IVF for Fertile Couples
Hesham Al-Inany, M.D, PhD
focus of this Talk
• Fertile couples who are likely to conceive
spontaneously but still need IVF
treatment!!!
For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health
Fertility Preservation
Incidence of Cancer in Young Women
AND
PRESERVATION OF FERTILITY
Why it is needed!
• ~15% of women cancer occur in
women<45 years of age
• Increasing survival rates among women
with cancer
Cancer treatments can results in
infertility.
ASAP
• The decision for fertility preservation
should be considered as soon as possible
to maximize the likelihood of succ...
Jeruss and Woodruff (2009) New England Journal of Medicine.
What
Technique
is
Appropriate
?
Female : embryo cryopreservation
• Requires 10–14 days of ovarian stimulation
from the beginning of menstrual cycle
• It i...
Oocyte cryopreservation
• Still experimental
• (3-4 times lower success rate than
standard IVF)
• Vetrification can be a g...
Male: Sperm cryopreservation
• Outpatient procedure;
• Cost approximately 1,500 for three
samples stored for 3 years
• Mos...
Safety
• no detectable increased risk of disease
recurrence associated with most fertility
preservation methods and pregna...
Offspring
• no evidence that a history of cancer
therapy, or fertility interventions increase
the risk of cancer or congen...
In brief
• The two methods of fertility preservation
with the highest likelihood of success are
sperm cryopreservation for...
For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health
Prevention
Of What!!
1% of births affected
• Online Mendelian Inheritance in Man (OMIM:
http://www.hgmp.mrc.ac.uk/omim/)
Genetic Risk is significant
Autosomal recessive (CF) 1:4 risk
X-linked recessive (Haemophilia, DMD) 1:2 males
Autosomal do...
X linked
(sex linked)
Carrier
female
Normal
female
AFFECTED
MALE
Unaffected
Male
Risk 1 in 2 males
Demographics: Thalassemia
• Found most
frequently in the
Mediterranean
Effects of haemophilia.
(a) Bleeding around elbow. (b) A retinal bleed. (c) Repeated bleeds into joints
produce severe art...
IVF + PGD
Transfer only unaffected embryos to the woman
affected affectedaffected
Embryo biopsy
Diagnosis
by
Transfer
2 unaffected
embryos
Fertilisation in vitro
(IVF or ICSI)
PCRFISH
Accurate
genetic
dia...
Using FISH for PGD of
X-linked disorders
• Three colour FISH
• X ( green)
• Y (red)
• Chromosome 18 to
control for normal
...
Al-Gazali, L. et al. BMJ 2006;333:831-834
Fig 1 Two Arab pedigrees showing high level of consanguinity, large family size,...
Al-Gazali, L. et al. BMJ 2006;333:831-834
Fig 2 Average rates of marriages between first cousins among Arabs
Premarital
• Some countries have started prevention
programs for certain common genetic
disorders, such as premarital carr...
Iran
• A premarital thalassaemia screening and
counselling programme resulted in
reduction in birth of affected babies by
...
But
• This approach is used in Bahrain, Saudi
Arabia, and Jordan. However, experience
from SA shows that most couples choo...
IVF + PGD
Transfer only unaffected embryos to the woman
affected affectedaffected
How effective is it?
Single gene disorders
Guy’s 97-04 Rome 99-04* ESHRE 98-03
>40 centres
Cycles 159 - -
Recovery 135 - 2...
monogenic disease
• may be a therapeutic tool in families with
an already affected offspring
Options
• not having children
• natural conception and hoping that the
coming child is unaffected
• natural conception and...
IVF + PGD + HLA
The Aim
• not only to avoid the birth of affected child
(prevention),
• At delivery, haematopoietic stem cells
HSC from th...
It is already done
• The first case performed for Fanconi
anaemia complementation group C (FA-
C), resulted in successful ...
• For Thalassemia, when an HLA identical
sibling marrow donor is available, the
chance of cure is currently over 90%.
Loca...
Preimplantation Genetic
Haplotyping (PGH)
Nash Case : Fanconi anaemia
• did her parents choose to have a healthy
baby because they wanted another child,
or because ...
ESHRE 2005
• Affected previous child of these parents
has malignant disorder or genetic disorder,
and the child is likely ...
For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health
Prevention of Cancer
Families with Cancer
• Familial Adenomatous Polyposis (FAP)
• Multiple Endocrine Neoplasia 2
• Retinoblastoma
• Breast can...
Options
• not having children
• natural conception and hoping that the
child is unaffected
• natural conception and geneti...
IVF + PGD
Transfer only unaffected embryos to the woman
affected affectedaffected
Susceptibility testing
Sex selection
• For family balancing
• poses numerous clinical, social, psychological,
ethical dilemma
Ethical issues
• Islamic legal viewpoint is that fetal sex
selection is lawful when it is practiced on
an individual basis...
Other conditions
What after screening!!
• Doctors successfully screened embryos
for gene mutation linked to early onset
Alzheimer's
JAMA, M...
Late-onset Disorders
• are complex and have both genetic and
environmental causes.
• such as Alzheimer’s, With no current
...
Limitations
Transfer only unaffected embryos to the woman
affected affectedaffected
10 oocytes
8 fertilized
5 survive biopsy
6 cleave to 8-16 cell
1 no diagnosis
1 aneuploid
2 males
1 female for replacement...
IVF associated risks
- high cost
- risk of not getting pregnant;
- increased risk of a multiple birth
- risk of OHSS (Diff...
• embryo biopsy may lower embryo
implantation rates (Mastenbroek et al,
2007)
For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health
To achieve this
• The Egyptian IVF-ET center has started its
Thalathemia prevention program and is
ready to help
IVF for fertile couples
IVF for fertile couples
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IVF for fertile couples

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In the future , IVF will not only be for infertile women but will be directed to help fertile couples getting health babies!! How !! this talk will help to illustrate that

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IVF for fertile couples

  1. 1. IVF for Fertile Couples Hesham Al-Inany, M.D, PhD
  2. 2. focus of this Talk • Fertile couples who are likely to conceive spontaneously but still need IVF treatment!!!
  3. 3. For Tomorrow Better health • Preservation of fertility • Prevention of disease • Improvement of health
  4. 4. Fertility Preservation
  5. 5. Incidence of Cancer in Young Women AND PRESERVATION OF FERTILITY
  6. 6. Why it is needed! • ~15% of women cancer occur in women<45 years of age • Increasing survival rates among women with cancer
  7. 7. Cancer treatments can results in infertility.
  8. 8. ASAP • The decision for fertility preservation should be considered as soon as possible to maximize the likelihood of success.
  9. 9. Jeruss and Woodruff (2009) New England Journal of Medicine. What Technique is Appropriate ?
  10. 10. Female : embryo cryopreservation • Requires 10–14 days of ovarian stimulation from the beginning of menstrual cycle • It is a surgical procedure • Requires husband • Cost: per cycle, storage fees
  11. 11. Oocyte cryopreservation • Still experimental • (3-4 times lower success rate than standard IVF) • Vetrification can be a good option
  12. 12. Male: Sperm cryopreservation • Outpatient procedure; • Cost approximately 1,500 for three samples stored for 3 years • Most effective way
  13. 13. Safety • no detectable increased risk of disease recurrence associated with most fertility preservation methods and pregnancy, even in hormonally sensitive tumors.
  14. 14. Offspring • no evidence that a history of cancer therapy, or fertility interventions increase the risk of cancer or congenital abnormalities in the offspring.
  15. 15. In brief • The two methods of fertility preservation with the highest likelihood of success are sperm cryopreservation for males and embryo freezing for females.
  16. 16. For Tomorrow Better health • Preservation of fertility • Prevention of disease • Improvement of health
  17. 17. Prevention Of What!!
  18. 18. 1% of births affected • Online Mendelian Inheritance in Man (OMIM: http://www.hgmp.mrc.ac.uk/omim/)
  19. 19. Genetic Risk is significant Autosomal recessive (CF) 1:4 risk X-linked recessive (Haemophilia, DMD) 1:2 males Autosomal dominant 1:2 • Early onset (Myotonic dystrophy, achondroplasia) • Late onset (Huntington’s disease)
  20. 20. X linked (sex linked) Carrier female Normal female AFFECTED MALE Unaffected Male Risk 1 in 2 males
  21. 21. Demographics: Thalassemia • Found most frequently in the Mediterranean
  22. 22. Effects of haemophilia. (a) Bleeding around elbow. (b) A retinal bleed. (c) Repeated bleeds into joints produce severe arthritis.
  23. 23. IVF + PGD Transfer only unaffected embryos to the woman affected affectedaffected
  24. 24. Embryo biopsy Diagnosis by Transfer 2 unaffected embryos Fertilisation in vitro (IVF or ICSI) PCRFISH Accurate genetic diagnosisAppropriate Genetic Counselling DENATURING ANNEALING EXTENSION PRIMER TAQ TAQ
  25. 25. Using FISH for PGD of X-linked disorders • Three colour FISH • X ( green) • Y (red) • Chromosome 18 to control for normal diploidy Male Female
  26. 26. Al-Gazali, L. et al. BMJ 2006;333:831-834 Fig 1 Two Arab pedigrees showing high level of consanguinity, large family size, and several affected children in different sibships
  27. 27. Al-Gazali, L. et al. BMJ 2006;333:831-834 Fig 2 Average rates of marriages between first cousins among Arabs
  28. 28. Premarital • Some countries have started prevention programs for certain common genetic disorders, such as premarital carrier screening for haemoglobinopathies
  29. 29. Iran • A premarital thalassaemia screening and counselling programme resulted in reduction in birth of affected babies by 70% within five years.
  30. 30. But • This approach is used in Bahrain, Saudi Arabia, and Jordan. However, experience from SA shows that most couples choose to marry despite a high risk of inherited genetic disease in their offspring.
  31. 31. IVF + PGD Transfer only unaffected embryos to the woman affected affectedaffected
  32. 32. How effective is it? Single gene disorders Guy’s 97-04 Rome 99-04* ESHRE 98-03 >40 centres Cycles 159 - - Recovery 135 - 2868 Biopsy 125 182 2701 ET 113 173 2173 Clin Preg (%/ET/biop/OR) 38 (33/30/28) 48 (28/26/?) 514 (24/20/18) Livebirth 33 37 411 * Fiorentino et al Hum Rep 2005•Assume 80% continue
  33. 33. monogenic disease • may be a therapeutic tool in families with an already affected offspring
  34. 34. Options • not having children • natural conception and hoping that the coming child is unaffected • natural conception and genetic testing of the fetus with an option of termination if the child is affected (Ethical??) • IVF and PGD, replacing only unaffected embryos.
  35. 35. IVF + PGD + HLA
  36. 36. The Aim • not only to avoid the birth of affected child (prevention), • At delivery, haematopoietic stem cells HSC from the newborn umbilical cord blood are collected and used for the haematopoietic reconstruction of the affected sibling (cure)
  37. 37. It is already done • The first case performed for Fanconi anaemia complementation group C (FA- C), resulted in successful haematopoietic reconstitution in the affected sibling by transplantation of stem cells obtained from the HLA-matched offspring (Verlinsky Y et al, 2001).
  38. 38. • For Thalassemia, when an HLA identical sibling marrow donor is available, the chance of cure is currently over 90%. Locatelli 2003 • whereas in the case of a acquired disease such as leukemia it is much lower (50%)(Eapen 2006) because here the patient also has to be cured from the tumour.
  39. 39. Preimplantation Genetic Haplotyping (PGH)
  40. 40. Nash Case : Fanconi anaemia • did her parents choose to have a healthy baby because they wanted another child, or because they wanted a source to help cure their daughter?
  41. 41. ESHRE 2005 • Affected previous child of these parents has malignant disorder or genetic disorder, and the child is likely to be cured or life expectancy to be substantially prolonged by cord blood stem cell transplantation from an HLA matched identical sibling
  42. 42. For Tomorrow Better health • Preservation of fertility • Prevention of disease • Improvement of health
  43. 43. Prevention of Cancer
  44. 44. Families with Cancer • Familial Adenomatous Polyposis (FAP) • Multiple Endocrine Neoplasia 2 • Retinoblastoma • Breast cancer (BRCA1 and BRCA2 genes ) • Hereditary non-polyposis colorectal cancer • All these cancers are autosomal dominant traits that usually manifest in adulthood, but can occur occasionally in children
  45. 45. Options • not having children • natural conception and hoping that the child is unaffected • natural conception and genetic testing of the fetus with an option of termination if the child is affected (Ethical??) • IVF and PGD, replacing only unaffected embryos.
  46. 46. IVF + PGD Transfer only unaffected embryos to the woman affected affectedaffected
  47. 47. Susceptibility testing
  48. 48. Sex selection • For family balancing • poses numerous clinical, social, psychological, ethical dilemma
  49. 49. Ethical issues • Islamic legal viewpoint is that fetal sex selection is lawful when it is practiced on an individual basis, to fulfill the wish of a married couple to have a boy or a girl through available medical means.
  50. 50. Other conditions
  51. 51. What after screening!! • Doctors successfully screened embryos for gene mutation linked to early onset Alzheimer's JAMA, March, 2002
  52. 52. Late-onset Disorders • are complex and have both genetic and environmental causes. • such as Alzheimer’s, With no current prospect for the treatment of Alzheimer's disease, prevention of an inherited predisposition to Alzheimer's is the only option for couples at risk
  53. 53. Limitations Transfer only unaffected embryos to the woman affected affectedaffected
  54. 54. 10 oocytes 8 fertilized 5 survive biopsy 6 cleave to 8-16 cell 1 no diagnosis 1 aneuploid 2 males 1 female for replacement Practical realities 6 Attrition of embryos Example for a sex linked disorder e.g. Haemophilia / Duchenne MD
  55. 55. IVF associated risks - high cost - risk of not getting pregnant; - increased risk of a multiple birth - risk of OHSS (Difficult to balance adequate egg numbers and the risk of OHSS ).
  56. 56. • embryo biopsy may lower embryo implantation rates (Mastenbroek et al, 2007)
  57. 57. For Tomorrow Better health • Preservation of fertility • Prevention of disease • Improvement of health
  58. 58. To achieve this • The Egyptian IVF-ET center has started its Thalathemia prevention program and is ready to help

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