This presentation briefs about an important aspect of infertility which deals about genes and its occurrence in future progeny. Genetics of Male & Female infertility which is not always discussed usually until unless a couple doesn't exhibit pregnancy losses or a major cause of infertility. lets read about Genetics of male and female infertility. Happy Reading <3

1. GENETICS OF MALE &
FEMALE INFERTILITY
DR. RAHUL SEN, PHD
CONSULTANT EMBRYOLOGIST

2. INTRODUCTION
• With The development of IVF techniques,
rapid expansion has been seen in investigation
for genetics of male & female infertility
• This allowed at risk couples to take informed
decisions before conception.
• It can be speculated that in about 15% of male
and 10% of female infertile subjects genetic
abnormalities could be present.

3. INFERTILITY

4. ELEMENTS OF INFERTILITY EVALUATION

5. Genetic Basis of Male & Female
Infertility
• Infertility affects 50 million couples world wide
(WHO) and prevalence is rising
• 25 to 30% of couples with Idiopathic infertility are
likely to have a genetic etiology for their
condition
• Genetic causes may be due to
1. Cytogenetic abnormalities
2. Gene defects
3. Epigenetic alterations

6. Why need to find genetic cause of
infertility
• To establish cause & diagnosis
• Personalizing therapy
• Recurrence in next generation

8. PRESENTATION OF CHROMOSOMAL ABNORMALITIES
ANEUPLOIDY, DELETION,
MICRODELETION, DUPLICATION
NORMAL GENE
FUNCTION

9. PRESENTATION OF CHROMOSOMAL
ABNORMALITIES

10. SPECTRUM OF GENETIC
CAUSES OF INFERTILITY
CHROMOSOMAL- SEX CHROMOSOMES, AUTOSOMES
MALE INFERTILITY FEMALE INFERTILITY
NUMERICAL ABNORMALITIES
STRUCTURAL ABNORMALITIES
GENE MUTATIONS & POLYMORPHISMS
EPIGENETIC ERRORS

11. SPECTRUM OF GENETIC TESTING
MALE FEMALE
FOETUS
EMBRYO
PRECONCEPTION
PRE-IMPLANTATION
PRENATAL

12. Why sperm cells are interesting…???
• Almost always in
Excess: not a
limiting factor
• Genetic uniqueness
in each sperm
provides a wide
variety of
phenotype
(Wang J, Fan HC, Behr B, Quake SR. The
Cell. 2012 )
• Spermatogenesis is
a continuous
process, chances of
chromosomal
abberations or
anomalies is also
high.

14. Semen Examination
• Hallmark for fertility evaluation in
male
• Provides more detailed
information on routine basis
• Abnormalities in sperm
production or function, alone or
in combination with other factors,
account for 30–50% of all cases of
infertility outcomes(W.H.O, 2010).

15. SEMEN EXAMINATION
Macroscopic parameters
• Volume
• Appearance
• Color
• Liquefaction
• Viscosity
• pH
Microscopic parameters
• Sperm concentration
• Sperm motility
• Morphology
• Leucocyte concentration
• agglutination

16. Cut off reference values for sperm parameters in
consecutive WHO manuals

17. SEMEN ANALYSIS & PRESENTATION OF
CHROMOSOME ANOMALIES
• OLIGOSPERMIA
- Abnormalities – 2-9%
- Mainly structural abnormalities
• AZOOSPERMIA
- Abnormalities – 2-7%
- Mainly sex chormosome abnormalities
Bonduelle, 2003

19. SPECTRUM OF MALE INFERTILITY

20. GENETIC TESTS IN MALE INFERTILITY

22. INDICATIONS FOR SPERM DNA ASSESSMENT
• Unexplained infertility
• Repeated ART Failures
• Recurrent Pregnancy Losses
• Prediction of ART outcomes
• Assessment of DNA/Genetic Integrity
- Post Chemotherapy
- Advanced Paternal Age

23. DETECTION OF SPERM DNA DAMAGE
Strand breaks in DNA
Strand breaks in DNA
Susceptibility
to
Denaturation

24. UTILITY OF SDF TESTS
• SDF is mainly oxidative stress mediated
• Elevated SDF is associated with infertility, Poor
ART outcomes and recurrent miscarriages
• SDF gives different information than routine
semen analysis and have better prognostic
value
≤ 15% DFI EXCELLENT TO GOOD SPERM DNA INTEGRITY
> 15% TO < 25% GOOD TO FAIR SPERM DNA INEGRITY
≥ 25% TO <50% FAIR TO POOR SPERM DNA INEGRITY
≥ 50% VERY POOR SPERM DNA INEGRITY

25. GENETICS OF MALE INFERTILITY
• Furthermore, a number of genetic disorders may affect
spermatogenesis, but clinical manifestations are so
complex that infertility represents a minor feature.
• Some forms of male infertility characterised by uniform
and permanent morphological and structural
alterations of the entire sperm population (such as
round headed sperm, mini acrosome etc.) are probably
the results of unknown genetic mutations.
• This aspect should be kept in mind during counseling
session with couple who undergoing ART.

26. Female infertility
• Female infertility has also been classified
primarily on clinical criteria, especially
abnormalities of the ovarian function resulting
in abnormal menstrual cycle.
• Even if recurrent fetal loss is not actually a
cause of primary infertility, it has been
included, given its clinical relevance and
frequency of genetic causes in this condition.

28. Follicle Maturation and
Ovulation
Oocytes
~2 million at birth
~40,000 at puberty
~400 ovulated over lifetime
Luteinizing Hormone surge (from
pituitary gland) causes changes in
tissues and within follicle:
• Swelling within follicle due to increased
hyaluronan
• Matrix metalloproteinases degrade
surrounding tissue causing rupture of follicle
Egg and surrounding cells (corona
radiata) ejected into peritoneum
Corona radiata provides bulk to facilitate
capture of egg.

32. • Following the progress of molecular biology, many studies have
been undertaken in recent years to clarify the genetic mechanisms
underlying female reproductive disorders.
• Apart from chromosomal abnormalities, alterations in female
sexual maturation or reproductive function may be caused by
gene defects at various levels.
• Moreover, the possibility of single or multiple gene defects in
common clinical conditions, such as polycistic ovary syndrome
(PCOS) or premature ovarian failure (POF).
• Technical progresses in ART have stimulated research in this field.
As a consequence, some clinical aspects specifically related to
these techniques, such as poor response to ovarian stimulation,
have been investigated as genetically determined.
• Finally, a causal relationship has been established between many
chromosomal abnormalities and the spontaneous early fetal
demise.

34. • The principles that led to prepare these recommendations
reside in the fundamental aims that specialists in this field
should always bear in mind:
(1) the need for a careful diagnosis of the infertility status &
(2) the evaluation of the risk for the child to be born after ART
and the appropriate management of the pregnancy to be
obtained.
• Not to consider all the possible genetic causes of
reproductive disorders, as well as technical aspects of each
diagnostic genetic test.

35. IMPORTANCE OF GENETIC
COUNSELING
• Genetic counseling should be offered to all couples
undergoing ART and it is further strongly
recommended when a genetic anomaly is found in
either one component of the couple. The final
decision whether to have a test should be left to the
patients, and it is the couple’s decision regarding
whether or not to proceed with ART.
• Mutation is predisposing to further expansion of the
repeat in the germ line, at high risk of delivering
abnormal child's

37. • The genomic basis of infertility is very complex and is determined by many
factors.
• These factors can influence either at levels of gamete, organ, physiology or at
embryo development stage.