TIME: Almanac 1993/TIME Almanac 1993.iso/time/caps/83/83capmed.1

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                                                                                September 20, 1983

SCIENCE

The New Origins of Life


How the science of conception brings hope to childless couples


A group of women sit quietly chatting, their heads bowed over
needlepoint and knitting in the gracious parlor at Bourn Hall.
The mansion's carved stone mantelpieces, rich wood paneling and
crystal chandeliers give it an air of grandeur, a reflection of
the days when it was the seat of the Earl De La Warr. In the
well-kept gardens behind the house, Indian women in brilliant
saris float on the arms of their husbands. The verdant meadows
of Cambridgeshire lie serenely in the distance. To the casual
observer, this stately home could be an elegant British country
hotel. For the women and their husbands, however, it is a last
resort.

Each has come to the Bourn Hall clinic to make a final stand
against a cruel and unyielding enemy: infertility. They have
come from around the globe to be treated by the world-renowned
team of Obstetrician Patrick Steptoe and Reproductive
Physiologist Robert Edwards, the men responsible for the birth
of the world's first test-tube baby, Louise Brown, in 1978.
Many of the patients have spent more than a decade trying to
conceive a child, undergoing tests and surgery and taking
fertility drugs. Most have waited more than a year just to be
admitted to the clinic. Some have mortgaged their homes, sold
their cars or borrowed from relatives to scrape together the
$3,510 fee for foreign visitors to be treated at Bourn Hall
(British citizens pay $2,340). All are brimming over with hope
that their prayers will be answered by in-vitro fertilization
(IVF), the mating of egg and sperm in a laboratory dish. "They
depend on Mr. Steptoe utterly," observes the husband of one
patient. "Knowing him is like dying and being a friend of St.
Peter's."

In the six years that have passed since the birth of Louise
Brown, some 700 test-tube babies have been born as a result of
the work done at Bourn Hall and the approximately 200 other IVF
clinics that have sprung up around the world. By year's end
there will be about 1,000 such infants. Among their number are
56 pairs of test-tube twins, eight sets of triplets and two sets
of quads.

New variations on the original technique are multiplying almost
as fast as the test-tube population. Already it is possible
for Reproductive Endocrinologist Martin Quigley of the Cleveland
Clinic to speak of "old-fashioned IVF" (in which a woman's eggs
are removed, fertilized with her husband's sperm and then placed
in her uterus). "The modern way," he notes, "mixes and matches
donor and recipients". Thus a woman's egg may be fertilized with
a donor's sperm, or a donor's egg may be fertilized with the
husband's sperm, or, in yet another scenario, the husband and
wife contribute their sperm and egg, but the resulting embryo
is carried by a third party who is, in a sense, donating the use
of her womb. "The possibilities are limited only by your
imagination," observes Clifford Grobstein, professor of
biological science and public policy at the University of
California, San Diego. Says John Noonan, professor of law at
the University of California, Berkeley:  "We really are plunging
into the Brave New World."

Though the new technologies have raised all sorts of
politically explosive ethical questions, the demand for them is
rapidly growing. Reason: infertility, which now affects one in
six American couples, is on the rise. According to a study by
the National Center for Health Statistics, the incidence of
infertility among married women aged 20 to 24, normally the
most fertile age group, jumped 177% between 1965 and 1982. At
the same time, the increasing use of abortion to end unwanted
pregnancies and the growing social acceptance of single
motherhood have drastically reduced the availability of children
for adoption. At Catholic Charities, for instance, couples must
now wait seven years for a child. As a result, more and more
couples are turning to IVF. Predicts Clifford Stratoon,
director of an in-vitro lab in Reno:  "In five years, there will
be a successful IVF clinic in every U.S. city."

It is a long, hard road that leads a couple to the in-vitro
fertilization clinic, and the journey has been known to rock
the soundest marriages. "If you want to illustrate your story
on infertility, take a picture of a couple and tear it in half,"
says Cleveland Businessman James Popela, 36, speaking from
bitter experience. "it is not just the pain and indignity of
the medical tests and treatment," observes Betty Orlandino, who
counsels infertile couples in Oak Park, Ill. "Infertility rips
at the core of the couple's relationship; it affects sexuality,
self-image and self-esteem. it stalls careers, devastates
savings and damages associations with friends and family."

For women, the most common reason for infertility is a blockage
or abnormality of the fallopian tubes. These thin, flexible
structures, which convey the egg from the ovaries to the uterus,
are where fertilization normally occurs. If they are blocked
or damaged or frozen in place by scar tissue, the egg will be
unable to complete its journey. To examine the tubes, a doctor
uses X-rays or a telescope-like instrument called a
laparoscope, which is inserted directly into the pelvic area
through a small, abdominal incision. Delicate microsurgery, and
more recently, laser surgery, sometimes can repair the damage
successfully. According to Beverly Freeman, executive director
of Resolve, a national infertility-counseling organization,
microsurgery can restore fertility in 70% of women with minor
scarring around their tubes. But for those whose tubes are
completely blocked, the chance of success ranges from 20% to
zero. These women are the usual candidates for in-vitro
fertilization.

Much has been learned about the technique since the pioneering
days of Steptoe and Edwards. When the two Englishmen first
started out, they assumed that the entire process must be
carried out at breakneck speed: harvesting the egg the minute
it is ripe and immediately adding the sperm. This was quite a
challenge, given that the collaborators spent most of their time
155 miles apart, with Edwards teaching physiology at Cambridge
and Steptoe practicing obstetrics in the northwestern mill town
of Oldham. Sometimes, when one of Steptoe's patients was about
to ovulate, the doctor would have to summon his partner by
phone. Edwards would then jump into his car and charge down the
old country roads to Oldham. Once there, the two would remove
the egg and mate it with sperm without wasting a moment; by the
time Lesley Brown became their patient, they could perform the
procedure in two minutes flat. They believed that speed was
the important factor in the conception of Louise Brown.

As it happens, they were wrong. Says Gynecologist Howard Jones,
who together with his wife, Endocrinologist Georgeanna Seegar
Jones, founded the first American in-vitro program at Norfolk
in 1978:  "It turns out that if you get the sperm to the egg
quickly, most often you inhibit the process."  According to
Jones, the pioneers of IVF made so many wrong assumptions that
"the birth of Louise Brown now seems like a fortunate
coincidence."

Essential to in-vitro fertilization, of course, is retrieval of
the one egg normally produced in the ovaries each month. Today
in-vitro clinics help nature along by administering such drugs
as Clomid and Pergonal, which can result in the development of
more than one egg at a time. By using hormonal stimulants,
Howard Jones "harvests" an average of 5.8 eggs per patient; it
is possible to obtain as many as 17. "I felt like a pumpkin
ready to burst," recalls Loretta Leyland, 33, of Melbourne, who
produced eleven eggs at an Australian clinic, one of which
became her daughter Zoe.

According to Quigley, the chances for pregnancy are best when
the eggs are retrieved during the three to four hour period when
they are fully mature. At Bourn Hall women remain on the
premises waiting for that moment to occur. Each morning,
Steptoe, now 71 and walking with a cane, arrives on the ward to
check their charts. The husband of one patient describes the
scene:  "looking at a woman like an astonished owl, he'll say
`Your estrogen is rising nicely.'  The diffidence is his means
of defense against desperate women. They think he can get them
pregnant just by looking at them."

When blood tests and ultrasound monitoring indicate that the ova
are ripe, the eggs are extracted in a delicate operation
performed under general anesthesia. The surgeons first insert
a laparoscope, which is about 1/3 in. in diameter, so that they
can see the target; the small, bluish pocket, or follicle,
inside the ovary, where each egg is produced. Then, a long,
hollow needle is inserted through a second incision, and the
eggs and the surrounding fluid are gently suctioned up. Some
clinics are beginning to use ultrasound imaging instead of a
laparoscope to guide the needle into the follicles. This
procedure can be done in a doctor's office under local
anesthesia; it is less expensive than laparoscopy but may be
less reliable.

Once extracted, the follicular fluid is rushed to an adjoining
laboratory and examined under a microscope to confirm that it
contains an egg (the ovum measures only four-thousandths of an
inch across). The ova are carefully washed, placed in petri
dishes containing a solution of nutrients and then deposited in
an incubator for four to eight hours. The husband, meanwhile,
has produced a sperm sample. It is hardly a romantic moment,
recalls Cleveland businessman Popela, who made four trips to
Cambridgeshire with his wife, each time without success. "You
have to take the jar and walk past a group of people as you go
into the designated room, where there's an old brass bed and a
couple of Playboy magazines. They all know what you're doing
and they're watching the clock, because there are several people
behind you waiting their turn."

The sperm is prepared in a solution and then added to the dishes
where the eggs are waiting. The transcendent moment of union,
when a new life begins, occurs some time during the next 24
hours, in the twilight of an incubator set at body heat. If all
goes well, several of the eggs will be fertilized and start to
divide. When the embryo is at least two to eight cells in size,
it is placed in the woman's uterus. During this procedure,
which requires no anesthetic, Steptoe likes to have the husband
present talking to his wife. "The skill of the person doing the
replacement is very important," he says. "The womb doesn't like
things being put into it. It contracts and tries to push things
out. We try to do it with as little disturbance as possible."

The tension of the next two weeks, as the couple awaits the
results of pregnancy tests, is agonizing. "Women have been
known to break out in hives," reports Linda Bailey,
nurse-coordinator at the IVF program at North Carolina Memorial
Hospital in Chapel Hill. Success rates vary from clinic to
clinic; some centers open and close without a single success.
But even the best clinics offer little more than a 20% chance
of pregnancy. Since tiny factors like water quality seem to
affect results, both physicians and patients tend to become
almost superstitious about what else might sway the odds. Said
one doctor: "if someone told us that painting the ceiling pink
would make a difference, we would do it."

In recent years, IVF practitioners have discovered a more
reliable way of improving results:  transferring more than one
embryo at a time. At the Jones' clinic, which has one of the
world's highest success rates, there is a 20% chance of
pregnancy if one embryo is inserted, a 28% chance if two are
used and a 38% chance with three. However, transferring more
than one embryo also increases the likelihood of multiple
births.

For couples who have struggled for years to have a child, the
phrase "you are pregnant" is magical. "We thought we would
never hear those words," sighs Risa Green, 35, of Framingham,
Mass., now the mother of a month-old boy. But even if the news
is good, the tension continues. One-third of IVF pregnancies
spontaneously miscarry in the first three months, a perplexing
problem that is currently under investigation. Says one veteran
of Steptoe's program:  "Every week you call for test results to
see if the embryo is still there. Then you wait to see if your
period comes."  The return of menstruation is like a death in
the family; often it is mourned by the entire clinic.

Many couples have a strong compulsion to try again immediately
after in vitro fails. Popela of Cleveland compares it to a
gambling addiction:  "Each time you get more desperate, each
time you say, `Just one more time.'"  In fact, the odds do
improve with each successive try, as doctors learn more about
the individual patient. But the stakes are high:  in the U.S.,
each attempt costs between $3,000 and $5,000, not including
travel costs and time away from work. Lynn Kellert, 31, and her
husband Mitchell, 34, of New York City, who tried seven times
at Norfolk before finally achieving pregnancy, figure the total
cost was $80,000. Thus far, few insurance companies have been
willing to foot the bill, arguing that IVF is still
experimental. But, observes Grobstein of UCSD, "It's going to
be increasingly difficult for them to maintain that position."

Second and third attempts will become easier and less costly
with the wider use of cryopreservation, a process in which
unused embryos are frozen in liquid nitrogen. The embryos can
be thawed and then transferred to the woman's uterus,
eliminating the need to repeat egg retrieval and fertilization.
Some 30% to 50% of embryos do not survive the deep freeze.
Those that do may actually have a better chance of successful
implantation than do newly fertilized embryos. This is because
the recipient has not been given hormones to stimulate
ovulation, a treatment that may actually interfere with
implantation.

Opinion is sharply divided as to how age affects the results of
IVF. Although most clinics once rejected women over age 35, many
now accept them. While one faction maintains that older women
have a greater tendency to miscarry, Quigley, for one, insists
that "age should not affect the success rate." Curiously, the
Joneses in Norfolk have achieved their best results with women
age 35 to 40. This year one of their patients, Barbara Brooks
of Springfield, Va., had a test-tube son at age 41; she can
hardly wait to try again.

Doctors are also beginning to use IVF as a solution to male
infertility. Ordinarily, about 30 million sperm must be
produced to give one a chance of penetrating and fertilizing the
egg. In the laboratory, the chances for fertilization are good
with only 50,000 sperm. "In vitro may be one of the most
effective ways of treating men with a low sperm count or low
sperm motility, problems that affect as many as 10 million
American men," says Andrologist Wylie Hembree of
Columbia-Presbyterian Medical Center in New York City.

While most clinics originally restricted IVF to couples who
produced normal sperm and eggs, this too is changing. Today,
when the husband cannot supply adequate sperm, most clinics are
willing to use sperm from a donor, usually obtained from one of
the nation's more than 20 sperm banks. An even more radical
departure is the use of donor eggs, pioneered two years ago by
Dr. Alan Trounson and Dr. Carl Wood of Melbourne's Monash
University. The method can be used to bring about pregnancy in
women who lack functioning ovaries. it is also being sought by
women who are known carriers of genetic diseases. The donated
eggs may come from a woman in the Monash IVF program who has
produced more ova than she can use. Alternately, they could
come from a relative or acquaintance of the recipient, providing
that she is willing to go through the elaborate egg-retrieval
process.

At Harbor Hospital in Torrance, Calif., which is affiliated with
UCLA School of Medicine, a team headed by Obstetrician John
Buster has devised a variant method of egg donation. Instead
of fertilizing the ova in a dish, doctors simply inseminate the
donor with the husband's sperm. About five days later, the
fertilized egg is washed out of the donor's uterus in a painless
procedure called lavage. It is then placed in the recipient's
womb. The process, which has to date produced two children,
"has an advantage over IVF." says Buster, "because it is
nonsurgical and can be easily repeated until it works." But the
technique also has its perils. If lavage fails to flush out the
embryo, the donor faces an unwanted pregnancy.

The most controversial of the new methods of reproduction does
not depend on advanced fertilization techniques. A growing
number of couples are hiring surrogate mothers to bear their
children. Surrogates are being used in cases where the husband
is fertile, but his wife is unable to sustain pregnancy, perhaps
because of illness or because she has had a hysterectomy.
Usually, the hired woman is simply artificially inseminated with
the husband's sperm. However, if the wife is capable of
producing a normal egg but not capable of carrying the child,
the surrogate can be implanted with an embryo conceived by the
couple. This technique has been attempted several times, so far
without success.

The medical profession in general is apprehensive about the use
of paid surrogates. "It is difficult to differentiate between
payment for a child and payment for carrying the child,"
observes Dr. Ervin Nicholas, director or practice activity for
the American College of Obstetrics and Gynecology. The college
has issued strict guidelines to doctors, urging them to screen
carefully would-be surrogates and the couples who hire them for
their medical and psychological fitness. "I would hate to say
there is no place for surrogate motherhood," says Nichols, "but
it should be kept to an absolute minimum."

In contrast, in vitro fertilization has become a standard part
of medical practice. The risks to the mother, even after
repeated attempts at egg retrieval, are "minimal," points out
Nichols. Nor has the much feared risk of birth defects
materialized. Even frozen-embryo babies seem to suffer no
increased risk of abnormalities. However, as Steptoe points out,
"we need more research before we know for sure."

The need for research is almost an obsession amount IVF doctors.
They are eager to understand why so many of their patients
miscarry; they long to discover ways of examining eggs to
determine which ones are most likely to be fertilized, and they
want to develop methods of testing an embryo to be certain that
it is normal and viable. "Right now, all we know how to do is
look at them under the microscope," says a frustrated Gary
Hodgen, scientific director at the Norfolk clinic.

Many scientists see research with embryos as a way of finding
answers to many problems in medicine. For instance, by learning
more about the reproductive process, biologists may uncover
better methods of contraception. Cancer research may also
benefit, because tumor cells have many characteristics in common
with embryonic tissues. Some doctors believe that these
tissues, with their tremendous capacity for growth and
differentiation, may ultimately prove useful in understanding
and treating diseases such as childhood diabetes. Also in the
future lies the possibility of identifying and then correcting
genetic defects in embryos. Gene therapy, Hodgen says
enthusiastically, "is the biggest idea since Pasteur learned to
immunize an entire generation against disease."  It is however,
at least a decade away.

American scientists have no trouble dreaming up these and other
possibilities but, for the moment, dreaming is all they can do.
Because of the political sensitivity of experiments with human
embryos, federal grant money, which fuels 85% of biomedical
research in the U.S., has been denied to scientists in this
field. So controversial is the issue that four successive
Secretaries of Health and Human Services (formerly Health,
Education and Welfare) have refused to deal with it. This
summer, Norfolk's Hodgen resigned as chief of pregnancy research
at the National Institutes of Health. He explained his
frustration at a congressional hearing:  "No mentor of young
physicians and scientists beginning their academic careers in
reproductive medicine can deny the central importance of
IVF--embryo transfer research."  In Hodgen's view the curb on
research funds is also a breach of government responsibility
toward "generations of unborn" and toward infertile couples who
still desperately want help.

In an obstetrics waiting room at Norfolk's in-vitro clinic, a
woman sits crying. Thirty-year-old Michel Jones and her husband
Richard, 33, a welder at the Norfolk Navy yard, have been
through the program four times, without success. Now their
insurance company is refusing to pay for another attempt, and
says Richard indignantly, "they even want their money back for
the first three times."  On a bulletin board in the room is a
sign giving the schedule for blood tests, ultrasound and other
medical exams. Beside it hangs a small picture of a soaring
bird and the message: "You never fail until you stop trying."
Michel Jones is not about to quit. Says she: "You have a dream
to come here and get pregnant. It is the chance of a lifetime.
I won't give up."

--By Claudia Wallis. Reported by Mary Cronin/London, Patricia
Delaney/Washington and Ruth Mehrtens Galvin/Norfolk