Infertility Flashcards
What are the requirements for fertility?
- production of normal sperm
- production of normal egg
- sperm traverse female tract to reach the egg - capacitation - time constraints
- sperm penetrate and fertilise the oocyte
- implantation of the embryo into the uterus
- normal pregnancy
What is the definition of the following:
- fertility
- fecundability
- fecundity
Fertility = measure of the actual outcome of the reproductive process - number of children born to an individual/couple Fecundability = probability of conceiving each month - the monthly chance of pregnancy, or monthly fertility rate, either for an individual (measured over time) or for a population (the number of conceptions occurring in one month) Fecundity = measure of ability to conceive AND produce a live birth
What is the definition of the following:
- infertility
- subfertility
Infertility = the inability to concede after a period of unprotected intercourse or the inability to carry a pregnancy to term Subfertility = a state of reduced fertility
How does NICE define infertility?
failing to get pregnant after two years of regular unprotected sex
What are the 5 female factors of infertility?
ovulatory disorders tubal damage endometriosis uterine abnormalities implantation, growth and development
What are the methods of diagnosing the causes of female infertility?
some by blood analysis (hormonal)
some by laparoscopy
hysterosalpingogram
What are 5 ovulation disorders?
Absent cycles Idiopathic ovarian failure Polycystic ovarian syndrome Anovulatory cycles - endocrinologically normal Abbreviated luteal following
Describe absent cycles
Secondary amenorhoea
Oligoammerhoea
Anovulatory cycles
- associated with stress, obesity, strenuous exercise, anorexia nervosa, drug use
- possible failure of maturation of neuroendocrine system at puberty
Describe idiopathic ovarian failure
- gonadotrophin secretion is normal but is insufficient to support a normal cycle
Describe PCOS
- associated with increased LH and ?androgen (mild increase in follicular phase)
Describe anovulatory cycles - endorcrinologically normal
luteinised unruptured follicle syndrome - eggs deficient
Describe abbreviated luteal phase
decrease progesterone –> poor luteinisation
What are the two major disorders of the female tract?
tubal obstruction
endometriosis
What can cause tubal obstruction?
What are its consequences?
- usually secondary consequences of pelvic infection
- increased incidence after STDs e.g. gonorrhoea.. chlamydia and tuberculosis
- post-abortal or post-pregnancy sepsis
- infection –> impaired oocyte and sperm transport due to loss of cilia on intraluminal cells and scarring –» adhesions
Describe endometriosis
endometrial tissue growth escalates in ectopic sites - oviduct, ovary or peritoneal cavity –> scarring/adhesions
What are the 4 maternal problems of infertile?
cervical incompetence
implantation defects (ectopic)
autoimmune e.g. lupus
immunological incompatibility - ABO or Rhesus blood group loci
What is the definition of a biochemical pregnancy?
What is the definition of a clinical pregnancy?
- tested by presence of hCG in blood and urine 18-30 days after the initiation of the last period
- ultrasound @ 5 weeks, foetal heart @ 7 heart
What % of conceptions lead to a live birth?
15-20%
What % of pregnancies are chromosomal abnormal?
10%
What are the 3 types of chromosomal abnormalities?
Translocations
Errors of policy = deletions or duplications of a complete set of haploid chromosomes
Errors of chromosome number or ‘somy’ = loss or gain of a single chromosome
What are the 5 male disorders that cause infertility?
- production of spermatozoa
- transport of spermatozoa
- transmission of spermatozoa
- sperm function in the female tract
- fertilisation and events after
What are the 5 goals in evaluation of the infertile male?
- identify potential correctable conditions e.g. ductal obstruction or hypogonadotrophic hypogonadism
- identify potentially irreversible conditions requiring assisted reproductive technique using sperm of the male partner
- identify irreversible conditions for which donor insemination or adoption are the possible options
- identify life threatening conditions that may underlie the infertility e.g. testicular cancer, pituitary tumours
- identify genetic abnormalities that may affect the health of the offspring if assisted reproductive techniques are to be employed
What is involved screening/diagnosis of male infertily
- reproductive history
- 2 semen analyses - one month apart
- a few via blood analyses
- many we cannot diagnose
What is involved in the examination of the male?
- general e.g. weight, BO, urinalysis
- secondary sexual characteristics
- signs of endocrine disease
- gynaecomastia
- abdominal examination
- genital examination
- digital PR
When might an endocrine evaluation be required?
- if abnormally low sperm concentration especially if <5million /ml
- impaired social function
- other clinical findings suggestive of a specific endocrinopathy
Ejaculate gradings: Define the following: - normozoospermic - oligozoospermic - asthenozoospermic - teratozoospermic - oligoasthenoteratozoospermic OATs
- normozoospermic = >15 million/ml, >32% rapid forward progressive motility and >4% normal morphology
- oligozoospermic = <15 million /ml
- asthenozoospermic = <32% rapid and medium progressive motility
- teratozoospermic = <4% spermatozoa with normal morphology
- oligoasthenoteratozoospermic = low count, low motility, abnormal morphology
What are the 4 categories of causes of failure in production of sperm?
Congential testicular deficiency
e.g. Kilnfelter, Y chromosome deletions
Cryptorchidism
- reduced spermatogenesis, increased TC risk
Acquired
e.g. trauma (testis torsion), orchitis (mumps)
Endocrine disorders
What clinical tests can be performed on semen and sperm?
- leucocytes in smell, >1 million/ml needs investigation and maybe treatment
- computer aided sperm analysis CASA
- sperm viability tests HOS test
- sperm vitality tests EN test
- antisperm antibodies
What are the 6 non-standard tests of sperm function?
DNA damage
Aneuploidy
Cervial mucus penetration and the post coital test
Hemizona assay
Acrosome reaction
Zona-free hamster egg sperm penetration assay
What are the 2 causes of failure in transmission?
- erectile dysfunction
- ejaculatory dysfunction e.g. retrograde ejaculation or defects of accessory sex glands
Describe the process of normal ejaculation
- contraction of musculature of prostate, semolina vesicles and vas deferent –> seminal fluid and sperm –> urethra
- under sympathetic nerve control
- contraction of uterthral and pelvic floor musculature –> ejaculation
- vesicular urethral sphincter closes bladder neck
Describe retrograde ejaculation
- incompetence of urethral sphincter
- ejaculation into the bladder the path of least resistance
- associated with diabetes, post-traumatic paraplegia, post bladder-neck surgery
- ejaculate volume nil or low
- confirmation in urine
What are the indications for post-ejaculatory urine analysis?
- low volume ejaculate <1ml
- absent ejaculate (aspermia)
- avoid if CBAVD/hypogonadism features
What are the causes of low volume/ no ejaculate?
retrograde ejaculation
lack of emission
ejaculatory duct obstruction
What are the causes of total failure in transport?
Post infectious
- bilateral epidydimal/vas occulusion
Congential bilateral absence of vas deferens
- CBAVD
Azoospermic semen samples - obstructive azoospermia
What are further diagnoses via imaging of male genitalia?
- trans rectal scale ot rule out ejaculatory duct obstruction
- done in azoo/oligospermic with low volume ejaculate and palpable vasa
- scrotal ultrasound if examination is difficult
- if testicular mass is suspected
What are the indications for genetic testing?
- genetic abnormalities may cause infertility by affected sperm production or sperm transport
- men with non-obstructive azoospermic or oligozoospermia
What are the chromosomal disorders that could cause male infertility?
Klinefeletrs, translocations, inversions, Y chromosome micro deletion
Describe CBAVD
linked to CFTR gene mutation on chromosome 7
Improper development of vas deferens
Can occur even when heterozygous for CFTR mutations
What are the 5 post fertilisation processes?
- centriole fusion (spindle formation)
- chromatin decondensation
- protamine exchange
- pronuclear fusion
- activation fo genes for placenta formation
What are the characteristics of unexplained infertility?
- normal frequency and distribution of unprotected intercourse
- no obstructions or malformations in female or male genital tracts
- normal follicle growth, maturation and ovulation; no signs of ongoing inflammatory reactions
- normal concentration of motile spermatozoa, no anti-sperm antibodies or other sings of ongoing inflammatory reaction
What are the assisted reproduction techniques and what are the barriers that they overcome?
intercourse or cerval insemination ------ cervial canal with mucus ----- IUI ----- uterotubal junction ----- GIFT/ZIFT/IVF ----- cumulus oophorus and ZP ----- SUZI ----- cell membrane ----- ICSI