1. 1
Elonva: A new
patient friendly
approach in ART
Daniel S. Seidman, MD
Department of Ob/Gyn,
Sheba Medical Center,
Sackler School of Medicine,
Tel-Aviv University
6. 6
6%
6%
8%
8%
9%
11%
25%
28%
0 5 10 15 20 25 30
Physical or Psychological Treatment Burden
is a Primary Reason for Dropout
Physical or psychological burden of treatment
Unknown
Relational problems/divorce
Ethical objections to ICSI treatment after failed
IVF treatment
Adoption
Poor embryo quality
Poor response/signs of ovarian aging
Other
Among 384 couples undergoing IVF treatment, 65 (17%) dropped out
Reason for Dropout
Percentage
Adapted from Verberg et al. Hum Reprod. 2008;23:2050.
7. 7
Reasons couples discontinued
treatments before achieving two live
children at each stage:
Ceased ART for 1st
child (25)
Did not return for
2nd child (13)
Ceased ART for 2nd
child (13)
Stage treatment
discontinued (n)
9 (36%)5 (38.5%)4 (30.8%)Psychological
burden
9 (36%)04 (30.8%)Lost hope of success
4 (16%)01 (7.7%)Medical staff advice
1 (4%)02 (15.4%)Bureaucratic
difficulties
2 (8%)3 (23.1%)1 (7.7%)Divorce
01 (7.7%)1 (7.7%)Major illness
04 (30.8%)0Not ready yet for 2nd
child
12 (48%)8 (61.5%)4 (30.8%)Eventually returned
/ plan to return for
treatments
Lande et al., 2014
8. 8
Reasons couples chose to cease ART
treatments before completing all
subsidized cycles
Brandes et al.Olivius et al.Smeenk et al.Lande et al.
15.3%21%20.5%34.3%*Drop-out rate
1-21-21.55.2**Number of
cycles
49%32.3%38.5%39.1%Psychological
burden
33%31%30.8%10.9%Physician
recommendation
9%18.1%08.7%Divorce /
relational
problem
18%1.9%04.3%Health problem
0021.8%8.7%Postpone
treatment
7%0028.3%Lost hope
9. 9
1 2 3 4 5 6
ECPR = expected cumulative pregnancy rate; RCPR = real cumulative pregnancy rate.
Schroder et al. RBM Online. 2004;8:600.
Difference between
expected and real
pregnancy rates is caused
by the diminishing size of
the cohort due to dropout
frequency
Dropouts Negatively Impact Real
Cumulative Pregnancy Rates
Data from 4102 IVF cycles in 2130 women
Cycles
0
10
20
30
40
50
60
70
Percent
Dropout rate ECPR RCPR
(n=2130) (n=1087) (n=518) (n=222) (n=74) (n=36)
10. 10
Patient-Centered Approach in
IVF
Increase cumulative live birth rates
Optimize risk/benefit ratio
–Individualization of management
strategies
– Reduce OHSS and cycle
cancellation
Reduce complexity and patient
burden
–Shorter treatment cycles
–Fewer overall injections
12. 12
The objective of the individualization
of the treatment strategy
To increase the
percentage of patients
with an appropriate
number of retrieved
oocytes, while reducing
the number of women at
high risk of cycle
cancellation due to poor
response or ovarian
hyperstimulation
syndrome (OHSS).
21. 21
Study Question:
Is the ovarian response to
controlled ovarian stimulation
(COS) related to the ongoing
pregnancy rate when taking into
account the main covariates
affecting the probabilities of
pregnancy following fresh embryo
transfer?
27. 27
Summary answer:
In patients treated with
corifollitropin alfa or daily
recombinant FSH (rFSH) in a
GnRH-antagonist protocol:
– A high ovarian response did NOT
compromise ongoing pregnancy
rates
– Increased cumulative pregnancy
rates following fresh and frozen-
thawed embryo transfer.
30. 30
Comparative incidence of OHSS
following ovarian stimulation with
corifollitropin alfa or recombinant
FSH
Overall, 1705 patients received
corifollitropin alfa and 5.6%
experienced mild, moderate or severe
OHSS.
In the randomized controlled trials,
Engage and Ensure, the pooled
incidence of OHSS with corifollitropin
alfa was 6.9% (71/1023 patients)
compared with 6.0% (53/880 patients) in
31. 31
Comparative incidence of OHSS
following ovarian stimulation with
corifollitropin alfa or recombinant
FSH
Adjusted for trial, the odds ratio for
OHSS was 1.18 (95% CI 0.81–1.71)
indicating that the risk of OHSS for
corifollitropin alfa was similar to that
for rFSH.
Despite a higher ovarian response with
corifollitropin alfa compared with rFSH
for the first 7 days of ovarian
stimulation, the incidence of OHSS was
43. 43
Objective:
To identify whether women with
poor ovarian response may benefit
from treatment with corifollitropin
alfa in a GnRH antagonist protocol.
Design: Retrospective pilot study.
Intervention: Corifollitropin alfa
(150 mg) followed by 300 IU rFSH
in a GnRH antagonist protocol.
Polyzos et al. Fertil Steril 2013
45. 45
Conclusions:
Treatment of poor ovarian
responders, as described by the
Bologna criteria, with
corifollitropin alfa in a GnRH
antagonist protocol results in low
pregnancy rates, similarly to
conventional stimulation with a
short agonist protocol.
Polyzos et al. Fertil Steril 2013
47. 47
Study Question:
Will sequential administration of
highly purified (hp)-HMG after
corifollitropin alfa in a GnRH
antagonist protocol benefit women
with poor ovarian response
according to the Bologna criteria?
50. 50
Endocrine profiles during the follicular phase
in women who are poor ovarian responders,
according to age
E2, estradiol. *P . 0.05 for all comparisons between age groups
at Days 2, 7, 9 and day of hCG triggering.
51. 51
Summary Answer:
Corifollitropin alfa followed by hp-
HMG in a GnRH antagonist
protocol results in very promising
pregnancy rates, albeit only in
young (<40 years old) poor ovarian
responders fulfilling the Bologna
criteria.
56. 56
Objective:
To identify predictors of ovarian
response in women undergoing
ovarian stimulation with
corifollitropin alfa in a GnRH
antagonist protocol and determine
specific thresholds for the
prediction of low and excessive
responders.
59. 59
Conclusions:
AMH and AFC are the best
predictors for low and excessive
response in women treated with
corifollitropin alfa in an antagonist
protocol.
Using AMH and AFC to select
suitable candidates for treatment
with corifollitropin alfa may result
in a safe and convenient
64. 64
Day When hCG Criterion Was Met
0
5
10
15
20
25
30
35
40
5 6 7 8 9 10 11 12 13 14 15 16 17 18
Stimulation day
%ofpatients
Corifollitropin alfa 150 µg
rFSH 200 IU/d
One-third of the patients did not require any rFSH
Engage
Adapted with permission from Fauser BC et al. Reprod Biomed Online. 2010;21:593‒601.
66. 66
Conclusions
Early responders receiving HCG prior
to or on stimulation day 8 have
advanced follicular development but
the final number and size of
preovulatory follicles is comparable to
those of normal responders.
A short follicular phase of stimulation
did not affect the number of oocytes
retrieved, the number of good-quality
embryos obtained or the ongoing
pregnancy rates.
71. 71
Study Conclusions
No significant differences were found
in any analysed parameters between
treatments.
However, when donors who had
undergone both treatments chose
which treatment they preferred, the
results clearly showed a positive trend
towards choosing corifollitropin a,
confirming that this protocol may
reduce treatment burden and increase
donor compliance.
72. 72
Overall Conclusions
Corifollitropin alfa offers an attractive
new option for ovarian stimulation.
Proper patient selection avoids over
response.
OHSS totally preventable by triggering
with GnRH agonist.
Corifollitropin alfa may offer an
advantage to young poor response
patients
Corifollitropin alfa use is associated
75. 75
Conclusions
Treatment flexibility of ovarian stimulation does not
substantially affect the clinical outcome in patients’
treatment following initiation of ovarian stimulation
with either corifollitropin alfa or with daily rFSH in a
gonadotropin-releasing hormone antagonist
89. 89
1.Usage of estradiol pretreatment for planning cycles
2. Elevated levels of progesterone at the start of
stimulation, approaches to manage it
3. When (which day) to start gonadotropins (particularly
ELONVA)?
4. Does hCG delay for 1-2 day influence on the chance
of pregnancy?
5. How “quickly” the ovaries will respond to Elonva
stimulation?
6. Trigger agonist
7. Which extra dose of rFSH required on the 8th day, if
not met the criteria for the hCG?
93. 93
Results
The total dose of rFSH at the end of the follicular
phase was significantly reduced in the CD4 group
compared with the CD2.
A significant reduction of total duration of rFSH
stimulation in the CD4 group was also observed.
The number of cumulus-oocyte-complexes was
comparable in both treatment groups
Ongoing pregnancy rates of 48% in the CD2 group
and 41% in the CD4 group were achieved.
Final oocyte maturation was triggered with GnRH
agonist instead of hCG in two patients in the CD2
group and in eight patients in the CD4 group,
because of an increased risk of ovarian
94. 94
Conclusion
If the approach of starting ovarian
stimulation on Day4 of the cycle
could be implemented in a large
population of infertile patients, it
would result in a significant
reduction of gonadotrophin
consumption.