Infertility and assisted reproductive technologies Flashcards
Reasons for the global decline in fertility rate
increased access to education
lower child mortality
increased cost of raising children
exposure to chemicals/hormones interfering with spermatogenesis
could be differences in counting assays
Oligozoospermia
low sperm count
occurs in 1/20 of males
accounts for 1/3 of difficulties
Asthenozoospermia
low sperm mobility
sperm movement impeded so they can’t reach egg
Teratozoospermia
abnormal sperm
may have an unusual shape
harder to move + fertilise
Azoospermia
no sperm
Possible problems with sperm production
varicoceles
undescended testes
chromosomal abnormalities
hormonal problems
lifestyle
Possible problems with sperm transport
infection
tube blockages
tumours
congenital absence of vas deferens
Possible problems with sexual dysfunction
retrograde ejaculation
spinal cord injury
prostate surgery
medicines
Fecundity
likelihood of conception
drops between 30-40 and 40-45
Varicoceles
most common on left side
when blood flows backwards down internal spermatic vein
causes dilation in vein of testes
How does varicoceles cuase infertility?
complex and multifactorial reasons
increases ROS is a key factor
Problems with oogenesis + ovulation
age decreased ovarian reserve + decline in quality
hormone imbalances
over/under active thyroid
premature ovarian failure
genetic causes
Problems with oocyte/zygote transport and implantation
tubal damage- infection or ectopic pregnancy
endometriosis
fibroids
surgical damage
pelvic inflammatory disease
Problems with pregnancy
chromosomal abnormalities
structural issues with uterus
autoimmune condition
lifestyle factors
Polycystic ovarian syndrome
most common endocrine disorder in females of reproductive age
associated with absent/irregular menstrual cycles
What is PCOS caused by?
imbalance in HPG axis
too much GnRH produced
How does increased GnRH cause polycystic ovarian morphology?
increased levels of LH
thecal cells expand + produce androgens but granulosa cells don’t due to lack of FSH in comparison
ovaries become full of half developed oocytes
What other effects does PCOS have?
higher testosterone- impacts insulin
hyperinsulinemia
impact on liver enzyme production
Diagnosis of infertility in males
semen analysis
then hormone analysis
Diagnosis of female infertility
blood hormone analysis
Assisted reproductive technologies
used to treat infertility and usually involves treatments where gametes are handled outside the body
IVF
in vitro fertilisation
mature eggs removed and fertilised in vitro before reinsertion into uterus
IVM
in vivo maturation
oocytes collected at antral phase and cultured in vivo in presence of FSH + other factors
ICSI
intra-cytoplasmic sperm injection
sperm/spermatids injected directly into egg cytoplasm
CT
cytoplasmic transfer
giving infertile women’s oocytes a boost with donor oocytes
mixed or heteroplasmic population of mitochondrial DNA
banned due to developmental worries
GIFT
gamete intra-fallopian transfer
eggs+ sperm combined in vitro and immediately inserted into fallopian tube through abdomen incision
ZIFT
zygote intra-fallopian transfer
same as GIFT but wait until fertilisation occurs
NT
nuclear transfer
What is the benefit of IVM?
women can avoid use of drugs
important if vulnerable to ovarian hyperstimulation syndrome
Why does IVF require fertility drugs?
suppression of HPG axis + natural cycle
stimulation of oocyte production by ovaries
suppression of ovulation
also addition of sperm capacitation factors
Stages of IVF treatment
ovarian hyperstimulation → egg retrieval → sperm preparation → co-incubation → embryo transfer → pregnancy
Benefits of ICSI
bypasses normal fertilisation + allows use of non-motile sperm
successful procedure
possibility for azoospermic patients if late stage spermatids used instead
What are the benefits of GIFT?
fertilisation happens inside the body + embryo transplants naturally
can be important for religious reasons
Methods of cyropreservation
slow freezing- traditional
vitrification- use of high initial cryoprotectants and ultra rapid cooling
Ethical and legal considerations for cryopreservation
unclaimed embryos
couples breaking up
death of partner
Mitochondrial transfer
similar to CT
aimed at people who have a high risk of passing on debilitating/fatal genetic diseases to their children
MT techniques
spindle transfer
pronuclear transfer
polar body transfer
Spindle transfer
metaphase II spindle removed from both of the eggs
patient chromosomes are inserted into the egg
fertilisation occurs and embryo forms
Pronuclear transfer
patients oocytes are fertilised
pronulcei are removed + transferred to enculceated egg with normal mitochondria
Problems with mitochondrial transfer
mutated mitochondria may gradually increase and reintroduce disease
Somatic cell nuclear transfer
similar to mitochondrial transfer
no recombination of chromosomes
associated with much higher levels of abnormalities/illness
Therapeutic cloning
embryo created using SCNT → pluripotent ESCs are harvested from inner cell mass of blastocyst → can differentiate in vitro into specific lineage