How to resolve debates in infertility management and reach a valid consensus. This talk illustrate how to do this in specific examples

1. HOW DEBATES IN
INFERTILITY CAN BE
RESOLVED?
2018
kasr al ainy school of Medicine
Cairo University

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

16. HYSTEROSCOPY BEFORE IVF
TO DO OR NOT TO DO

17. LET’S START FROM THE END : 2016

18. WHAT ABOUT RIF?

19. ALL CENTERS?

20. IS IT REALLY OF VALUE?

21. PRACTICAL ISSUES: IS IT ALWAYS OFFICE
HYSTEROSCOPY?

22. PRACTICAL ISSUES II : COST
 Additional cost burden on patient ~ 1500 E.P

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

25. FIBROID & IVF : DEBATE
CONTINUES

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

36. AZOOSPERMIA : MAY 2014

37. BEWARE
 Testicular teratoma has been reported after SC
injection in azoospermic man

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

40. THANK YOU
Dr. Hesham Al-Inany MD, PhD
e-mail : kaainih@yahoo.com