2. WHY DEBATE
Innovations continue to develop
Not all innovations are beneficial
So what to do?
3. SHOULD BE EVIDENCE BASED
RCT take long time and huge funds
Systematic Reviews
4. WE ARE NOT TALKING ABOUT ETHICAL
DEBATES LIKE
Abortion
fertility : is it human right?
5. WE ARE TALKING ABOUT CLINICAL DEBATES BEST
EXAMPLE : BREECH DELIVERY
NVD vs CS
Breech trial : change in practice
6. SECOND BEST EXAMPLE : GN FOR IVF!
Recombinant vs. Urinary gonadotrophins
No difference, known since mid 1990s
“It is obvious why 7339 patients were included in
redundant trials: industry funding” 6
5-3-2018
7. WE ARE FOCUSING ON DEBATES IN
PRACTICE?
Day 3 vs day 5 ET
Hysteroscopy before IVF
Myoma & IVF
Stem cells for ttt of infertility
8. ET : DAY 3 VS DAY 5
kasr al ainy school of Medicine
Cairo University
ِيم ِحهالر ِن َٰمْحهالر ِ هاَّلل ِمْسِب
9. WHAT IS THE PROBLEM?
Culture media have improved to allow for Day 5
transfer
Should it be routine?
10. WHAT IS THE PROBLEM? CONT.
Is there a real value?
Is it practical?
11. QUESTIONS TO BE ANSWERED
Are there any adverse effects ?
Is it suitable for all women?
12. IS IT REALLY OF VALUE?
For single embryo transfer : Yes
If DET or TET : No
13. PGS: routine or not
ASRM/ESHRE 2015
? Neonatal and maternal outcome
after blastocyst transfer: a
population based registery study
Ernestad et al, Am J Obstet
Gynecol, March 2016
In Sweeden from 2002 to 2013, compare
delivieries after blastocyst versus cleavage
versus spontaneous 4819 blastocyst, 25747
cleavage, 1,196,394 spont.
Preterm birth was higher with blastocyst. PP
and placental abruption higher with BET
14. IS IT SUITABLE FOR ALL WOMEN?
Women with less than 8 embryos on day 1 have a
chance to reach day 5 with no embryos
So day 5 should not be offered for any woman with
limited number of oocytes
15. IS IT PRACTICAL?
IVF center should have large number of incubators
to allow for Day 5 transfer
If keeping quality control standards
Not suitable at all for busy center
23. PRACTICAL ISSUES III: WHY
If endometrial scratching : then pipelle currette is
much cheaper
If visualising the uterine cavity : 4D US is non
invasive and much cheaper
24. On the other hand hysteroscopy is still a gold
standard strongly recommended in cases with
suspected intrauterine anomalies undergoing ivf
BEST OF ESHRE& ASRM 2012
Dr Shashwat Jani. 2014
26. Localization
Number of studies
includeda
Breslow–Day test (P-
value)
Common OR (95% CI)
Clinical pregnancy rate
Submucosal 2 0.92 0.3 (0.1–0.7)
Intramural 7 0.38 0.8 (0.6–0.9)
Subserosal 3 0.92 1.2 (0.8–1.7)
Intramural and/or
subserosal
11 0.30 1.0 (0.8–1.2)
All types 16 0.24 0.8 (0.7–1.0)
Delivery rate
Submucosal 2 0.79 0.3 (0.1–0.8)
Intramural 7 0.09 0.7 (0.5–0.8)
Subserosal 3 0.94 1.0 (0.7–1.5)
Intramural and/or
subserosal
11 0.68 0.9 (0.7–1.1)
All types 16 0.43 0.8 (0.6–0.9)
Meta-analysis on the influence of fibroids on IVF outcome according to the localization of the lesions
(Somigliana et al, 2007)
27. SO IT IS LOGIC TO DO MYOMECTOMY BEFORE
IVF ?!!
This is the real problem
28. EVIDENCE GRADE I
Submucous myoma : should be treated
Best way : hysteroscopic approach
29. EFFECT OF MYOMECTOMY !!!!
does not have a significant effect on CPR when
compared to controls with fibroids in situ ( RR
3.765, 95%CI 0.470–30.136),
Miscarriage rate (RR 0.758, 95%CI 0.296–1.943) or
OPR⁄LBR (n = 1, RR 1.671, 95%CI 0.750–3.723).
(kroon et al, 2013)
30. SO WHAT TO DO WITH INTRAMURAL MYOMA
Myomectomy only if :-
Failed IVF cycle
If close to endometrium
If size > 3cm distorting uterine cavity
Otherwise conservative management
31. NOW
Day 3 vs day 5 ET
Hysteroscopy before IVF
Myoma & IVF
Stem cells for ttt of infertility
32. WHAT ABOUT STEM CELLS: IN POF?
AFSCs were transplanted into the ovaries of mice
with POF six weeks post induction using
chemotherapeutic drugs.
the transplanted AFSCs did not differentiate into
germ line cells in vivo.
33. Stem cells
types
References
Stem cells and
germ cells
markers
Chemotherapy
Morphologicall
y of ovary after
stem cells
transplanted
Hormone or cytokines
profile changes
Tracking of stem cells
Bone marrow
transplantation
Lee et al.43 / / /
BMP15, FMR1, FSHR, INHA,
AMH, NOBOX, FOXO3,
EIF2B, FIGLA and GDF9
Reactivate host oogenesis;
not generate oocytes
CD44 +/CD105
+ human
amniotic fluid
mesenchymal
stem cells
Liu et al.73
CD29, CD44,
CD73, CD90,
CD105 and
CD166
Intraperitoneal
injection of
cyclophosphami
de
/ / /
Adipose-
derived stem
cells
Sun et al.63 /
Intraperitoneal
injection of
cyclophosphami
de
Follicle number
, ovulation
number and
apoptotic GCs¯
HGF , VEGF, PGF and TGF-
β
Not participate in follicle
regeneration
Umbilical cord
mesenchymal
stem cells
Wang et al.64
CD29,
CD44,CD90
and CD105
Intraperitoneal
injection of
cyclophosphami
de
Apoptosis of
GC¯, number of
folliclesand
oocyte
containing
follicles
E2 Not develop into follicles
Human
amniotic fluid
cells
Lai et al.72
Intraperitoneal
injection of
cyclophosphami
de and
busulphan
Oocytes at all
stages
AMH and FSHR
Differentiated into GCs; not
germ cell
34. SUMMARY OF RESULTS
No evidence of differentiation into oocytes
But risk of developing GC tumour is potential
(Botman , 2014)
So till now, use of stem cells for POF in human is
not valid
35. WHAT ABOUT MALE INFERTILITY?
studies have reported differentiation of mouse and
human germ cells from pluripotent stem cells
(PSCs) in vitro,
However, differentiation of human germ cells from
SCs in vivo has not been reported
38. HUMAN TRIALS?
Patients accepted such treatments and were eager
to take part because they have no other choice
(RBMonline, 2014)
39. ETHICAL DEBATE CAN ALSO BE SOLVED
the World Health Organization (WHO)
acknowledged that infertility should be considered a
disease to all intents and purposes, as it diminishes
the health and wellbeing of the individuals who
suffers from it.
Accordingly it is a human right to get infertility
treatment