic ovarian syndrome, stress and weight gain or loss. These issues can be overcome by using an oral medication called clomiphene citrate (Clomid), by injection of the hormone FSH, or by IVF.

Normal sperm
A semen analysis is performed to evaluate semen volume, sperm count, percentage of normal motility and percentage of normally shaped sperm. Sperm factors account for twenty-five percent of all infertility and may be due either to malignancies or to genetic, hormonal or environmental issues. There are several treatments used to improve sperm function. Among these are artificial insemination, in which the sperm are washed and the healthiest are introduced into the uterus with a catheter; and IVF using intracytoplasmic sperm injection (ICSI), the injection of a single sperm into an egg. For men who do not ejaculate sperm, vasectomy reversal or harvesting procedures such as MESA, or TESE can be performed.

Open fallopian tubes and normal uterine cavity
In order for the egg and sperm to meet and for the embryo to be transported to the uterus, the fallopian tubes must be open. Once the embryo reaches the uterus, it must be able to implant in the uterine cavity. If the tubes are scarred and blocked as a consequence of prior pelvic surgery, sexually transmitted disease or a condition called endometriosis; or if polyps, tumors or scar tissue are present in the uterus, implantation may not occur. A hysterosalpingogram (HSG) is a test to assure that the tubes are open and that the uterine cavity is normal. Radiologists conduct the HSG on an outpatient basis. In this test, a small balloon is placed in the cervix and dye is introduced into the uterus and tubes with a syringe. The dye makes it possible to see the fallopian tubes and the contour of the uterine cavity by x-ray. Alternatively, a hydrosonography can be performed. This test utilizes saline rather than dye and makes the uterus (and to some extent, the fallopian tubes) visible via ultrasound. If the tubes are blocked they may need to be opened or removed prior to fertility therapy.

Healthy eggs
The quantity and quality of a woman's eggs decline with age. Typically, by age thirty-eight, only 25,000 eggs remain in the ovaries. For an egg to be fertilized and develop into a genetically normal embryo, it must be of good quality. As the egg ages it is more likely to give rise to a genetically abnormal embryo. Usually, such embryos will not give rise to a pregnancy or are miscarried during the first trimester. Thus, as a woman ages, she experiences more infertility or miscarriage. Age alone is an independent risk factor for infertility and there is a significant drop in pregnancy rates after age forty. When FSH testing reveals an elevated FSH level, it indicates that the body is producing more FSH to compensate for diminished egg reserves. In such cases, egg donation may be considered, as the function of the uterus does not decrease with age and an older woman can successfully carry a pregnancy to term using donor eggs.

Unexplained infertility
Occasionally, a couple may be unable to conceive, yet their infertility tests yield normal results. This condition is called unexplained infertility and is usually caused by sperm-egg interactions and factors related to the female reproductive tract. Fertility treatments can be very effective in treating this condition.

Recurrent miscarriage
An investigation for recurrent miscarriage is warranted when two or more pregnancies are spontaneously lost. Though recurrent miscarriage can be caused by inherited chromosomal or genetic abnormalities from one or both parents, these are seen less frequently. Instead, most miscarriages are the result of chromosomal and genetic abnormalities that arise during embryo development. These losses frequently correlate with the age of the female partner although recent data suggest that the age of the male partner may also play a role. Other causes for recurrent miscarriage relate to anatomical distortion of the uterine cavity caused by birth defects, fibroids or scar tissue, and to autoimmune conditions of pregnancy that give rise to blood clots in the developing placenta. The work-up for recurrent miscarriage can include testing the blood for diabetes, thyroid problems, autoimmune antibodies, clotting factors and parental chromosomes (karyotype). An HSG can also be performed to determine the configuration of the uterine cavity. There are proven treatments for most causes of recurrent pregnancy loss.

Other tests that often accompany the infertility evaluation
Male Tests
Infectious diseases tests
These tests are required by law and include Hepatitis B and C, syphilis, HIV and HTLV 1.
Semen culture
A test to diagnose bacterial contamination of the semen.
Female Tests
Prolactin is a hormone produced by the pituitary gland that stimulates the production of breast milk. Prolactin is a common cause of ovulatory disturbance.
Thyroid stimulation hormone (TSH)
A test to detect problems affecting thyroid gland function.
A test for male hormones (androgens). Presence of testosterone or DHEAS can cause ovulatory disturbance and may be a sign of polycystic ovarian syndrome.
Fasting insulin/glucose ratio
This test can diagnose diabetes and polycystic ovarian syndrome.
Anti-cardiolipin antibody
A test to detect a type of antibody associated with recurrent pregnancy loss.
Lupus anticoagulant
A test to detect a type of antibody associated with recurrent pregnancy loss.
Prenatal screening tests
CBC, chemistry panel, Rubella titer, fasting glucose, lipid profile, blood type and screen, PT/PTT, TSH, HIV, Hepatitis B and C, syphilis, PAP smear and possibly mammogram.
Genetic screening tests
Cystic fibrosis and other specific tests based on ethnic background: Jewish (Tay Sachs, Familial Dysautonomia, Canavans); African American (Sickle Cell); Mediterranean (Thalassemia).

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