There is no doubt that
IVF and the newer assisted reproductive technologies
( ART) represent one of modern medicine's success stories.
Today, there is practically no couple whom we cannot
help to make a baby. This can be best exemplified by
the following story of one of our patients.
Mrs DF was a 35 year old woman who first came to us
for a second opinion regarding her primary infertility
in 1991. She had been married for 3 years, but had failed
to conceive. Her family doctor had referred her to a
gynecologist, who promptly did a laparoscopy and confirmed
she was normal. She was asked to then get her husband’s
semen analysis done. After a lot of persuasion, she
finally managed his to get his semen tested –
and much to her dismay, the report came back as azoospermia.
The husband flatly refused to believe the report –
how can my sperm count be zero when I can have sex thrice
a night ? However, when repeated testing confirmed the
report, he finally agreed to visit the doctor. The gynecologist
then referred them to a urologist, who advised him to
get a testis biopsy done, to find out if he had a block
so they could repair it surgically, if possible. He
was so worried about the prospect of surgery on his
testes, that he refused to visit any doctor for further
treatment. His wife got increasingly desperate as time
went by, because she had to suffer the taunts and barbs
of friend and relatives for her “barrenness”
– and to protect her husband’s ego, she
couldn’t tell them about his problem.
I asked her to come back for a consultation with her
husband, explaining to her that infertility is always
a couple’s problem, and we need to see both the
partners together. I then requested him to repeat the
semen analysis from a reliable lab, and evaluated the
report carefully. This confirmed he had azoospermia;
and also showed his seminal volume was normal; the fructose
was positive; and the pH was alkaline . The analysis
also showed that there were sperm precursor cells present
in the ejaculate. I then requested him to perform a
sequential ejaculate – two semen samples, ejaculated
after a one hour interval. In order to help him produce
a second sample, we gave him 100 mg of Viagra. The first
sample again showed no sperm. A preliminary examination
of the second ejaculate also showed no sperm, but when
the sample was centrifuged and the pellet examined carefully,
we saw occasional motile sperm per high power field.
This confirmed he had cryptozoopsermia, and that his
problem was partial testicular failure ( non-obstructive
azoospermia). We had to explain to him that there was
no treatment for this problem ( remember this was in
1991) and the only treatment option we could offer him
would be donor insemination.
He flatly refused this option, and would not consider
adoption either. He was very intelligent and highly
motivated. He asked – “Doctor, why can’t
you inject my sperm into my wife’s eggs in the
test tube baby lab. After all, you only need one sperm
to fertile one egg, don’t you ?”
We had to explain to him that this was not possible,
and that for IVF, we needed at least 1,00,000 sperm.
Since he refused to consider the option of donor sperm,
he went back home disappointed.
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In 1994, he came back to us again, excitedly holding
a newspaper report of an article about how doctors in
Belgium had invented a new technique, in which they
could fertilise a single egg with a single sperm. He
wanted us to do this new treatment called intracytoplasmic
sperm injection or ICSI for him. We learnt about this
major new advance in IVF technology, which allowed us
to ensure that 1 sperm plus 1 egg = 1 embryo, and since
this was the only method by which he could have a baby
with his own sperm, they agreed to go ahead.
We performed an ICSI cycle in July 1995. Since his
wife was now 39, we were worried about her ability to
produce eggs, so we superovulated her aggressively.She
was superovulated with 6 ampuoles of HMG ( Human Menopausal
Gonadotropins, Menogon, 450 IU daily) from Day 3, after
downregulation with Suprefact ( Buserelin , GnRH analog,
0.5 ml sc daily from Day 1, short protocol). However,
her ovarian response was poor, because of her advanced
age, and we were forced to abandon the cycle. They were
very disappointed, but now wanted to explore the alternative
of using donor egg ICSI. They accepted this option readily,
and we then did a donor egg ICSI cycle for her in October
1995.
We synchronised the cycles of the donor and the wife
by treating them with birth control pills. The egg donor
was superovulated with 3 ampuoles of HMG ( Human Menopausal
Gonadotropins, Menogon, 225 IU daily) from Day 3, after
downregulation with Suprefact ( Buserelin , GnRH analog,
0.5 ml sc daily from Day 1, short protocol). At the
same time, the wife’s endometrium was primed by
treating her with 6 mg estradiol valerate daily, after
downregulation with Suprefact.
12 oocyte cumulus complexes were recovered under vaginal
ultrasound guidance on 11 Oct 1995. The oocyte complexes
were stripped using hyaluronidase, and 11 eggs were
found to be mature ( metaphase II). Two sequential semen
sample were washed with culture medium containing HEPES
( IVF flushing medium, Medicult), and then centrifuged.
2 ul of the pellet was then added to a 10 ul droplet
of PVP ( Medicult, Denmark) and overlaid with mineral
oil ( Vitrolife, Scandinavia). Motile sperm were then
identified and immobilized; and ICSI performed using
Narishige micromanipulators mounted on an Olympus IX-70
inverted microscope, equipped with Hoffman contrast
modulation optics, in which a single sperm was injected
into each egg. The injected eggs were then cultured
in IVF medium ( Vitrofile) in a CO2 incubator for 48
hours. Of the 11 injected eggs, 10 fertilised and a
non-contact diode laser ( Cronus, Research Instruments,
UK) was then used to drill a hole in the zona to perform
assisted hatching for 3 4-cell Grade A embryos , which
were then transferred into the wife’s uterine
cavity using a Rocket embryo transfer catheter on 13
October 1995. The supernumerary 7 embryos were cryopreserved
in liquid nitrogen. Luteal phase support was provided
with daily Progynova and vaginal progesterone suppositories.
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She conceived in this cycle as documented by rising
beta HCG levels and serial ultrasound scans which revealed
a healthy twin pregnancy with growth appropriate for
dates . She required a caesarean section, and now has
2 healthy babies – one son and a daughter.
This story highlights a number of issues. Firstly,
the key importance of having a reliable laboratory to
perform the semen analysis. Since a semen analysis is
no inexpensive, it is often performed badly, and the
results are very unreliable. An incorrect report can
mislead the doctor, leading to inappropriate treatment.
Doctors must insist that the semen analysis be performed
at a trustworthy lab, which specializes in semen analysis.
The need for close cooperation between the lab and the
doctor is also critical. Your doctor must let the lab
know what he is suspecting, so they can intelligently
process the semen sample.
It is important also that the infertile couple be treated
as a unit. Unfortunately, most gynecologists just refer
the infertile man to a urologist, with the result that
care becomes fragmented and incomplete. It is essential
that your specialist be well-informed about male fertility
. He should be knowledgeable about interpreting a semen
analysis report ; and also know how to examine the infertile
man .
This story also emphasizes the dramatic advances which
assisted reproductive technology can offer today in
helping infertile couples to start their own family.
A TV program produced in the USA in 2002 described
18 ways to make a baby.
These included:
Natural sex
Artificial insemination -- of mother with father's
sperm
Artificial insemination -- of mother with donor sperm
Artificial insemination -- with egg and sperm donors,
using surrogate mother
In vitro fertilization (IVF) -- using egg and sperm
of parents
IVF -- with Intra-Cytoplasmic Sperm Injection (ICSI)
IVF -- with frozen embryos
IVF -- with Preimplantation Genetic Diagnosis (PGD)
IVF -- with egg donor
IVF -- with sperm donor
IVF -- with egg and sperm donor
IVF -- with surrogate using parents' egg and sperm
IVF -- with surrogate and egg donor
IVF -- with surrogate and sperm donor
IVF -- with surrogate using her egg, sperm from baby's
father
IVF -- with surrogate using egg and sperm donors*
Cytoplasmic transfer
Nuclear transfer and cloning
If you now add additional options such as TESA ( testicular
sperm aspiration) and PESA ( percutaneous epididymal
sperm aspiration);assisted hatching and embryo fragment
removal, the list becomes even longer !
The bottom line is that today there is a solution for
every infertility problem – and doctors and patients
need to apply their mind, so they can decide what’s
best for each individual couple !
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