Artificial Insemination

Husband's Sperm

Definition:

Artificial insemination is the process of taking the husband's semen
obtained by masturbation and placing it by artificial means into one of
the following:

Into the cervical mucus: cervical insemination.
Through the cervix into the uterine cavity: intrauterine insemination.
Through the cervix and uterine cavity into the fallopian tube:
intratubal insemination.

Intracervical insemination is performed by placing an "unprocessed"
semen specimen into the cervical mucus and then placing a cervical cap
or specially designed vaginal tampon to hold the semen against the
cervix. Success rates with intracervical insemination have varied
widely, but unfortunately, only 10 to 15% of couples will obtain a
pregnancy following 4 to 6 well timed cycles of insemination.

Intrauterine insemination was developed in an attempt to improve the
chance of pregnancy. Intrauterine insemination involves both a special
processing of the semen to maximize its fertility potential and its
placement into the uterine cavity. Thus the maximum number of sperm are
placed in close proximity to the egg. Recent scientific studies found a
significantly increased number of patients had living sperm within the
fallopian tubes and peritoneal cavity surrounding the ovary following
intrauterine insemination.

The placement of sperm into the uterine cavity involves a special
processing procedure of the semen sample. The seminal fluid that
contains the sperm does not normally pass the cervical mucus barrier and
gain access to the uterine cavity. Thus it is generally best not to
artificially place the seminal fluid into the uterine cavity. The first
step of the semen processing procedure is to separate the sperm from the
seminal fluid so that only the sperm are placed beyond the cervical
mucus into the uterine cavity. Secondly, the semen processing procedure
is performed to maximize the husband's fertility potential. In some
cases the artificial insemination is performed to overcome a sperm
abnormality. A semen processing procedure is selected which will attempt
to specifically improve upon the identified abnormality. The exact type
of semen processing will be individualized after the best technique has
been determined for the husband. He will be given specific instructions
on how to collect the semen sample and what particular semen preparation
procedure we will utilize.

Once a couple has entered the insemination program the semen samples
will be monitored carefully at each insemination procedure.

In a study conducted the following results were reported.

Less than 3% of the timed intercourse cycles resulted in pregnancy while
9 of 39 intrauterine inseminations resulted in pregnancy (23%).
Intratubal insemination has been investigated in an attempt to improve
upon the success rates already obtained by intrauterine insemination.
The same processing techniques as used for intrauterine insemination
separates the sperm from the seminal fluid and maximizes the sperm's
fertility potential.

Intratubal insemination, however, involves a more difficult and involved
technique of placing the sperm. This requires the use of a specially
designed catheter that is placed through the cervix, into the uterine
cavity, and into the uterine opening of the fallopian tube. This is
technically a much more difficult procedure than intrauterine
insemination and may carry with it more risk. The use of hysteroscopy or
ultrasound is necessary to guide the catheter appropriately into the
fallopian tube. Unfortunately, studies have not demonstrated an
significant improvement in pregnancy rates with this technique.
In couples where the husband has very low sperm count or motility this
technique may possibly improve the odds of pregnancy more significantly
than intrauterine insemination. There is also the possibility that this
method may be superior to intrauterine insemination in couples where a
strong antisperm antibody is suspected. At this point, intratubal
insemination is investigational, but the initial results are
encouraging.

Clinical indications for intra-uterine insemination.

A. Cervical factors

1.Mucus - poor quality and/or quality
Good cervical mucus should change its physical characteristics so that
it can store, mature, and transport sperm from the cervix where it is
deposited to the uterine cavity and fallopian tubes where fertilization
occurs. Abnormalities in the production of "fertile" cervical mucus are
sometimes correctable with medical treatment. When medical treatment
fails to normalize cervical mucus production, intrauterine insemination
is utilized to bypass the cervical mucus and place the sperm directly
into the uterine cavity.

2.Anatomic - Stenosis

The cervical openings can sometimes be excessively narrowed, causing a
"stenotic cervix". This is usually a result of a prior surgical
procedure performed on the cervix such as a conization, but it can also
occur after vaginal delivery, or in some cases be congenital in origin.
Cervical stenosis can result in poor mucus production and decreased
sperm transport. If an insemination devise can be passed through the
narrowed cervix, this problem can be bypassed.

3.Immunologic - presence of antibodies directed against sperm

A woman's body does not normally make antibodies that are specifically
targeted towards killing or immobilizing sperm. As part of our natural
defense mechanism we develop an immune response to foreign material such
as viruses and bacteria which allows us to fight off infections. Part of
this immunological response is the making of a specific antibody that is
targeted towards the bacteria, virus, or foreign tissue. The antibody is
manufactured by our white blood cells. Although sperm are foreign cells
to a women's body, they do not usually trigger an immunological
response. In some instances however, for reasons that are unclear, some
women develop an immunological response that produce antibodies directed
against sperm. These antibodies may appear in the blood, tubal fluid,
uterine fluid, or cervical mucus. When these antibodies occur in the
woman's reproductive tract they can immobilize and kill the sperm before
they have a chance to reach the egg within the fallopian tube.
A number of therapies have been proposed to overcome antisperm
antibodies:

Condom Therapy

The use of condoms limits the exposure of sperm to the female genital
tract, hopefully reducing the stimulus to produce further antibodies.
This does not appear to be successful. It is only applicable for sperm
antibodies in the women.

Steroid Therapy

The use of high dose steroids (cortisone-like medication) suppresses the
immunological system and decreases all antibody formation. This
technique has resulted in serious side effects and is rarely
recommended.

Intrauterine Insemination

Placement of a large number of sperm within close proximity to the egg,
bypassing cervical mucus antibodies.

Intratubal Insemination
Placement of a large number of motile sperm at the point of fertilization
within the fallopian tube bypassing the cervical mucus and uterine fluid
which may contain antisperm antibodies.

Assisted Reproductive Technology (Gamete intrafallopian tube transfer,
In Vitro Fertilization, etc.)
Placing sperm and egg with direct contact with each other, thus
minimizing the effects of antibodies in all areas of the reproductive
tract.

Short of the assisted reproductive technologies, intrauterine
insemination has been shown to be the most effective mode of therapy.
Experimental evidence has indicated that antisperm antibody levels tend
to be the highest concentration within the cervical mucus. Bypassing the
cervical mucus, therefore, places the maximum number of sperm beyond its
biggest barrier. Antibody concentrations with the uterine fluid and
fallopian tube fluid are often not great enough to immobilize all of the
sperm if sufficient numbers are placed in the uterine cavity. Thus,
placement of a large number of motile sperm within the uterine cavity
offers the advantages. Intratubal insemination is presently under
investigation with the hopes that this will further improve results by
placing the sperm even closer to the point of fertilization. Intratubal
insemination, however, is technically more difficult, expensive and
possibly may carry a greater risk of complications.

B. Male factors

Sperm quality - Defects in sperm production such as decreased sperm
count and/or diminished sperm motility.
Any sperm production problem that results in a decreased number of
normal motile sperm can result in a decreased male fertility potential.
A normal ejaculate contains millions of normally formed motile sperm. It
is estimated that following intercourse only a few hundred sperm make it
to the point of fertilization. This is because the vast majority of
sperm are lost from their point of deposition in the vagina as they make
their way up the reproductive tract to the point of fertilization in the
fallopian tube. When a decreased number of normally functioning sperm
are ejaculated into the vagina during intercourse there is a decreased
chance that an adequate number of normal spermatozoa will reach the
crucial point of fertilization by providing an increased number of sperm
in closer proximity to the egg. Although insemination procedures can
provide an increased number of sperm at the fertilization site, the
sperm reaching the egg must be able to penetrate and fertilize the egg.
Insemination procedures can not improve the chance of pregnancy if the
sperm are unable to fertilize the egg. The ability to improve fertility
through artificial insemination is highly depended upon the sperm defect
and its severity.

Immunological - sperm directed autoantibodies in the male reproductive
tract.

Sperm are normally kept isolated from the male immunological system by
the blood-testis barrier. Under normal condition sperm within the male
reproductive tract never stimulate the male immunological system to
produce antibodies against sperm. In certain situations however, this
separation mechanism fails and sperm are exposed to the immunological
system, stimulating the production of antisperm antibody. The antibody
is present in the seminal fluid which is mixed with the sperm at the
time of ejaculation. The antibody coats the sperm and can immobilize
them, cause the sperm to react adversely to the cervical mucus, or
disrupt their ability to penetrate the egg. The process of intrauterine
insemination of intratubal insemination attempts to select out those
sperm that have not been coated with antibody and place as many as
possible in close proximity to the egg. The insemination procedure is
sometimes coupled with steroid therapy in the male in order to decrease
the amount of antibody production.

Ejaculatory

Any sexual disfunction or ejaculatory abnormality that interrupts the
normal placement of sperm during intercourse reduces the possibility of
pregnancy. Depending on the specific problem being treated, one of the
artificial insemination procedures should be ideal for placing the sperm
in the female reproductive tract.

C. Miscellaneous

Abnormal Huhner's Post Coital Test
The post coital test is a clinical exam that checks for the number of
motile sperm within the cervical mucus following intercourse. A normal
post coital test requires that an adequate number of motile sperm be
deposited correctly during ejaculation and are able to survive for the
appropriate length of time in the cervical mucus. A normal post coital
test is associated with a good fertility potential. A poor post coital
test often reflects a sperm production problem, sperm placement problem,
or hostile cervical mucus. A persistently abnormal post coital test is
often an indicator for an artificial insemination procedure, regardless
of the etiology.

Infertility of unclear ediology.

Some couples remain infertile in spite of the fact that a complete
infertility evaluation has not elucidated a clear cause for the
infertility. Many of these couples will be helped through intrauterine
insemination alone or in combination with superovulation. Although the
exact mechanism is unknown, it is thought that the placement of an
increased number of motile sperm higher in the reproductive tract is
responsible for the increased chance of pregnancy. This may be because
some patients have an undetectable abnormality in sperm transport from
the cervix to the fallopian tube.

Success of conception with artificial insemination

A cumulative pregnancy rate (the overall chance of a couple obtaining a
pregnancy with four to six cycles of intrauterine insemination) averages
about 25% (1 in 4 couples will achieve a pregnancy). The result varies
significantly however, depending on the reason that the insemination is
being performed. Male factor infertility with severe abnormalities and
sperm count or motility have the worse prognosis with only 10 to 15% of
couples achieving a pregnancy. Male factor infertility with only
moderate abnormalities, couples with cervical factor or immunological
factor infertility has been shown to have the best prognosis with 35 to
40% of couples achieving a pregnancy.

Unfortunately there is no direct correlation between the absolute values
of sperm count, motility, morphology, and the chance of obtaining a
pregnancy. Certainly the more severe the sperm production abnormality,
the less likely pregnancy will occur. Pregnancy has been achieved with
as few as 400,000 progressively motile sperm placed within the uterus at
the time of insemination. Thus it is usually impossible for the
physician to give a specific percentage chance of success for a given
couple. If a minimum number of motile sperm are present most physicians
will recommend a trial of intrauterine insemination as an appropriate
course of therapy. We recommend a 4 to 6 cycle trial of intrauterine
insemination. Most pregnancies that occur as a result of insemination do
so in the first 4 cycles of therapy. During those 4 cycles the chance of
obtaining a pregnancy is about the same each cycle. This means that the
chance of becoming pregnant on the 3rd or 4th cycles is similar to the
chance of obtaining a pregnancy on the 1st or 2nd cycle. Beyond 4 cycles
pregnancies are uncommon and beyond 6 cycles are highly unlikely.

Intratubal insemination is presently being investigated to determine whether
further improvement in pregnancy rates can be obtained by use of this
technique. Results are preliminary but there is a possibility that in certain
situations intratubal insemination may offer a better chance of pregnancy
than intrauterine insemination.

Possible complications of intrauterine insemination.

Fortunately the side effects, adverse reactions, or possible
complications from intrauterine insemination are infrequent and rarely
severe. All of the potential problems associated with intrauterine
insemination are associated with the bypassing of the normal cervical
mucus barrier to the female reproductive tract and the artificial
placement of sperm beyond the cervical mucus. The possible problems
associated with artificial insemination can be categorized as follows:

1.Uterine cramping

Uterine cramping will occur in approximately 5% of all patients
undergoing intrauterine insemination. The suspected causes of uterine
cramping are as follows:

Introduction of the catheter into the uterine cavity which may act as a
foreign body causing a cramping reflex.

Disruption of a small portion of the endometrium (uterine lining) by
the insemination cannula causing the release of prostaglandin (a hormone
responsible for causing intrauterine cramps) leading to cramping 2 to 4
hours following the procedures.

Residual seminal fluid prostaglandins remaining in the semen despite
the wash procedures resulting in cramping occurring within a few minutes
following the actual insemination procedure.

Uterine cramping is not a serious problem and can be easily treated with
a nonsteroidal anti-inflammatory medication such as Anaprox. It does not
denote infection.

2.Mild spotting

Mild spotting occurs in approximately 1% of the patients following
intrauterine insemination. This spotting is a result of minor irritation
to the cervical glands caused by threading the insemination cannula
through the cervical os into the uterine cavity. This bleeding will
usually subside without any treatment within several hours of the
procedure.

3.Gastrointestinal Upset

Mild nausea or diarrhea occur in approximately 0.5% of patients
undergoing intrauterine insemination. Like uterine cramping, this is
usually secondary to the presence of prostaglandins which can be
upsetting to the gastrointestinal tract. This usually subsides within a
few hours of the insemination procedure.

4.Pelvic Infection

The potentially most serious complication and fortunately the most
infrequent, is infection. In a recent study from the University of
California at Irving, less than 0.2% of their patients developed pelvic
infections following over 3,000 intrauterine inseminations during a 3
year period. Most studies to date have shown less than 1% of couples
experience pelvic infection following intrauterine insemination.
Although this complication is uncommon, if it occurs the results can be
devastating. An infection in the uterine cavity can spread to the
fallopian tubes and the surrounding pelvic structures, which can lead to
the need for hospitalization, and intravenous antibiotics. The infection
can cause permanent scarring within the fallopian tubes and surrounding
structures, leaving a patient sterile.

The reason for pelvic infection following intrauterine insemination is
that the normal mucus barrier of the cervix is broken at the time of the
placement of the catheter. If an aggressive bacteria is present in the
cervical mucus or in the sperm placed into the uterine cavity, infection
may occur. It appears that patients who have had previous pelvic
infections or certain types of tubal surgery may be at increased risk of
infection. This increased risk is likely due to the decreased natural
defense mechanisms resulting from previous tubal damage. The use of
artificial insemination in patients at increased risk for infection
should be weighed carefully. There are many times, however, when the
potential benefit from intrauterine insemination in these patients
outweighs the potential risk.

The early symptoms of pelvic infection are cervical or uterine
tenderness during intercourse, lower abdominal pain made worse by
movement or activity, fever, and possibly a foul or bloody vaginal
discharge. If an infection follows artificial insemination, the symptoms
generally begin within a few days to a week after the insemination
procedure. Should a patient who has undergone artificial insemination
begin experiencing any symptoms of pelvic infection, they should notify
their physician immediately and if infection is suspected, promptly
start antibiotic therapy.

The Insemination Procedure

Timing of the Insemination Procedure
The proper timing of artificial insemination is vital when attempting to
maximize success. A number of techniques have been developed to insure
optimum timing so that the sperm and egg will meet at the time of
ovulation.

1.Ovulation Predictor Kits
Ovulation is triggered by the release of LH from the pituitary gland.
The ovulation predictor kits measure the presence of the LH hormone in
the urine. The daily measurement of urinary LH concentrations with the
predictor kits will accurately predict ovulation in most patients. We
recommend that our patients test their urine before noon. When testing
urine in this manner, most patients will ovulate in the morning
following a positive test. Although the ovulation predictor kits are
expensive, they ultimately save money by eliminating the need for extra
inseminations per cycle. The improved accuracy of the insemination is
also more likely to make it successful early in the treatment program,
lessening the need for multiple insemination cycles. The majority of
patient will have their insemination timed in this manner.

2.Ultrasound Timing

Some patients will be undergoing specialized ovulation induction
treatment for the purpose of stimulating ovulation. These patients often
have ovulation triggered artificially with an injection of human chronic
gonadotropin (HCG). In this case the HCG is often administered in the
early evening as directed by the physician with artificial insemination
scheduled 36 to 40 hours after the injection. The timing for
insemination timing is a result of a slightly different timing of egg
release that results from the use of HCG vs. the natural LH surge.