Fertilisation and Fertility

Question 1

Describe how the polar bodies are formed

Answer 1

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.

Question 2

Where are the polar bodies in relation to the oocyte?

Answer 2

Inside the zona pellucida

Question 3

Liquefaction

Answer 3

The process by which the seminal coagulum breaks down after vaginal insemination

Question 4

Role of the seminal plasma

Answer 4

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.

Question 5

Role of cervical mucus in fertilisation

Answer 5

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.

Question 6

Where are some areas that sperm can wait for an egg?

Answer 6

The crypts of the cervix

The isthmus of the fallopian tube

Question 7

Phagocytosis of sperm

Answer 7

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

Question 8

Induction of the acrosome reaction

Answer 8

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.

Question 9

Capacitation

Answer 9

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.

Question 10

Acrosome

Answer 10

Membranous pouch containing proteinases and other enzymes such as hyaluronidase

Question 11

Partial acrosome reaction

Answer 11

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.

Question 12

Acrosome reaction

Answer 12

Fusion of the acrosomal and plasma membranes of the sperm head, allowing release of acrosomal contents into the environment

Question 13

Peri-implantation window

Answer 13

Time that the egg can survive unfertilised, normally around 24 hours

Question 14

Corona radiata

Answer 14

Layer of tightly packed follicle cells that surrounds the zona pellucida. Sperm must digest through these to make contact with the ZP.

Question 15

ZP3

Answer 15

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

Question 16

Perivitelline space

Answer 16

Gap between the ZP and the oocyte

Question 17

What is the cell membrane of the oocyte called?

Answer 17

The oolemma

Question 18

Cortical reaction

Answer 18

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.

Question 19

Cortical granules

Answer 19

Proteases and beta-hexosaminidase which cleave ZP2 and digest ZP3, linking them together and with ZP1 to make the polyspermy block.

Question 20

Resumption of meiosis upon fertilisation

Answer 20

Calcium rise causes destabilisation of protein complex which help the chromosomes in metaphase II. Loss of this complex allows meiosis to resume.

Question 21

What part of the zygote becomes the placenta?

Answer 21

The trophectoderm

Question 22

What part of the zygote becomes the embryo?

Answer 22

The inner cell mass

Question 23

Nidation

Answer 23

The hatched blastocyst comes into physical contact with the receptive decidua and attaches to it via adhesion molecules

Question 24

Infertility

Answer 24

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

Question 25

Why have the NZ fertility rates fallen to below population replacement level?

Answer 25

People are having smaller families and delaying childbearing

Question 26

How does men's age impact fertility?

Answer 26

With age, there is a decrease in semen volume, sperm motility and sperm morphology

Question 27

3 ways to assess ovarian reserve

Answer 27

Family history of early menopause Antral follicle count using ultrasound AMH blood test

Question 28

Why is AMH testing useful for assessing ovarian reserve?

Answer 28

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.

Question 29

Factors affecting female gamete health

Answer 29

``` Age Mediterranean diet Smoking Alcohol Caffeine Weight Drugs Medication Folic acid and vitamin intake ```

Question 30

Factors affecting male gamete health

Answer 30

``` Age Mediterranean diet Smoking Alcohol Antioxidants Weight Frequent sex Temperature of testes ```

Question 31

Oligomenorrhea

Answer 31

More than 35 days without menstruation

Question 32

Treatment for anovulation

Answer 32

Weight gain or loss Moderate exercise Clomiphene citrate Letrozole

Question 33

Clomiphene citrate

Answer 33

Blocks the action of estradiol on the pituitary, thereby increasing FSH release

Question 34

Letrozole

Answer 34

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

Question 35

Endometriosis diagnosis

Answer 35

Laparoscopy

Question 36

Endometriosis treatment

Answer 36

Laparoscopy Lipiodol flushing IUI and IVF for pregnancy

Question 37

Symptoms of PCOS

Answer 37

``` Irregular/absent periods Subfertility Unwanted hair growth Acne Metabolic syndrome ```

Question 38

Ovarian hyperstimulation syndrome

Answer 38

Overtreatment in women wanting to have children with letrozole leading to overproduction of FSH

Question 39

Semen analysis

Answer 39

Used to check for FSH, chromosomal abnormalities, CFTR mutation, endocrine imbalances e.g. Kallmann's

Question 40

Physical examination for male infertility

Answer 40

Check for varicoeles or abnormal swelling

Question 41

History taking for male infertility

Answer 41

Ask about testicular trauma, mumps, vasectomy, chlamydia, previous surgeries, undescended testes

Question 42

Testicular biopsy

Answer 42

Can biopsy either testicle itself or epididymis | Confirms presence of sperm

Question 43

IVF ovarian stimulation

Answer 43

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

Question 44

PGT-A

Answer 44

Pre-implantation genetic testing for aneuploidy

Question 45

PGT-SR

Answer 45

Pre-implantation genetic testing for structural rearrangements of chromosomes

Question 46

PGT–M

Answer 46

Pre-implantation genetic testing for monogenic disorders (single gene defects)

Question 47

Sperm normal limits

Answer 47

``` 15 M/mL 40% progressive 1.5 mL 39 million sperm in total ejaculate 58% live ```

Question 48

Preimplantation testing

Answer 48

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

Question 49

Which contraceptions can be used for emergency contraception?

Answer 49

The copper IUD due to prevention of implantation | Levonelle – the emergency contraceptive pill

Question 50

Informed consent around contraception

Answer 50

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

Question 51

Contraceptive

Answer 51

The ability to prevent pregnancy via interference with ovulation, fertilisation or implantation

Question 52

Interceptive

Answer 52

An agent which prevents implantation rather than preventing fertilisation

Question 53

UK MEC

Answer 53

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

Question 54

How does the OCP work?

Answer 54

1) Suppresses ovulation 2) Reduces sperm transport in the upper genital tract 3) Alters endometrium, inhibiting implantation 4) Thickens cervical mucus

Question 55

Ginet

Answer 55

Type of OCP with anti-androgen properties | Good for acne but increased risk of DVT

Question 56

Advantages of OCP

Answer 56

``` Cheap Ability to regulate own periods Can make periods lighter and less painful No problems with insertion No evidence of weight gain or depression ```

Question 57

Disadvantages of OCP

Answer 57

Pill free interval carries pregnancy risk Increased blood pressure Risk of DVT/VTE/CVA Relies on patients ability to adhere to medication

Question 58

Danger of the pill free interval

Answer 58

Suppressive effect of oestrogen decreases causing a rise in FSH, which increases the chance of follicular development and ovulation

Question 59

Contraindications of the OCP

Answer 59

``` Focal migraines Smoking status Obese High blood pressure Some epileptic medications ```

Question 60

Protection when starting the OCP

Answer 60

If day 1–5 of cycle, protected straight away | Any later in the cycle, 7 days of other contraception/abstinence required

Question 61

OCP interaction with antibiotics

Answer 61

No interaction with antibiotics except rifampicin

Question 62

The rules of missed pills

Answer 62

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

Question 63

POP

Answer 63

Progesterone only pill Useful if unable to take OCP or breastfeeding Lower failure rate because it suppresses ovulation Unfunded

Question 64

Starting the POP

Answer 64

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

Question 65

Depo Provera

Answer 65

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

Question 66

Jadelle

Answer 66

Slow-releasing progesterone Very effective – failure rate around 0.05% Stops ovulation and prevents implantation

Question 67

Jadelle mechanism of action

Answer 67

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

Question 68

Jadelle disadvantages

Answer 68

Can be visible Bleeding Interactions with enzyme-inducing medication

Question 69

Copper IUD mechanism of action

Answer 69

Copper on stem directly toxic to sperm Induces microscopic reaction in endometrium to prevent implantation (makes it thinner) Makes cervical mucus thicker

Question 70

Complications of CIUD

Answer 70

Can fall out of migrate – both rare

Question 71

Disadvantages of CIUD

Answer 71

Painful upon insertion | Can make periods heavier and more painful

Question 72

Indications of Mirena

Answer 72

Contraception Heavy menstrual bleeding Endometrial protection with hormone replacement therapy

Question 73

Uses of Mirena

Answer 73

Dysmenorrhoea Endometriosis Endometrial hyperplasia

Question 74

Levonelle mechanism of action

Answer 74

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