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CHANGING TRENDS IN INFERTILITY MANAGEMENT
Dr Jatin P Shah MD DGO
ART Specialist
Mumbai Fertility Clinic & IVF Centre, Mumbai
In an over populated nation such as ours, the
problem of infertility is still a major health
problem. As per WHO statistics in 1982, 1 out of
every 16 couples was reported to be infertile.
Today the figure stands at 1 in 8 couples. Late
marriage, delayed child bearing, increased use of
contraceptives and the increasing incidence of medical
disorders such as endometriosis, polycystic ovaries,
genital tuberculosis and male sub fertility have all
contributed to this increased incidence. Current data
suggests that male factor infertility is on the rise.
In almost 50% of couples, low sperm count, poor sperm
motility and zero sperm count are the prime causes of
infertility.
Preliminary evaluation of the couple involves a clinical
history, examination of the female partner by transvaginal
ultrasonography, semen analysis, hormone estimations
(Day 2 serum FSH, LH, Prolactin, and TSH) and a diagnostic
laparoscopy and hysteroscopy. On completion of the investigations,
the diagnosis is established as one of:
- Hormonal problems: failure to produce eggs and irregular menses
- Blocked fallopian tubes - tuberculosis being a common cause in our country
- Endometriosis - menstruation occurs inside the body in the ovaries or elsewhere causing cysts and infertility
- Male factor - low sperm counts, poor sperm motility or zero sperm counts
- Unexplained infertility - where there is no apparent cause for the infertility.
Conventional management by medical or surgical means would help
approximately 40% of couple to conceive. These would include
laparoscopic surgery for fibroids, endometriosis, surgery for
opening the fallopian tubes, hysteroscopic surgery for septum,
polyps, submucous fibroids and metroplasty for small or T-shaped
uterus. In addition, ovulation induction (drugs given to stimulate
egg production) with clomiphene citrate and gonadotropins would
benefit the women with PCOS or other endocrine anomalies.
Correction of associated endocrinopathies such as high prolactin
levels or poor thyroid function is also important. Sperm anomalies
would require evaulation by a urosurgeon / andrologist and medical
or surgical therapy such as varicocele ligation in select cases.
For the remaining 60% Assisted Reproductive Technologies have
emerged as a great boon over the past three decades. Today, it is
possible to retrieve a human oocyte from the ovary, fertilize it
outside the body in the laboratory with the husband's sperm and
replace it into the uterus for achieving an offspring. We shall
describe the primary ART methods in some detail.
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Intrauterine insemination: This entails
deposition of washed and capacitated sperm into the uterus
at the time of spontaneous or induced ovulation.
The indications include borderline male factor infertility
such as reduced counts and sperm motility, sexual
dysfunction and sperm deposition problems, poor sperm
migraiton in the female genital tract and women with
hormonal defects. Some amount of controlled ovarian hyper
stimulation is required in the form of clomiphene or
gonadotropin injections with hCG being added as the
ovulation trigger. Several techniques are available for
sperm washing such as layering, double spin or density
gradients. The success rate with this procedure is in the
range of 10 - 20% @ indication and 3 - 6 cycles are
generally advocated before proceeding to higher ART forms.
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In vitro fertilization and embryo transfer (IVF-ET) -
The birth of Louise Brown in 1978 (world's first IVF baby)
revolutionized the treatment of moderate to severe female
factor infertility. This was the original test tube baby procedure
wherein the woman is subjected to controlled ovarian
hyperstimulation with gonadotropins for obtaining more than
one egg (oocyte). Once the follicles are at the size of 18 mm,
hCG is administered and the oocytes are aspirated at 36 hours
post hCG (before they rupture) and transfered to the IVF
laboratory. Here they are cultured in petri dishes containing
culture medium. Subsequently, the oocytes are fertilized with the
husband's sperm after 4 - 6 hours of incubation. After 16 - 20 hours,
the oocytes are checked for the 2 pronuclear stage implying
successful fertilization. After another 24 hours of culture, the best
3 - 4 embryos (4-cell stage) are transferred back to the uterus.
In the event of one of them implanting, successful pregnancy
is established. Indications for this procedure include tubal
block, severe endometriosis and PCOD, unexplained infertility and
infertility due to any cause refractory to conventional medical
and surgical management. Success rates are in the range of
30 - 40% per cycle and 3 - 5 cycles are recommended before opting
for alternate treatment options
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Intracytoplasmic sperm injection (ICSI):
This technique has been the greatest boon to male factor
infertility which does not respond to conventional
management. With this technique, men with severe
oligo or asthenosoospermia can still their own child
without taking resort to a semen bank. As with IVF,
the wife's oocytes are aspirated. On a special microscope
with a micromanipulator, a single sperm is picked up in
fine microneedle and injected manually into the oocyte.
Embryos are transferred after 48 to 72 hours. The couple
can expect a 30 - 40% chance of conception per cycle.
For azoospermic men with an obstructive pathology
(eg: Congenital absence of vas deferens) sperm can be
aspirated directly from the epididymis (PESA) and used
for ICSI. In addition, for azoospermic men with a
non-obstructive pathology, sperm can be retrieved
directly from the testis (TESA) and used for ICSI.
Almost miraculously, PESA or TESA with ICSI gives the
same results as with ejaculated sperm (30-40% per cycle).
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Oocyte Donation:
Women who are menopausal or suffering from premature
ovarian failure and amenorrhoea can now hope to become
mothers with the application of oocyte donation and IVF.
Here, the uterus is prepared for conception with
estrogen / progesterone priming. Once suitable oocytes
are available, IVF is performed with the husband's sperm
and the embryos transfered to the recipient. 40 %
pregnancy rates per cycle can be expected with this
technique.
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Therapeutic insemination with donor sperm:
Where finance is an issue, patients suffering
from severe male factor infertility who can not afford
ICSI or patients with primary testicular failure can opt
for donor sperm from a semen bank. This remains one of
the oldest ART methods known to mankind.
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Embryo donation:
In the event of the wife being menopausal and the
husband being azoospermic, the infertile couple can
still hope for a pregnancy with embryo donation.
This helps fulfill the biological desire of a woman to
be a mother Vis a Vis adoption. It also helps certain
patients with repeated miscarriages or repeated IVF
failures.
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Surrogacy:
In cases of end organ failure, such as for example
uterine damage owing to genital tuberculosis, the
couple can hope to have their own genetic offspring by
IVF with transfer of the embryos to a surrogate mother
who carries the child for nine months and then hands over
the baby to the biological parents.
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Preimplantation genetic diagnosis (PGD):
implies IVF and biopsy of the resultant embryos for
diagnosis of genetic disease. This would help couples
with recurrent miscarriages and repeated implantation
failures
Facts, Not Myths:
Most cases of PCOD benefit with currently available ovulation
inducing agents. IVF remains a promising option for resistant
cases of anovulatory infertility. Cases of genital tuberculosis
with tubal damage and a normal uterus are excellent candidates
for conception with IVF. Stage III and IV endometriosis patients
are benefited with IVF. Most cases of severe oligo or astheno-
zoospermia can expect to have their own biological child with
ICSI Azoospermic men with some sperm production in the testes
can hope to father their own child with PESA or TESA with ICSI
Menopausal women can expect to conceive with success rates on par
with younger women with the technique of oocyte donation and IVF
IMPORTANT COUNSELLING AFTER CYCLE FAILURE
Please remember that success rates in the best IVF centers in
the world are in the range of 30 - 40% per started cycle. The
clinic has an impressive 38% take home baby rate for the year 2009.
It is important for the patient to remember that the cumulative success rate a
fter 3 cycles of IVF is in the range of 67%. This is an important statistic that
highlights the need to do repeated cycles.
Dr Jatin is always available for counseling after a failed
cycle. It is important to have this discussion to understand
the gravity of the problem. Often, the first cycle reveals
problems of oocyte (egg quality) or fertilization failure
or problems with embryo development which need to be discussed and solved.
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