Parenting - Prenatal to preschool/Parenting_PrenatalToPreschool.bin/dp/0046/00460.txt

Text File | 1993-06-15 | 52KB | 818 lines

$Unique_ID{PAR00460}
$Pretitle{}
$Title{Fertility:  IVF and its "Cousins"}
$Subtitle{}
$Author{
Berger, Gary S
Goldstein, Marc
Fuerst, Mark}
$Subject{IVF test-tube in vitro fertilization superovulation hormones eggs
sperm chemical clinical pregnancies pregnancy rate dropped cycles freezing egg
donor eggs donors Ovulation Induction Pergonal clomiphene citrate pure
follicle stimulating hormone FSH Metrodin human chorionic gonadotropin hCG
estradiol ovarian follicles luteal phase GnRH agonists leuprolide acetate
Lupron Metrodin Egg Retrieval laparoscopic laparoscopy Semen Collection sample
Fertilization polyspermy Embryo Transfer Freezing Frozen embryos Post-Embryo
Transfer Cancellation Cycle Age Factor Gamete Intra Fallopian Transfer GIFT
Zygote ZIFT Intravaginal Culture IVC Ultrasound}
$Log{}

The Couple's Guide to Fertility


CHAPTER 10:  IVF AND ITS "COUSINS"


     When Miriam and Roberto married six years ago, they wanted above all
     else to have a baby.  They were heartbroken when they found out it wasn't
     going to be easy.  Miriam, a thirty-five-year-old policewoman, had
     conceived while taking Pergonal, but the pregnancy was ectopic.  The
     diagnosis did not come until after the fallopian tube ruptured, causing
     internal bleeding that required emergency surgery.  By that time, the
     fallopian tube was severely damaged.  With more fertility drugs, she
     conceived again and had another ectopic pregnancy.  To avoid yet another
     ectopic pregnancy, Miriam had her remaining tube sealed off completely.
       With her ovaries still functioning, but no healthy fallopian tube,
     Miriam became an ideal candidate for in vitro fertilization.  She again
     took Pergonal to stimulate her ovaries, and had three eggs retrieved and
     fertilized with Roberto's sperm.
       When her pregnancy test was positive, Miriam says, "We were ecstatic,
     overwhelmed."  She went back to work as a detective, but took a leave of
     absence shortly afterward.  Nine months later, with Roberto present, she
     gave birth to their son Omar.  "I was happy to hear him cry so loud,"
     says Roberto, a thirty-nine-year-old teacher.  "I was happy but at the
     same time relieved that we had finished the whole thing."
       Some day, Miriam and Roberto plan to tell their son the miraculous
     story of how he was conceived.  "We plan to show him the pictures taken
     through the microscope only forty-eight hours after the eggs were
     retrieved, and the ultrasound pictures taken at twenty-one days and at
     about fifteen weeks from the transfer into the uterus," says Roberto.
     "We will tell him exactly what happened, about the whole exciting process
     of seeing his total development."

     Somewhere in the world, a "test-tube" baby is born every day.  The
miracle of babies born through in vitro fertilization (IVF) no longer seems so
miraculous.  In fact, fertilization outside the human body is now available
throughout the Western world.  In North America, about two hundred centers
perform IVF, and the best report pregnancy rates of 15 to 20 percent per cycle
after embryo transfer.  That's not too far off the 20 to 25 percent chance of
natural pregnancy in any given month under ideal conditions.

What Is In Vitro Fertilization?

     Simply stated, IVF involves removing eggs from a woman, fertilizing them
in the laboratory (in a culture dish, actually, not a test tube) and then
transferring the fertilized eggs, or "pre-embryos," into the uterus a few days
later.
     More specifically, after superovulation with hormones to produce multiple
eggs, the IVF team places the retrieved eggs in sterile culture media along
with washed sperm and keeps them at normal body temperature inside an
incubator, where fertilization and early cell division take place.  Then the
team returns the pre-embryos to the uterus.  From that point, if the embryos
implant successfully, the pregnancy progresses as it would naturally.

What to Look For in an IVF Clinic

     There are about two hundred IVF clinics in the United States and Canada,
and finding the right one for you is just as important as your search for the
right fertility specialist.
     Inquire about the program's patient selection process, including any age
limitations and the types of infertility patients it accepts.  Most programs
won't accept a woman over the age of forty.  You should know the number of
cycles the clinic is performing each week and how soon you can be seen.
Waiting can be one year or longer in the busiest centers.
     Ask straightforwardly about your chances of achieving a pregnancy at that
clinic.  How does this compare with your chances at other IVF centers?  How
does it compare with that of other couples with similar diagnoses at that
particular clinic?
     When you ask about the pregnancy rate, you should be aware that various
IVF centers report results in different ways.  Some include in their pregnancy
rates both "chemical" pregnancies and "clinical" pregnancies.
     Chemical pregnancy refers to a rise in hCG levels about ten to fourteen
days after hCG administration, but many chemical pregnancies never make it to
the more advanced stage at which the pregnancy can be seen with an ultrasound
exam of the uterus.
     The clinical pregnancy rate is a more important statistic.  A clinical
pregnancy continues at least until it can be documented with an ultrasound
exam showing the presence of a fetus.  But even pregnancies that reach this
stage can miscarry, and--as after natural conception--up to one-third of all
clinical pregnancies established through IVF don't progress to a live birth.
By far the most important statistic you want is the clinic's live birth rate.
The live birth rate should be calculated by taking into account all of the
couples who have had treatment there over a specified length of time. Ask what
your chances are of taking home a baby, based on the clinic's past experience.
     The method of calculating the pregnancy rate varies from one clinic to
the next.  A program may report its pregnancy rate per patient, per cycle, per
embryo transfer, per month, per year, or from its inception.  Find out how
many cycles were done before the clinic had its first pregnancy and what the
success rate has been since then.
     It may also help you evaluate a program to find out the "dropped cycle"
rate.  A "dropped cycle" means the woman began ovarian stimulation but never
got to the stage of attempting egg retrieval.  A high rate of dropped cycles
(30 percent or more) may reflect a poor ovulation induction technique, or it
may just mean that the clinic has stringent criteria before proceeding to egg
retrieval.
     Cost is obviously important.  Does your health insurance policy cover any
of the costs incurred during the IVF cycle?  Many clinics now offer
transvaginal ultrasound-guided egg retrieval instead of laparoscopy, which
decreases the cost of the egg retrieval of by as much as 20 to 30 percent.

Other Options

     Another way to assess a clinic's suitability for you is to examine the
variety of services and support systems it offers.  For example, some IVF
clinics provide embryo freezing.  The clinic may also provide adjuncts to IVF
as well, such as egg freezing and embryo or egg donor programs.
     Embryo freezing--actually freezing and storing fertilized eggs or
pre-embryos--allows preservation for transfer in future spontaneous ovulation
cycles.  This is an advantage if many eggs are retrieved and fertilized, since
most centers prefer to transfer back no more than four embryos per IVF cycle
due to the increased risk of multiple pregnancy.  If the center offers
freezing, ask whether any basic research, using animal models, has been
performed to assess the viability of the freezing and thawing technique.
     There should be a clear-cut policy regarding any remaining frozen embryos
that are left after a woman becomes pregnant.  What happens to them?  How long
will they be kept in storage?  Would you consent for them to be donated to
other couples after you have your child?
     IVF is an exceedingly difficult technique to perform with good results.
Launching and maintaining an IVF program is an expensive, time-consuming
process.  Strict quality-control standards need to be established and met.  A
team of committed professionals, each with a specialized expertise, is
essential.  Besides a reproductive surgeon and reproductive endocrinologist,
the team will probably include an embryologist, IVF lab technician(s),
nurse-coordinator, and a counselor.  Familiarize yourself with the
qualifications and previous experience of the staff of the program.  Its O.K.
to ask about their credentials and experience.

Patient Education and Support

     Before you decide to undergo treatment at any clinic, you should
understand the entire IVF process, step-by-step, including when drug therapy
begins, how often the woman needs blood tests and ultrasound monitoring, and
when egg retrieval will likely take place.  If you have traveled from
out-of-town, the clinic should help arrange for a place for you to stay during
the IVF treatment.  Also, a doctor in your area should be contacted to assist
in follow-up tests after you have returned home following embryo transfer.
     Your first set of tests may duplicate the general fertility workup--blood
tests for both partners to rule out immunological problems and to confirm that
the woman is ovulating; a complete physical exam for the woman, including a
measurement of her uterine cavity to determine how far to place the embryos
into her uterus; and a semen analysis for the man.  You should also receive
instructions on how to administer the fertility drugs the wife will take to
induce multiple egg production.

Ovulation Induction

     "It was odd giving my wife the injections," says Sam, aged forty, a local
     councilman.  He and his wife Jennifer, also forty, had tried to have a
     baby for nearly four years before they went to see Dr. Goldstein.  He
     found that Sam had a low sperm count, probably due to a varicocele, which
     was repaired microsurgically.  In the meantime, Jennifer's gynecologist
     could find nothing wrong with her after a fertility workup.  Sam's
     post-op semen analysis showed that his sperm count was still low.  He
     tried clomiphene for three months, but his sperm count did not rise, so
     he and Jennifer decided to try IVF.
       At the start of their first IVF cycle, Sam gave Jennifer an injection
     of Pergonal in the buttock every night for a week.  "I thought, "I can't
     stick a needle in there.'  But she said she hardly felt any pain."

     The goal of any IVF program is to maximize the couple's chances of having
a baby.  To achieve pregnancy, there must be successful responses to ovulation
medication, egg collection, fertilization, embryo replacement, and subsequent
implantation.  Failures can occur at any step along the way.
     For example, of thirty women who start ovulation induction, six may have
the cycle dropped because of inadequate stimulation.  Of the remaining
twenty-four women who undergo egg retrieval, only twenty-one may get to the
point of embryo transfer, with three having eggs that didn't fertilize and
divide.  Of the twenty-one who have embryo transfers, only three might achieve
a clinical pregnancy if the clinic's pregnancy rate is 15 percent per embryo
transfer.  One of those three is likely to miscarry, leaving only two couples
that may have a live born infant.  This means the live birth rate is 2/30 or 7
percent.
     To maximize a couple's chances of pregnancy, all successful IVF programs
use some combination of ovulation inducing agents to make multiple
fertilizable eggs available at the time of scheduled egg retrieval.
     The first attempts at IVF, a concept developed and made successful by the
late British gynecologist Dr. Patrick Steptoe and his co-researcher,
embryologist Robert Edwards, had little success because only one egg was
recovered during a spontaneous ovulation cycle.  These unstimulated cycles
required the IVF team to detect the very beginning of the woman's LH surge,
and then closely monitor her to find the best time to retrieve her egg.
Following her spontaneous LH surge, Steptoe and Edwards would often have to
perform egg retrievals very late at night or during early morning hours.
     The success of IVF improved dramatically with the use of superovulation
with Pergonal, first advocated by the Norfolk, Virginia, group headed by Drs.
Georgianna and Howard Jones.  Larger numbers of eggs could be recovered and,
the IVF team could better time egg retrieval.  Now, the use of superovulation
has become routine with IVF.  Recently, gonadotropin releasing hormone (GnRH)
s have also been introduced prior to beginning controlled ovulation to
prevent the woman from having her own spontaneous LH surge so that egg
retrieval timing can be strictly controlled and the chance of a "dropped"
cycle minimized.
     Generally, the woman begins taking ovulation inducing drugs between the
first and fifth days of her cycle to stimulate the development of multiple
follicles.  Several eggs are stimulated to develop at the same time so that a
group of eggs will be available for fertilization.  This "superovulation" is
usually accomplished with combinations of the same hormone medications used to
stimulate ovulation in other treatment cycles, such as for IUI:  clomiphene
citrate, Pergonal, pure follicle stimulating hormone (Metrodin), and human
chorionic gonadotropin (hCG).
     Many couples are already familiar with these medications since they may
have used them in previous treatment cycles, before ever considering IVF.
Usually, a member of the IVF team teaches the husband how to give his wife the
daily injections so that she doesn't have to go to the doctor's office for her
medication.  Although this may be difficult to do at first, it gives the
couple some control over their own treatment.
     There are almost as many individual stimulation regimens as there are IVF
programs.  Most IVF clinics start providing high doses of hormones, either
alone or in combinations, early in a woman's cycle--when more follicles can be
recruited to progress and mature.  The woman's response to stimulation is
carefully monitored by estradiol levels, ultrasound exams, cervical mucus
examination and, possibly, progesterone and LH levels to determine how the
follicles containing the eggs are developing.  Blood hormone levels may be
obtained intermittently during the first week of stimulation, then daily,
along with ultrasound exams and cervical mucus monitoring, as ovulation
approaches.  The doctor adjusts the stimulation schedule to maintain a steady
growth in the size of ovarian follicles and a steady rise of estradiol levels.
When the follicles reach maturity, usually after seven to ten days of
medication, an hCG injection is administered to trigger egg maturation in
anticipation of egg retrieval from the follicles.
     At first, most IVF clinics had one standard way to induce ovulation.  If
a woman's follicles weren't stimulated sufficiently, she had no egg retrieval,
and the cycle was canceled.  Today most programs individualize ovulation
induction, which has reduced IVF cancellation rates.
     Since some women do better with larger amounts of hormones, and others
with lesser amounts, hormone stimulation should be individualized as much as
possible.  Doctors often determine individual hormone doses based upon the
woman's response to previous cycles of hormone therapy or to previous IVF
cycles.
     IVF researchers have learned that high amounts of gonadotropins can often
disrupt and shorten a woman's luteal phase, making it difficult for
implantation to occur or for her to carry the pregnancy to term.  To help
support the luteal phase, most IVF teams now provide progesterone daily from
the day of egg retrieval until a pregnancy test is performed two weeks later.
Others also provide repeated injections of hCG in the luteal phase of the
cycle to keep the ovaries producing progesterone.
     Unfortunately, between 10 and 20 percent of women attempting IVF have a
poor ovarian response to ovulation-inducing drugs and never reach the stage of
egg retrieval.  Increasing the dose of gonadotropins in the early phase of the
menstrual cycle may enhance egg recruitment for such poor responders.
     Recently, several IVF teams have pretreated these poor responders using
GnRH agonists such as leuprolide acetate (Lupron) to wipe the hormone slate
clean, and then initiated gonadotropin ovulation induction.  GnRH
pretreatment, followed by Pergonal, alone or with Metrodin, increases the
number of eggs collected, the fertilization rate, the length of the luteal
phase, and pregnancy rates.  After pretreatment with a GnRH , however,
it usually takes larger amounts of Pergonal to produce ovulation than when no
GnRH  is used.
     This more controlled stimulation with GnRH and Pergonal has the advantage
of fewer cancelled IVF cycles due to a spontaneous LH surge or premature
luteinization of the follicles than with Pergonal alone.  If a woman has an LH
surge, most programs now cancel cycles because it's difficult to predict
ovulation accurately, and retrieval of the eggs may be performed either too
early or too late.  Cycles may also be canceled due to a low number (less than
three) of mature follicles, inadequate estradiol production, or poor follicle
development.
     Because of the improved ability to time a woman's egg retrieval to get
mature eggs, many IVF teams now use GnRH routinely in IVF cycles.  The
disadvantages of pretreating the woman with GnRH  include a longer
duration of treatment, more Pergonal injections, and an increased cost (for
extra Pergonal and because Lupron itself is expensive).  However, these
disadvantages are counterbalanced by fewer canceled cycles.
     A recent survey of U.S. IVF clinics by Serono, the manufacturer of
Pergonal, reveals that 89 percent used GnRH s in at least some cycles
in 1988, compared to only 2 percent in 1987.  At present, to stimulate
ovulation most U.S. IVF clinics only use GnRH in conjunction with Pergonal for
those who respond poorly to Pergonal alone.

Egg Retrieval

     Married for two years, Marilyn, aged thirty-six, and Edward, aged
     forty-six, wanted a baby.  Since they had been unsuccessful after trying
     for a year, they each went to fertility specialists.  Even though he had
     fathered two children in his first marriage, Edward showed a borderline
     low sperm count.  Marilyn had intermittent high prolactin levels and
     elevated androgen levels.  The following years were fraught with
     frustration as they both tried hormone treatments and numerous artificial
     inseminations without success.  Their next alternative was an IVF
     procedure.
       In their first IVF attempt, Marilyn had her eggs retrieved
     laparoscopically.  "I didn't feel a thing when I was asleep, and I
     remember having a pleasant dream.  In fact, I was annoyed that they had
     awakened me when it was over," says Marilyn.  "Then my belly hurt where
     they had made the incision for the laparoscope, my hand hurt where the IV
     tube had been in place and I felt nauseous."  Although three of her eggs
     were fertilized and transferred into her uterus, the attempt failed.
       During her next IVF attempt, Marilyn had her eggs retrieved, with
     ultrasound guidance, through her vagina.  "I felt a little uncomfortable
     when they were rinsing my ovaries, but it wasn't bad," she says.  "I
     hardly felt when they stuck the needle into my follicles.  After it was
     over, I didn't feel any pain."

     If a woman doesn't take GnRHs, then as she nears the middle of
her cycle she usually begins to monitor herself with a home test kit several
times a day to check for her LH surge.  The IVF team retrieves her eggs based
on the prediction of when she will ovulate naturally after the LH surge, or
after administering hCG, which is usually more accurate.  In most cases, after
taking Pergonal, the woman receives an hCG injection and the IVF team
retrieves her eggs thirty-four to thirty-five hours later.
     The team retrieves the woman's eggs either with a laparoscopic procedure
or an ultrasound-guided needle placed through the vagina.  She receives
general anesthesia or local anesthesia with intravenous sedation and possibly
takes mild analgesics.
     With laparoscopy, the surgeon makes a small incision in the woman's
abdomen near the belly button for the laparoscope and two smaller incisions in
the pubic hair line for egg retrieval instruments.  He punctures the follicles
with a thin needle inserted through the laparoscope or through a separate
second puncture site in the abdomen.  Then he withdraws fluid from each
follicle and gives the fluid to an embryologist in the operating room or in an
adjacent lab, who examines the follicular fluid under a microscope for eggs.
The embryologist puts eggs found in the fluid into culture medium and
incubates them.  Meanwhile the surgeon irrigates the follicles with sterile
solution and again collects the fluid to check for any additional eggs.
Laparoscopy usually yields an egg from 60 to 80 percent of the follicles.
     For ultrasound-guided retrieval, the IVF team covers an ultrasound probe,
specifically designed for pelvic imaging, with a sterile condom or latex glove
and inserts the probe into the woman's vagina.  With the aid of a needle guide
attached to the probe, the doctor harvests her eggs by puncturing the
follicles and removing the follicular fluid.  The embryologist immediately
identifies and places the eggs in nutritive media in an incubator.
     Ultrasound-guided egg retrieval has made the most physically demanding
part of the IVF procedure less traumatic.  In some centers, husbands can be
with their wives during the egg retrieval.  The procedure is usually easier on
the woman than laparoscopy, and is equally effective in retrieving eggs.  The
quality and number of eggs, and the pregnancy rates, from ultrasound-guided
egg retrieval compare favorably to those of laparoscopic retrieval.  It is
also usually less costly, faster, and leads to a quicker recovery than
laparoscopic retrieval.
     Because of these advantages, at many IVF clinics ultrasound-guided egg
retrieval is more common than laparoscopic retrieval.  Laparoscopy may be
reserved for women who need a simultaneous assessment of pelvic anatomy
through a diagnostic laparoscopy, but the best-equipped IVF clinics will have
both retrieval methods available to pick the best method for a particular
woman.
     With either method, on average, the IVF team retrieves from six to eight
eggs from the woman's follicles.  Typically, three or four of the eggs are
fully mature.

Semen Collection

     "At first, it was embarrassing providing the sample because of all those
     people in the waiting room," recalls Sam.  "They all knew what I was
     there for.  But then I realized that all the guys were there for the same
     reason."

     Before the start of the IVF cycle, the husband makes an appointment to
give a semen sample for evaluation.  In some cases, the husband's sperm can be
frozen as a backup for the day of egg retrieval.  As with a semen analysis, he
is asked to refrain from ejaculation for two or three days beforehand to
increase the number of sperm in the semen.  On the day of egg retrieval, he
provides a semen sample through masturbation, and the sample undergoes a
standard semen analysis along with sperm washing and "swim up" to recover the
healthiest sperm.

Egg Fertilization

     For men with normal semen, about 50,000 of the most motile sperm are
incubated with each of his wife's eggs.  For a man with abnormally shaped
sperm or a mild to moderately low sperm count or motility, as many as 500,000
sperm are mixed with each egg.  An embryologist inspects the eggs, allows them
to incubate in culture media, and then mixes the sperm with mature eggs.  From
two to twelve hours after egg retrieval, the embryologist places the mixture
in an incubator overnight, and the following morning checks the eggs for
fertilization.
     There are four basic steps to fertilization:  the egg's metabolism must
be turned on, the sperm must be incorporated into the egg, a barrier must be
erected to keep other sperm out, and the nuclei and chromosomes from the egg
and the sperm must be united inside the egg.
     Generally, about 80 percent of mature eggs become fertilized at this
stage.  Eggs penetrated by more than one sperm (polyspermy), which produces an
abnormal embryo, are not transferred back to the wife's uterus.
     In some IVF programs, the team allows immature eggs (about 50 percent of
the retrieved eggs) to ripen in culture media for twelve hours or longer and
then fertilizes them with the husband's sperm.  A few IVF clinics even
reinseminate eggs that haven't fertilized believing that the eggs were too
immature at first and that incubating them in culture medium matures them
enough for a second insemination.  Usually, immature eggs don't often become
fertilized and lead to a pregnancy.
     By about thirty hours after fertilization, the sperm and egg have become
a two-celled embryo.  By forty-eight hours after fertilization, the embryo
should have four cells, and by sixty hours it should have divided into eight
cells.  The embryo is usually transferred into the wife's uterus anywhere from
the two-cell to the eight-cell stage.
     If 80 percent of the retrieved eggs become fertilized, why do at best
only 15 to 20 percent of women who go to IVF clinics become pregnant?  The
answer may lie with several factors.  The uterus may not be properly prepared
for implantation.  A woman's hormonal support after embryo transfer may be
inadequate.  With IVF, embryos are transferred into the uterus much more
quickly (after two days) than they would normally appear in the uterus in a
natural cycle (five to seven days after ovulation).  That is because after the
first few days in incubation outside of the body, eggs won't keep dividing
normally.

Embryo Transfer

     Of the six eggs retrieved from Jennifer's follicles, three became
     fertilized by Sam's sperm and were transferred into her uterus.  "We were
     ecstatic about the three fertilizations after spending a tense weekend
     waiting to hear about the results," Sam says.  "We came in early Sunday
     morning for the embryo transfer.  Two other couples were also in the
     office for the same thing, so we shared bagels and lox together.  It was
     the most unusual Sunday brunch I have ever had."

     When the fertilized eggs have divided, the woman returns to the IVF
clinic for the transfer procedure.  The reproductive surgeon threads a thin
plastic catheter through the vagina, through the cervical canal, and into the
uterus, and transfers the fertilized egg through the catheter.  The patient's
husband may be allowed to stay with his wife during the transfer process.
     This ten-minute, outpatient procedure requires no anesthesia.  The woman
may experience some uterine cramping and discomfort, however, and possibly a
small amount of bleeding.  After resting for a few hours, she returns home and
usually can resume normal activities in a day or two.
     To enhance the embryo transfer rate, some IVF clinics now have the woman
go through a mock embryo transfer using radiopaque dye in a pre-IVF cycle.  A
fluoroscope reveals where the dye (which is like the fluid that will contain
the embryo) ends up.  In certain body positions, such as with the woman on her
back, the dye may run out of her vagina.  She may be better off having her
embryos transferred while she is in a knee-chest position (on her stomach, not
her back).  Others have devised equipment that holds the uterus tilted
downward, hoping to use gravity to help the transferred embryos implant in the
uterus.
     The chances of having a child through IVF are also improved by
transferring up to four embryos into the uterus.  Transferring more than four
embryos doesn't seem to improve the overall pregnancy rate, but does increase
the likelihood of multiple pregnancy.  Most IVF teams like to transfer three
or four embryos during each IVF cycle.  If more than four eggs are retrieved,
all mature eggs are fertilized and the extra embryos may be frozen.  If
freezing is unavailable, the couple may be asked to donate the eggs to another
infertile couple or to allow the IVF team to use them to refine culturing
methods and embryo handling techniques.

Embryo Freezing

     If an IVF procedure fails, the couple should wait at least one month
while the wife recovers before undergoing superovulation and egg retrieval
again.  Saving eggs for future use by fertilizing them with sperm and then
freezing them as embryos can be helpful.  Frozen embryos can be transferred
during subsequent spontaneous (natural) ovulation cycles without subjecting
the wife to any additional medications and another egg retrieval.
     At the right time to transfer the embryos during succeeding treatment
cycles, the frozen embryos are thawed and transferred into the uterus as with
any IVF attempt.
     The ability to preserve embryos for future use lowers the total cost of
repeated IVF treatments since the most costly first few stages (ovulation
induction, egg retrieval, fertilization) don't have to be repeated.  Another
advantage is that the embryos can be transferred during a natural ovulation
cycle when the woman's uterus is naturally ready for implantation.
     About half of frozen embryos survive thawing, and 10 to 20 percent lead
to pregnancies.  From fifteen to twenty U.S. centers are now freezing embryos,
and they have reported dozens of births.  Improved freezing and thawing
techniques are currently being developed and will almost certainly lead to
more centers offering embryo freezing in the future.
     If a couple has embryos frozen, they have to pay the IVF clinic a storage
fee.  After a certain length of time, the couple must decide what to do with
any unused frozen embryos, such as whether to donate them to another infertile
couple.
     Some IVF clinics, such as the one at Cornell University, have the couple
sign an agreement stating that the frozen embryos are the joint property of
the couple.  Upon the woman's forty-fifth birthday, the frozen embryos become
the property of the Cornell IVF team.  This ethical dilemma of survivorship
gained worldwide attention when a wealthy California couple died in a plane
crash without designating what to do with their frozen embryos left in
Australia.  After a lengthy court battle, the rights to the frozen embryos
were transferred to the couple's estate.

Post-Embryo Transfer

     "The first seven days after the embryo transfer were exciting," says Sam.
     "Jennifer's eggs were implanted in her womb and in a way she was
     pregnant.  Everything was going well."  As it got closer to two weeks and
     the pregnancy test, they spent more time together, nurturing each other.
     The pregnancy test result came back as borderline, and Sam and Jennifer
     had to wait another two days.  In that time, her hCG levels crashed, and
     Jennifer got her period.
       "That was hard for us to take.  We started to think again that we would
     never have a baby," says Sam.  "I told Jennifer that this was only our
     first IVF cycle, that she should keep her spirits up.  Although they told
     us we only have a 20 percent chance, I reminded her that even though we
     have a male fertility problem, we had fertilizations.  We're looking
     forward to the next attempt."

     The two weeks of waiting after embryo transfer often become the most
difficult part of the IVF treatment emotionally.  After the embryo transfer,
the woman may continue to take hCG or progesterone to help support the uterine
lining built up in the first half of the cycle.  During this period, various
blood hormone levels are measured to track the wife's progress.  If necessary,
she receives more progesterone to help maintain the endometrial lining and
prevent premature menstruation.  Two weeks following embryo transfer, she
returns for a pregnancy test.
     If her pregnancy test is negative, the IVF team usually encourages the
couple to schedule a follow-up visit with the clinic's doctor and a counselor,
usually a social worker or psychologist, to ask any questions and to discuss
their next step.  The couple may decide to try another IVF attempt.  A woman
who goes through the IVF procedure four times has about a 50 percent chance of
taking home a baby.  After four attempts, the odds don't get any better.
     If her pregnancy test is positive, the woman still has a 20 to 40 percent
chance of miscarrying (women over forty tend to have a higher miscarriage
rate, as high as 60 percent), which is slightly higher than the natural
miscarriage rate, and about a 5 percent chance of an ectopic pregnancy, also
higher than for the general population.  Within two weeks after a positive
pregnancy test, she returns for an ultrasound scan to confirm the presence of
a fetal heartbeat and to see whether she is carrying more than one baby. Since
most IVF clinics now limit the number of transferred embryos to four, the
incidence of multiple pregnancies isn't much higher than with superovulation
without IVF.
     In the more than fifteen thousand IVF births worldwide, so far there is
no evidence of an increased risk of birth defects or premature births.  Most
IVF clinics don't consider IVF pregnancies high-risk pregnancies, except for
the risk of miscarriage, for which many provide progesterone supplements to
help maintain the pregnancy to term.
     If the woman becomes pregnant, she will be referred back to her
obstetrician.  If she doesn't have an obstetrician, the clinic usually helps
her find one.  Genetic counseling and amniocentesis are usually recommended
for any woman over thirty-five; a genetic abnormality, however, can occur at
any age.  Chorionic villus sampling is a newer alternative to diagnose a
genetic disorder in the first trimester, but it carries a slightly higher risk
of miscarriage than amniocentesis, which is performed in the second trimester.
As always, you should discuss the need for and risks of genetic testing with
your doctor.

Cancellation of a Cycle

     Occasionally, an IVF team will decide not to attempt to retrieve a
woman's eggs, but rather to cancel the treatment cycle.  Sometimes the woman
doesn't respond optimally to the medications and the blood tests and
ultrasound exams don't reveal successful follicle growth.  Her eggs may be
immature, or too mature, to be fertilized.  Or the eggs may fertilize, but not
continue to divide, in which case they will not be transferred back into the
uterus.
     You have to realize that your chances for success in any one IVF cycle,
even at the best clinics, is no higher than 20 percent once you have gotten to
embryo transfer.  Of all the couples who start IVF treatment, only 7 to 10
percent take home a baby.  These percentages are likely to increase as
fertility specialists gain more experience with IVF.

Who Are the Candidates for IVF?

     The woman with the best chances for a successful IVF procedure is younger
than thirty-five and has normal menstrual cycles, a good response to
controlled ovarian hyperstimulation, and a husband with a good sperm count.
     IVF can bypass most causes of infertility, including irreversibly blocked
fallopian tubes, antisperm antibody problems, endometriosis, a cervical factor
problem, very low sperm counts, and even unexplained causes of infertility.
IVF is a particularly good alternative for a woman who produces mature eggs
but can't conceive naturally because of blocked fallopian tubes, and for a
woman with luteinized unruptured follicle syndrome, who develops but doesn't
release mature eggs from her follicles.

     The Age Factor

     The chances of an IVF birth depend heavily on the wife's age.  Younger
women have higher pregnancy rates than older women.  Women over age forty have
only a rare chance of IVF success.  Yet, even knowing the odds, many women
over forty say they want to go through at least one IVF cycle before giving up
their hopes of having a baby.
     One way to determine whether a woman over forty has a strong chance of
success may be to measure her estradiol and FSH levels on day three of the IVF
cycle.  At the Jones Institute, researchers have seen a trend toward higher
pregnancy rates and fewer canceled cycles for women over forty when their FSH
level is low on cycle day three.

     The Male Factor

     For four years, Diane and John tried to have a baby with no success, even
     after a dozen attempts at intrauterine insemination.  A loan officer in a
     bank, John, aged forty-eight, had a borderline low sperm count, low sperm
     motility, and poor sperm morphology.  When an IVF clinic opened near
     their home, their fertility specialist suggested they give it a try.
       "Our first attempt, with all the injections I had to give her every
     night, brought us closer together," John says.  Four of Diane's healthy
     eggs were fertilized and transferred, but the attempt failed.  They
     decided to try again.  "This time we knew the routine, but we were both
     feeling bad since we didn't expect to have to go through the procedure
     twice," he says.  That attempt also failed.  John and Diane, a
     thirty-eight-year-old school counselor, took some time off and came back
     for another attempt three months later.
       This time, the test showed that Diane was pregnant.  "We were scared
     because we thought it might be a false positive pregnancy test," she
     says.  Then they had an ultrasound exam.  "We actually saw a tiny,
     beating heart.  It was a beautiful moment, so exciting to see the fruits
     of our labor," John says.  Their daughter Doreen is fourteen months old.

     Although IVF offers new hope to infertile couples, it's not the answer
for all causes of infertility.  Most IVF programs usually require a man to
have a sperm concentration of more than 10 million sperm per ml with more than
20 percent normal sperm motility and at least 5 percent normally shaped sperm.
Below these values, a couple rarely achieves a pregnancy without using donor
sperm.  Male factor patients already have a one-third less chance of
fertilizing their wife's eggs in the lab than men with normal sperm counts.
     Besides a semen analysis, the IVF clinic should also check the man and
his wife for sperm antibodies, which reduce the chances of fertilization of
both normal and oligospermic men.  Many IVF clinics also test a man's sperm
function using sperm penetration assays with zona-stripped hamster eggs.
Although not totally reliable (some men score poorly and still fertilize their
wife's eggs), the hamster test gives an indication of a man's fertilizing
ability.
     The most important determinant of IVF success for a male factor patient
is his ability to fertilize his wife's eggs.  After two cycles with no
fertilization, most men will continue to fail to fertilize in subsequent
cycles.  If a couple with a male factor problem produces no fertilized eggs
after two attempts, they should consider pursuing other alternatives, such as
donor sperm or adoption.
     Sperm from men with male factor infertility can have difficulty both in
getting the sperm to the egg, and in penetrating the egg.  Once the eggs
become fertilized in the IVF lab, however, these couples with a male factor
problem have pregnancy rates equal to infertile couples with no male factor
problem.  In other words, once a sperm fertilizes the egg, its mission has
been accomplished and the outcome of pregnancy is just as good as for eggs
fertilized by sperm from men with no known male factor problem.  To improve
the live birth rate of male factor patients, IVF researchers are looking for
ways to improve the fertilizing ability of a man's sperm.

Competition

     In their third IVF attempt, Marilyn and Edward had only one two-cell
     embryo that degenerated, and they never got to the embryo transfer stage.
     "We had gone to a big place that sent couples through like herds of
     cattle," Marilyn says.  "They tried to tell us what was "best' for us
     without stopping to understand our needs.  They kept saying my eggs would
     never be fertilized with Edward's sperm, and that donor insemination was
     for us.  But I told them that donor sperm was difficult for me to accept.
     I'm adopted, I don't know who my father was and I didn't want my baby not
     to know who his or her father was.  They didn't bother to listen.  I was
     so frustrated, that evening I went home and smashed several boxes of
     light bulbs, one at a time, in our backyard.  It was very therapeutic."

     As IVF has become one of the fastest-growing areas of infertility
treatment, it has also become ripe for exploitation.  Couples desperate for a
baby may be lured by IVF clinics promising results they can't achieve.
     Entrepreneurs are cashing in on a surging fertility industry, and the
most controversial aspect of this commercialization of conception is IVF,
which by some estimates is itself a $100 million industry.
     Of the approximately two hundred U.S. and Canadian IVF clinics, about
one-third are at university centers and the rest have private funding or are
associated with for-profit hospitals.  The most successful centers have long
waiting lists, and new IVF clinics are opening all the time.  Many programs
have never had a live birth.  Some programs that shut down after a year or
more with no pregnancies are reopening after refining their techniques.
     Yet, the bulk of IVF births comes from a small number of large programs.
Those infertile couples who have gone through IVF treatment have found that
IVF can cost them tens of thousands of dollars, with no money-back guarantees
and stiff odds against success.  Unfortunately, after all the expenses,
heartache, poking, and prodding, most couples go home childless.
     Doctors at the larger centers say that a high volume of patients is
necessary to establish a track record, to perfect techniques, to maintain a
level of competency, and to support the necessary staff specialists.  They
claim that a commitment of at least two years and an expenditure of $1 million
is necessary for a new program to establish itself, and that physicians who
dabble in IVF won't have comparable results if they don't make similar
investments.
     But large programs aren't trouble-free.  Some couples at large clinics
feel as if they are being put through an assembly line.
     It's difficult to pinpoint the right balance.  If a clinic performs too
many cycles, it may be impersonal.  Too few cycles, and the clinic staff may
not have the experience to give couples the best chances of having a baby.
     As the number of IVF clinics has grown, so has the professional and
public pressure to regulate them.  Exaggerated estimates of success have led
doctors, insurance companies, members of Congress, and infertile couples to
push for stronger regulation.
     The American Fertility Society has an IVF registry, but in the past has
divulged only cumulative data, not information about individual IVF clinics
and their success rates.  However, clinics that want to have their own data
released can now do so through the registry.
     A couple can check with the American Fertility Society to see whether an
IVF clinic is listed in its registry.  The more than a hundred official
members of the Society for Assisted Reproductive Technology (SART) is
restricted to IVF programs that can account for at least forty patients and
three live births.
     Scientists have also been urging the federal government to take a more
active role in IVF research to improve a couple's odds.  The government, which
placed a moratorium in 1980 on federal funding for any research involving
human embryos or fetuses, recently took a preliminary step toward allowing
federal funding for IVF research.  An ethics advisory board that was disbanded
in 1980 has been resurrected and will take another look at the funding
question.

IVF "Cousins"

     Once considered a last-chance technology, IVF has spawned the development
of other procedures that use variations of the same assisted reproductive
techniques.  These technologies offer couples the advantages of the years of
experience that went into making IVF a viable infertility treatment.  They
carry IVF technology along to the next logical step in an attempt to help more
infertile couples have babies.

     Gamete Intra Fallopian Transfer (GIFT)

     In addition to IVF as a treatment, most IVF clinics offer a more natural
approach to fertilization, called Gamete (for egg and sperm) Intra Fallopian
(within the fallopian tube) Transfer (GIFT).  This combines eggs with sperm
and then places the egg/sperm combination directly into the fallopian tubes,
where conception occurs naturally.
     The GIFT procedure requires a woman to have at least one normal fallopian
tube.  The ovulation induction and monitoring procedures for GIFT are
basically the same as for IVF.  After the surgeon retrieves the eggs, the
embryologist draws up small amounts of sperm for each egg, and places up to
two eggs plus 100,000 sperm into each fallopian tube.  If the sperm fertilize
the egg, it happens as it would naturally--inside the fallopian tube rather
than in an incubator outside the body, as in IVF.
     Except for women with two damaged fallopian tubes, candidates for IVF are
also candidates for GIFT, which in many centers has a higher pregnancy rate
(20 to 30 percent) than IVF.  It is most suitable for couples with unexplained
infertility, cervical or male factor problems, mild endometriosis, or
luteinized unruptured follicle syndrome.  GIFT also seems to offer women over
forty a better chance at live birth than IVF.
     GIFT has some disadvantages when compared to IVF.  At present, GIFT
usually requires laparoscopy to transfer the eggs and sperm into the fallopian
tubes, making it a more major procedure than an IVF embryo transfer through
the vagina and cervix into the uterus.  (This difference in the two techniques
may change with the use of hysteroscopes or ultrasound guidance to transfer
sperm and eggs through the cervical canal into the tubes.)  More important, if
the GIFT procedure fails, there is no way of knowing whether the woman's eggs
were fertilized, which is readily apparent with IVF.

     IVF + GIFT = "ZIFT"

     Because of this lack of knowledge about fertilization, some couples with
a male factor problem now receive a combination of IVF and GIFT.  The wife's
eggs, retrieved with ultrasound guidance, are exposed to her husband's sperm
in the lab.  Within twenty-four hours, the fertilized egg (known as a zygote)
is transferred to her fallopian tube, usually by laparoscopy.
     Since this procedure uses the zygote, not the separate eggs and sperm,
it's called Zygote Intra Fallopian Transfer (ZIFT).  This has an advantage
over a pure GIFT procedure, particularly for male factor couples, because the
embryologist will know whether the wife's eggs have been fertilized by her
husband's sperm.  If his sperm don't fertilize her eggs, then the couple may
decide at that point to accept donor insemination rather than pursue further
efforts to achieve a pregnancy with the husband's sperm.

     Intravaginal Culture (IVC)

     Another technique that takes advantage of the body's own environment is
intravaginal culture (IVC).  After retrieval the eggs are placed with the
husband's sperm in a culture medium inside a sterile, hermetically sealed
container carried inside the vagina.  A vaginal diaphragm holds the container
in place.  This maintains the egg and sperm at normal body temperature as well
as, if not better than, any incubator in a laboratory.  Two or so days later,
the doctor opens the container and transfers any fertilized, dividing eggs
into the uterus.
     The simplicity of this procedure is appealing, and may lead to further
reductions in costs and more widespread availability of treatment than
classical IVF.

     Ultrasound GIFT

     To avoid the surgery involved in GIFT, some clinics perform the procedure
entirely with ultrasound guidance, both for egg retrieval and tubal transfer
of the eggs and sperm.  This new technique, first reported from Australia, is
gaining popularity in North America.
     As IVF procedures multiply, researchers are learning more and more about
the miracles of conception.  By sampling the fluids and protein substances
found inside the fallopian tube, they are getting a better understanding of
the tube's normal environment.
     If what's happening inside the fallopian tube and the conditions leading
to successful implantation can be better understood, then more couples will
have babies through IVF and related treatments.  Some researchers believe that
it may even be possible eventually to better the 20 to 25 percent natural
conception rate per cycle.
     For the moment, IVF, even at a 10 percent live birth rate, is an
acceptable alternative for many couples.  But even IVF isn't the last resort.


What Couples Should Ask When Looking for an IVF Clinic:

  -  Do you have any limitations on the age or types of infertile couples
     you accept into your program?

  -  What is your pregnancy rate per embryo transfer?  Does this rate include
     only clinical pregnancies, or does it also include chemical pregnancies?

  -  What is your pregnancy rate for couples our age with our particular
     problem?

  -  What percentage of your couples initiating an IVF cycle don't make it
     to transfer?

  -  What percentage of your IVF patients who have egg retrievals go on to
     embryo transfer?

  -  What percentage of your couples have a male factor problem, and what
     is your success rate in treating them?

  -  How many cycles does your program induce in a year?

  -  How much does the procedure cost, including hormone treatments?
     (Costs generally range from about $6,000 to $7,000, including the drugs.)

  -  Do you freeze embryos?

  -  What happens to frozen embryos after we achieve a pregnancy?

  -  Do you offer egg freezing, embryo donation, or egg donation programs?

  -  Do you offer GIFT or other advanced procedures involving assisted
     reproductive technology?

  -  What is your live birth rate among all couples who have started an IVF
     cycle in your program?