Principles and practices in individualizing in ART

1.
Principles
and
Prac-ces
of
Individualiza-on
in
ART
UAE Reproductive Symposium 2015 - Dubai
Sandro
C.
Esteves,
MD.,
PhD.
Medical
Director,
ANDROFERT
Andrology
&
Human
Reproduc=on
Clinic
Campinas,
BRAZIL

2. Learning
Objec-ves
1. Individualiza-on:
a
quality
concept
2. How
to
individualize
COS
to
different
pa-ent
subgroups
3. How
to
individualize
triggering
4. How
to
individualize
luteal
support
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 2
2015
ANDROFERT

3. Why
individualize?
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 3
2015
ANDROFERT

4. Maximize
beneficial
effects
of
treatment
Minimize
complica-ons
and
risks
Why
individualize?
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 4
2015
ANDROFERT

5. Top
3
clinical
dimensions
for
quality
improvement
in
infer-lity
care
• Effec-veness:
Technical
aspects
to
deliver
the
best
possible
outcome
(e.g.
pregnancy,
live
birth,
cumula=ve
LBR)
• Safety:
Complica=ons
(OHSS),
adverse
effects,
risks
(pa=ent
&
offspring),
errors/mistakes
• Pa-ent-­‐centeredness:
Informa=on
and
pa=ent
involvement,
competence
and
aPen=on
of
clinic
and
staff,
accessibility,
coordina=on
and
integra=on,
emo=onal
support
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 5
2015
ANDROFERT
Dancet
et
al.
Hum
Reprod
2011;
Mainz
Int
J
Qual
Health
Care
2013

6. How
stakeholders
value
the
top
3
quality
dimensions
of
infer-lity
care
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 6
2015
ANDROFERT
0%
50%
100%
Doctors
&
embryologists
Nurses
Pa-ents
Safety
Effec-veness
Pa-ent-­‐
centeredness
Dancet
et
al.
Hum
Reprod
2013

7. Lack
of
psychological
support
and
poor
quality
of
service
~60%
treatment
discon-nua-on
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 7
2015
ANDROFERT
22
studies
21,453
pa=ents
8
countries

8. Individualiza-on
is
a
quality
concept
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 8
2015
ANDROFERT
Safety
Pa-ent-­‐
centeredness
Effec-veness

9. How
to
individualize?
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 9
2015
ANDROFERT

10. Individualizing
S-mula-on
Protocols
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 10
2015
ANDROFERT
• Clinical
characteris-cs
• Ovarian
biomarkers
Iden-fy
who
is
who
• Pa-ent-­‐centered
• Effec-ve
• Safe
Protocol

11. What biomarker do you value
more?
a. Basal FSH
b. AMH
c. AFC
d. Age

12. AMH
~
AFC
>
FSH
>
Age
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 12
2015
ANDROFERT

13. Popula-on
Cutoff
Sensi-vity
Specificity
Accuracy
AMH
ng/mL
High-­‐
responder1
2.1
85%
79%
0.82
Poor
responder2
0.82
76%
86%
0.88
*Beckman-­‐Couter
genera-on
II
assay;
1>20
oocytes
retrieved;
2≤4
oocytes
retrieved
Leão
RBF,
Nakano
FY,
Esteves
SC.
Fer5l
Steril
2013;
100
(Suppl.):
S16
AMH
&
AFC
should
be
internally
validated
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 13
2015
ANDROFERT

14. Quality-­‐based
individualiza-on
in
COS
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 14
2015
ANDROFERT
High
responders*
Normal
responders*
Low
responders*
Biomarkers
Safety
Pa-ent-­‐
centeredness
Effec-veness
*expected

15. High
responders
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 15
2015
ANDROFERT
• Main
goal:
Safety
• Clinical
quality
indicator:
OHSS
• Protocol
of
choice*:
Antagonist
(flexible;
cetrorelix)
Tailored
recFSH
(112.5-­‐150
IU/d;
follitropin
alfa;
pen
injector)
*Androfert,
Brazil

16. GnRH
antagonists
in
high
responders
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 16
2015
ANDROFERT
9
RCT;
966
PCO
women
Rela-ve
Risk
Dura-on
of
ovarian
s-mula-on
-­‐0.74
(95%
CI
-­‐1.12;
-­‐0.36)
Gonadotropin
dose
-­‐0.28
(95%
CI
-­‐0.43;
-­‐0.13)
Oocytes
retrieved
0.01
(95%
CI
-­‐0.24-­‐0.26)
Risk
of
OHSS
Mild
Moderate
and
Severe
20%
vs
32%
1.23
(95%
CI
0.67-­‐2.26)
0.59
(95%
CI
0.45-­‐0.76)
Clinical
PR
1.01
(95%
CI
0.88;
1.15)
Miscarriage
rate
0.79
(95%
CI
0.49;
1.28)
Pundir J et al. RBM Online 2012; 24:6-22

17. iCOS
(n=118):
rec-­‐hFSH
112.5-­‐150
IU
+
GnRH
antagonist
(flexible)
cCOS
(n=131):
rec-­‐FSH
150-­‐225
IU
+
GnRH
agonist
(nafarelin)
39.3
18.5
14.0
57.0
14.3
14.7
4.8
56.0
0
10
20
30
40
50
60
Observed
Excessive
Response
(%)
Oocytes
retrieved
(N)
OHSS
(%)
Pregnancy
(%)
cCOS
iCOS
*p<0.05
*
*
Individualized
vs
conven-onal
COS
in
high
responders
Excessive
response
>20
oocytes
retrieved;
Mild/severe
OHSS
reported;
Leão
RBF,
Nakano
FY,
Esteves
SC.
Fer5l
Steril
2013;
100
(Suppl.):
S16
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 17
2015
ANDROFERT
*

18. Poor
responders
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 18
2015
ANDROFERT
• Main
goal:
pa-ent-­‐centeredness
• Clinical
quality
indicators:
– Compliance
(drop-­‐out
rate)
– Pa-ent
burden
(cancela-on
rate)
• Protocol
of
choice*:
Antagonist
(flexible;
cetrorelix)
recFSH
+
recLH
(follitropin
alfa
+
lutropin
alfa
2:1
ra=o:
300
IU
recFSH
+
150
IU
recLH);
start
D1
s=mula=on
*Androfert,
Brazil

19. Pregnancy
rates
increased
by
30%
in
poor
responders
treated
with
rLH+rFSH
Lehert et al Reprod
Biol
Endocrinol
2014,
12:17
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 19
2015
ANDROFERT

20. Lehert et al 2012
Increase
of
≈1
oocyte
per
1,000
UI
in
poor
responders
treated
with
rLH
+rFSH
Lehert et al Reprod
Biol
Endocrinol
2014,
12:17
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 20
2015
ANDROFERT

21. Individualized
vs.
Conven-onal
COS
in
Expected
Poor
Responders
(N=118)
72.0
3.5
45.0
20.0
46.6
4.8
23.3
26.8
0
20
40
60
80
Observed
Poor
Response
(%)
Oocytes
retrieved
(N)
Cancella=on
(%)
Pregnancy/cycle
(%)
cCOS
(Long
GnRHa
+
300-­‐450
IU
recFSH
alone)
iCOS
(GnRH
antagonist
+
rFSH
(225-­‐300
IU)
+rLH
(75-­‐150
IU))
Expected
poor
response:
AMH<0.82
ng/dL;
Observed
poor
response
<5
oocytes
retrieved;
Leão
RBF,
Nakano
FY,
Esteves
SC.
Fer5l
Steril
2013;
100
(Suppl.):
S16
*p<0.05
*
*
*
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 21
2015
ANDROFERT

22. Normal
responders
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 22
2015
ANDROFERT
• Main
goal:
effec-veness
• Clinical
quality
indicators:
number
oocytes
• Protocol
of
choice*:
<35yr:
Antagonist
+
recFSH
cetrorelix
(flexible);
187.5-­‐262.5
IU/d
follitropin
alfa
pen
injector
>35yr:
Antagonist
+
recFSH/recLH
cetrorelix
(flexible);
follitropin
alfa
+
lutropin
alfa
2:1
ra=o;
225-­‐300
IU/d;
from
s=mula=on
D1
*Androfert,
Brazil

23. Nega-ve
predictor
Posi-ve
predictor
van Loendersloot et al. Hum Reprod Update 2010; 16: 577–589
Female
Age
(OR=0.95;
CI:
0.94-­‐0.96)
Number
of
oocytes
retrieved
(OR=1.04;
CI:
1.02-­‐1.07)
Level
1a
Predictors
of
pregnancy
in
IVF
14
studies
>30,000
pa=ents
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 23
2015
ANDROFERT

24. What is the optimum number
of retrieved oocytes to
increase pregnancy rates ?
a. 4 to 8
b. 9-12
c. 13-17
d. The higher the better

25. 0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 20 25 30 35 40
Livebirthrate(%)
Oocyte number
Observed live birth rate Predicted live birth rate
Sunkara
et
al.
Hum
Reprod
2011
450,135 IVF cycles
Best
chance
of
live
birth
is
associated
with
~15
oocytes
number of oocytes that
best optimized LBR was 15
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 25
2015
ANDROFERT

26. ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 26
2015
ANDROFERT
...irrespec-ve
of
age
group

27. Do you take into account the
severity of male factor
infertility when planning COS?
a. Yes
b. No
c. Never though about it

28. 41.4
47
43.3
20
100
64
61
34.2
Sperm
retrieval (%)
2PN
Fertilization
(%)
Top Quality
Embryos (%)
Live Birth (%)
Non-obstructive (N=365)
Obstructive (N=146)
P<0.01
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 28
2015
ANDROFERT

29. 3,412
cycles
Oocyte
number
and
LBR
at
Androfert
(ICSI
cycles
involving
severe
male
factor)
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 29
2015
ANDROFERT
0%
10%
20%
30%
40%
50%
60%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
20
25
Number
of
oocytes
Clinical
pregnancy
Live
birth

30. Each
addi-onal
warming
cycle
increases
the
chance
of
achieving
a
live
birth
40.4% 48.0%
ET #3
(FET) 49
ET #2 (FET)
239
ET #1 (fresh)
822
50.5%
+18.8%
+25.0%
Female Age ≤38
332/822
63/239
17/49
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 30
2015
ANDROFERT

31. Oocyte yield by gonadotropin
↑
1.5
oocytes
(GnRH
antagonist
cycles)
Devroey
et
al.,
2012
↑
3.1
oocytes
(GnRH
antagonist)
Bosch
et
al.,
2008
↑
1.8
oocytes
(GnRH
agonist
cycles)
MERIT
Study,
2006
↑
2.8
oocytes
(GnRH
agonist
cycles)
Hompes
et
al.,
2008
↑
2.1
oocytes
(16
RCT;
different
protocols)
Lehert
et
al.,
2010
Higher
with
rec-­‐FSH
vs.
hMG,
HP-­‐hMG,
and
uFSH
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 31
2015
ANDROFERT

32. LH
supplementa-on
improves
clinical
pregnancy
in
women
>35
yr
Hill
et
al.
Fer5l
Steril
2012
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 32
2015
ANDROFERT

33. LH
ac-vity
by
rec-­‐LH
vs
hMG
Adapted
from:
Leao
&
Esteves.
Clinics
2014;
69(4):
279–293.
Product
LH
ac-vity
(IU/vial)
LH
content*
Purity
hMG
75
hCG
~5%
HP-­‐hMG
75
hCG
~70%
Lutroprin
alfa
(rec-­‐hLH)
75
LH
>99%
2:1
Follitropin
alfa
+
Lutroprin
alfa
(rec-­‐hFSH
+
rec-­‐hLH)
75
LH
>99%
*hCG
concentrated
or
added
during
purifica-on
process
(8IU
hCG
~
75IU
LH)
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 33
2015
ANDROFERT

34. LH
and
hCG
elicit
different
gene
expression
LH
hCG
LHR
and
FSHR
expression
(Trafficking
of
re=noic
acid
:
RXRB,
TTR,
ALDH8A1)
Meiosis
and
follicular
matura-on
(TRA
:
RXRB,
TTR,
ALDH8A1;
IL11;
AKT3)
Follicular
development
(IL11;
AKT3)
Cellular
growth
(RXRB,
TTR,
ALDH8A1;
IL11;AKT3)
Ovarian
stereodogenesis
(TRA
:
RXRB,
TTR,
ALDH8A1)
Embryo
development
&
survival
(AKT3)
Aromatase
inhibi-on
(PPARS)
Apoptosis
enhancement
(DNAsi)
LH
hCG
Grondal
ML
et
al.
FerCl
Steril
2009;
Menon
KM
et
al.
Biol
Reprod
2004;
Ruvolo
et
al.
Fer=l
Steril
2007
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 34
2015
ANDROFERT

35. COS
with
LH
ac-vity
delivered
by
rec-­‐
LH
vs
hMG
in
IVF
Authors,
yr.
Design
N
Main
findings
Buhler
&
Fisher,
2011
Matched
case-­‐
control
4719
Higher
CPR
in
fixed
2:1
rec-­‐
FSH
+
rec-­‐LH
(31%)
vs
hMG
(26%)
and
vs
combo
(rec-­‐FSH
+
hMG,
25%);
p=0.02
Fábregues
et
al,
2013
Cross-­‐over
study
66
Higher
N
oocytes
in
fixed
2:1
rec-­‐FSH
+
rec-­‐LH
(9.8)
vs
HP-­‐
hMG
(7.3);
p<0.01.
Higher
N
frozen
embryos
in
recLH
Dahan
et
al,
2014
Observa=onal
201
Higher
N
oocytes
in
rec-­‐LH
(12)
vs
hMG
(10);
p=0.008.
Higher
CPR
rec-­‐LH
(36%
vs
20%;
p=0.02)
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 35
2015
ANDROFERT

36. Individualizing
trigger
and
LPS
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 36
2015
ANDROFERT
High
responders
Normal
responders
Low
responders
Safety
Pa-ent-­‐
centeredness
Effec-veness

37. 14h
14h
20h
48h
0
20
h
Natural
LH
surge
hCG
Adapted
from
Chan
et
al.
Hum
Reprod.
2003;18:2294-­‐7
Day
6
hCG
and
GnRHa
elicit
final
follicular
matura-on
as
surrogates
for
the
mid-­‐cycle
LH
surge
GnRHa
36-48 h
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 37
2015
ANDROFERT
Day
8

38. GnRH-­‐agonist
vs
hCG
trigger
Fresh
autologous
cycles
Moderate/
severe
OHSS
OR
0.10
0.01-­‐0.82
Live
birth
OR
0.44
0.29-­‐0.68
Youssef et al. Cochrane Database Syst Rev. 2011
High
responders
Fresh
ET
Freeze
all
GnRH-­‐a
trigger
One
size
trigger
does
not
fit
all
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 38
2015
ANDROFERT

39. Freeze-­‐all
embryo
policy:
is
it
for
all?
• Non-­‐inferior
in
effec-veness
in
high-­‐
quality
vitrifica-on
programs,
but…
• Safety
– Increase
ART
unit
workload
– Perinatal
outcome
• Higher
rate
of
large
for
gesta-onal
age
(Wennerholm HR 2013)
• Pa-ent-­‐centeredness
– Psychological
&
cost
burden
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 39
2015
ANDROFERT

40.
Modified
LPS
for
fresh
ET
in
GnRH-­‐a
trigger
No.
follicles
day
OPU
1,500
IU
hCG
at
OPU
&
1,000
OPU+5
&
standard
LPS
≤
14
1,500
IU
hCG
at
OPU
+
standard
LPS
15-­‐25
1,000
IU
hCG
at
OPU
+
standard
LPS
or
Freeze
all
26-­‐30
Freeze
all
>30
Humaidan
et
al.
Hum
Reprod.
2013;28(9):2511-­‐21
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 40
2015
ANDROFERT
14h
14h
20h
48h
0
20
h
4h
GnRHa
Natural
LH
surge
Luteal
phase
defect

41. Individualizing
trigger
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 41
2015
ANDROFERT
Normal
&
poor
responders
rec-­‐hCG
u-­‐hCG
hCG
trigger

42. RCT
N
Effect
Oocytes
retrieved
9
1409
MD:
-­‐0.04
95%
CI:
-­‐0.69
to
0.61
Live
birth
6
1,019
OR:
1.04
95%
CI:
0.79
to
1.37
Miscarriage
7
1,106
OR:
0.69
95%
CI:
0.41
to
1.18
Severe
OHSS
3
549
OR:
1.49
95%
CI:
0.54
to
4.1
Youssef
et
al.
Cochrane
Database
Syst
Rev.
2011;
13(4):CD003719
Databases
searched
up
to
January
2010
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 42
2015
ANDROFERT

43. Farrag et al. JARG 2008; 25:461-6
8.4
7.3
7.1
4.7
0
2
4
6
8
10
No. Retrieved oocytes
No. MII with mature
cytoplasm
rec-hCG (250 mcg; n=42)
u-hCG (10,000 IU; n=47)
*p<0.01
*
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 43
2015
ANDROFERT

44. Effec-veness
RCT
comparing
trigger
with
rec-­‐hCG
(250
mcg)
vs
u-­‐hCG
(10,000
IU)
on
delivery
rates
in
eSET
antagonist
cycles
26.7%
44.1%
Delivery rate (%)
u-hCG
rec-hCG
N=119
aged<32
OR:
2.16
(95%
CI:
1.01-­‐4.67;
p=0.04)
Papanikolaou
EG
et
al.
Fer5l
Steril
2010;
94:2902-­‐4
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 44
2015
ANDROFERT

45. RCT
N
Odds-­‐ra-o
Local
site
reac-ons*
rec-­‐hCG
vs.
u-­‐hCG
3
374
0.39
95%
CI:
0.25
to
0.61
Driscoll
et
al.
2000:
27%
vs
42%
ERHCG
group
2000:
23%
vs
45%
Abdelmassih
et
al.
2005:
23%
vs
45%
Youssef et al. Cochrane Database Syst Rev. 2011; 13(4):CD003719
* Pain and/or inflammation
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 45
2015
ANDROFERT

46. hCG
preferences
in
treatment-­‐
experienced
pa-ents
at
Androfert
Total (n=76)
60%
29%
3%
8%
prefer new pen
prefer pre-filled syringe
prefer lyophilized powder to reconstitute
Not matter
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 46
2015
ANDROFERT

47. Individualizing
LPS
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 47
2015
ANDROFERT
Normal
&
poor
responders
Fresh
ET
FET

48. In
FET
cycles,
all
of
the
current
methods
of
endometrial
prepara-on
appear
to
be
equally
effec-ve
in
terms
of
ongoing
pregnancy
rate*
• Meta-­‐analysis
of
20
compara=ve
studies
• ~13,000
cycles
• Natural
and
ar=ficial
cycles
with
and
w/o
GnRH
agonist
• Safety
&
pa-ent-­‐centeredness
not
addressed
Groenewoud
ER
et
al.
Hum
Reprod
Update.
2013;19:458-­‐70
*in
eumenorrhoic
pa-ents
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 48
2015
ANDROFERT

49. Luteal
phase
abnormal
in
s-mulated
cycles
• Corpus
luteum
func-on
dependent
on
pulsa-le
LH
release
from
pituitary
• Supraphysiologic
steroid
levels
(by
mul-follicular
development)
inhibits
LH
secre-on
• Low
LH
levels
causes
luteolysis,
implanta-on
failure
and
shortened
luteal
phase
Jones 1996; Albano et al 1998; Beckers et al 2000; Tavaniotou et al Hum Reprod 2000;
Fauser & Devroey 2003; Trinchard-Lugan et al 2002; Sherbahn 2013
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 49
2015
ANDROFERT

50. LPS
mandatory
in
s-mulated
cycles
• hCG
vs.
Placebo
or
No
treatment:
Higher
ongoing
PR
(OR=1.75; 95% CI: 1.09-2.81)
• Progesterone
vs.
Placebo
or
No
treatment:
Higher
clinical
PR
(OR=1.83; 95% CI: 1.29-2.61)
Higher
ongoing
PR
(OR=1.87; 95% CI: 1.19-2.94)
Higher
live
birth
rates
(OR=2.95; 95% CI: 1.02-8.56)
Level
1a
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 50
2015
ANDROFERT

51. Gelbaya et al Fertil Steril. 2008; Kolibianakis et al Hum Reprod. 2008;
Jee et al Fertil Steril. 2010; van der Linden et al Cochrane Database 2011
High-­‐quality
evidence
on
LPS
in
s-mulated
cycles
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 51
2015
ANDROFERT

52. P routes & types Evidence Effect Conclusion
Vaginal as effective
as IM/oral
13 RCT; 2
MA; >2,000
cycles
Similar CPR, LBR
& miscarriage True
Vaginal safer and
more patient-
friendly than IM/oral
3 RCT; 1
MA; >2,000
cycles
Lower side effects;
Increased patient
satisfaction
True
Among vaginal P,
patients prefer gel
7 RCT; 1
MA; >2,400
cycles
Easier to use;
better adherence;
lower discharge
True
Schoolcraft et al 2000; Yanushpolsky et al-2008; Zarutskie & Phillips 2009; Polyzos et al 2010;
van der Linden et al Cochrane 2011
High-­‐quality
evidence
on
LPS
in
s-mulated
cycles
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 52
2015
ANDROFERT

53. Principles
and
Prac-ces
of
Individualized
ART
at
Androfert
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 53
2015
ANDROFERT
High
responders
Normal
responders
Low
responders
Clinical
features
+
AMH
Antagonist
protocol;
tailored
COS
rec-­‐FSH
(112.5-­‐150
IU)
+
tailored
trigger
(GnRHa
or
rec-­‐hCG);
tailored
LPS
(modified
LPS
or
vaginal
P
gel
OPU)
Antagonist
protocol;
tailored
COS
w/rec-­‐
FSH
(<35yr)
or
rec-­‐FSH+rec-­‐LH
2:1
ra-o
(>35
yr);
rec-­‐hCG
trigger;
LPS
vaginal
P
gel
Antagonist
protocol;
recFSH
+
recLH
2:1
ra-o
+
rec-­‐hCG
trigger;
LPS
vaginal
P
gel

54. Principles
and
Prac-ces
of
Individualiza-on
in
ART
Conclusions
• Individualiza-on
is
a
quality
concept
• Safety,
effec-veness
and
pa-ent-­‐centeredness
are
important
principles
in
a
quality-­‐based
individualized
infer-lity
care
• Novel
biomarkers
combined
with
new
devices
&
drug
regimens
can
be
used
to
deliver
a
high
quality
evidence-­‐based
individualized
ART
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 54
2015
ANDROFERT

55. Thank
you
‫ا‬‫شكر‬ Obrigado
This
presenta-on
is
available
at
hwp://www.slideshare.net/
sandroesteves