Fertility Treatments

Fertility treatments fall into two categories; one in which there is a specific problem and one in which no problem has been found. Since this a topic that could fill a textbook, we will outline each treatment briefly.

TREATING A SPECIFIC PROBLEM

Lack of ovulation

Most treatment for anovulation falls into one of two regimens:

  • clomiphene citrate (Clomid)
  • human menopausal gonadotropins (hMG) or follicle stimulating hormone (FSH) with or without clomiphene

Exceptions to use of these drugs would be in patients with documented hormone problems which can be overcome by the administration of a specific hormone to correct the problem. Patients falling into this category would include those with an elevated prolactin level with or without galactorrhea or evidence of a microadenoma of the pituitary gland. These people will be treated specifically with bromocriptine (Parlodel) or cabergoline (Dostinex), which will reduce the level of prolactin, eliminate the galactorrhea, shrink the microadenoma, and allow ovulation to return to normal.

Another example of the use of specific medication occurs in women who may have symptoms of excessive hair growth, acne, and lack of a menstrual cycle due to excessive adrenal hormones. These women can be treated specifically with a cortisone-like drug such as dexamethasone, usually taken at bedtime. Again, this treatment is specific, effective, relatively inexpensive, and free of side effects with short-term treatment. A third example involves women who are low in thyroid hormone and whose lack of ovulation can be corrected with simple and inexpensive thyroid hormone pills. Women with polycystic ovaries (PCOS) can specifically treat their insulin resistance (IR) with one of several drugs designed to treat IR such as metformin which can lead to spontaneous ovulation in about 30% of cases.

But the vast majority of patients with ovulatory problems will be treated with the three major drugs.

Clomiphene Citrate (Clomid)

The first drug available for ovulation induction was discovered by accident. It is an antiestrogen and was being studied as a contraceptive agent designed to block the implantation process in animals. When it was applied to humans it was noticed that it increased gonadotropins and caused ovulation. For well over 30 years it has been used as the first-line drug for the induction of ovulation.

Clomiphene is used in patients whose ovulatory problem is caused by a malfunction in the hypothalamus and in patients with polycystic ovaries. On a practical basis, clomiphene is often tried first in patients who are producing adequate amounts of estrogen because it is relatively inexpensive, easy to monitor, and readily available to all physicians. It is taken orally, starting the third to fifth day of the cycle. A pelvic examination or ultrasound is usually done prior to starting treatment to make sure that no ovarian cysts are present. The drug is usually taken for five days and, if ovulation does not occur, the dose is increased in succeeding cycles. As infertility treatments go, the cost of clomiphene is modest. Risks include:

  • multiple pregnancy in about eight percent of patients (most often twins)
  • development of ovarian cysts
  • overstimulation of the ovaries (rare with clomiphene)

Human Menopausal Gonadotropin (hMG-Menopur, Repronex), Pure Follicle Stimulating Hormone (FSH- Bravelle, Follistim, Gonal-F)

HMG, consisting of both FSH and LH, or pure FSH is generally used in patients who do not produce their own gonadotropins and secrete inadequate amounts of estrogen. It is also helpful in those patients who do not respond to clomiphene.

Because of the high cost of gonadotropins, their need to be administered by injection, and their side effects, most notably multiple pregnancy, efforts should first be made to achieve pregnancy by simpler means.

The risks of hMG or FSH are similar to, but considerably more significant than, those of clomiphene. Side effects may include ovarian cysts, abdominal distention and pain, multiple pregnancy, and ovarian hyperstimulation. Most of these do not progress and will usually resolve if the hMG or FSH is stopped, hCG is not given, and the patient does not become pregnant. Overstimulation can be mild, with fluid retention, enlarged ovaries, and abdominal discomfort. When severe, significant fluid imbalance may require hospitalization. Mood swings may occur while on the medication. In addition, you may notice an increased amount of cervical mucus because of the increased amounts of estrogen. Overall, the incidence of birth defects in patients using hMG or FSH to induce ovulation is not any higher than that of the general population.

Male factor

When you consider that a fairly large proportion of infertility is due to the male factor, it is surprising that treatment options for the male have been limited until recently. Nearly 30 years ago, all we could offer the couple with significant male factor infertility was artificial insemination with semen from a donor, artificial insemination with the husband's semen into the cervical mucus, or repair of a varicocele.

During the last decade, we've seen a great deal of interest in the workup and treatment of the male. This interest has paralleled advances in assisted reproductive technology (ART) and the need to prepare the sperm for these advanced techniques. Changes in habits, when possible, should be recommended first to try to maximize the couple's chances of conceiving. For the male partner these would include changes in sexual frequency and timing, eliminating heated spa-type baths, and avoiding drugs, body-building supplements, smoking, and exposure to toxins.

In the complete absence of sperm, a hormone workup will help reveal the nature of the problem. If the man's gonadotropins (FSH and LH) are very high, it can be assumed that he has testicular failure. Retrieval of sperm from a testicular biopsy for use in intracytoplasmic sperm injection (ICSI) is now possible in about one-half of such cases. The only other treatment available is artificial insemination with the semen of a donor. If the couple is unwilling to have donor insemination, or unable to afford ICSI, they could consider adoption.

If his gonadotropins are normal or slightly elevated, he may have an obstruction of the ductal system and could have an operation called a scrotal exploration to determine the location of the obstruction and attempt to correct it. In cases of congenital absence of portions of the tubular system, microsurgical procedures are now being used to retrieve sperm directly from the epididymis for use in conjunction with ART procedures involving the direct injection of sperm into an egg, intracytoplasmic sperm injection (ICSI). In fact, now in any case of obstruction, whether congenital or acquired, epididymal sperm aspiration (MESA or PESA), or a testicular biopsy (TESE) usually yields sperm which can be used in ICSI. In percutaneous epididymal sperm aspiration (PESA), sperm can even be retrieved in the office by passing a tiny needle through the skin into the epididymis.

A more subtle abnormality that may be found is a varicocele (varicose veins in the scrotum). If detected, surgery may be considered after other nonsurgical problems, such as hormonal or environmental causes, have been looked for and corrected.

Of course, our basic premise applies here: that the simple, safe, and less expensive treatments must be explored first.

In many men with reduced count, motility, and/or morphology, no apparent cause is found. Intrauterine insemination (IUI) following sperm washing can be successful, particularly with mild to moderate abnormal sperm. Most pregnancies will occur within four to six cycles of IUI. IUI in conjunction with hMG or pure FSH increases the chance of fertilization because there are more eggs available. Finally, IVF is highly effective, since 50,000 to 500,000 sperm are concentrated around the egg. If more than a mild male factor is present, ICSI is generally advised.

Endometriosis

The treatment of endometriosis has traditionally fallen into two general categories-medical and surgical. Now emerging is a third category-no treatment. This is because an accumulating body of evidence indicates that infertility patients with minimal to mild stages of endometriosis who undergo no treatment may have the same conception rate as those treated by medications or surgery. That's probably because women with this degree of endometriosis are not truly infertile, but "subfertile," with a 1% to 3% lower than average possibility of pregnancy per cycle. Actually, endometriosis treatment is very complex and dependent on symptoms, location, and degree of the disease. Its thorough consideration is beyond the scope of this article.

Tubal problems

The most important advance in tubal surgery has been the use of microsurgical techniques: the operating microscope, small sutures, microsurgical instruments, and new tissue-handling techniques to reduce the risk of postoperative adhesions, such as peritoneal patches. The most recent advance is the ability of many surgeons to perform these procedures using the laparoscope. However the success rates for tubal surgery are generally lower then for in vitro fertilization and it is not utilized as frequently as IVF. The one exception is tubal blockage as the result of a tubal ligation. When conditions are optimal, tubal repair results are fairly comparable to IVF.

Luteal phase defect (LPD)

This infrequent problem is the inadequate production of progesterone (too little or for too short a time) resulting in a poorly receptive endometrium, or one which starts to break down before implantation has become established. Diagnosis of LPD has been highly controversial because of the inaccuracy of diagnosis and variable result of treatment. Several types of treatment are possible.

Since there is a deficiency in the production of progesterone, the doctor can prescribe progesterone by vaginal gel, suppositories, capsules, or the new FDA-approved Endometrin. This would be continued from just after ovulation until obtaining the results of a pregnancy test two weeks later. If the pregnancy test is positive, the progesterone is continued. If it is negative, the progesterone is stopped and the menstrual period will occur.

Another approach is the use of clomiphene to improve an inadequate luteal phase. It is taken in the same manner as in patients who are not ovulating. Clomiphene increases progesterone secretion by stimulating better follicle maturity.

Cervical problems

One of the more popular infertility treatments is intrauterine insemination (IUI) with washed sperm. Previous treatments, including antibiotics to decrease inflammation, estrogen to improve mucus production, guaifenesin (Robitussin) to thin the mucus, and insemination into the cervical mucus were not very effective. Placing the sperm in the uterus bypasses the mucus and eliminates the cervical problem as a factor. It is known to be useful in the treatment of poor-quality mucus or mucus that has antibodies which clump and immobilize sperm. As mentioned, this technique is also successful for mild to moderate reductions of semen quality.

Uterine problems

While uterine problems are relatively uncommon causes of inability to conceive, they can cause miscarriage. If fibroids are constricting the cavity and thought to be related to infertility or early pregnancy loss, they can be removed. Removal by hysteroscopy is often possible. This involves placing a telescope through the cervix under general anesthesia. Surgical instruments placed through channels in the scope can both cauterize and cut to remove certain types of fibroids. Hysteroscopy can also be used to cut adhesions bridging the uterine cavity (Asherman's syndrome) and to correct certain specific congenital abnormalities, such as a uterine septum. Even though hysteroscopy is usually done as a day surgery, the costs are significant.

If fibroids need to be removed through an abdominal incision, the procedure (abdominal myomectomy) would carry all the risks, recuperation time, and costs of any major abdominal surgery. Risks include bleeding, infection, and anesthesia. In addition, there would be the significant risk of the development of adhesions at the sites where fibroids were removed.

Any serious uterine condition can ultimately be overcome by retrieving eggs from the infertile woman and using a surrogate to carry the pregnancy safely.

UNEXPLAINED INFERTILITY

If none of the tests has shown an abnormality, the cause of the infertility is said to be unexplained. In some such couples there may be sperm defects or egg abnormalities that have not been detected by standard tests. For example, examination of sperm for more minor defects of sperm morphology (strict morphology) has shown that many failures of fertilization with IVF are explained by a very low percentage of sperm that are truly normal. In some cases this can be remedied in vitro by adding a large number of sperm to each egg or utilizing Intracytoplasmic Sperm Injection (ICSI). In other instances, the sperm may look normal but be unable to penetrate the egg. On the other hand, we now know that some women have poor-quality eggs. However, most couples with unexplained failure to conceive have normal sperm and eggs; the problem may be that they are not meeting in adequate numbers to achieve fertilization.

The number of sperm getting to the egg and staying there may be decreased by either fewer coming up the genital tract or more being removed from around the egg by scavenger cells in the pelvis. Actually, the sperm don't make their way up the genital tract under their own steam, but require contractions of the woman's reproductive organs. Problems can be caused by alterations in the muscular movements of the uterus or lower-than-normal levels of contraction-producing substances in the man's semen. Women with an infertility problem may also have increased numbers of scavenger cells (macrophages) in the pelvic cavity, which can reduce the numbers of sperm available. In other women the tubes may not have the normal capacity to pick up the egg.

In line with these basic problems of getting sperm and eggs together, such patients are often advised to have a short course of IUI. Then, to increase the numbers of eggs available to meet the sperm, the ovaries are stimulated with hMG or FSH, as in the anovulatory patient. IVF is the most direct solution, wherein the eggs and sperm are placed directly together either in the laboratory.

It is clear that one should not persist with unending cycles of gonadotropins with IUI before moving on to IVF.

THE BOTTOM LINE

Many well-meaning friends, family members, and even health professionals often will give couples advice to relax, forget it, or adopt a baby. Generally that is bad advice. Stress reduction strategies like acupuncture or a Mind-Body program along with continuing fertility treatment is usually the best option.

Most of the time one of the conventional treatments will end up with a pregnancy. But when conventional treatments do not work in a reasonable period of time, couples should consider moving on to in vitro fertilization. Those who have egg quality issues might best consider using an egg donor.