Reproductive treatments

Question 1

How would you carry out testosterone replacement in.a male not desiring fertility?

Answer 1

Treat Symptoms- loss of early morning erections, libido, decreased energy, shaving
At least 2 low measurements of serum testosterone before 11am.
Investigate the cause of low testosterone.

Question 2

What are the options for testosterone replacement?

Answer 2

Daily Gel (eg Tostran). Care not to contaminate partner.
3 weekly intramuscular injection (eg Sustanon)
3 monthly intramuscular injection (eg Nebido)
Less Common (Implants, oral preparations)

Question 3

What are the safety concerns associated with testosterone replacement?

Answer 3

Increased Haematocrit (risk of hyperviscosity and stroke)
Prostate (Prostate Specific Antigen (PSA) levels)

Question 4

How would you induce sperm production in someone with primary Hypogonadism?

Answer 4

Difficult to treat

Question 5

How would you induce sperm production in somebody with Secondary hypogonadism?

Answer 5

(deficiency of gonadotrophins ie hypogonadotrophic hypogonadism):
Treat with Gonadotrophins (ie LH and FSH) to induce Spermatogenesis

Question 6

How do LH and FSH help Sperm induction?

Answer 6

LH stimulates Leydig cells to increases intratesticular testosterone to much higher levels than in circulation (x100).

FSH stimulates seminiferous tubule development and spermatogenesis

Question 7

What would the treatment be for someone who is desiring fertitlity and has Secondary hypogonadism?

Answer 7

Give hCG injections (which act on LH-receptors)
If no response after 6 months, then add FSH injections.
Simply giving testosterone would lower LH/Fsh and thus spermatogenesis.

Question 8

What are the features of Hypothalamic Amenorrhea?

Answer 8

Low body weight
Excessive exercise 
Stress
Irregular periods
Genetic susceptibility

Question 9

What are the aims of Ovulation induction?

Answer 9

Develop one ovarian follicle

Aim to cause a small increase in FSH

Question 10

What are the risks if you stimulate more than one follicle e?

Answer 10

Multiple pregnancies, risk for mother and baby during pregnancy

Question 11

How would you carry out Ovulation stimulation in somebody with PCOS?

Answer 11

1. Lifestyle / Weight Loss / Metformin
2. Letrozole (Aromatase inhibitor)
3. Clomiphene (Oestradiol receptor modulator)
4. FSH stimulation

Question 12

How does Letrozole work?

Answer 12

Aromatase inhibitor, aromatases converts testosterone to oestradial, so you limit oestradiol. Oestradiol feedbacks negatively on the hypothalamus, reducing LH/FSH. By lowering it you increase GnRH and LH/FSH.

Question 13

How does Clomiphene work?

Answer 13

Oestradiol receptor antagonist. Reduces negative feedback of oestradiol on hypothalamus. increases GnRH & LH/FSH.

Question 14

What are the basics of IVF?

Answer 14

1 - Oocyte retrieval
2 - Fertilisation in vito
    - IVF, Intra-cytoplasmic sperm injection ICSI
3 - Embryo Incubation
4 - Embryo transfer

Question 15

Describe how the first step of IVF?

Answer 15

Give FSH to develop multiple follicles, prevent LH surge to stop premature ovulation. Give LH exposure to mature eggs ( diploid to haploid).

Question 16

How do you prevent a premature rise in FSH?

Answer 16

1 - GnRH Antagonist SHORT protocol, FSH on day 2 GnRH on day 6.
2 - GnRH Agonist LONG protocol, give agonist 7 days before the cycle starts. GnRH needs to be given in a pulsatile manner to stimulate LH, however continuously sly it causes desensitisation.

Question 17

What is the most common hormone used to stimulate Oocyte maturation?

Answer 17

hCG, longer acting than simply LH.

Question 18

What is the timeline for IVF?

Answer 18

Day 2 - FSH
Day 6 - GnRH antagonist
Day 11 - hCG to trigger LH
Day 13 - Oocyte retrieval + Fertilisation
Day 18 - Embryo transfer to endometrium
After 11 days do pregnancy blood test

Question 19

What are the main methods of contraception?

Answer 19

Barrier: male / female condom / diaphragm or cap with spermicide
Combined Oral Contraceptive Pill (OCP)
Progestogen-only Pill (POP)
Long Acting Reversible Contraception (LARC)
Emergency Contraception

Question 20

What are the permanent methods of contraception?

Answer 20

Vasectomy

Female sterilisation

Question 21

What are the positives of Condoms?

Answer 21

Protect against STI’s
Easy to obtain – free from clinics
/ No need to see a healthcare professional
No contra-indications as with some hormonal methods

Question 22

What are some of the negatives of Condoms?

Answer 22

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

Question 23

How does the Oral contraceptive pill work?

Answer 23

Contains oestrogen and progesterone, decrease GnRH, LH & FSH. Progesterone thickens cervical mucus & thinning of endometrial lining.

Question 24

What are the benefits of the OCP?

Answer 24

Easy to take – 
  one pill a day (any time of day)
 Effective
 Doesn’t interrupt sex
 Can take several packets back to back and avoid withdrawal bleeds
 Reduce endometrial and ovarian cancer
 Weight Neutral in 80% 
  (10% gain, 10% lose

Question 25

What are the negatives of the OCP?

Answer 25

It can be difficult to remember No protection against STIs P450 Enzyme Inducers may reduce efficacy Not the best choice during breast feeding

Question 26

What are possible side effects of the OCP?

Answer 26

``` Spotting (bleeding in between periods) Nausea Sore breasts Changes in mood or libido Feeling more hungry (try different OCPs to see which suits best) very rare - blood clots. ```

Question 27

What are some non-contraceptive uses of the OCP?

Answer 27

Helps make periods lighter and less painful (eg endometriosis or period pain or menorrhagia) Withdrawal bleeds will usually be very regular PCOS: help reduce LH and hyperandrogenism

Question 28

What are the positives of the Progesterone only pill?

Answer 28

Works as OCP but less reliably inhibits ovulation Often suitable if can't take oestrogen ``` Easy to take – one pill a day, every day with no break It doesn’t interrupt sex Can help heavy or painful periods Periods may stop (temporarily) Can be used when breastfeeding ```

Question 29

What are some negatives of the Progesterone only pill?

Answer 29

Can be difficult to remember No protection against STIs Shorter acting – needs to be taken at the same time each day

Question 30

What are possible side effects of the progesterone only pill?

Answer 30

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

Question 31

How does the Intra-Uterine Device IUD ie Copper coil work?

Answer 31

mechanically prevent implantation, decrease sperm egg survival. Lasts 5-10yrs. Can cause heavy periods, and 5% can come out especially during first 3months with periods

Question 32

How does the Intra-Uterine System eg Mirena coil work?

Answer 32

Secretes progesterone to thin lining of the womb and thicken cervical mucus (can be used to help with heavy bleeding). Last 3-5yrs.

Question 33

What are the options for emergency contraception?

Answer 33

1. Copper intrauterine device (IUD) most effective can be fitted up to 5 days after unprotected sex (<1% chance of pregnancy) Emergency contraceptive pill: 2. Ulipristal acetate 30 mg (ellaOne) Ulipristal acetate stops progesterone working normally and prevents ovulation. Must be taken within 5 days of unprotected intercourse (earlier better). 3. Levonorgestrel 1.5 mg (Levonelle) least effective (esp if BMI >27 kg/m2) Synthetic Progesterone prevents ovulation (don’t cause abortion). Must be taken within 3 days of unprotected intercourse. Side effects- 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.

Question 34

What are the factors to take into consideration when choosing contraception?

Answer 34

``` 1. Risk of Venous Thromboembolism (VTE) / CVD / Stroke Comorbidities- Avoid OCP if: Migraine with aura (risk of stroke) Smoking (>15/day) + age >35yrs Stroke or CVD history Current Breast cancer Liver Cirrhosis Diabetes with complications eg retinopathy/nephropathy/neuropathy ``` 2. Other conditions that may benefit from OCP eg Menorrhagia / Endometriosis / Fibroids 3. Need for prevention of Sexually Transmitted Infections (STI’s) ``` 4. Concurrent medication — P450 liver enzyme-inducing drugs (eg anti-epileptics, some antibiotics) Teratogenic drugs (eg lithium or warfarin), more effective methods of contraception needed (eg progestogen-only implant, or intrauterine contraception).  ```

Question 35

What are the Risks for Venous thrombo-embolism associated with HRT

Answer 35

Oral oestrogens undergo first pass metabolism in liver Oral >> Increase SHBG, Triglycerides, CRP Transdermal estrogens are safer for VTE risk than oral Avoid oral oestrogens in BMI > 30 kg/m2

Question 36

What are the cancer risks associated with HRT?

Answer 36

Breast Cancer Slight increase only in women on Combined HRT (ie oestrogen AND progesterone) Risk related to duration of treatment and reduces after stopping Continuous worse than Sequential Assess risk in each individual before prescribing Ovarian cancer- Small increase in risk after long-term use. Endometrial Cancer- Must prescribe Progestogens in all women with an endometrium ! Progestogens: synthetic progestins and the natural hormone progesterone.

Question 37

When would you assess HRT efficacy?

Answer 37

Efficacy at 3 months and then annually Unscheduled bleeding is common within first 3 months. Post-menopausal bleeding could indicate endometrial cancer

Question 38

What are the cardiovascular risks associated with HRT?

Answer 38

No increased risk if started before age 60 yrs Increased risk if started 10 years after menopause Possible benefits of oestrogen supplementation in young women e.g. Premature Ovarian Insufficiency (POI) 4. Risk of Stroke (cerebrovascular disease) Small increased risk Oral > transdermal oestrogens Combined > oestrogen only

Question 39

What are the benefits of HRT?

Answer 39

Relief of low oestrogen symptoms | Less osteoporosis related fractures

Question 40

What is the treatment for transgender transition?

Answer 40

Prepubertal Young people – GnRH agonist for pubertal suppression and then sex steroids. Post-treatment regret 1-2% Gender Reassignment surgery after 1-2 yrs of hormonal treatment Masculinising Hormones for Transgender Men: Testosterone (injections, gels) (S/E: Polycythaemia, lower HDL, Obstructive Sleep Apnoea (OSA). No increase in CVD). Progesterone to suppress menstrual bleeding if needed (endometrial hyperplasia 15%) In 1 to 6 months: Balding (depending on your age and family pattern)  Deeper voice / Acne / Increased and coarser facial and body hair Change in the distribution of your body fat Enlargement of the clitoris    Menstrual cycle stops Increased muscle mass and strength

Question 41

What would be the feminising hormones for Transgender women?

Answer 41

1. Estrogen (transdermal, oral, intramuscular) High dose oestrogen eg 4-5mg per day to aim for estradiol levels of 734 pmol/L. (Side Effects: VTE dose-related at 2.6%, high BP, Cardio-Vascular Disease, high Triglycerides, hormone sensitive cancers eg breast cancer, abnormal Liver Function tests 3%) 2. Reduce Testosterone GnRH agonists (induce desensitisation of HPG axis) Ant-Androgen medications (eg Cyproterone acetate, Spironolactone) - Height, voice and Adam’s apple will not change. - Consider Sperm Banking before starting hormone therapy. 1 TO 3 MONTHS: Decrease in sexual desire / function (including erections) / Baldness slows or may reverse 3 TO 6 MONTHS: Softer skin / Change in body fat distribution / Decrease in testicular size / Breast development / tenderness 6 TO 12 MONTHS: Hair may become softer and finer