Here is a sneak peak into Dr. Servy’s new book.
Chapter 1
First Intra Uterine Insemination Worldwide
“Don’t judge each day by the harvest you reap but by the seeds that you plant.”
Robert Louis Stevenson
Intra Uterine insemination (IUI) is the most common procedure performed
worldwide in Assisted Reproduction. It was first performed in our Augusta
clinic and laboratory in 1978. We found a new lab procedure causing sperm
purification and concentration and allowing the ideal placement of the sample
in the uterine cavity. This particular technology has not changed since our first
publication.
Male infertility
Infertility is due, in one third of the cases, to a lack of or abnormal sperm
production by the male partner.
It has been known since the beginning of time that semen was causing
pregnancy. Artificial placement of semen in animals dates back to the 14th
century when Arabs used it to breed stallions. An Italian priest and biologist,
Lazzaro Spallanzani, is known as the first to use the technique to breed dogs
in 1784. He studied various forms of microscopic life and confirmed the view
of the Dutch scientist Anton van Leeuwenhoek who in 1677 was the first one
to describe “sperm cells” that he visualized with a microscope. Such forms
of living organisms were later on, in 1836, called “spermatozoa.” In London
in 1793, John Hunter was the first person reported to achieve a successful
human pregnancy by insemination. Subsequently a few sporadic attempts have
been made using the husband’s sperm, but the first reported case of artificial
insemination by donor occurred in 1884.
Sperm Freezing or Cryopreservation
The process of freezing and thawing sperm successfully was developed
and refined in 1953 by Dr. Jerome K. Sherman from the University of Arkansas
for Medical Sciences in Little Rock. He introduced a simple method using
glycerol, but he combined this with a slow cooling of sperm, and storage at
minus 196 degrees Celsius. He also demonstrated for the first time that frozen
sperm, when thawed, were able to cause fertilization and reported the same
year the first successful human pregnancy using frozen sperm. The news was
well received and promptly exploited in Veterinary Medicine. Frozen-thawed
sperm has been extensively used in cattle and swine, but it has also been used
in sheep, horses, dogs, zoo animals, turkeys and creatures as tiny as honeybees.
Insemination and its History 39
Artificial insemination is commonly used instead of natural mating in many
species of animals because of the benefits it can reap. These benefits include
increased safety of the animals and producer, increased production efficiency
and better genetics.
In humans, Doctors had to face a hostile climate in the 50’s. Several State
Supreme Courts considered insemination “contrary to public policy and good
morals.” Artificial insemination with fresh human sperm was first performed
in the mid 60’s and the first sperm banks opened in the early 70’s. In Augusta
GA, Dr. Armand Karow, professor of Pharmacology at the Medical College of
Georgia founded in 1975 “Xytex” a private sperm bank.
Vaginal or Intra Cervical Insemination
There was an absolute rule: “Never try to insert sperm directly into the uterus!” Indeed, the few physicians who had tried to do so learned quickly
their lessons. If the fluid serving as sperm vehicle, called seminal plasma,
is introduced in the uterus it will cause major problems to their recipients.
First, it contains prostaglandins, a hormone-like substance that can be used
in synthetic form to induce labor. It causes severe uterine contractions and
nausea. Then if there is any trace of prostate inflammation or infection in
the sperm provider, which is not uncommon, severe pelvic infections can be
expected. Anaphylaxis, a serious life-threatening allergic reaction can also
take place.
In the 60’s and 70’s inseminations were performed by depositing the semen
with a tuberculin syringe at the opening of the cervix, being careful not to push
the semen into the uterus. A device called the “Mylex Insemination Cup” was
also available. It was a plastic cup that could be applied on the cervix, like a
diaphragm, preventing sperm exposure to the hostile vaginal environment.
X and Y Sperm Separation
Although the first IVF baby was born in 1978, at that period in time
“Assisted Reproduction” was still in its infancy. The same year, a major
event that would change the way to treat infertility occurred in my practice. In
our Endocrinology Lab, my friend John Black Ph.D. was working on adapting
a veterinarian technique to separate X-bearing and Y-bearing spermatozoa to
human sperm, the Ericsson Method for Gender Selection. It was a technique
based on the idea that Y sperm are lighter and swim faster than the heavier X
sperm. Ronald Ericsson Ph.D. patented it in 1976.
The sperm was placed atop a “column” of increasingly thicker layers of
albumin, and allowed to swim down into the solution. After a certain time
period had elapsed, the sperm could be separated into the faster and slower
swimmers. If the couple desired a male baby the faster swimmers were
inseminated and if the couple desired a female baby the same procedure
would be enacted with the slower swimmers. The Y sperm taking the gold
colloidal stain, our laboratory confirmed the separation in vitro but it was
never complete. We could not do better than 90% Y / 10% X or vice-versa.
With the means of our time and minimal advertisement we were able to
recruit 24 couples “wishing for a boy.” Most of them were already parents
of two to four girls*. Since we could not obtain a total separation of Y and X
sperm, we could not guarantee the results and the couples understood. After
completion of the lab procedure, the unsafe-for-the-uterus seminal plasma
being completely eliminated, John Black and I had a wonderful idea. We felt
that we should insert the solution directly into the uterus. The spermatozoa
were being separated from the seminal plasma and re-suspended in a sterile
physiologic medium, similar to the natural liquid environment found in the
uterus.
First Intra Uterine Insemination Worldwide in Augusta GA
Thanks to the new process of separation and filtration, we could bypass
the cervical obstacle or barrier. I designed the first Intra Uterine Insemination
(IUI) catheter using a tuberculin syringe, a sawed off 18-gauge needle and a
#6 French red rubber catheter. It was easy to use and it could be sterilized in
our office autoclave**.
As far as offspring were concerned, the results were not satisfactory. We
obtained 50% boys and 50% girls in 20 pregnancies for families wishing for
a boy***. Mother Nature has a strange way to bring us back down to earth.
Although some clinics are still advertising for the procedure, we have not
pursued the use of the Ericsson Method after our original study since the odds
of good results were only 50%.
While the attempt to use it for sex selection was not successful, it gave
me the opportunity to design the first IUI catheter and perform the first safe
IUIs in the world. At that period in time, we didn’t guess how important IUI
would become in reproduction clinics. Subsequently it was also performed in
all my infertile couples having normal semen analysis when we suspected an
abnormal cervical passage after surgery or old inflammation.
Let’s review why and when IUI would be needed. The cervical mucus is
a natural and necessary filter used to allow safe and invigorating passage of the
spermatozoa in the uterus toward the site of fertilization in the fallopian tubes.
The quality of the mucus is not always optimal and can even be hostile to any
penetration. The quantity and quality of sperm can be inadequate, making
it impossible to reach or overcome the cervical passage. We have slightly
modified the protocol, using physiologic solutions instead of albumin and
since then, we have performed many IUIs. We obtained very encouraging
results that were published****.
It took a little time for the rest of the country and the world to catch on.
About seven years later we started seeing some similar works being published
by other practices. Now IUI is the most commonly performed procedure in
Assisted Reproduction everywhere around the world. It was great to be a part
of history in making it the modern procedure it is today.
The main reason for the renewed interest in artificial insemination in
humans was associated with the refinement of techniques for the preparation
of washed motile spermatozoa in the early years of IVF. Nowadays, IUI is the
most popular and commonly performed procedure in reproductive medicine
worldwide. These days, most clinics use disposable, specially manufactured
plastic catheters that have been sterilized with ionizing radiations (gamma
rays). Finally, we can legitimately claim that IUI started in 1978 in Augusta,
Georgia.
References:
*E.J. Servy and J.B. Black. Results of a self-limited experience in insemination after
separation of X and Y spermatozoa for sex preselection. 7th Annual Meeting of the
American Society of Andrology – Hilton Head SC, February 23, 1982.
**J.B. Black and E.J. Servy. Male factor infertility treated by isolation of progressively
motile sperm. 34th Annual Meeting of the American Fertility Society- New Orleans
LA, March 29, 1978.
**E.J. Servy and J.B. Black. Semen manipulation in male factor infertility. Southern
Medical Association Scientific Assembly – Atlanta GA, November 11, 1978.
***E.J. Servy and J. Scholer. A new look at intra Uterine Insemination. International
IVF-Andrology Meeting – Kiawah Island SC, February 9, 1984
****S.P. Kirsch and E.J. Servy. Intrauterine Insemination in infertility practice. 41st
Annual Meeting of the American Fertility Society – Chicago Il, October 2, 1985.