Some Treatment of Infertile Patients
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I. Normal Pregnancy Rates

The chance of conception in any given month among fertile couples
attempting to conceive is approximately 20%. Clinical studies of couples
having unexplained infertility of mild endometriosis, however, have
indicated that the chance of achieving a pregnancy in any given month
(referred to as "fecundity") is severely reduced compared to normal
couples. Only 2-5% of these couples conceive each month. The
appropriatness of any therapy for these patients must be decided only
after that therapy has been shown to increase the monthly fecundity rate
beyond the 2-5% noted in couples receiving no therapy.

II. Early Developments and History

In Vitro Fertilization (IVF) was originally devised as an alternative
treatment for women with irreparable or .absent fallopian tubes. It's
success, however, has lead to the application of In Vitro Fertilization 
(IVF) to treat fertility problems other than tubal abnormalities,
(endometriosis, unexplained infertility, cervical factors and even male
infertility). Further studies indicated that IVF is generally as
effective for treatment of these "nontubal" problems as it is for tubal
disorders. The notable exception was male infertility.

The rational for IVF in women with blocked fallopian tubes is easy to
understand. Fertilization outside the body and placement of early
pre-embryos directly into the uterus bypasses the blokced fallopian
tube. The application of IVF in patients with disorders other than tubal
problems is not as easily understood.

Physicians began to notice pregnancies in patients who had received
Pergonal, but for various reasons did not complete their IVF cycle. This
lead investigators to suspect that many IVF successes in patients with
normal fallopian tubes might be due to factors other than fertilization
outside the body. Perhaps these pregnancies were due to other aspects of
the IVF treatment protocol, such as the release of more eggs as a result
of Pergonal stimulation.

Since the initial publications in 1985 there have been a number of
clinical studies that have confirmed a significantly improved pregnancy
rate with Pergonal stimulated superovulation. This improvement in
fecundity (monthly pregnancy rate) was noted in couples having: cervical
factors, luteal phase defects, mild endometriosis or infertility of
unknown etiology and who have failed the usual therapeutic approaches.

III. Explanation of Procedure

At a time in the cycle when the ovarian follicles reach a designated size,
and estrogen levels are appropriate, an injection of the hormone HCG is
given to trigger ovulation. Ovulation usually occurs 36-48 hours after the
HCG injection. Thus, intercourse or insemination should be timed accordingly.
Not all women have a satisfactory response from the ovary.
In that event, future cycles will use only injectable medications.

Performing intrauterine insemination may result in an increase in the
number of sperm at the site of fertilization in the fallopian tube.
Generally only 1 of 2000 sperm ejaculated into the vagina make can later
be found in the fallopian tube. Therefore, adding insemination to
Pergonal stimulated cycles may further improve the pregnancy rate.
Although there is no "proof" that adding intrauterine insemination to
Pergonal induced superovulation definitely improves the chance of
pregnancy, most scientific reports suggest an increased pregnancy rate
associated with the addition of intrauterine insemination. One of these
reports demonstrated a 26% pregnancy rate per cycle with intrauterine
insemination and superovulation versus 6% with superovulation alone. At
this point, we recommend adding intrauterine insemination to
superovulation, based on the results of these studies.
The additional cost and risk of insemination are minor. In order to 
perform the intrauterine insemination (I.U.I) the man produces the sperm 
specimen by masturbation. The sperm are concentrated and "washed" by a 
centrifugation technique. The specially prepared and concentrated sperm
are then instilled directly into the uterus through the cervix with a
small plastic tube. The specimen can be obtained at home using a special
condom and sperm nutrient media. Care must be taken to insure that the
specimen does not get chilled or overheat prior to processing. If the
specimen is obtained in the office, about 45 minutes to one hour will be 
required for processing. The insemination procedure is usually no more 
painful than a pap smear. After this minor office procedure the patient
remains lying flat for ten minutes and then can resume all normal 
activities.

IV. Results

Several reports in the fertility literature discuss the results of
superovulation and intrauterine insemination. The fecundity (the odds of
getting pregnant each treatment cycle), in most cases equaled or
exceeded the success reported with in vitro fertilization and G.I.F.T.
For couples with normal fallopian tubes and sperm, the chance of
becoming pregnant in a treatment cycle was consistently between 10-20%.

If the same couple was treated for three or four cycles, they had a
cumulative pregnancy rate of between 30% and 50%. These results were
also noted in the recent evaluation at the University of Minnesota.
Another key issue is that the monthly cycle fecundity is the same for the
first four to six treatment cycles. Thus the chance of conceiving during
any of the first four cycles is identical and a couple should not become
discouraged if they do not become pregnant in the first few treatment cycles.
Unfortunately, it also appears that after approximately four to six cycles
of treatment, the chance of obtaining a pregnancy with further
superovulation treatment falls off dramatically. This has lead most
infertility clinics to recommend no more than a four cycle trial of this
therapy.

V. Potential Risks.

The major risk of superovulation is directly related to the use of these
potent ovulation inducing drugs.
Approximately 20% have twins, 2-3% are triplets and 1% or less have 4 or
more. The incidence of premature delivery will also be higher if a multiple
pregnancy in conceived.

Early pregnancy monitoring is suggested to determine the number of
pregnancies conceived as well as ruling out a tubal pregnancy. A tubal
pregnancy usually requires surgery for its removal.
Another possible side effect is  ovarian hyperstimulation. This condition
results from enlarged tender ovaries often beginning approximately one week
after ovulation.

Mild ovarian hyperstimulation is common, rarely causes difficulty, and
is self limited. In severe ovarian hyperstimulation the ovaries become
very large and painful. The woman may have swelling from retaining
excessive amounts of body fluid in the tissues. Fluid may leak from the
vessels into the abdomen and chest resulting in serious fluid and
electrolyte imbalance and potentially significant complications.
Fortunately, severe hyperstimulation is rare, occurring in only about
one percent of treatment cycles. If pregnancy and ovarian rupture do not
occur, the syndrome resolves in approximately one week. Should the
patient become pregnant, the syndrome may last for several weeks.

This problem rarely occurs if the ovulatory dose of HCG is withheld. The
major reason for the lower incidence of severe hyperstimulation is the
close monitoring with frequent blood estrogen determinations and
ultrasounds during the critical part of the treatment. If a patient is
judged to be at high risk for hyperstimulation, the drug is stopped and the
HCG injection withheld.

Unfortunately, however, even close monitoring cannot completely
eliminate the risk of hyperstimulation.

Recent studies have suggested that patients having taken clomiphene for
12 cycles or more may be at greater risk for developing ovarian cancer.

If intrauterine insemination is used as part of the treatment protocol,
it has its own risks different from those of the described drugs.

Two potential risks of intrauterine insemination have been identified.
The cervix and its mucus are a natural barrier to infection. In the
process of intrauterine insemination, this natural barrier is bypassed
by placing the sperm into the uterine cavity. If the sperm or cervical
mucus are infected with bacteria, an infection could be introduced into
the uterus and, subsequently, the fallopian tubes. An infection in the
uterus or fallopian tubes is potentially serious and could result in
irreparable tubal blockage and subsequent sterility.

A rare, but potentially severe side effect of intrauterine insemination
is a sudden allergic reaction to the sperm similar to the dramatic
allergic reaction that some people experience to bee stings, certain
foods, or medications. This type of allergic reaction can be severe and
even result in death. Fortunately, this potential severe reaction is
extremely rare.

Uterine cramping, either during or following insemination, is common and
does not denote either an allergic reaction or an infection. The
development of fever, pelvic tenderness, or abdominal pain within the
first week following an intrauterine insemination may be the signs of an
early infection and should be reported immediately.

VI. Cost Benefit Analysis.

As with any medical treatment, attention needs to be paid to the
relative costs and benefits of treatment. The expected benefit of
superovulation and I.U.I. is a normal pregnancy. The value of a
biological pregnancy can only be determined by each couple.

VII. Summary.

Unfortunately, a number of couples have infertility of unknown etiology, 
or have failed to conceive following the standard therapies for 
endometriosis, cervical factor, and ovulatory dysfunction. 
Superovulation with or without insemination offers a pregnancy rate 
approximately equal to that of in vitro fertilization of G.I.F.T. 
Because this alternative is less expensive and less stressful, it is 
reasonable to offer superovulation to couples with these problems before 
attempting either in vitro fertilization of G.I.F.T.