Infertility Flashcards
Fecundity by age 25, 35, 40
25%
15%
5% respectively
Incidence of infertility
1 in 6 couples (15%)
- primary (no prev pregnancies) in 70%
- secondary in 30%
Cause of anovulatory infertility
Hypogonadotrophic hypogonadism (WHO Type I)
Hypergonadotrophic hypogonadism (WHO Type III)
Endocrine
Causes of hypogonadotrophic hypogonadism
This is failure of the hypothalamus to produce pulsátiles GnRH or failure of the pituitary to produce gonadotrophins:
- hypothalamus- stress, weight loss, excessive exercise, CNS lesions, head injury, irradiation, Kallman’s
- pituitary- surgery or irradiation of anterior pituitary, Sheehan’s syndrome, prolactin- secreting adenomas
Causes of hypergonadotrophic hypogonadism
This is failure of the ovaries to respond to gonadotrophins ie premature ovarian failure.
CAR PIG
Chromosomal- Turners, Swyer
Autoimmune
Radiation/ chemotherapy/ surgery to ovaries/ pelvis
Primary ovarian insufficiency
Infection- mumps oophoritis
Genetic- fragile X, galactosemia
Endocrine causes of anovulation
PCOS (normogonadotrophic)
Hypothyroidism
Adrenal- CAH, Cushing’s, virilising adrenal tumour
Tubal causes of infertility
Infection
- PID (chlamydia most common) affects cilia function
- 1 episode 12% infertility
- 2 episodes 23% infertility
- 3 episodes 54% infertility
- Endometriosis
- due to distorted anatomy/ adhesions
- due to inflammatory response to the presence of endometriotic tissue
- tubal surgery
Uterine causes of infertility
Intrauterine adhesions
- endometritis
- trauma from excessive curettage ie Ashermans
Submucosal fibroids- distorts cavity and/ or tubal/ Ostia obstruction
Congenital uterine anomalies
- canalisation defects (septum) but not unification defects (uni/ bicornuate, didelphys)
Isthmocoele
What is unexplained infertility
Made when all basic investigations are normal.
Significant contributor is age
Accounts for 40% of female infertility, second most common cause of infertility in couples
Up to 60% of couples with unexplained infertility will conceive spontaneously within 3 years
Normal semen analysis
Volume >/= 1.5ml
pH >/= 7.2
Sperm concentration >/= 15 million per ml
Total sperm count >/= 39 million/ ejaculate
Progressive motility >/= 32%
Total motility >/= 40%
Morphology >/= 4% normal forms
Vitality >/= 58% living spermatozoa
Progressive motility is the most predictive
Repeat after 3 months (spermatogenesis cycle is 76 days)
Routine investigations for male factor infertility
Semen analysis
Gonadotrophins- FSH and testosterone
- normal, normal = obstructive cause
- high FSH, low T = complete testicular failure/ hyper- hypo-
- low FSH, low testosterone= hypo- hypo-
Karyotype
Mechanism of infertility with endometriosis
Mild/ moderate disease:
- pro- inflammatory state which may have a toxic effect on gametes, tubal motility and folliculogenesis
- impaired implantation due to local inflammation and defective endometrial receptivity
In severe disease:
- adhesions and endometrioma impair oocyte release, sperm transport and tubal function
- reduced ovarian reserve in endometriomas (through mechanical stretching, toxins such as free irons)
Mode of action of letrozole
Aromatase inhibitor
Reversible binding to CYP450 unit prevents peripheral conversion of testosterone to oestrogen and androstenedione, resulting in reduced negative feedback at the pituitary and increased FSH output
How to take letrozole
2.5mg PO daily on days 3-7 (can go up to 7.5mg/ day)
Check mid- luteal progesterone- >10 means ovulation has occurred
If available, can do a mid- cycle scan to time intercourse
Mode of action of clomiphene
Selective oestrogen receptor modulator (SERM)
Blocks the action of oestradiol on hypothalamus and pituitary gland so that it produces more FSH due to absence of negative feedback
Selective agonist to ovarian receptors and enhances stimulation of FSH and LH receptors on granulosa cells to induce follicular development and ovulation
Anti- oestrogenic effect to vagina, uterus and cervix
How to take clomiphene
50mg po daily from day 2-6, can increase up to 150mg in subsequent doses
Options when no response to ovulation induction with clomiphene or letrozole
Pulsatile GnRH therapy
Administration of recombinant FSH- if no access to GnRH therapy
Ovarian drilling- when monitoring is not possible or when anovulation despite OI
Indications for simple IUI
Obstructive make factor infertility
When sperm has been frozen prior to cancer treatment
When using donor sperm
Indication for stimulated IUI (controlled ovarian stimulation + IUI)
Unexplained infertility
Mild endo
Low sperm concentration or poor sperm motility
If coitus can’t take place- severe sexual dysfunction or HIV/ hepatitis
IVF steps
Stimulation with daily FSH injections for 2 weeks (start 1-2 days after periods), track follicular development by uss
Trigger
- once > 2 follicles are > 16mm
- usually in the form of HCG
- sometimes use GnRH agonist if using antagonist protocol- esp if > 20 follicles and at risk of early OHSS
Egg collection 36 hours after trigger
Fertilisation
- incubate egg + sperm together OR
- ICSI if severe male factor infertility
Embryo transfer day 3-5, single embryo transfer! Placed in uterine cavity under ultrasound guidance
Luteal support by HCG injections or vaginal progesterone
Pathophysiology of OHSS
Hallmark is fluid shift with massive extra vascular exudate accumulation combined with profound intravascular volume depletion and haemoconcentration.
There is increased capillary permeability in response to HCG, leading to third spacing and intravascular dehydration.
Hyperstimulated ovaries release vasoactive products such as VEGF, angiotensin II
there is decreased sodium and osmolslity due to resetting of osmotic thresholds of vasopressin and thirst
Pre- existing risk factors for IVF
Young age <35
Low BMI
PCOS with >24 antral follicles combined
Previous OHSS
High AMH (>3.36)
IVF risk factors for OHSS
Hcg trigger
Super ovulation
High or rapidly rising oestradiol levels before an HCG trigger shot
Multiple pregnancy
Antral follicles >14
Fresh embryo transfer
Prevention of OHSS
Use GnRH agonist instead of HCG as trigger shot
Withhold embryo transfer
Luteal support with progesterone instead of hcg
Metformin use during stimulation for those with PCOS
Single embryo transfer
Cabergoline at the time of trigger reduces the release of VEGF hence reduces risk of OHSS
