IVF will remain the solution for infertile couples. But its future will dramatically be directed to fertile couples !!!! This talk will discuss these issues

1. Future of IVF
Hesham Al-Inany, M.D, PhD

2. For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health

3. Fertility Preservation

4. Why it is needed!
• ~15% of women cancer occur in
women<45 years of age
• Increasing survival rates among women
with cancer

5. Cancer treatments can results in
infertility.

6. ASAP
• The decision for fertility preservation
should be considered as soon as possible
to maximize the likelihood of success.

7. Existing Practice Guidelines
 ASRM (American Society for Reproductive Medicine)
 “Parents may act to preserve fertility of cancer patients who are minors if the
child assents and the intervention is likely to provide net benefits to the child”
Lee et al., 2006; ASRM, 2006
 ASCO (American Society of Clinical Oncology) Decision Tree
Assessment of risk for infertility
Communication with patient
Patient at risk for treatment-induced infertility
Patient interested in fertility-preservation options
Refer to specialist with expertise in fertility-preservation method
Eligible for proven fertility preservation method Investigational fertility preservation technique
 Cryopreservation of ovarian or testicular tissue
 Cryopreservation of oocytes
 Ovarian suppression
Male
- Sperm cryopreservation
Female
 Egg/Embryo cryopreservation
 Conservative gynecologic surgery
 Oophoropexy

8. Jeruss and Woodruff (2009) New England Journal of Medicine.
What
Technique
is
Appropriate
?

9. Limitations
• Some female treatments are dependent
upon phase of the menstrual cycle and
can be initiated only at monthly intervals

10. Male: Sperm cryopreservation
• Outpatient procedure;
• Cost approximately 1,500 for three
samples stored for 3 years
• Most effective way

11. 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

12. Oocyte cryopreservation
• Vetrification can be a good option

13. Indications
• Single woman > 35
• SLE
• Rheumatoid
• Cancer patient

14. KEEP IT TILL U NEED IT
Single woman > 35 yrs

15. Delayed marriage
• Increasing problem
• Social pressures
• Single or divorced woman

16. The best indication?
• Luxury of time : use long protocol
• Divorced woman : No problem at all
• Virgin : needs certain precautions
• OHSS free clinic

17. IS IT COMMON?
SLE & Rheumatoid patients

18. SLE & Rheumatoid
• In its severe forms, requires chemotherapy
• Mainly MTX
• Usually 6-12 course
• AMH decline markedly
• Deserve fertility preservation

19. Alternatives?
• are not effective
Agonist depot
Antagonists

20. INCREASING SURVIVAL RATES
Cancer Patient

22. Effects of cancer treatment on
fertility

23. “Based on the current state of evidence, modern
procedures to cryopreserve oocytes should no
longer be considered experimental.

24. Now
• Focus on :-
– oocyte cryopreservation
– ovarian tissue preservation
»Practical issues

25. Cost
• Same as ICSI
• No additional costs

26. Is it satisfactory?
Embryo
cryopreservati
on
Cumm Pregnancy
Rate:
>60%
Oocyte
preservation
Oocyte survival: > 68%
Fertilisation rate: > 50%
Pregn. rate: >30%
Sonmezer et al 2004; Oktay et al 2004; Seli et al 2005, Georgescu et al 2008

27. OTC : emerging
• No Delay in cancer treatment
• Survival of the graft >90%
• Restoration of ovarian function > 70%
• More than 130 live births
• Duration of graft activity
– >4 years: if no chemotherapy before cryopreservation
– <2 years: if chemotherapy before cryopreservation
Amorim, 2017

30. Egypt ProFam protocol
• 3D assessment of cortical perimeter
• Types of surgery
• Standard decortication
• Maximum decortication
• Unilateral oophorectomy

31. Clinical pregnancy rate Fertilisation rate

32. Unilateral
• Bivalve the ovary
• Remove the medulla
• Thinning of the cortex (1mm)
• Make it into minute strips
• Shake each in Cryomedia
• Load in cryotank

33. Tissue
processing

35. Survival of the graft
• Thickness of the graft
• Uniformity of the graft
• Proper fixation of the graft
• Avoiding fluid accumulation
• Vascularity of the host site

36. Widening the scope
• Partial decortication
• Can be done by laparoscopy
• Can be done during CS in elderly
primigravida

37. Safety
• no detectable increased risk of disease
recurrence associated with most fertility
preservation methods and pregnancy,
even in hormonally sensitive tumors.

38. For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health

39. Prevention
Of What!!

40. What after screening!!
• Doctors successfully screened embryos
for gene mutation linked to early onset
Alzheimer's
JAMA, March, 2002

41. Genetic Risk is significant
Autosomal recessive (SMA, Tay Sachs, 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)

42. IVF + PGD
Transfer only unaffected embryos to the woman
affected affected
affected

43. Embryo biopsy
Diagnosis
by
Transfer
2 unaffected
embryos
Fertilisation in vitro
(IVF or ICSI)
PCR
FISH
Accurate
genetic
diagnosis
Appropriate
Genetic
Counselling
DENATURING
ANNEALING
EXTENSION
PRIMER
TAQ
TAQ

44. Demographics: Thalassemia
• Found most
frequently in the
Mediterranean

45. Effects of haemophilia.
(a) Bleeding around elbow. (b) A retinal bleed. (c) Repeated bleeds into joints
produce severe arthritis.

46. Al-Gazali, L. et al. BMJ 2006;333:831-834
Fig 2 Average rates of marriages between first cousins among Arabs

47. Iran
• A premarital thalassaemia screening and
counselling programme resulted in
reduction in birth of affected babies by
70% within five years.

48. monogenic disease
• may be a therapeutic tool in families with
an already affected offspring

49. 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.

50. IVF + PGD + HLA

51. 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)

52. 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).

53. • 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.

54. 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?

55. For Tomorrow Better health
• Preservation of fertility
• Prevention of disease
• Improvement of health

56. Prevention of Cancer

57. 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

58. Direct transmission from
an affected parent to an
affected child.
Transmission can
occur from affected
father to affected son.
Approximately a 1:1 ratio of affected vs. unaffected
progeny with one affected parent.
AUTOSOMAL DOMINANT
(Affected children always
have an affected parent.)

59. 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.

60. IVF + PGD
Transfer only unaffected embryos to the woman
affected affected
affected

61. Sex selection
• For family balancing
• poses numerous clinical, social, psychological,
ethical dilemma

62. 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.

63. Other conditions

64. 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

65. Chromosome Translocation
• Discovered during infertility or RPL
investigations
• insufficient evidence supporting the use of
PGD for the detection of chromosomal
translocations as a method to improve live
birth rates; or recurrent spontaneous
abortions.

66. 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

67. 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 ).

68. Future of IVF
• Preservation of fertility
• Prevention of disease
• Improvement of health

69. THANK YOU
Dr. Hesham Al-Inany MD, PhD
e-mail : hesham@khosoba.com