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Author: John D. Musil, Pharm.D.
The ability to acheive and maintain a pregnancy is a desire most couples expect to have in their lifetime. However, infertility affects eight to fifteen percent of the American population. With new advances in reproductive technology all couples can have a means to conceive and deliver a new life into our world.
A descriptive definiton of primary infertility refers to the inability to become pregnant after one year of regular (two to three times per week) unprotected intercourse. Secondary infertility refers to a couple that has successfully acheived conception in the past but cannot repeat it afterwards.
Infertility affects both male and female partners. In about thirty percent of couples seeking inferdlity treatment there is a male factor causing the infertility. In forty to fifty percent a female factor can be identified. In the remaining twenty to thirty percent both partners contribute to infertility. Unexplained infertility occurs in less than ten percent of couples seeking infertility treatment.
FEMALE INFERTILITY
One of the most common causes of female infertility is anovulation, or the inability to stimulate and release an egg from the ovary. Several disorders are associated with anovulation and they are: polycystic ovary (PCO) disease, endometrial hyperplasia, abnormal uterine bleeding for at least six months, and virilism. Endometriosis, or endometrial hyperplasia, is a condition where the endometrial tissue has been displaced outside of the uterus and continues to respond to normal hormonal cycles. Current medical literature remains unclear as to the exact cause of how endometriosis affects fertility.One of the most effective determinants of ovulation is the daily recording of basal body temperature along with home ovulation prediction kits (Ovukit, Ovuquick). This method is the most inexpensive of all infertility treatments and must be carried out with meticulous detail. Basal body temperature should be taken at the same time each morning before getting out of bed and prior to any activity. Misleading alterations in temperature may occur if electric blankets or a heated waterbed are used, or if a viral infection is present. Ovulation usually occurs just after a slight drop in basal body temperature (about 0.2 degrees Farenheit) followed by a rapid rise (0.5 to 0.8 degrees Farenheit). The temperature remains elevated until the next menstrual cycle.
Table 1- Methods to determine ovulation
- Basal body temperature charting
- Serum progesterone concentrations
- Home ovulation prediction kits
- Endometrial biopsy
Induction of ovulation is initiated when a couple cannot conceive after one year and when premature ovarian failure has been ruled out by measuring folicular stimulating hormone (FSH) and leutinizing hormone (LH) concentrations.
Clomiphene citrate (Clomid, Serophene) was introduced in the United States in 1967 as the first medical treatment for infertility. Clomiphene citrate still remains one of the most commonly prescribed fertility treatments and is the most non-invasive treatment available.
Clomiphene citrate inhibits the detection of estrogen by the hypothalamus which results in an increased production of gonadotropin-releasing hormone (GnRH), the hormone responsible for stimulating the ovaries to produce an egg. This increase in GnRH increases the amount of FSH and LH produced by the body and increases the likelihood of ovulation. Clomiphene citrate is usually begun on the fifth day of a monthly cycle, after a spontaneous or induced menstrual period and continued for the next five days.
An important factor to keep in mind is that prostaglandins, a substance naturally produced by the body, are necessary to expell an egg from the ovary. Non-steroidal antiinflammatory drugs (NSAID's) such as ibuprofen, naproxen, or aspirin inhibit the production of prostaglandins by the body and may inhibit ovulation. Avoiding NSAID's a few days prior to and following ovulation may also enhance response to ovulation. Clomiphene citrate should only be used for one cyle at a time. If conception does not occur after a cycle of clomiphene citrate, an ultrasound of the ovaries needs to be done to determine if an ovarian cyst is present. Clomiphene citrate may also be used in conjunction with human chorionic gonadotropin (Pregnyl, hCG) to induce ovulation. During clomiphene citrate therapy, the ovaries are monitored by ultrasound to follow folicular development to determine the optimal dosing time for hCG.
Ovulation occurs in up to eighty percent of women taking prescribed regimens of clomiphene citrate. Pregnancy rates vary from thrity to fifty percent with a multiple birth rate of about ten percent. The most common side effects associated with colmiphene citrate are: headaches, nausea and vomiting, "hot flashes", bloating, abdominal pain, ovarian enlargement, insomnia, nervousness, and visual disturbances.
Another cause of inferdlity in women who do not ovulate is due to an excess production of prolactin by the body. Prolactin is a hormone that suppresses the release of GnRH. There have been many medicines used to treat this overproduction but bromocriptine (Parlodel) appears most effective.
Therapy with bromocriptine is started slowly at first, usually 1.25 mg to 2.5 mg once daily. After one week the dose of bromocriptine is increased to twice daily. The slow increase of bromocriptine is done mainly to avoid stomach and intestinal upset caused by bromocriptine. The incidence of side effects while taking bromocriptine is high, about sixty nine percent, and include: nausea and vomiting, dizziness, headache, and fatigue.
ENDOMEIRIOSIS
The scope of this article cannot span the vast information available as to the cause and surgical treatment of endometriosis and will only focus on the medicinal treatment of endometriosis. In order to have a controlled atmosphere for ovulation induction in women who have or have had endometriosis, the body's own mechanism for producing, ripening, and releasing eggs must be turned off. Leuprolide acetate (Lupron(g)) is used to produce this effect. Leuprolide acetate is given as a subcutaneous (under the skin) injection, similar to the type of injection a diabetic may give themself, once daily in the thigh or the stomach area and is usually given for up to six weeks. The most common side effects are: possible bone loss, "hot-flashes", headache, insomnia, and vaginal dryness.INJECTABLE MEDICINES FOR OVULATION INDUCTION
Human menopausal gonadotropin (Humegon, Pergonal) or menotropins for injection, USP is a purified product containing both FSH and LH in a 1:1 ratio. It is the most potent infertility agent currently available and is used in women who do not currently ovulate but may have functioning ovaries. The use of menotropins is used in conjunction with hCG (Pregnyl), which triggers ovulation, during in-vivo and in-vitro fertilization programs.Menotropins are given for seven to twelve days by intramuscular injection usually between 5 p.m. and 8 p.m. Folicular development is followed daily by ultrasound to determine proper size and timing to give hCG to trigger ovulation. The pregnancy rate associated with menotropins is similar to that of clomiphene citrate, about twenty percent. Minor reports of side effects include: swelling or rash at the site of injection, abdominal pain, bloating, ovarian hyperstimulation, ovarian enlargemnt, fever, possible rupture of an ovarian cyst, and multiple births.
Urofillotropin for injection, USP (Metrodin) is a purified product of FSH only. Urofillotropin is used in women with polycystic ovary disease who have not responded to an adequate trial of clomiphene citrate. As with menotropins, urofillotropin is used in conjuction with hCG to stimulate ovulation.
Urofillotropin is given for seven to twelve days as an intramuscular injection. Blood estrogen levels and folicular size are monitored to determine proper folicular development and timing to administer hCG.
Urofillotropin multiple birth rate is similar to that of menotropins, about seventeen percent. Side effects associated with urofillotropin include: pain or swelling at the site of injection, ovariaen hyperstimulation, ovarian enlargement, breast tenderness, nausea and vomiting, headache, and multiple births.
The newest agent used for the treatment of infertility is a synthetic GnRH (Lutrepulse). In anovulatory women who do not produce sufficient amounts of GnRH, pulsatile doses of GnRH are administered using a small pump device. Normal pituitary and ovarian function are required for GnRH to work.
Ultrasound monitoring of the ovaries is necessary to determine proper folicular size and to schedule days of intercourse to achieve pregnancy. Also, the use of home ovulation prediction kits increase the likelihood of conception. The main side effect associated with GnRH is redness and pain at the site of injection which may be pump-related.
OTHER AGENTS
Some women have a tendency to achieve pregnancy bwt cannot sustain the pregnancy for a number of different reasons. In some, a lack of progesterone may cause a spontaneous abortion. Progesterone is the hormone responsible for maintaining a pregnancy by keeping the endometrium thick and viable for the fertilized egg. Supplemental progesterone is given to women who have had a history of spontaneous abortion or whose blood level of progesterone may be low.Progesterone is available as a suppository, lozenge, or by intramuscular injection. The type of fertility treatment used will determine the type of supplemental progesterone used. Progesterone may be used up to the end of the first tri-mester to help sustain the pregnancy. Because progesterone is a naturally occuring hormone, side effects are similar to what is experienced during a normal menstrual cycle: tenderness of the breasts, bloating, mood alteration, and weight gain.
On the horizon there are some new products which may provide some potential benefits to the infertile couple. Some of these new products or technologies will focus their attention to the male as the source of infertility. It will not be long before a man who produces little or no sperm may father his very own child.
Table 2 - Relative Costs © 1996 by John D. Musil, all rights reserved
Copyright 1996. The American Surrogacy Center, Inc.(TASC), Marietta, GA
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