Understanding the Menstrual Cycle
Polycystic Ovary Syndrome (PCOS)
Asian Patients Have Lower Rates Of Pregnancy And Live Birth Than Caucasian Patients
Infertility
Infertility is one of the most challenging problems a couple can face in their relationship. It is usually the most frustrating because the couple will attempt everything within their power and still have no results. Guilt, depression, and anxiety often complicate the process of starting a family because often the problem is beyond the couple’s control. Often people assume that “It is not supposed to be work; it is just supposed to happen.” Many have tried to conceive for years without success and their dream for parenthood feels as if it is fading away.
About 6 million Americans, roughly 10 percent of the reproductive age population, are infertile. According to the American Society of Reproductive Medicine, a couple is considered “Infertile” if they have had unprotected intercourse for a year and no pregnancy has resulted. Some say the figure should be six months if the female is over 35 years of age. Many couple’s first approach to dealing with infertility is a visit to their obstetrician/gynecologist who is usually capable of evaluating and treating many basic forms of infertility. If the couple is unsuccessful, they are usually referred to a Reproductive Endocrinologist, a specialist in infertility.
Reproductive Endocrinology is a sub-specialty within Obstetrics and Gynecology. A Reproductive Endocrinologist receives special training to diagnose and treat problems such as infertility, recurrent pregnancy loss, hormonal imbalances, and menopause. A board certified Reproductive Endocrinologist has undergone 2-3 additional years of training beyond their four years of OB/GYN training; passed a second written examination and a second oral examination in Reproductive Endocrinology and Infertility; and spent a minimum of one year in independent practice. To date, there are less than 800 physicians with this distinction.
Understanding the Menstrual Cycle
The menstrual cycle refers to the culminating steps leading to pregnancy in humans. It begins with the development of the egg in the ovary. This development is controlled by signals produced in the brain. There are two important signals from the brain that manipulate the ovary. The first is FSH or Follicle Stimulating Hormone. FSH stimulates the eggs to develop into fluid filled sacs or cysts, known as follicles. It takes approximately two weeks for an egg to mature in the ovary. During this time, the female hormone “estrogen” is produced by the developing follicles. Estrogen causes the lining of the uterus, the endometrium, to grow so as to become receptive to the developing embryo. The second signal from the brain is LH or Lutenizing Hormone, which signals ovulation. Ovulation is the release of the mature egg, and usually occurs around day 14 of the cycle. The released egg makes its way into the uterus through the fallopian tube. When sperm are introduced into the vagina during intercourse, they make their way into the uterus through the cervix and into the tubes where they join with, or fertilize, the egg to form the embryo. Several days after ovulation and if fertilization occurs, the embryo then implants into the endometrial lining where it develops into the fetus. A number of problems can occur in this process, causing infertility for the couple.
Fertility and Age
Age is the most important predictor of fertility. As a woman ages, her eggs age also, and become less likely to fertilize and result in a pregnancy. Women are born with a certain number of eggs. Over time, the number of eggs carried by the female decreases, as does their quality - so when you are younger it is much easier to become pregnant compared to when you are older. This is solely due to the quality of the egg. Some tests can help predict “Ovarian Reserve.” These tests are an indirect measurement of how your eggs are doing in your ovaries. Many studies have found that a drop in pregnancy rates occurs at approximately 35 years of age and drops dramatically after 37 years of age. The quality of the oocytes drops dramatically as age increases, and the number of genetically abnormal eggs also increases with age.
The increase in abnormal oocytes leads to an increase in embryos with an abnormal number of chromosomes. Chromosomes are where our genetic material is stored. We each are composed of cells possessing 23 pairs of chromosomes. One set comes from the sperm and one set comes from the egg. The architecture inside the egg at fertilization must bring these chromosomes together just right. As we get older, the architecture inside the cell becomes older and sometimes does not align the chromosomes as accurately as it did when the eggs were younger, resulting in an increase in the number of embryos that have what is called “Aneuploidy” or an irregular number of chromosomes. The most famous form of aneuploidy is Down’s Syndrome, which is a normal complement of 23 pairs of chromosomes, plus an additional number 21 chromosome, called Trisomy 21, or 3 copies of the number 21 chromosome. Aneuploidy also decreases the rate of implantation of embryos, reducing fertility rates as well as increasing miscarriage rates.
Polycystic Ovary Syndrome (PCOS)
Polycystic ovary syndrome is one of the most common causes of irregular ovulation and infertility. PCOS is really a misnomer. Often one of the signs seen in women who have this syndrome are many small follicles on their ovaries, which are detected when evaluated by ultrasound. Many women assume the problem is the presence of these small cysts, when the real problem is the imbalance of cyclic hormones in the body and the sensitivity of those women’s brain to these hormones, causing irregular menses, infertility, and sometimes extra hair growth. Women with this disorder are sometimes overweight. The hormones involved in reproduction can be dissolved in fat and some overweight women have extra stores of these hormones in their extra fat tissue. Their hormone levels can be artificially high, preventing the brain from instructing the ovary to develop an egg. This prevents ovulation, which prevents the opportunity for conception.
Irregular Ovulation
Ovulation is the release of the matured egg into the fallopian tube. Irregular or absent menstrual cycles may be a sign that the ovaries are not producing, or that they are developing eggs irregularly. This is also called oligomenorrhea. There are many causes of irregular or absent ovulation. The cells in the brain that control reproduction are adjacent to cells that control other hormones in the body, so if you have an abnormality in another hormone such as the one for the thyroid gland, which regulates metabolism, or with the hormone Prolactin, which regulates breast milk production, this can impact the cells that control ovulation. Correction of these other hormone abnormalities often corrects irregular menstrual cycles and promotes regular ovulation
Endometriosis
A third area of interest associated with infertility is endometriosis. Approximately eight percent of the female population has endometriosis, but up to 20 percent or more of infertile women have endometriosis. Endometriosis is tissue, just like the endometrial lining of the cavity of the uterus, except it is located outside of the uterus. It can be present on the ovaries, tubes, uterus, bladder or bowel. It behaves just like endometrial tissue, so it grows in the beginning of the cycle and bleeds just as if you were having a period. Blood is very irritating to the abdominal cavity and it is thought that this irritation causes an inflammatory response with the formation of scar tissue and adhesions. This can cause kinking of the tubes, blockage of the tubes, and formation of endometriomas, which are basically big blood blisters of growing and bleeding endometrium. It is also thought that endometriosis forms toxic factors and cytokines that are detrimental to the developing egg and embryo.
Tubal Disease
Anatomic defects such as tubal disease may contribute to problems in achieving pregnancy. Tubes are not just tubes, they are organs. They have muscles in their walls that contract and little fingers lining the inside of the fallopian tube that beat to move the egg and embryo through the tube into the uterus. A common problem involving the tubes is the damage that a sexually transmitted disease like chlamydia or gonorrhea can cause. These infections can enter the uterus and get into the tubes, damaging the muscles, preventing them from contracting, and causing them to accumulate fluid. This is called a hydrosalpynx. In addition, the fingers can be stuck together, preventing them from beating the egg or embryo into the uterus and perhaps allowing an ectopic pregnancy (a pregnancy that implants in the tube) to occur. Scar tissue can form around the tube preventing it from acquiring the egg from the ovary, or even blocking the tube altogether.
Uterine Factors
Anatomic problems of the interior cavity of the uterus may include fibroid tumors and/or polyps. Fibroids are smooth muscle tumors of the uterus. They are the most common tumor among women, and most are not cancer. They also do not turn into cancer. These tumors can be in the cavity of the uterus making implantation difficult; or can be in the walls possibly blocking a tube, or just large enough to disrupt the function between the tube and ovary. Polyps or soft tissue tumors, which can be described as akin to a “skin tag” of the uterus, can cause irregular bleeding or possibly interfere with implantation of the embryo into the endometrium.
Male Factors
Another estimated forty percent of infertility cases are due to male factors, including: low sperm counts, low sperm activity, and low sperm morphology. Morphology describes the percentage of normal looking sperm. There are many causes of male factor infertility. Decreases in the number of sperm may be caused by: excessive use of alcohol, tobacco, or other illicit drugs; infections of the genital organs such as the prostate or urethra; sexually transmitted diseases that can cause sperm blockage; exposure to toxins and chemicals in the environment; exposure to radiation; testicular exposure to overheating such as a prolonged high fever; genetic disorders such as Klinefelter’s syndrome, cystic fibrosis, or a defective gene on the Y chromosome. Abnormal sperm may be caused by inflammation of the testicles; twisted or swollen veins in the scrotum (varicocele); abnormally developed testicles; exposure to toxins and chemicals; and increased testicular temperature.
Male infertility may also occur from physical or structural abnormalities such as premature ejaculation; retrograde ejaculation (semen forced back into the bladder); erectile dysfunctions; and any structural abnormalities that affect the testes, tubes, or other reproductive structures. Blockage of the duct that carries sperm or genetic defects called deletions are also causes of male factor infertility. The effect of aging is not clear, however there is some evidence of decreased sperm quality with advancing age, especially after age 70.
The effects of medications on sperm quality and count have not been extensively studied, and many medicines are commonly prescribed without knowing whether they impair fertility. Known medications that may affect male fertility include: steroids, cimetidine (Tagamet), sulfasalazine (Azulfidine), salazopyrine, colchicine, methadone, methotrexate (Folex), phenytoin (Dilantin), corticosteroids, spironolactone (Aldactone), clonidine (Catapress), thioridazine (Mellaril), and calcium channel blockers(for high blood pressure)
Other medical conditions such as severe injury, major surgery, diabetes, HIV, thyroid disease, liver or kidney failure, heart attack, and chronic anemia may effect sperm quality.
Treatments for male factor infertility may include: antibiotic treatment for infection, or hormone treatment if a hormone imbalance is identified; avoiding radiation and environmental toxins, chemicals, pesticides, and lubricants; avoiding excessive alcohol, smoking, and drug abuse; therapy to treat ejaculation problems; and surgery to correct structural abnormalities. Dietary supplements such as Proxeed and Fertile One are formulated to enhance male fertility and may improve overall sperm quality.
One way to overcome male factor problems is through the use of artificial insemination. This is a procedure in which a man’s sperm is inserted into a woman’s vagina, cervix or uterus around the time of ovulation. An advanced technique called intra-cytoplasmic sperm injection or ICSI, in which a single sperm is injected directly into an egg to achieve fertilization, is highly effective. It is often used in cases with very low sperm counts. For men with very low counts or absent sperm, sperm donors represent another option. Even for men with no sperm, some new techniques to directly acquire the sperm from the testes or the ducts that deliver sperm have been used with great success.
Asian Patients Have Lower Rates Of Pregnancy And Live Birth Than Caucasian Patients
A study performed in 2007 at the University of San Francisco has shown that the Asian population does poorly with In Vitro Fertilization, showing significantly lower pregnancy rates compared to similar Caucasian patients.
We understand this at the Advanced Reproductive Center of Hawaii, and we offer one of the most experienced and successful programs in the nation focused on working with Asian patients.
Analyzing national and clinic-specific data, researchers in San Francisco and Wichita have determined that Asian women undergoing IVF have significantly fewer clinical pregnancies and live births than Caucasian women do.
Both national data from the CDC’s Assisted Reproductive Technology Registry and data from the clinic at the University of California, San Francisco were analyzed for the study. Nationally, 26.9 % of first cycles in Asian patients resulted in a live birth while 34.9% of Caucasian first cycles resulted in a live birth. At UCSF, 28.6% of Asians’ first cycles resulted in a delivery and 37.5% of Caucasian patients delivered after their first cycle of Assisted Reproductive Technologies (ART).
The national registry contained data that was collected in 1999 and 2000 by the Center for Disease Control and the Society for Assisted Reproductive Technology, and included 25,843 Caucasian and 1,429 Asian patients who reported they were undergoing their first ART treatment. The other data set came from an academic clinic with a particularly high concentration of Asian patients; of the 567 patients whose first cycle data was included, 197 reported Asian ancestry.
The discrepancy could not be accounted for by differences in diagnoses of infertility or by patient characteristics such as age, hormone levels, or number of embryos produced.
(Purcell et al, Asian ethnicity is associated with reduced pregnancy outcomes after assisted reproductive technology, Fertility and Sterility, Volume 86, Number 5, November 2006)