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Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR FLUID AND EMBRYO QUALITY IN PATIENTS WITH ENDOMETRIOSIS SUBMITTED TO IVF CYCLES Cunha- Filho JS 1 , Bezerra G 1 , Olsen P 1 , Souza CAB 1 , Chapon R 1 , Passos MP 1 , Goidanich MC 1 , Genro V 2 1 UFRGS, Porto Alegre , Brazil, FIPE/HCPA, Porto Alegre , Brazil 2 HCPA, Porto Alegre , Brazil

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Page 1: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

Porto Alegre, dezembro de 2014.

ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN

FOLLICULAR FLUID AND EMBRYO QUALITY IN PATIENTS WITH ENDOMETRIOSIS SUBMITTED TO IVF CYCLES

Cunha-Filho JS1, Bezerra G1, Olsen P1, Souza CAB1, Chapon R1, Passos MP1, Goidanich MC1, Genro V2

1UFRGS, Porto Alegre, Brazil, FIPE/HCPA, Porto Alegre, Brazil 2HCPA, Porto Alegre, Brazil

Page 2: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

Endometriosis and Infertility

•  20-40% infertility associated endometriosis

•  Several mechanisms: oocyte incompetence, LH SNP, ovarian reserve and IVF results

Fertil Steril, 2008; JARG, 2015; BJOG, 2013

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BJOG, 2013

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Page 5: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

Elisa SA, et. al., 1990. Fuzzi B, et al., 2002.

Fanchin R, et al., 2007.

immunomodulation

Gestacional tolerance

PREGNANCY

Endometrial receptivity

S HLA-G Human Reproduction

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Page 7: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR
Page 8: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

RBM Online, 2009

Page 9: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

sHLA-G and FF

Yonsei Med J 52(6):967-971, 2011

Page 10: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

Rationale

•  Endometriosis is associated to infertility •  Endometriosis is an immunological

disease •  Endometriosis is associated to lower IR

after IVF •  And about s-HLAG in the FF as a marker

for oocyte competence?

Page 11: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

Objective 1.  Embryo Score

2.  Follicular fluid S-HLAG

Endometriosis x control

Page 12: ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN … · Porto Alegre, dezembro de 2014. ASSOCIATION BETWEEN THE CONCENTRATION OF HUMAN LEUKOCYTE ANTIGENS-G (HLA-G) MEASURED IN FOLLICULAR

73 IVF patients Less than 39y Endometriosis group vs control (tubal/male) sHLA-G were measured by ELISA the in folicullar fluid from these women undergoing ovulation induction for IVF (pool of FF). Embryo quality was classified according to the Graduated Embryo Score (GES) criteria.

Methods

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Ethics

! IRB # 572.334

Statistics

!  qui-square, t-student or Mann-Whitney-U

! Correlations: Spearman

! Multivariable (logistic regression)

! P < 5%

! Power calculation (sample size): 60 patients

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Results

EDT (n=32)

Control (n=41)

P

Age (y) 32.8±2.9 31.5±3.5 0.085 FSH dose (IU)

2483±890 2284±905 0.354

# oocytes 6±0.8 8±0.7 0.037 # embryos 3±0.6 3±0.4 0.540 Mean TE score 71±23 68±28 0.608 # TE 1.6±0.9 1.6±0.6 0.922 Clinical Pregnancy

31% 34% 0.808

S-HLA-G positive

21% 27% 0.626

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0

1

2

3

4

5

6

EDT Control

Results sHLA-G

P=0.57

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We found a significant association between age and total oocytes (r = -0.31, p = 0.009) and other study variables: anti-Müllerian hormone (AMH) and age (r = -0.38; p = 0.003) and between AMH and total oocytes (r = 0.53; p <0.05)

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Logistic regression (forward stepwise model)

# oocytes was associated to EDT (P=0.044) sHLA-G and embryo score were refuted

Results

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Patients with endometriosis did not present an altered follicular fluid sHLA-G compared to non endometriosis. Furthermore, It is still controversial use of sHLA-G in FF as a prognostic marker of oocyte/embryo quality.

Conclusion

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•  ART procedure (ICSI x IVF) •  Endometriosis (I-IV) , (peritoneal, ovarian, deep) •  FF Pool or single •  Culture media •  ELISA kit (9 HLA-G types) •  Methodology (OD)

Drawbacks