Fertilisation and Fertility Flashcards
Describe how the polar bodies are formed
Following the LH surge, meiosis in the primordial follicle resumes from the end of prophase I and the first division is completed, resulting in an oocyte and a polar body. The process then arrests in second metaphase, the state in which it is ovulated. After fertilisation it again resumes and completes the next division, resulting in another polar body.
Where are the polar bodies in relation to the oocyte?
Inside the zona pellucida
Liquefaction
The process by which the seminal coagulum breaks down after vaginal insemination
Role of the seminal plasma
Because the vagina is acidic (around 4.7 pH), sperm motility and survival is inhibited. Seminal plasma buffer the vaginal pH to around 7.2, allowing sperm to become motile.
Role of cervical mucus in fertilisation
Apart from a very short window around the time of ovulation, cervical mucus is thick and hostile to sperm. When it is spinnbarkeit, the cadence of the sperm moving in synchronisation causes swaying of the fibres of the cervical mucous, allowing sufficiently motile sperm to move through. If the sperm is abnormal, it retards the progress of the sperm and thus is an efficient barrier to undesirable sperm.
Where are some areas that sperm can wait for an egg?
The crypts of the cervix
The isthmus of the fallopian tube
Phagocytosis of sperm
Sperm in the female reproductive tract induce an innate immune response causing leukocytosis and phagocytosis of dead or dying sperm
Theory that this allows exposure to paternal antigens, preparing a woman for pregnancy
Induction of the acrosome reaction
Granulosa cells of the egg release progesterone, producing a progesterone gradient that the sperm swim up. Together with ZP3, a calcium influx is triggered, allowing the acrosome reaction to begin.
Capacitation
The removal of inhibitory substances from the sperm, including a loss of cholesterol, leading to sperm hyperactivation. These sperm move faster and more vigorously, facilitating movement through the fallopian tubes and allowing sperm to undergo the acrosome reaction.
Acrosome
Membranous pouch containing proteinases and other enzymes such as hyaluronidase
Partial acrosome reaction
Cumulus oophorus releases progesterone, triggering hyaluronidase release from the acrosome. This digests the basement membrane of the egg, allowing the sperm to squeeze between cumulus cells and contact the zona pellucida.
Acrosome reaction
Fusion of the acrosomal and plasma membranes of the sperm head, allowing release of acrosomal contents into the environment
Peri-implantation window
Time that the egg can survive unfertilised, normally around 24 hours
Corona radiata
Layer of tightly packed follicle cells that surrounds the zona pellucida. Sperm must digest through these to make contact with the ZP.
ZP3
Protein of the zona pellucida which is considered the primary sperm receptor. Contact between this and the sperm ligand for ZP3 induces the complete acrosome reaction
Perivitelline space
Gap between the ZP and the oocyte
What is the cell membrane of the oocyte called?
The oolemma
Cortical reaction
Entry of a sperm into an oocyte causes intracellular calcium release which is followed by regular spikes of calcium in the oocyte, inducing resumption of meiosis. Cortical granules are then released into the perivitelline space, causing crosslinking of ZP proteins and producing the polyspermy block.
Cortical granules
Proteases and beta-hexosaminidase which cleave ZP2 and digest ZP3, linking them together and with ZP1 to make the polyspermy block.
Resumption of meiosis upon fertilisation
Calcium rise causes destabilisation of protein complex which help the chromosomes in metaphase II. Loss of this complex allows meiosis to resume.
What part of the zygote becomes the placenta?
The trophectoderm
What part of the zygote becomes the embryo?
The inner cell mass
Nidation
The hatched blastocyst comes into physical contact with the receptive decidua and attaches to it via adhesion molecules
Infertility
A disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months of more of regular unprotected sexual intercourse
Why have the NZ fertility rates fallen to below population replacement level?
People are having smaller families and delaying childbearing
How does men’s age impact fertility?
With age, there is a decrease in semen volume, sperm motility and sperm morphology
3 ways to assess ovarian reserve
Family history of early menopause
Antral follicle count using ultrasound
AMH blood test
Why is AMH testing useful for assessing ovarian reserve?
AMH is released from granulosa cells of developing follicles, so lots of AMH = lots of follicles.
Also useful for testing for PCOS for the same reason.
Factors affecting female gamete health
Age Mediterranean diet Smoking Alcohol Caffeine Weight Drugs Medication Folic acid and vitamin intake
Factors affecting male gamete health
Age Mediterranean diet Smoking Alcohol Antioxidants Weight Frequent sex Temperature of testes
Oligomenorrhea
More than 35 days without menstruation
Treatment for anovulation
Weight gain or loss
Moderate exercise
Clomiphene citrate
Letrozole
Clomiphene citrate
Blocks the action of estradiol on the pituitary, thereby increasing FSH release
Letrozole
Decreases estradiol production in the ovary, therefore increasing FSH release from the pituitary in the absence of the negative feedback mechanism
Also decreases the incidence of twins
Endometriosis diagnosis
Laparoscopy
Endometriosis treatment
Laparoscopy
Lipiodol flushing
IUI and IVF for pregnancy
Symptoms of PCOS
Irregular/absent periods Subfertility Unwanted hair growth Acne Metabolic syndrome
Ovarian hyperstimulation syndrome
Overtreatment in women wanting to have children with letrozole leading to overproduction of FSH
Semen analysis
Used to check for FSH, chromosomal abnormalities, CFTR mutation, endocrine imbalances e.g. Kallmann’s
Physical examination for male infertility
Check for varicoeles or abnormal swelling
History taking for male infertility
Ask about testicular trauma, mumps, vasectomy, chlamydia, previous surgeries, undescended testes
Testicular biopsy
Can biopsy either testicle itself or epididymis
Confirms presence of sperm
IVF ovarian stimulation
Stimulation by increasing FSH
Control ovulation by preventing it with GnRH antagonists
Trigger ovulation when needed by stimulating ovarian hCG or using a GnRH agonist
Support the corpus luteum by giving progesterone
PGT-A
Pre-implantation genetic testing for aneuploidy
PGT-SR
Pre-implantation genetic testing for structural rearrangements of chromosomes
PGT–M
Pre-implantation genetic testing for monogenic disorders (single gene defects)
Sperm normal limits
15 M/mL 40% progressive 1.5 mL 39 million sperm in total ejaculate 58% live
Preimplantation testing
Performed on embryos produced by IVF
Test women of advanced menstrual age, recurrent miscarriage, multiple failed IVF cycles
Used to select best embryo for transfer
Which contraceptions can be used for emergency contraception?
The copper IUD due to prevention of implantation
Levonelle – the emergency contraceptive pill
Informed consent around contraception
No restriction of prescribing contraception to under 16s without parental consent as long as the assessment of competence is sound i.e., the child should have sufficient understanding and maturity to fully comprehend the proposed treatment
Contraceptive
The ability to prevent pregnancy via interference with ovulation, fertilisation or implantation
Interceptive
An agent which prevents implantation rather than preventing fertilisation
UK MEC
Medical eligibility criteria – evidence based guidance for providers of contraception
MEC 1 –no restriction on use
MEC 2 – Advantages of use of method generally outweighs disadvantages
MEC 3 –Disadvantages of use generally outweigh advantages
MEC 4 –Do not use
How does the OCP work?
1) Suppresses ovulation
2) Reduces sperm transport in the upper genital tract
3) Alters endometrium, inhibiting implantation
4) Thickens cervical mucus
Ginet
Type of OCP with anti-androgen properties
Good for acne but increased risk of DVT
Advantages of OCP
Cheap Ability to regulate own periods Can make periods lighter and less painful No problems with insertion No evidence of weight gain or depression
Disadvantages of OCP
Pill free interval carries pregnancy risk
Increased blood pressure
Risk of DVT/VTE/CVA
Relies on patients ability to adhere to medication
Danger of the pill free interval
Suppressive effect of oestrogen decreases causing a rise in FSH, which increases the chance of follicular development and ovulation
Contraindications of the OCP
Focal migraines Smoking status Obese High blood pressure Some epileptic medications
Protection when starting the OCP
If day 1–5 of cycle, protected straight away
Any later in the cycle, 7 days of other contraception/abstinence required
OCP interaction with antibiotics
No interaction with antibiotics except rifampicin
The rules of missed pills
1) Don’t miss any pills in the first week because ovulation is not suppressed
2) If a pill is missed or more than 12 hours late, 7 day rule applies –ECP if sex has taken place
3) Can miss 2 pills in week 2 because ovulation is suppressed
4) Can miss 2 pills but PFI should be skipped
POP
Progesterone only pill
Useful if unable to take OCP or breastfeeding
Lower failure rate because it suppresses ovulation
Unfunded
Starting the POP
Start up to day 5 of cycle without additional contraception
Any later requires 48 hours additional precautions
1 missed POP or more than 3 hours late requires 48 hours additional precautions
Depo Provera
Centrally switches off FSH causing ovary to become quiescent
Also thickens cervical mucus, making it harder for sperm to move through
Prolonged amenorrhoea, weight gain, delayed return of fertility
Oestrogen free
Jadelle
Slow-releasing progesterone
Very effective – failure rate around 0.05%
Stops ovulation and prevents implantation
Jadelle mechanism of action
1) Prevents endometrium from preparing to accept an egg (progesterone keeps it in constant thin state)
2) Thickens cervical mucus
3) Prevents release of egg by keeping it constantly in progesterone-dominated state
Jadelle disadvantages
Can be visible
Bleeding
Interactions with enzyme-inducing medication
Copper IUD mechanism of action
Copper on stem directly toxic to sperm
Induces microscopic reaction in endometrium to prevent implantation (makes it thinner)
Makes cervical mucus thicker
Complications of CIUD
Can fall out of migrate – both rare
Disadvantages of CIUD
Painful upon insertion
Can make periods heavier and more painful
Indications of Mirena
Contraception
Heavy menstrual bleeding
Endometrial protection with hormone replacement therapy
Uses of Mirena
Dysmenorrhoea
Endometriosis
Endometrial hyperplasia
Levonelle mechanism of action
Effective for up to 72 hours post intercourse but efficacy decreases with time
Postpones ovulation for 5 days, at which time sperm are dead/gone
Ineffective if ovulation has already occurred
