MID - Cytogenetic Infertility (Quiz)

I. Identification (10 items):

1. The inability to conceive after one year of unprotected intercourse. Answer: Infertility

2. The absence of sperm in semen. Answer: Azoospermia

3. A significantly low sperm count in semen. Answer: Severe Oligospermia

4. The region on the Y chromosome critical for sperm production, where deletions can cause infertility. Answer: AZF (Azoospermia Factor) region

5. A numerical chromosomal abnormality in males characterized by a 47, XXY karyotype.¹ Answer: Klinefelter’s syndrome

6. A numerical chromosomal abnormality in males characterized by a 47, XYY karyotype.² Answer: 47, XYY syndrome

7. A numerical chromosomal abnormality in females characterized by a 45, X karyotype. Answer: Turner syndrome

8. A type of structural chromosomal abnormality where a segment of a chromosome is inverted. Answer: Inversion

9. A structural chromosomal abnormality involving the exchange of genetic material between non-homologous chromosomes, common in infertile couples. Answer: Robertsonian translocation

10. Very small, unidentified additional chromosomes that can be associated with infertility. Answer: Marker chromosome

II. Multiple Choice (10 items):

11. According to the text, approximately what percentage of couples worldwide experience infertility?

    a) 5-10%

    b) 10-15%

    c) 20-25%

    d) 30-35%

    Answer: b) 10-15%

12. Deletions in which region of the Y chromosome are strongly associated with male infertility?

    a) Short arm

    b) Centromere

    c) AZF region

    d) Telomere

    Answer: c) AZF region

13. Klinefelter’s syndrome (47, XXY) arises due to:

    a) Deletion of a Y chromosome

    b) Duplication of an X chromosome during paternal meiosis

    c) Non-disjunction of the X chromosome during meiosis

    d) Robertsonian translocation involving sex chromosomes

    Answer: c) Non-disjunction of the X chromosome during meiosis

14. Which of the following numerical chromosomal abnormalities in females is often associated with early onset of menopause?

    a) 45, X (Turner syndrome)

    b) 47, XXX

    c) 47, XXY

    d) Trisomy 21

    Answer: b) 47, XXX

15. The most common Robertsonian translocation observed in infertile males is:

    a) t(21q22q)

    b) t(13q14q)

    c) t(14q21q)

    d) t(9p11q13)

    Answer: b) t(13q14q)

16. What is the primary effect of Y chromosome microdeletions on male fertility?

    a) Increased sperm motility

    b) Production of abnormal sperm morphology

    c) Absence or severe reduction in sperm count

    d) Hormonal imbalances affecting libido

    Answer: c) Absence or severe reduction in sperm count

17. Mutations in the CFTR gene can lead to male infertility by causing:

    a) Hormonal imbalance

    b) Obstructive azoospermia due to congenital absence of the vas deferens

    c) Impaired sperm motility

    d) Premature ejaculation

    Answer: b) Obstructive azoospermia due to congenital absence of the vas deferens

18. Which of the following chromosomal abnormalities is characterized by the loss of an X chromosome (45, X) and is a cause of infertility in females?

    a) Klinefelter’s syndrome

    b) 47, XXX

    c) Turner syndrome

    d) Down syndrome

    Answer: c) Turner syndrome

19. Inversions in chromosomes can lead to infertility because they increase the risk of:

    a) Sperm DNA fragmentation

    b) Production of abnormal gametes during meiosis

    c) Hormonal resistance

    d) Blockage in the reproductive tract

    Answer: b) Production of abnormal gametes during meiosis

20. Down syndrome (Trisomy 21) in males typically results in:

    a) Increased fertility

    b) Normal sperm production

    c) Sterility due to spermatogenic arrest

    d) Early puberty

    Answer: c) Sterility due to spermatogenic arrest

III. Fill in the Blanks (10 items):

21. Infertility is defined as the failure to conceive after one year of ____________________ intercourse.³ Answer: unprotected

22. The World Health Organization considers infertility a human ____________________ problem of global concern.⁴ Answer: health

23. Deletions in the ____________________ region on the Y chromosome can lead to azoospermia.⁵ Answer: AZF

24. Males with Klinefelter’s syndrome typically have a karyotype of ____________________. Answer: 47, XXY

25. The 47, XYY syndrome in males arises due to non-disjunction of the ____________________ chromosome in paternal meiosis II. Answer: Y

26. Females with a 47, XXX karyotype may experience an early onset of ____________________ around the age of 30. Answer: menopause

27. Turner syndrome is characterized by a loss of the ____________________ chromosome, resulting in a 45, X karyotype. Answer: X

28. Robertsonian translocations are common ____________________ chromosomal rearrangements seen in the general population.⁶ Answer: structural

29. The most common Robertsonian translocation observed in infertile males involves chromosomes ____________________ and ____________________. Answer: 13, 14

30. Carriers of ____________________ chromosomes are at risk of infertility because of meiotic arrest and instability. Answer: marker

IV. True or False (10 items):

31. Infertility affects approximately 50 to 80 million people worldwide. Answer: True

32. Male infertility is solely caused by genetic factors. Answer: False

33. Deletions in all three sub-regions of the AZF region on the Y chromosome invariably lead to azoospermia. Answer: True

34. Individuals with Klinefelter’s syndrome are typically phenotypically female. Answer: False

35. Males with the 47, XYY karyotype usually have fertility problems.⁷ Answer: False

36. Females with Turner syndrome are typically fertile and can conceive spontaneously. Answer: False

37. Robertsonian translocations always result in infertility in the carriers. Answer: False

38. Balanced reciprocal translocations do not usually affect fertility. Answer: False

39. Mutations in the CFTR gene only affect the respiratory system and not male fertility. Answer: False

40. Cytogenetic analysis is a crucial tool in the diagnosis and management of infertility. Answer: True

V. Situational/Application Questions (5 items):

41. A couple has been trying to conceive for two years without success. The male partner has a very low sperm count (oligospermia). What initial cytogenetic test might be recommended for the male partner and why?

    Answer: A karyotype analysis and Y chromosome microdeletion testing might be recommended to check for numerical or structural chromosomal abnormalities and specific deletions in the AZF region, which are known causes of oligospermia or azoospermia.

42. A female patient is diagnosed with Turner syndrome (45, X). Based on the provided text, what information would you give her regarding her fertility?

    Answer: I would inform her that most females with Turner syndrome are infertile due to a rapid loss of eggs within the ovaries. Spontaneous pregnancies are rare.

43. A male individual is found to have a 47, XXY karyotype (Klinefelter’s syndrome). What potential impact could this have on his fertility?

    Answer: Klinefelter’s syndrome often leads to reduced testosterone levels and impaired sperm production, which can result in infertility.8

44. A couple with no known family history of infertility has experienced multiple miscarriages. What cytogenetic test could be considered for both partners to investigate a possible cause?

    Answer: A karyotype analysis for both partners could be considered to check for balanced chromosomal rearrangements like reciprocal or Robertsonian translocations, which can lead to the production of unbalanced gametes and recurrent miscarriages.

45. A male patient with obstructive azoospermia due to congenital absence of the vas deferens (CAVD) is being evaluated for infertility. What specific gene mutation is often associated with this condition that could be tested for?

    Answer: Mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene are commonly associated with congenital absence of the vas deferens and obstructive azoospermia.9

VI. Essay Questions (3 items):

46. Discuss the role of numerical chromosomal abnormalities in both male and female infertility, providing specific examples from the text.

    Answer: Numerical chromosomal abnormalities, involving an abnormal number of chromosomes, play a significant role in both male and female infertility.10 In males, Klinefelter’s syndrome (47, XXY) is a common cause of infertility due to impaired testicular development and reduced sperm production.11 The presence of an extra X chromosome disrupts the normal hormonal balance required for spermatogenesis. Similarly, the 47, XYY syndrome can sometimes be associated with fertility issues, although often milder.12 In females, Turner syndrome (45, X) is a primary cause of infertility. The loss of one X chromosome leads to the premature depletion of ovarian follicles, resulting in primary ovarian insufficiency and infertility.13 Additionally, females with a 47, XXX karyotype may experience early menopause, affecting their reproductive lifespan.14 These examples highlight how deviations from the normal chromosome number can significantly impact reproductive function in both sexes.

47. Explain how structural chromosomal abnormalities, such as translocations and inversions, can contribute to infertility.

    Answer: Structural chromosomal abnormalities involve alterations in the structure of chromosomes.15 Translocations, particularly reciprocal and Robertsonian translocations, can lead to infertility due to problems during meiosis.16 In a reciprocal translocation, segments of non-homologous chromosomes are exchanged.17 While carriers of balanced translocations may be phenotypically normal, they produce abnormal gametes with duplications or deletions of chromosomal segments during meiosis. When these unbalanced gametes fertilize, they often result in miscarriages or the birth of children with congenital abnormalities. Robertsonian translocations involve the fusion of the long arms of two acrocentric chromosomes.18 Carriers of balanced Robertsonian translocations are also at risk of producing unbalanced gametes, leading to infertility or recurrent pregnancy loss.19 Inversions, where a segment of a chromosome is reversed, can also cause infertility.20 While balanced inversions might not have an immediate impact, they can lead to the formation of loop structures during meiosis for proper pairing.21 Crossovers within these loops can produce recombinant chromosomes with duplications and deletions, resulting in abnormal gametes and potential infertility or miscarriages.

48. Based on the provided text, describe the common genetic causes of infertility in females.

    Answer: The provided text primarily highlights Turner syndrome (45, X) as a significant genetic cause of infertility in females.22 Turner syndrome is characterized by the loss of one X chromosome, leading to several physical features and, most importantly regarding fertility, the premature loss of ovarian follicles. This results in primary ovarian insufficiency, meaning the ovaries do not develop or function properly, leading to a lack of oocytes and thus infertility. The text mentions that spontaneous pregnancies are rare in women with Turner syndrome.23 While the text briefly mentions that most females with Turner syndrome are infertile, it doesn't delve into other specific genetic causes of infertility in females. However, based on general knowledge of cytogenetics and infertility, other potential causes could include other numerical abnormalities like trisomy X (47, XXX) which can be associated with early menopause and thus reduced fertility later in life, as mentioned in the context of the multiple choice questions. The text emphasizes the commonality of infertility in girls with Turner syndrome due to the rapid depletion of eggs within the ovaries.