Severe seminal alteration: Consequences on embryo and offspring?

Edson Borges Jr.

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http://fertility.com.br/producao-cientifica-2017/

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USA: 1-2%

Europe / Japan: 4%

Denmark – Finland: 6-8%

Brasil: 30.000 IVF-ICSI cycles / year

~ 6,000 children born: ~ 0,2%

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Distribution of ICSI procedures Fertility Medical Group 2005 - 2016

Others 7%

Endometriosis 14%

Idiophatic 8%

Ovarian factor 23% Tubal factor

8%

Male factor 40%

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Sperm quality

Consequences on embryo

518 ICSI cycles

TMSC: normal > 20 millions sptz

Definition: TMSC = volume x conc/ml x % A+B / 100%

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9

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Epididimal spermatozoa

Testicular spermatozoa

EJACULATED SPERMATOZOA

PERCUTANEOUS

EPIDYDIMAL

SPERM

ASPIRATION

MICRO

TESTICULAR

SPERM

EXTRACTION

TESTICULAR

SPERM

. ASPIRATION

. EXTRATION

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219 117

54

4812

0

500

1000

1500

2000

2500

3000

3500

4000

PESA TESA MICRO-TESE EJACULADO

Fertility Medical Group 2010-2015

PESA TESA MICRO-TESE EJACULATE

Cycles (n) 219 117 54 4812

Age ± SD 34.9 ± 4.6 34.8 ± 5.4 32.2 ± 2.7 35.8 ± 4.7

Follicles ± SD 20.4 ± 15.4 18.1 ±11.3 15.9 ± 14.4 15.8 ± 12.4

Oocytes retrieved ± SD 14.2 ± 10.8 13.3 ± 9.3 11.0 ± 11.4 11.0 ± 9.0

Oocytes micromanipulated ± SD 9.8 ± 6.4 8.9 ± 5.1 8.0 ± 6.9 7.8 ± 5.8

Cyc

les

(n)

12

70,8

60,2

74,4 74,5

0

20

40

60

80

PESA TESA MICRO-TESE EJACULADO

Fer

tiliz

atio

n r

ate

(%)

2,1 2,3

1,8

2,2

0

0,5

1

1,5

2

2,5

PESA TESA MICRO-TESE EJACULADO

Em

bry

o t

ran

sfer

P

PESA VS TESA < 0.001

PESA VS MICRO-TESE > 0.05

PESA VS EJACULATE > 0.05

TESA VS MICRO-TESE > 0.05

TESA VS EJACULATE < 0.001

MICRO-TESE VS EJACULAte > 0.05

P

PESA VS TESA > 0.05

PESA VS MICRO-TESE > 0.05

PESA VS EJACULATE > 0.05

TESA VS MICRO-TESE > 0.05

TESA VS EJACULATE > 0.05

MICRO-TESE VS EJACULATE > 0.05

ANOVA

ANOVA

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Fertility Medical Group 2010-2015

32,8 33,8

42,9

34,8

0

10

20

30

40

50

PESA TESA MICRO-TESE EJACULADO

Pre

gn

acy

rate

(%

)

24,8 28.0

38,1

24,9

0

5

10

15

20

25

30

35

40

45

PESA TESA MICRO-TESE EJACULADO

Imp

anta

ion

rat

e (%

)

P

PESA VS TESA > 0.05

PESA VS MICRO-TESE > 0.05

PESA VS EJACULATE > 0.05

TESA VS MICRO-TESE > 0.05

TESA VS EJACUALTE > 0.05

MICRO-TESE VS EJACULATE > 0.05

P

PESA VS TESA > 0.05

PESA VS MICRO-TESE > 0.05

PESA VS EJACULATE > 0.05

TESA VS MICRO-TESE > 0.05

TESA VS EJACUALTE > 0.05

MICRO-TESE VS EJACULATE > 0.05

ANOVA

QUI-QUADADRO

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Fertility Medical Group 2010-2015

13(1):44-50, 2010

Edson Borges Jr., et al1,2

(n=103) (n=171)

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13(1):44-50, 2010

Edson Borges Jr., et al1,2

(n=103) (n=171)

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13(1):44-50, 2010

Edson Borges Jr., et al1,2

(n=103) (n=102)

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13(1):44-50, 2010

Edson Borges Jr., et al1,2

(n=103) (n=102)

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P=0.076

P=0.854

P=0.684

P=0.045

P<0,001

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Awarded by the Society for Assisted Reproductive Technology (SART) as best work presented at the 69th annual meeting of the

American Society of Reproductive Medicine, 2013 (ASRM)

ICSI Failure (IF)

Implantation

Pregnancy

Micarriage

ICSI Failure (IF)

Implantaion

Pregnancy

Male Factor

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IMSI:

Lower incidence of sexual chromosomes aneuploidy (23,5% x 15,0%) OR= 0,57 (0,37-0,90; p= 0,015) Lower incidence of chaotic embryos (27,5% x 18,8%)

OR=0,64 (0,43-0,96; p=0,032) Lower chance of cycle cancellation (11,8 % x 2,5%)

OR=0,26 (0,11-0,62; p=0,001)

Edson Borges Jr., et al1,2

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Messages

The worse is the seminal analysis (TMSC), the worse is the sperm behavior on ART cycles

The non-ejaculated sperm is worse in comparing with the ejaculated in terms of fertilization. But once the oocyte is fertilized, they are as good as the first one

The worse is the testicle histology, the worse is the sperm

retrieved

The selection techniques, to obtain the best sperm, promote better results on ART cycles (the better sperm, the better outcome)

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Sperm quality

Consequences on offspring

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Outcome Overal effect: RR (IC-95%)

Antipartum hemorrhage 2,49 (2,30 a 2,69)

Congenital anomalies 1,67 (1,33 a 2,09)

Hypertension 1,49 (1,39 a 1,59)

Premature rupture of membranes 1,16 (1,07 a 1,26)

Caesarean Section 1,56 (1,51 a 1,60)

Birth weight< 2.500 g 1,65 (1,56 a 1,75)

Birth weight < 1.500 g 1,93 (1,72 a 2,17)

Perinatal mortality 1,87 (1,49 a 2,37)

Delivery at 37 weeks 1,54 (1,47 a 1,62)

Delivery at 32 weeks 1,68 (1,48 a 1,91)

Transfer to NICU 1,58 (1,42 a 1,77)

Gestacional diabetes 1,48 (1,33 a 1,66)

Induction of labour 1,18 (1,10 a 1,28)

Small for gstacional age 1,39 (1,27 a 1,53)

Pandey S, et al. Hum Reprod Update. 2012 Sep-Oct;18(5):485-503.

ART: obstetric and perinatal outcomes

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Birth criteria – Preterm (PT)

1982 – 2012, PUBMED, Cochrane, 65 studies

Fertile x Subfertile (AOR= 1,35)

FIV/ICSI x subfertile (AOR= 1,55)

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334.628 birth and fetal death, 2004-2008

3 groups:

ART: 11.271, subfertile: 6.609, fertile: 316.748

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ART singleton x subfertile: > preterm and low birth weight

(AOR=1,23 – 1,26, respectively)

ART and subferile x fertile: > preterm and low birth weight

(OR= 1,3)

ART children (all treatments) 65 g lighter x Natural conceived pars

ICSI/FIV x Natural conceive: > risk lower birth weight (OR= 1,4) and preterm

delivery (OR= 1,3)

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Overall neonatal health in terms of birth parameters, major anomalies and chromosomal aberrations of children born by the use of non-ejaculated sperm seems reassuring in comparison to the outcome of children born after the use of ejaculated sperm.

Birth Defects

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124.468 children: FIV/ICSI compared with Natural conceived

RR Congenital anomalies: 1,37 (95%; CI: 1,26-1,48)

FIV (46.890) x ICSI (27.754): no difference

(RR: 1,05, 95%; CI: 0,91-1,02)

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Relationship between Fertility and Congenital Malformations The increased risk of congenital birth defects may not be due to the

ART, but rather genetic or environmental factors that link the two outcomes

An increased risk of death due to Congenital Malformations (CM) in

First Degree Relatives (FDR), but not Second DR, of men with lower semen parameters

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Conclusions: There was an increase in imprinting disorders in children conceived though IVF and ICSI

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In human sperm from compromised spermatogenesis, sequence-specific DNA hypomethylation is observed repeatedly.

Transmittance of sperm and oocyte DNA methylation defects is

possible.

ART can induce epigenetic variation that might be transmitted to the next generation.

Messages

Worse obstetric and perinatal outcomes in children conceived after ART

Increase preterm delivery and low birth weight comparing ART x subfertile x fertile children

Neonatal outcome ejaculated x non-ejaculate sperm: no difference

Increase birth defects in ART children Increased risk of death due to Congenital Malformations (CM) in First Degree Relatives (FDR) of men with lower semen parameters Increased risk of Imprinting Disorders in ICSI/IVF children related to compromised spermatogenesis

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