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African Journal of Reproductive Health
Women's Health and Action Research Centre
ISSN: 1118-4841
Vol. 7, Num. 1, 2003, pp. 121-124
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African Journal of Reproductive Health, Vol. 7, No. 1, April, 2003 pp.
121124
Live Births after Intracytoplasmic
Sperm Injection in the Management of Oligospermia and Azoospermia in Nigeria
RA Ajayi1,
JH Parsons2 and VN Bolton2
1The Bridge Clinic Limited,
1397a Tiamiyu Savage Street, P. O. Box 70294, Victoria Island, Lagos, Nigeria.
E-mail: bridge@om.metrong.com 2The Assisted Conception Unit, 7th
Floor, Ruskin Wing, King's College Hospital, Denmark Hill, London SE5 9RS.
Correspondence: R.A. Ajayi, The Bridge Clinic Limited,
1397a Tiamiyu Savage Street, P. O. Box 70294, Victoria Island, Lagos, Nigeria.
E-mail: bridge@om.metrong.com
Code Number: rh03015
ABSTRACT
Intracytoplasmic sperm
injection has revolutionised the management of male infertility. We report
two cases that demonstrate the successful application of this technology in
Nigeria in the management of both oligospermia and azoospermia. The first case
relates to the treatment of a 31-year-old woman who required intracytoplasmic
sperm injection of her husband's sperm for the treatment of both tubal fertility
and male infertility. She had three embryos transferred on 9th June 1999 and
was delivered of healthy male and female infants by caesarean section in January
2000 at 33 weeks gestation. The second case describes a 38-year-old woman who
required intracytoplasmic sperm injection of the husband's surgically collected
sperm for the management of azoospermia. She had two embryos transferred on
16th December 1999 and was delivered of a healthy male infant by caesarean
section on 19th July 2001. (Afr J Reprod Health 2003; 7[1]: 121124)
RÉSUMÉ
Des naissances vivantes
suite à l'injection intra-cytoplasmique du sperme dans le traitement de l'oligospermie
et de l'azoospermie au Nigéria. L'injection intracytoplasmique du sperme
a transformé radicalement le traitement de la stérilité masculine. Nous
présentons deux cas qui illustrent le operati accompli dans l'application
de cette technologie au Nigéria dans le domaine du traitement de l'oligosperme
et de l'azoosperme. Dans le premier cas, il s'agit du traitement d'une femme âgée
de 31 ans qui devait avoir besoin de l'injection introcytoplasmique du sperme
de son mari pour le traitement de la fécondité tubaire et de la stérilité masculine. On
a transféré trios embryons le 9 juin 1999. En janvier 2000, à la fin de
33 semaines de gestation, elle a accouché à l'aide d'une operation césarienne,
deux enfants en bonne santé, un garcons et une fille. Le deuxième cas présente
une femme âgée de 38 ans qui devait avoir besoin de l'injection intracytoplasmique
du sperme de son mari collecté chirurgicalement, pour le traitement de l'azoospermie. Deux
embryons ont été transféré le 16 décembre 1999 et elle avait accouché un
fils en bonne santé le 19 juillet 2001 à l'aide d'une operation césarienne. (Rev
Afr Santé Reprod 2003; 7[1]: 121124)
KEY WORDS: Male
infertility, azoospermia, testicular sperm, oligospermia, intra-cytoplasmic
sperm injection (ICSI), ejaculated
sperm, Nigeria
CASE REPORT 1
The couple presented to our clinic in Lagos in November 1998 requesting assistance
in achieving a pregnancy. They had been trying to conceive since 1993. The
woman, aged 30 years, and her husband, aged 37 years, had achieved two pregnancies
together previously. The first was in 1993, which ended as a first trimester
loss, the second in 1994, resulting in a laparotomy and right salpingectomy
for a right ectopic pregnancy. The husband had fathered two pregnancies with
a previous partner neither of which had resulted in live birth. The woman had
had her appendix removed in 1989. A hysterosalpingogram carried out following
the right salpingectomy in 1994 revealed that the left fallopian tube was not
opacified, and it was concluded that the tube was blocked. There was no other
significant past medical history.
The woman weighed 67kg, was 1.6
metres tall and her early follicular phase gonadotrophin levels were normal.
Trans-vaginal ultrasound revealed a normal uterus and polycystic ovaries.1 There
were no other abnormal findings. The husband produced a 1.2ml semen sample;
sperm concentration of 14 million per ml, 66% of which were motile and 9% of
which were morphologically normal. The couple was advised that semen of this
quality would almost certainly fail to achieve fertilisation with conventional
in vitro fertilisation (IVF) treatment, and they agreed to undergo a cycle
of intra-cytoplasmic sperm injection (ICSI).
At that time, all the assisted
conception procedures at the Lagos clinic were carried out with the direct
assistance of clinicians and embryologists from the assisted conception unit
of the King's College Hospital, London.2 Therefore, the couple's
treatment was scheduled for June 1999 to coincide with the visit of the team
from United Kingdom.
Pituitary down regulation using
buserelin acetate (Suprefact®, Hoecht Marion Roussel, UK), ovarian
stimulation using human menopausal gonadotrophin (Pergonal®, Serono,
UK), human chorionic gonadotrophin (Profasi®, Serono, UK) and transvaginal
ultrasound-directed follicle aspiration were carried out as described previously.3 Oocytes
and embryos were cultured in universal IVF medium (Medi-Cult, Copenhagen, Denmark)
and ICSI was carried out as described previously.4,5
Of the 25 oocytes retrieved, 16
were metaphase II stage (MII). The repeat semen sample contained 4 million
spermatozoa per ml, of which 66% were motile and 9% were morphologically normal.
Each of the 16 MII oocytes were
injected with a single spermatozoon as described previously4, and
12 fertilised normally, as indicated by the development of two pronuclei by
1618 hours post-injection. All 12 zygotes underwent cleavage and three four-cell
embryos, all of which showed good morphology,6 were transferred
to the woman's uterus on 9th June 2001, two days after oocyte retrieval. The
remaining embryos were discarded according to the couple's wishes. The luteal
phase was supported with 400mg progesterone daily (Cyclogest®, Shire
Pharmaceuticals Ltd, UK). A positive pregnancy test was performed 14 days after
embryo transfer, on 23rd June 2001, and a viable triplet pregnancy was confirmed
with the identification of three fetal hearts using ultrasound two weeks later.
The antenatal course was complicated
by the intrauterine death of one of the fetuses at 19 weeks gestation, but
the remaining fetuses were not compromised and the pregnancy continued without
complications until 33 weeks when the woman went into premature labour. A live
male infant weighing 1.8kg and a live female infant weighing 1.6kg were delivered
by caesarean section on 12th January 2000. The children are well and have achieved
all developmental milestones.
CASE REPORT 2
The couple presented for treatment in June 1999, having been trying to achieve
a pregnancy since 1992. The woman, aged 38 years, and her husband, aged 46
years, had never achieved a pregnancy together. The man was confirmed azoospermic
in 1993. Since then he had had various treatments including bilateral varicocoelectomy
in 1995.
The woman weighed 89kg and was
1.7m tall. Her early follicular phase gonadotrophin levels were normal. Trans-vaginal
ultrasound revealed the uterus to be normal sized and anteverted, containing
two intramural fibroids of 1.5cm and 1.3cm respectively. The fibroids were
not near the endometrial echo, which was clear and not distorted. Both ovaries
were normally placed and had normal appearances. The man's semen was found
to contain no spermatozoa even after centrifugation at 1800g on two separate
occasions. His serum FSH was 4 IU/L and he had normal genitalia.
Elective testicular sperm extraction
(TESE)7 was carried out under local anaesthesia on 11th June 1999.
Percutaneous epididymal sperm aspiration (PESA)8 and testicular
sperm aspiration (TESA)9 had both failed to yield sperm. A sample
containing six non-motile spermatozoa per slide was obtained from the right
testis, and one containing five spermatozoa per slide, of which only one was
motile, was obtained from the left testis. The samples were divided into two,
one of which was cryopreserved for subsequent ICSI. The other was sent for
histological assessment, which showed both testes to have severe hypospermatogenesis.
The implications of these findings
were explained to the couple and they elected to undertake a cycle of ICSI
treatment. At that time, all the assisted conception procedures at the Lagos
clinic were carried out with the direct assistance of clinicians and embryologists
from the assisted conception unit of King's College Hospital, London.2 Therefore,
the couple's treatment was scheduled for December 1999, to coincide with the
visit of the team from United Kingdom.
Pituitary down regulation using
buserelin acetate (Suprefact®, Hoescht Marion Roussel, UK), ovarian
super ovulation using human menopausal gonadotrophin (Pergonal®,
Serono, UK) and human chorionic gonadotrophin (Profasi®, Serono,
UK), and transvaginal ultrasound directed follicle aspiration were carried
out as described previously.3 Oocytes and embryos were cultured
in universal IVF medium (Medi-Cult, Copenhagen, Denmark), and ICSI was carried
out as described previously.4,5
Of the five oocytes retrieved,
four were MII stage. On thawing, the cryopreserved testicular sample was found
to contain no motile spermatozoa. A second TESE procedure was carried out and
samples containing approximately 10 non-motile spermatozoa per slide were obtained
from each testis. A single twitching spermatozoon was seen on a slide prepared
from one of the samples after incubation for four hours. This sample was used
for ICSI.
Each of the four MII oocytes was
injected with a single spermatozoon that had shown twitching movements prior
to injection and two fertilised normally, as indicated by the presence of two
pronuclei 1618 hours post-injection. Both zygotes cleaved to generate good
quality four-cell and five-cell stage embryos6 which were transferred
to the woman's uterus on 16th December 1999, two days after oocyte retrieval.
The luteal phase was supported with 400mg progesterone daily (Cyclogest®,
Shire Pharmaceuticals Ltd, UK). A positive pregnancy test was performed 14
days after embryo transfer, on 30th December 1999, and a viable singleton pregnancy
was confirmed with the identification of a beating fetal heart using ultrasound
three weeks later. The antenatal course was complicated by the onset of pre-eclampsia
and she was delivered of a live male infant at 33 weeks gestation, on 19 July
2001. He is currently very well and has achieved all developmental milestones.
DISCUSSION
These reports describe the first conception and live birth following ICSI
in Nigeria and, to our knowledge, in any other West African country. In developed
countries, assisted conception techniques such as IVF and ICSI10 for
the treatment of infertility have become routinely available, but couples in
the developing world have more limited access, usually having to travel overseas
at considerable expense. We have been able to achieve success with this highly
specialised treatment in Nigeria through collaboration between a newly established
clinic in Lagos, Nigeria, and a long established assisted conception unit at
King's College Hospital, London, UK. Its success demonstrates how such collaboration
can lead to the transfer of technology, making this specialised form of infertility
treatment more accessible to those in developing countries who may need it.
The success of ICSI using spermatozoa
recovered from the epididymis7 or the testes8,9 is well
established in the treatment of infertility due to azoospermia, and in developed
countries, the limiting factor for success in such cases is whether or not
it is possible to retrieve sperm.
The presumed diagnosis in the management
of the second couple was obstructive azoospermia and, therefore, sperm retrieval
was attempted first using percutaneous epididymal sperm aspiration.8 When
this was unsuccessful, testicular sperm aspiration9, and then the
more invasive testicular sperm extraction7 were attempted. Even
with TESE, few motile spermatozoa were retrieved, suggesting that the patient's
azoospermia was, in fact, non-obstructive.
The initial TESE procedure was
carried out in advance of the proposed date for treatment of the woman in order
to confirm successful sperm retrieval before she embarked on expensive ovarian
stimulation. Satisfactory fertilisation and pregnancy rates have been achieved
with cryopreserved testicular sperm, and the facilities and expertise for cryopreservation
were available in the Lagos clinic through collaboration with the centre in
the UK. Despite this, the spermatozoa did not survive cryopreservation and
thawing and it was necessary to perform a further TESA procedure on the day
of the woman's oocyte retrieval.
An alternative approach would have
been to perform the sperm extraction procedure after oocyte retrieval, having
prepared the couple in advance with appropriate counselling and informed consent
for the use of donor sperm in the event of failure to retrieve spermatozoa.
ICSI has always been considered
a risky procedure from its inception. The injection process is invasive to
the oocyte and has the potential risk of causing biochemical or mechanical
damage. More importantly, ICSI bypasses natural selection in that the sperm
being injected into the oocyte is usually incapable of fertilising the oocyte
without assistance and may carry structural defects or genetic abnormalities. Although
these abnormalities may not impair the fertilisation process, they may manifest
at birth or later in life. Initial studies confirmed these suspicions and demonstrated
an increased risk of sex chromosone aneuploides in ICSI children.11
A Swedish follow-up study of 1,139
ICSI children also showed that when compared to children conceived normally,
the ICSI children had a slightly higher number of cases of congenital malformations,
but these malformations were mainly the result of the high rate of multiple
births in ICSI children. The same study showed that the incidence of hypospadias
was higher in ICSI children and this was probably related to paternal sub fertility.12 The
largest study to date compared 2,995 IVF children and 2,899 ICSI children.
It showed that there is no higher risk of neonatal complications or major malformations
with ICSI and that the malformation rate in ICSI is not related to sperm origin
or sperm quality.
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