Lectures 17&18 - Assisted reproduction Flashcards
Where does fertilisation occur in the uterus
Ampulla region - the egg turns into a zygote
How many days into development is the embryo in the uterus
5-6
Explain human preimplantation embryo development
1 cell -> 2 cell (early blastocyst) -> 4 cell (expanding blastocyst) -> 8 cell (fully expanded blastocyst) -> morula ( hatching blastocyst)
embryos all enclosed within a glycoprotein coat called Zona Pellucida - prevents the embryo from implanting as it moves along the fallopian tube
When does the embryo begin to change in size
at the expanding blastocyst stage, before this stage the blastomeres become progressivly smaller as the embryo divides through the four cell stage and to the 8 cell stage
What is the last stage of embryonic development that you can see distinct cells within the embryo
8 Cell stage - fully expanded blastocyst
What is the first morphological event of development called? when does it occur
Compaction - occurs at the fully expanded blastocyst stage (8 cells) goes from a pre-compact 8 cell to a compact 8 cell
cells compact down onto one another and you get a morula stage embryo (about 16 cell stage)
Explain the process of embryo compaction
Occurs at 8-cell stage mediated by E-cadherin - member of the Ca2+-dependent cell adhesion molecules
E-cadherin redistributed in each blastomere to being localised to the cell contact sites
Causes cells to flatten and adhere to one another (compacting)
Concurrent onset of cell polarity with loss of microvilli from contact sites
Gap and tight junctional complexes also form - so cells can communicate with each other
How/when does differential division occur in embryo development, what is this process called
Cavitation
when the morula (16 cell) is formed
whereby cells inheriting the apical domain of parental 8-cell blastomeres will form part of the trophectoderm at the 32-cell stage
whereas cells inheriting the basaldomain, will remain on the interior and give rise to the inner cell mass (ICM)
the ICM gives rise to the embryo proper
What is the second morphological event that occurs in preimplantation development?
Cavitation (blastocyst formation)
Explain Cavitation
Blastocyst formation
Results in the first two lineages of development:
Trophectoderm (TE) – gives rise to extraembryonic lineages
Inner cell mass (ICM) – gives rise to the embryo proper
TE is a transporting epithelium responsible for the passage of nutrients and ions into the blastocoel cavity for use by the ICM.
Basal membranes contain the sodium pump (Na+, K+, ATPase). Transports ions across the TE resulting in the
vectorial transport of water into the blastocoel
Tight junctional complex is a necessity – provides impermeable seal allowing fluid to accumulate,
regulates paracellular transport and contributes to a polarisation of the distribution of the Na+, K+, ATPase.
What are statistics on infertility?
Affects between 1 in 6 and 1 in 7 couples in UK around 3.5 million people
Most common reason for women aged 20-45 to visit their GP after pregnancy alone
What are the different types of infertility?
30% male factor
10% uterine
20% tubal
25% ovulatory
25% unexplained
in 40% of cases, disorders are found in both man and woman
NICE 2013
What are the female causes of infertility?
Problems with ovulation:
-polycystic ovarian syndrome
- luteal phase defects
Tubal problems:
- infection
- previous ectopic pregnancy
- congenital abnormality
- endometriosis
- hydrosalpinx
Uterine problems:
- fibroids
- uterine polyps
Age
What are the male causes of infertility?
poor sperm quality
azoospermia
sperm dysfunction
ejaculation disorders
What are ovulation disorders classified into?
- anovulation
- oligoovulation
- luteal phase defects
What are the primary causes of ovulation disorders?
surgical removal of ovary
ovaries damaged radiotherapy/chemotherapy
premature menopause (affects 1-2% <40 years)
congenital defect
Polycystic ovaries
What are the secondary causes of ovulation disorders?
severe stress
recent large gain or loss of weight
tumour
excess prolactin
disturbances in thyroid and adrenal gland
What incidences of female infertility are due to ovulation problems?
25%
Explain the ovulation problem: Luteal phase defect
Defect of progesterone secretion by corpus luteum or defective response of the endometrium to hormonal stimulation
- Results in inadequate endometrium for embryo implantation
Due to:
1) Poor follicle production
2) Premature failure of corpus luteum
3) Failure of uterine lining to respond to progesterone
What is the most common cause of ovulation disorders in women of reproductive age?
Polycystic ovarian syndrome (PCOS)
Explain Polycystic ovarian syndrome (PCOS)
Characterised by many minute follicles in the ovaries and an excess production of androgens.
Associated with weight gain, excessive hair growth, irregular, infrequent or absent periods and infrequent or absent ovulation.
What are the incidences of Polycystic ovarian syndrome (PCOS)
Incidence
90% women with oligomenorrhoea
30% women with amenorrhoea
70% women with anovulation
What are the treatments for Polycystic ovarian syndrome (PCOS)
Lose weight if over weight
Induce ovulation with clomiphene tablets
Controlled ovarian stimulation with FSH and hCG
Surgery
Explain tubal problems
Tubal damage common cause of infertility. Incidence ~20%
Damaged fimbriae prevent movement of oocyte into the Fallopian tube
Adhesions may distort the tube
Tubal blockage prevents the sperm from reaching the oocyte, or prevents the zygote from moving to the uterus, leading to an increased incidence of ectopic pregnancy
what are the causes of tubal problems
- Infection – most common cause
● Previous pelvic infection
● Sexually transmitted diseases eg chlamydia and gonorrhoea
● Intrauterine contraceptive device - can lead to uterine infection, which spreads to Fallopian tubes
● appendicitis, bowel infection
● after termination of pregnancy, miscarriage or delivery -Previous ectopic pregnancy - Congenital abnormality
- Hydrosalpinx – blocked, dilated, fluid filled Fallopian tube usually caused by previous pelvic infection
- Endometriosis
Explain features of endometriosis
Misplaced endometrial tissue outside the uterus
Commonly affects the ovaries and Fallopian tube, less commonly the bowel and bladder
If severe may reduce fertility
Associated with mild, severe or chronic pain during menstruation and sexual intercourse may be painful
Affects up to 10% of women of childbearing age
Explain treatments of endometriosis
Pain relief with NSAIDs
Prevent fluctuation in the woman’s hormone levels to remove the stimulation for growth of the endometriosis eg the oral
contraceptive pill
What are the infertility incidents in uterine problems
generally no problems with getting pregnant, tend to miscarry - incidence for this is 10%
What are the causes for uterine problems?
Fibroids - Benign growths arising from smooth muscle of the uterus
Many are fertile and have no problems maintaining the pregnancy unless fibroids distort the uterine cavity and may prevent implantation
Uterine Polyps - Small grows of endometrial tissue dangling in the uterus may interfere with implantation
Uterine adhesions - may be consequence of infection or surgery may occlude uterine cavity
Congenital problems - absent uterus, hypoplastic uterus, double uterus, uterine septum etc
Explain how female age affects fertility
Reproductive function declines as a woman ages, particularly after 35
Women delay starting a family due to career demands, education, financial stability, suitable partner etc
However, women have a finite number of eggs
Egg quality decreases with age
Chromosomal abnormalities increase in late 30s
Ageing also affects hormone production and ovulation
Higher incidence of miscarriage in women in their late 30s
