REPRODUCTIVE TREATMENTS Flashcards by Eric Lee

To which type of patients is testosterone replacement given to?

Men not desiring fertility
Wish to treat loss of early morning erections, libido, decreased energy and shaving

Must have had at least 2 low measurements of serum testosterone before 11am

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How can testosterone replacement carried out?

Daily gel
3 weekly intramuscular injection
3 monthly intramuscular injection
Less common implants, orals

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What do you monitor for the safety of a patient who is taking testosterone replacement?

Haematocrit

Prostate (prostate specific antigen (PSA) levels)

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If a patient with hypogonadism wishes to be fertile and produce sperm, how do you treat?

Primary hypogonadism - difficult

Secondary hypogonadism - give gonadotrophins to induce spermatogenesis

LH stimulates Leydig cells to increase intratesticular testosterone
FSH stimulate seminiferous tubules development and spermatogenesis

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What is the role of LH and FSH in spermatogenesis?

LH - stimulates Leydig cells to increase intratesticular testosterone

FSH - stimulates seminiferous tubule development and spermatogenesis

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What is the aim for ovulation induction and why?

Aim to develop 1 ovarian follicle

If > 1 follicle develop risks multiple pregnancy (twin…) which has risks for mother and baby during pregnancy

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How is ovulation induction carried out in e.g. PCOS?

Lifestyle/weight loss/metformin
Letrozole (aromatase inhibitor)
Clomiphene (oestradiol receptor antagonist)
FSH stimulation (low dose FSH)

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Why is an aromatase inhibitor used in ovulation induction?

Prevents testosterone becoming oestradiol which decreases the negative feedback on hypothalamus and pituitary gland so increased LH and FSH

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Why is an oestradiol receptor antagonist used in ovulation induction?

Decreases the negative feedback on hypothalamus and pituitary gland so increased LH and FSH

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List the 4 main steps of IVF treatment

Oocyte retrieval
Fertilisation in vitro by IVF or intra-cytoplasmic sperm
injection (ICSI)
Embryo incubation
Embryo transfer

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List the steps of oocyte retrieval in IVF

FSH stimulation to induce growth of follicles
(superovulation)
Prevent premature LH surge
LH exposure for egg maturation from diploid (metaphase
1) to haploid (metaphase 2)

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Why must a premature LH surge be prevented in IVF?

Stops premature ovulation so that there will be eggs in the ovary to collect

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What are the 2 ways we use to prevent premature LH surge?

GnRH antagonist protocol (short protocol: day 6-9)

GnRH agonist protocol (long protocol: day -7-9)

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Should you use pulsatile or non-pulsatile GnRH when trying to suppress LH?

Non-pulsatile as it causes desensitisation and after an initial flare LH is inhibited

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List some methods of contraception?

Barrier (condoms, diaphragm/cap with spermicide)
Combined oral contraceptive pill (OCP)
Progestogen-only pill (POP)
Long acting reversible contraception (LARC)
Emergency contraception

Permanent methods:

Vasectomy
Female sterilisation

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What are the positives of condoms?

Protect against STI
Easy to obtain
No contra-indications

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What are the negatives of condoms?

Can interrupt sex
Can reduce sensation
Can interfere with erections
Some skill to use
Two are not better than one

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How does the oral contraceptive pill (OCP) work?

Contains oestrogen and progesterone which:

More -ve feedback so less LH/FSH (anovulation)
Thickens cervical mucus (reduce sperm entering)
Thins endometrial lining (reduces implantation)

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What are the positives of the OCP?

Easy to take (one a day)
Effective
Doesn’t interrupt sex
Can take several packets back to back and avoid
withdrawal bleeds
Reduces endometrial and ovarian cancer
Weight neutral

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What are the negatives of the OCP?

Difficult to remember to take
No protection against STI
Not best choice during breast feeding
P450 enzyme inducers may reduce efficacy
Adverse effects

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What are the possible side effects of the OCP?

Spotting (bleeding in between periods)
Nausea
Sore breasts
Changes in mood/libido
More hungry
Blood clots in legs/lungs (extremely rare)

What are the non-contraceptive uses of the OCP?

Makes periods lighter and less painful
Withdrawal bleeds usually very regular
Reduces LH and hyperandrogenism for PCOS

What are the positives of the progesterone only pill (POP)/”Mini-pill”

Works like OCP but less reliable to inhibit ovulation
Suitable if you can’t take oestrogen
Easy to take
Doesn’t interrupt sex
Helps heavy/painful periods
Periods may stop temporarily
Can be used when breastfeeding

What are the negatives of the progesterone only pill (POP)/”Mini-pill”

Difficult to remember
No protection against STIs
Shorter acting - needs to be taken at same time each
day
Side effects

What are the possible side effects of the progesterone only pill (POP)/"Mini-pill"

``` Irregular bleeding Headaches Sore breasts Changes in mood Changes in sex drive ```

List examples of long-acting reversible contraceptives (LARCs)

Intra-uterine device (IUD) Intra-uterine systems (IUS) Progesterone-only injectable contraceptives/sub-dermal implants

Explain what an IUD is

ie copper coil which mechanically prevents implantation, decreases sperm egg survival. Lasts 5-10 years Can cause heavy periods

Explain what an IUS is

Secretes progesterone to thin lining of the womb and thicken cervical mucus (helps with heavy bleeding) Lasts 3-5 years

What is the most effective emergency contraception?

IUD can be fitted up to 5 days after unprotected sex | < 1% chance of pregnancy

List some emergency contraceptive pills

``` Ulipristal acetate (ellaOne) Levonorgestrel (Levonelle) - least effective ```

How does ulipristal acetate work?

Progesterone antagonist preventing ovulation Must be taken within 5 days of unprotected sex Emergency contraceptive pill

How does levonorgestrel work?

Synthetic progesterone which prevents ovulation | Must be taken within 3 days of unprotected sex

What are the possible side effects of emergency contraceptive pills?

Headache Abdominal pain Nausea Liver P450 enzyme inducer medications make it less effective If vomit within 2-3hrs of taking it, need to take another

Patients with what medical history should avoid the OCP and why?

``` Migraine with aura Smoking + age > 35 years Stroke/CVD history Current breast cancer Liver cirrhosis Diabetes with complications e.g. retinopathy/nephropathy/neuropathy ``` Risk of venous thromboembolism (VTE)/ CVD/Stroke

What should you consider when choosing a contraception for a patient?

Risk of venous thromboembolism (VTE)/ CVD/Stroke Other conditions that may benefit Need to prevent STI? Other current medication

What concurrent medications should cause you to reconsider to a more effective method of cotnraception?

P450 liver enzyme-inducing drugs e.g. anti-epileptics | Teratogenic drugs e.g. lithium, warfarin

What are the risks of HRT?

Venous thrombo-embolism (DVT/PE) Hormone sensitive cancers Increased risk of CVD (if age > 60) Small increased risk of stroke

Why should patients with a BMI > 30 avoid oral oestrogens?

Oral oestrogens undergo first pass metabolism in liver causing increase in SHBG, triglycerides and CRP Increases risk of venous thrombo-embolism Use transdermal oestrogens instead

How is breast cancer risk affected by HRT?

Slight increase only in women with combined HRT | Duration of treatment and continuity increases risk

How is ovarian cancer risk affected by HRT?

Small increase in risk after long-term use

How is endometrial cancer risk affected by HRT?

Must prescribe progestogens in all women with an endometrium Assess HRT safety/efficacy at 3 months and then annually Unscheduled bleeding common in first 3 months

What type of bleeding could indicate endometrial cancer?

Post-menopausal bleeding

What are the hormone sensitive cancers?

Breast cancer Ovarian cancer Endometrial cancer

Which type of HRT (oral or transdermal) (combined/oestrogen only) has a greater risk of stroke?

Oral combined HRT

What increases the risk of CVD when taking HRT?

If started 10 years after menopause

What are the benefits of HRT?

Relief of symptoms of low oestrogen | Less osteoporosis related fractures

How is gender reassignment carried out in prepubertal young people?

GnRH agonist for pubertal suppression and then sex steroids | Gender reassignment surgery after 1-2 years of hormonal treatment

What are the masculinising hormones for transgender men?

Testosterone (injections/gels) | Progesterone to suppress menstrual bleeding if needed

What are the feminising hormones for transgender women?

Oestrogen (transdermal, oral, intramuscular) Hormones which reduce testosterone: - GnRH agonists (induce desensitisation of HPG axis) - Anti-androgen medications e.g. spironolactone

What is the time frame of male to female gender reassignment?

1-3 months: decrease in libido/function, baldness slows/reverses 3-6 months: softer skin, change in body fat distribution, decrease in testicular size, breast development 6-12 months: hair becomes softer and finer

What is the time frame of female to male gender reassignment?

1-6 months: balding, deeper voice, acne, change in distribution of body fat, enlargement of clitoris, menstrual cycle stops, increased muscle mass and strength