The document discusses the challenges of ovarian stimulation and embryo quality, focusing on infertility, oocyte efficiency, and the effects of aging on ovarian function. It highlights the importance of maximizing oocyte retrieval to improve live birth rates and suggests potential solutions like early conceiving and ovarian rejuvenation. Additionally, it emphasizes the need for tailored patient strategies in response to variations in ovarian response and embryo quality.

1. Ovarian Stimulation and
Embryo Quality
www.slideshare.net/MatheusRoque1/
Matheus Roque, M.D.
Scientific Director - ORIGEN - Center for Reproductive Medicine - BRAZIL

2. Ovarian Stimulation and
Embryo Quality
www.slideshare.net/MatheusRoque1/
Matheus Roque, M.D.
Scientific Director - ORIGEN - Center for Reproductive Medicine - BRAZIL

4. PROBLEM???

5. YESNO
SOLUTION???
YES NO
ALTERNATIVE???
YESNO
PROBLEM???

6. INFERTILITY
PROBLEM? SOLUTION? ALTERNATIVE?

7. PROBLEM?

8. PROBLEM ?OOCYTE EFFICIENCY
Goldman et al. Fertil Steril 2013;100:712-7
%
0
1,05
2,1
3,15
4,2
4,2
2,7
Cryopreserved Fresh
Live Birth Rate per Mature Oocyte Retrieved

9. PROBLEM ?OOCYTE EFFICIENCY
Goldman et al. Hum Reprod 2017;32:853-859
Live birth prediction by age and number of
mature oocytes retrieved

10. Esteves et al., ESHRE 2018; O-007;
Esteves et al. PanMinerva Medica 2018
Euploidy probability vs. female age
Courtesy Dr. Sandro Esteves
Progressive Decrease in the
Probability of a Blastocyst
Being Euploid with Female Age
PROBLEM ?
OVARIAN AGING…

11. Esteves et al. ESHRE 2018 O-007: Estimation of age-dependent decrease in blastocyst euploidy in IVF/ICSI cycles
Geometric mean of the yearly variation: 13,6%
!11
Progressive age-dependent decrease in the probability of having
euploid blastocyst
Courtesy Dr. Sandro Esteves
PROBLEM ?

12. PROBLEM ?

13. PROBLEM ?
Oocyte efficiency + Ovarian aging - INDIA
Iglesias et al. Fertil Steril 2014;102:244-9
SPANISH INDIAN P value
Age 37.5 31.5 <0.0001
AMH (ng/mL) 1.6 2.5 0.03
AFC 9.5 9.9 0.40
Oocytes
Retrieved
8.8 8.8 0.90
Total
Gonadotropin
(IU)
2,420 2,910 <0.001
Indian women: ovarian aging!!!
6-year advancement in ovarian aging

14. PROBLEM ?
Oocyte efficiency + Ovarian aging - INDIA
Maalouf et al. BJOG 2016; doi: 10.1111/1471-0528.14241
United Kingdom (UK) Database
2000 to 2010: 38,709 women
Live Birth Rate and effect of ethnicity
White British White
European
South Asian
India
Mean age 34.4 34.9 32.8
Mean no. Of
oocytes
collected
9.5 10.1 9.9
LIVE BIRTH
RATE *
1 1.04
(0.96-1.13)
0.85
(0.75-0.97)
* coefficient and 95% CI - adjusted for age, cause of infertility and treatment type (IVF or ICSI)
Effect on patient counseling and adaptation of Ovarian Stimulation

15. YES!
SOLUTION???
PROBLEM???
Low oocyte efficiency and ovarian aging

16. SOLUÇÃO?
Get pregnant earlier ?
Ovarian Rejuvenation ?

17. YES!
SOLUTION???
NO!
ALTERNATIVE???
PROBLEM???
Low oocyte efficiency and ovarian aging

18. ALTERNATIVE?
ONE-AND-DONE CONCEPT

19. ALTERNATIVE?
ONE-AND-DONE CONCEPT
Vaughan et al. Fertil Steril 2017; 107:397-404
1-3 oocytes 4-9 oocytes 10-14 oocytes 15-25 oocytes >25 oocytes
15,1
12,210,1
6,62
57,9
53,9
43,9
31
13,3
30,9
37,1
31,5
27,8
12,8
>= 1 LBR cycle 1 - Fresh >= 1 Live Birth all cycles >= 2 Live Birth all cycles

20. ALTERNATIVE?
ONE-AND-DONE CONCEPT
Vaughan et al. Fertil Steril 2017; 107:397-404
1-3 oocytes 4-9 oocytes 10-14 oocytes 15-25 oocytes
12,210,1
6,62
53,9
43,9
31
13,3
37,1
31,5
27,8
12,8
>= 1 LBR cycle 1 - Fresh >= 1 Live Birth all cycles >= 2 Live Birth all cycles
One-and-done concept:
- A single COS to retrieve a maximal
number of oocytes could better serve
couples;
- With improvements in cryopreservation
and freeze-all strategy, it may now be
time to RETHINK mild approaches

21. YES!
SOLUTION???
NO!
ALTERNATIVE???
PROBLEM???
YESMaximize the number of retrieved oocytes per cycle
Low oocyte efficiency and ovarian aging

22. PROBLEM???
Sunkara et al., Hum Reprod 2011; 26:1768-74.
?
400,135 treatment
FRESH CYCLES
Oocyte Number vs. Live Birth

23. PROBLEM???
Oocyte Number vs. Live Birth
Polyzos et al., Fertil Steril 2018; 110:661-670.
5 10 15 20 25 30
10
20
30
40
50
60
70
80
90
100

24. PROBLEM???
Venetis et al., Hum Reprod 2018; doi: 10.1093/humrep/dey342.
A larger oocyte yield is
independently associated with
more euploid embryos

25. PROBLEM???
Labarta et al., BioMed Research International 2017; 2017:5637923.
↑Ovarian Response:↑ number of Euploid Embryos

26. PROBLEM???
Labarta et al., BioMed Research International 2017; 2017:5637923.
P<0.05 P>0.05
1.↑ retrieved oocytes -> ↑ euploid embryos
2. Gonadotropin dose -> NO correlation with Aneuploidy Rate

27. PROBLEM???
Labarta et al., BioMed Research International 2017; 2017:5637923.
Ovarian Sensitivity Index (OSI)
Correlation between gonadotrophins dose
and the number of retrieved oocytes

28. Ovarian Stimulation vs. Embryo Quality
Thus…
- It seems that the problem is not related to the ovarian
stimulation or to the total absolute dose of gonadotropins;
- The problem may be related to THE PATIENT’S PROFILE
PROBLEM???

29. Is the problem related to the patient’s profile?
Wood et al. J Clin Endocrinol Metab 2007; 92:705-713.
PCOS vs Normal Responders
-15 genes involved in the meiotic/
mitotic cell cycle pathway
e x h i b i t e d a l t e r e d m R N A
abundance in PCOS oocytes
PROBLEM???

30. YES!
SOLUTION???
NO!
ALTERNATIVE???
PROBLEM???
YESMaximize the number of retrieved oocytes per cycle
Low oocyte efficiency and ovarian aging

31. ALTERNATIVE???
PROBLEM???
YESMaximize the number of retrieved oocytes per cycle
NO!
OVARIAN STIMULATION AND
EMBRYO QUALITY