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Director of Assisted Reproductive Medicine,
The Institute for Reproductive Medicine and Science at Saint Barnabas
 Key aspects of modern infertility treatment include: ovulation
induction (OI), in vitro fertilization (IVF), intracytoplasmic sperm
injection (ICSI) for treatment of severe sperm factor infertility;
and sometimes includes special procedures such as micro-epididymal
sperm extraction (MESA), testicular sperm extraction (TESE), and
single sperm freezing (SSF). In addition to reviewing these treatment
areas, I will also discuss Pre-implantation Genetic Diagnosis (PGD)
as a treatment for recurrent pregnancy loss; the impact of maternal
aging and the importance of day 3 FSH levels; and exciting developments
in cryopreservation of embryos as well as eggs.
Approximately 30 percent of infertility arises from ovulatory dysfunction.
Eggs live in cysts in the ovaries called follicles, and the only
thing that ripens the egg inside the follicle is Follicle Stimulating
Hormone (FSH). There are only two places to get FSH: from the pituitary
gland in the brain, or a medication out of a box.
There are two medications that stimulate FSH production by the
pituitary:
- Clomiphene citrate (Clomid® and Serophene®) causes the
pituitary to increase production of FSH. Anti-estrogen side effects
of clomiphene citrate (in about 20 percent of women) include thickening
cervical mucous, which may make it more difficult for sperm to penetrate,
as well as decreasing the thickness of the endometrium and decreasing
the chances of implantation.
- It is hoped that the newer medication, Letrozole, will decrease
the side effects of clomiphene citrate while giving the same safety,
ovulation and pregnancy rates. With these oral medications there
is an 80 percent chance of ovulation, a 5 to 15 percent pregnancy
rate per cycle, and a very low multiple birth rate of only 5 percent,
mostly twins.
- If these medications are not successful, ovulation induction
with FSH medications, such as Gonal F, Follistim or Menopur, can
be used. These medications have a higher rate of ovulation and pregnancy,
but they are injections, and more expensive, and have a 20 percent
multiple birth rate. Women with polycystic ovarian disease (PCO)
may also be treated with medications to decrease their insulin levels,
such as Metformin, which may also aid in induction of ovulation.
IVF continues to be the superior treatment for female infertility
due to tubal disease. It is frequently more efficient than surgical
intervention, since pregnancy rates have increased so greatly during
the 1990s. Improvements have been made in embryo culture systems,
which has led to increased selection of “hardier” embryos,
like blastocysts, for implantation and higher pregnancy rates, as
well as decreasing multiple birth rates.
ICSI has revolutionized the treatment of sperm factor infertility.
Even those men with no sperm in ejaculated semen can be helped if
there are sperm in the testes, which can be attained by such surgical
procedures as MESA (aspirating sperm from the epididymis in the
testis) or TESE (removing sperm from a testis biopsy). Prior to
these techniques, donor sperm may have been needed.
Single Sperm Freezing (SSF) is a technique that is only available
at the Institute for Reproductive Science and Medicine (IRMS) at
Saint Barnabas. SSF allows the TESE to be performed many weeks before
an actual ICSI cycle. This allows a couple to know that sperm will
be available for the ICSI cycle before the wife starts cycle medications,
so they do not need donor sperm available for back-up use.
PGD continues to aid in increasing the live birth rates in IVF by
decreasing miscarriages due to chromosomal abnormalities of the
fetus, some of which increase with advancing maternal age. PGD for
gene problems, such as cystic fibrosis or sickle disease, has been
possible for many years but not widely used due to the technical
difficulties of false positives and negatives. These techniques
are improving greatly and we will begin to see a much greater use
of PGD for genetic diagnosis of specific gene disorders.
The importance and impact of maternal age on fertility is not new,
but if I had a single take home message in this article to impart,
it is that maternal age is still one of the most important factors
affecting the treatment outcomes with any infertility treatment.
The younger the potential mother, the higher the pregnancy rates
with IUI, IVF, medications or surgery. In any individual situation, “it
is what it is;” women cannot change their situations or certainly
not make themselves any younger. However, if there are prospective
choices regarding a relationship and/ or having children, I advise
women with a choice to choose parenting sooner rather than later.
The unfair female biological clock is real, no matter how young
a woman feels, or how good she is about weight, exercise or sun
block. FSH levels on day 3 of the menstrual cycle may give information
about ovarian reserve and the likelihood of responding to FSH medications. “It
is essential for women to plan where they want to be at 45 and work
backward, armed with the knowledge that the window for having children
is narrower than they have been led to believe, and once it begins
to swing shut, science can do little to pry it open.” (TIME,
4/15/2002)
Cryopreservation of embryos has been performed successfully for many
years. What will be coming into the forefront in this millennium
will be the successful freeze-thawing of oocytes (eggs) with improved
pregnancy rates. There are thousands of babies born from freeze-thawed
embryos but only a few hundred from frozen eggs. This is because
good techniques were developed first for embryo freezing, and pregnancy
success has been better to date with frozen-thawed embryos than
eggs. However, there is certainly a need for improved egg freezing
techniques for women without a partner who do not want to use a
sperm donor to make embryos, but would rather freeze their eggs
for later use. The most obvious candidates are single women with
cancer who may be rendered infertile by their treatment. Another
group is younger women who have no partner presently but want to
cryopreserve their eggs for a future pregnancy when they find a
partner but are older and less fertile. Ovum donation would also
be more accessible and affordable if ovum donor banks could be started
with cryopreserved eggs.
Approximately 20 percent of couples who are of childbearing age are
infertile. Sadly, only about 50 percent of these people seek treatment.
Of this group, about 25 percent seek treatment from their general
ob-gyn physician and never see a fertility specialist. At a time
when there are so many options for successfully having a child,
most of these couples never complete testing or receive appropriate
treatments. My second “take home message” (after the
first, which is starting to get pregnant younger), is to see a reproductive
endocrinologist earlier for testing and treatment. Don’t waste
precious months or years with incomplete testing or ineffective
therapies.
The Institute for Reproductive Medicine and Science of Saint Barnabas
is recognized internationally and maintains pregnancy rates that
are among the highest in the world and treats patients from 43 states
and 17 foreign countries.
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