Reproductive Treatments Flashcards
If not desiring fertility - male
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.
Testosterone Replacement: 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)
Safety Monitoring:
Increased Haematocrit (risk of hyperviscosity and stroke)
Prostate (Prostate Specific Antigen (PSA) levels)
Desiring fertility - male
Primary Hypogonadism- difficult to treat
Secondary Hypogonadism-
(deficiency of gonadotrophins ie hypogonadotrophic hypogonadism):
Treat with Gonadotrophins (ie LH and FSH) to induce Spermatogenesis
Give hCG injections (which act on LH-receptors)
If no response after 6 months, then add FSH injections.
LH stimulates Leydig cells to increases intratesticular testosterone to much higher levels than in circulation (x100).
FSH stimulates seminiferous tubule development and spermatogenesis.
Polycystic Ovary Syndrome (PCOS) and Hypothalamic Amenorrhoea
PCOS - hyperandrogenism and PCO morphology
HA - low body weight, stress, genetic, excessive exercise
Both have irregular periods
Ovulation induction
Aim to develop one ovarian follicle
If >1 follicle develops, this risks multiple pregnancy (ie Twin / Triplet)
Multiple pregnancy has risks for mother and baby during pregnancy
Ovulation induction methods aim to cause small increase in FSH
Restore Ovulation
- Lifestyle / Weight Loss / Metformin
- Letrozole (Aromatase inhibitor)
- Clomiphene (Oestradiol receptor modulator)
- FSH stimulation
Letrozole
Aromatase inhibitor
Blocks conversion of testosterone to oestradiol
Oestradiol normally causes negative feedback on Hypothalamus and Pituitary Gland
Decreases negative feedback, thus increasing GnRH and increased FSH
Clomiphene
Oestradiol Receptor Antagonist
Decreased negative feedback to hypothalamus and anterior pituitary, thus increased FSH
IVF
Inject FSH to stimulate multiple follicles produced
Fertilisation in vitro naturally by putting sperm with eggs in dish or intracytoplasmic sperm injection where sperm is injected into egg (when male factor is also included)
Embryo incubation
Embryo transfer into uterus
Prevent premature ovulation
Suppress LH surge
Short protocol - GnRH antagonist started day 6, FSH started day 2 of menstruation cycle
Long protocol - GnRH agonist started day -7, FSH started day 2
GnRH is pulsatile, if given continuously there is an initial LH flare but then LH level flattens and inhibition
Induce egg maturation
Expose to LH
From diploid in metaphase I to haploid in metaphase II
Use hCG
Second commonest is GnRH agonist
Contraception methods
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
Vasectomy
Female sterilisation
Condoms (Barrier Contraception)
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
Can interrupt sex Can reduce sensation Can interfere with erections Some skill to use eg correct fit. Two are not better than one
Oral contraceptive pill mechanism
Oestrogen and progesterone negatively feedback to hypothalamus and pituitary - decreasing FSH and LH - anovulation
Progesterone also thicken cervical mucus and thin endometrial lining - reduce implantation
Combined Oral Contraceptive Pill (OCP)
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)
It can be difficult to remember
No protection against STIs
P450 Enzyme Inducers may reduce efficacy
Not the best choice during breast feeding
Possible side effects: Spotting (bleeding in between periods) Nausea Sore breasts Changes in mood or libido Feeling more hungry (try different OCPs to see which suits best)
Extremely rare side effects:
Blood clots in the legs or lungs (2 in 10,000)
Non-contraceptive uses:
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
Progesterone Only Pill (POP)
Works as OCP but less reliably inhibits ovulation
Often suitable if can’ttake 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 usedwhen breastfeeding
Can be difficult to remember
No protection against STIs
Shorter acting – needs to be taken at the same time each day
Possible side effects Irregular bleeding Headaches Sore breasts Changes in mood Changes in sex drive
Long-Acting Reversible Contraceptives (LARC)
Coils are suitable for most women incl Nulliparous (no previous children).
Exclude STI’s and cervical screening up to date before insertion
Prevent implantation of conceptus – important for some religions
Rarely can cause ectopic pregnancy
Can be used as emergency contraception
- Intra-Uterine Device (IUD) ie Copper Coil- 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. - Intra-Uterine Systems (IUS)which secretes progesterone (eg Mirena Coil) to thin lining of the womb and thicken cervical mucus (can be used to help with heavy bleeding). Last 3-5yrs.
- Progestogen-only injectable contraceptives or subdermal implants
Emergency Contraception
Morning After Pill & IUD
- 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 30mg (ellaOne)
Ulipristal acetate stops progesterone working normally and prevents ovulation.
Must be taken within 5 days of unprotected intercourse (earlier better).
- Levonorgestrel 1.5mg (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.
Considerations for Choice of Contraception
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
- Other conditions that may benefit from OCP eg Menorrhagia / Endometriosis / Fibroids
- 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).
Risks of HRT
- Venous Thrombo-embolism: Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
Oral oestrogens undergo first pass metabolism in liver
Oral»_space; Increase SHBG, Triglycerides, CRP
Transdermal estrogens are safer for VTE risk than oral Avoid oral oestrogens in BMI > 30 kg/m2 - Hormone Sensitive Cancers:
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.
Assess HRT Safety / Efficacy at 3 months and then annually
Unscheduled bleeding is common within first 3 months.
Post-menopausal bleeding could indicate endometrial cancer
- Concern about increased risk of Cardiovascular disease
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) - Risk of Stroke (cerebrovascular disease)
Small increased risk
Oral > transdermal oestrogens
Combined > oestrogen only
Benefits of HRT
Relief of symptoms of low oestrogen eg Flushing, disturbed sleep, decreased libido, low mood
Less osteoporosis related fractures - decreased by one third
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
Feminising Hormones for Transgender Women
- Estrogen (transdermal, oral, intramuscular)
High dose oestrogen eg 4-5mg per day to aim for estradiol levels of 734 pmol/L. - Reduce Testosterone
GnRH agonists (induce desensitisation of HPG axis)
Anti-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
Gender does not match assigned sex
Gender non-conforming
when gender non-conforming causes distress
Gender Dysphoria
Gender does not match to traditional binary gender understanding, includes agender, bigender, pangender, gender fluid
Non-binary
POC differential
Hypothalamic amenorrhoea
