Genetics answering Genetics answering reproductive questionsreproductive questions

Senior Lecturer Claudia Bănescu, MD Oana Nechifor

BackgroundBackground

InfertilityInfertility

the failure to conceive following twelve months of unprotected intercourse

BackgroundBackground

! Global infertility range between 8 and 12%, affecting between 50 and 80 million people

! 1/6 affected couples

! social and environmental, physiological and

genetic factors; sexually transmitted diseases (STDs) or reproductive tract infections all around

Africa and Latin America

BackgroundBackground

BackgroundBackground• Genetic causes of infertility :

chromosomal abnormalities chromosomal abnormalities && single gene disorders single gene disorders && phenotypes with multifactorialphenotypes with multifactorial

inheritanceinheritance

• Hypogonadotropic hypogonadism in Prader-Willi, Lawrence-Moon-Biedl, Kallman, Klinefelter's Klinefelter's syndromesyndrome(KS 47,XXY) (KS 47,XXY) - the most common genetic form in males . Live birth prevalence rate of 4.3 to 15.0 per 10,000 live births. KS

- common in azoospermia and severe male factor infertility, followed by Y chromosome terminal deletions (Yq-)Y chromosome terminal deletions (Yq-) and structural structural autosomal autosomal abnormalitiesabnormalities.

severe impairment of spermatogenesis

( Eg. 10% non-obstructive azoospermia, 3%-5% oligozoospermia )

• 15% to 20% 15% to 20% of pregnancies end in spontaneous abortion(SAB)abortion(SAB). 50%50% chromosomal abnormalities incidence in SAB balanced translocation balanced translocation carriers.  In SAB, the majority of chromosomal anomalies (95%) are numerical.

• 7% of couples with at least two SAB balanced chromosome rearrangement in one parent SAB 25% to 50%.

BBloodlood co coagulation agulation protein/protein/PPlatelet latelet

defectsdefects

BackgroundBackground

Confirmed Confirmed pregnancypregnancy

Death of Death of conception product conception product

before wk 20 before wk 20

AAnatomic natomic anomaliesanomalies

SABSABEndocrineEndocrine

abnormalitiesabnormalities

GGenetic/enetic/CChromosomal hromosomal abnormalitiesabnormalities

21.421.4%%

ObjectivesObjectives

Illustrating the findings in cytogenetic investigations conducted on infertile men and women and also on females facing spontaneous abortion (SAB) in the reported cases.

Material and methodMaterial and method

Cross-sectional analysis

Years of 2010 2013

128 people investigated for fertility ailments

55,47% (71) are males and 44,53% (57) are females

Groups of ages 25-30, 30-35, 35-40,

over 40

ResultsResults “At 35 you’re half as fertile as when you were at 25; at 40 you’re half as fertile as when you were 35″

ResultsResults

Robert E. Anderson , M. D. Reproductive Medicine

Age groupsAge groups

ResultsResults

Results SABResults SAB

SAB SAB CountCount

SAB Rate Age

5-10% 25-30

20% 30-35

25% 35-40

33% >40

46,XX,t(2;15)(q31;q25) 46,XY, 9qh+ 45,XY, der(13;14)(q10,q10) 3 F heterozygous for the factor V Leiden gene mutation

Robert E. Anderson ,M. D. Reproductive Medicine

SABSAB

ResultsResults

Cytogenetics Semen analysis

46XY 9qh+ SAB

45XY, der(13;14)(q10,q10)

Oligospermia

47XXY azoospermia

46,XY/47,XXY oligospermia

ResultsResults

Previous studies

Our data

Yq-Yq-

ConclusionsConclusions

• Cytogenetic analysis as part of etiological investigation

! 5% of analyzed couples have had previous SAB

! 1 in 6 couples has infertility ailments

• Identification of a rearrangement in a parent evidence

explanation for the misscarriages

the existent risk for a born anomalous child

the exposure to future SAB

Family undergoing chromosomes testing

receiving appropriate prenatal diagnosis

• Assisted Reproductive Technology and Third Party Assisted ART handful and innovative chance Comprehensive genetic counseling

A REAL OPPORTUNITY TO PARENTA REAL OPPORTUNITY TO PARENT