Infertility II ( treatments) Flashcards
What would you do to replace testosterone if fertility is not desired
Treat Symptoms- loss of early morning erections, libido, decreased energy, shaving
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)
What investigation must you make before you start testosterone replacement
At least 2 low measurements of serum testosterone before 11am.
Investigate the cause of low testosterone.
What must you monitor while on testosterone replacement
Safety Monitoring:
Increased Haematocrit (risk of hyperviscosity and stroke)
Prostate (Prostate Specific Antigen (PSA) levels)
How do you secondary hypogonadism for males
/ testosterone deficiency with fertility required
Secondary Hypogonadism-
(deficiency of gonadotrophins ie hypogonadotrophic hypogonadism):
Treat with Gonadotrophins (ie LH and FSH) to induce Spermatogenesis.
DON’T GIVE TESTOSTERONE
give hCG injection with act on Lh receptors
LH stimulates Leydig cells to increases intratesticular testosterone to much higher levels than in circulation (x100).
FSH stimulates seminiferous tubule development and spermatogenesis
How do you treat primary hypogonadism in men
you don’t –> difficult to treat
what is PCOS
Cysts on ovaries making to much hormone will cause hyperandrogenism
anterior pituitary makes too much LH, at least double the amount as FSH
excessive LH causes the theca cells to produce excess amounts of androstenedione, way too much for those granulosa cells to convert.
excess androstenedione flows into the blood and some of it gets converted into estrone by aromatase in fat or adipose tissue
estrone, like estradiol, is a member of the estrogen family, and it acts as a negative feedback signal, stopping the anterior pituitary from releasing FSH.
Because LH levels are really high, there’s no LH surge to trigger the dominant follicle to break away from the ovary, so it may remain there, appearing as a cyst, or it might degenerate with the other follicles. Essentially, ovulation does not occur.
What are the symptoms of PCOS
Symptoms can be weight gain, oligomenorrhea , hiruisism , acne
What is a condition linked with PCOS
majority of patients have insulin resistance, it is thought that this contributes to excess LH
How to diagnose PCOS
Rotterdam PCOS diagnostic criteria (2 out of 3)
Oligomenorrhoea or amenorrhoea
Assessed by menstrual frequency <21d or >35d <8-9 cycles per year >90d for any cycle
Clinical evidence of androgen excess
(Hirsutism (Ferriman-Galleway score), acne, alopecia (Ludwig score) or biochemical evidence: raised androgens
Polycystic ovaries ( PCO morphology found on ultrasound)
>12 antral follicles in one ovary . Do not use US until 8y post-menarche (due to high incidence of multi-follicular ovaries at this stage).
What is hypothalamic amenorrhoea
Insufficient energy causes hypothalamus to decrease in function → insufficient energy for ovulation
what are methods to treat PCOS
1) ovulation induction ( fertility related)
2) Non fertility related: progesterone (prevents endometrial cancer), creams, waxing, diet, lifestyle, oral contraceptive (irregular menses), metformin (irregular menses and insulin resistance)
3) OCP to reduced Lh and hyperandrogenism
What is ovulation induction
and why must you only develop 1 follicle
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
How can you restore ovulation to anovulatory PCOS
weightloss/metformin
Letrozole
Clomiphene
fsh stimulation (superovulation
what is the function and mechanism of action of letrozole?
Letrozole : aromatase inhibitor
inhibits the aromatase-mediated conversion of testosterone to oestradiol
levels of oestradiol drop, hence there is less negative feedback exerted on GnRH secretion ( aka GnRH will increase)
Greater GnRH pulsatile release increases FSH and LH levels. FSH is required to stimulate ovaries to grow a follicle.
What is the function and the mechanism of action of clomiphene
Clomiphene: oestradiol receptor modulator ( aka can act as agonist and antagonist)
prevents negative feedback of oestrogen being exerted on hypothalamic-pituitary axis leading to a marked response with increased GnRH and FSH/LH.
describe the process of IVF treatment
1) FSH stimulation (superovulation)
2) Prevent premature LH surge (this reduces premature ovulation) . 2 methods:
GnRH antagonist protocol (short protocol) aka pulistile GnRH – this blocks LH release from gonadotrophs.
Note this can be given in short term to restore ovulation
GnRH agonist protocol (Long protocol) aka continuous GnRH – disrupts the pulsatility of gonadotrophin release and causes desensitization of LH due continuous stimulation (Initial flare is proceeded by LH inhibition).
3) Egg maturation with hcG
4) 2 ways to fertilize in vitro : IVF or ICSI ( sperm injection into egg → used when male factor sperm is not working properly)
5) Embryo incubation
6) Embryo transfer into uterus
what is short protocol GnRH used for in IVF
Prevent premature LH surge (this reduces premature ovulation)
GnRH antagonist protocol (short protocol) aka pulistile GnRH – this blocks LH release from gonadotrophs.
Note this can be given in short term to restore ovulation
what is long protocol GnRH used for in IVF
(Long protocol) aka continuous GnRH – disrupts the pulsatility of gonadotrophin release and causes desensitization of LH due continuous stimulation (Initial flare is proceeded by LH inhibition).
What are the 2 ways to fertilise and egg in vitro
IVF and ICSI ( sperm injection into egg → used when male factor sperm is not working properly)
what is ovarian hyperstimulation
gonadotropin therapy used for ovulation induction may cause ovarian hyperstimulation syndrome, especially in individuals with PCOS
Symptoms range from mild, like abdominal discomfort and distention, enlarged ovaries with multiple cysts, to severe forms with nausea, vomiting, ascites, pleural effusion, hypovolemia and oliguria or anuria.
Critical presentation: signs of end-organ damage - like respiratory distress, acute kidney injury, cardiac arrhythmias and disseminated intravascular coagulation
suggest some methods of 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
Permanent methods:
Vasectomy
Female sterilisation
what are the pros of using 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
what are the consof using barrier contraception
Can interrupt sex Can reduce sensation Can interfere with erections Some skill to use eg correct fit. Two are not better than one
what is the OCP and what does it do
OCP can be oestrogen / progesterone. THis will reduced -ve feedback on the hypo-pit system causes reduced LH/FSH . This will :
Prevent anovulation ( o + prog)
Thicken cervical mucus ( prog only)
Thin endometrial lining to reduce implantation ( prog only)
can be used for non contraceptive uses
what is the Combined oral contraceptive pill
pill with O and prog
what are the pros of taking the OCP
Positives 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)
