Infertility Flashcards
What is infertility?
A disease of the reproductive system defined by the failure to achieve a clinical pregnancy after ≥12 months of regular unprotected sexual intercourse
What is primary infertility?
When you have not had a live birth previously
What is secondary infertility?
When there has been a live birth in the past 12 months
What are the impacts of infertility on couples?
Psychological: no biological child Impact on child wellbeing Impact on larger family Investigations Treatment
What are the impacts of infertility on society?
Less births
Less tax income
Investigation
Treatment costs
What are pre testicular causes of infertility in males?
Congenital or acquired eg Klinefelter 47 XXY, Y chromosome deletion, HPG, Testosterone, Prolactin
What are testicular causes of infertility in males?
Congenital Cryptorchidism Infections (STDs) Immunological (Antisperm Abs) Vascular (Varicocoele) Trauma/ Surgery Toxins (Chemo/DXT/Drugs/Smoking)
What are post testicular causes of infertility in males?
Congenital (absence of vas deferens in CF) Obstructive azoospermia Erectile dysfunction (retrograde ejaculation, mechanical impairment, psychological) Iatrogenic (vasectomy)
What is cryptorchidism? Where does it commonly happen in the body?
Undescended testes (90% in inguinal canal)
What are causes of infertility in females?
Ovarian causes (40%)- anovulation, corpus luteum insufficiency Tubal causes (30%) - tubulopathy due to infection, trauma, endometriosis Uterine causes (10%) -unfavourable endometrium due to chronic endometriosis, fibroid, adhesions (synechiae), congenital malformation Cervical causes (5%) - ineffective sperm penetration due to chronic cervicitis or immunological (antisperm Abs) Unexplained (10%) Pelvic causes (5%)- endometriosis, adhesions
What is endometriosis? How many women does it affect?
Presence of functioning endometrial tissue outside the uterus
5% of women
(responds to oestrogen)
What are symptoms of endometriosis?
Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
How is endomertriosis treated?
Hormonal (e.g. continuous OCP, prog)
Laparoscopic ablation
Hysterectomy
Bilateral Salpingo-oophorectomy
What are fibroids in infertile women? How many women does it affect?
Benign tumours of the myometrium
Affects 1-20% of pre-menopausal women (increases w age)
Responds to oestrogen
What are symptoms of fibroids?
Usually asymptomatic ↑ Menstrual pain Menstrual irregularities Deep dyspareunia (painful ntercourse) Infertility
How are fibroids treated?
Hormones (e.g. continuous OCP, prog, continuous GnRH agonists)
Hysterectomy
What are LH, FSH and testosterone levels in a male with hyperprolactinemia?
LH-low
FSH-low
Testosterone-low
What are LH, FSH and testosterone levels in a male with Klinefelters (primary testicular failure)?
LH- high
FSH-high
Testosterone-low
What male infertility problems arise due to hypothalamus problems?
Congenital hypogonadotropic hypogonadism (Kallmann syndrome- anosmic or normosmic)
Acquired hypogonadotropic hypogonadism (low BMI, excess exercise, stress)
Hyperprolactinaemia
What are Gnrh, LH, FSH, testosterone levels in infertile males when the problem is in the hypothalamus?
All low
What male infertility problems arise due to anterior pituitary problems?
Hypopituitarism: tumour, Infiltration, Apoplexy, Surgery, Radiation
What are LH, FSH, testosterone levels in infertile males when the problem is in the hypothalamus?
All low
What male infertility problems arise due to gonad problems?
Congenital primary hypogonadism (Klinefelters 47 XXY)
Acquired primary hypogonadism (cryptorchidism, trauma, chemo, radiation)
What are LH, FSH, testosterone levels in infertile males when the problem is in the testes?
LH/FSH high
Testosterone low
What is Kallmann’s syndrome?
Failure of migration of GnRH neurons with olfactory fibres (to the olfactory placode)
How will Kallmann’s syndrome present?
Cryptorchidism Failure of puberty -Lack of testicle development -Micropenis -Primary amenorrhoea Infertility Anosmia
What hormone blocks kisspeptin neurones? How does it do this?
Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
Inhibits kisspeptin release.
Decreases downstream GnRH/LH/FSH/T/Oest
How does hyperprolactinemia present?
Oligo (>35d menses) or amenorrhoea (3-6m no menses)/ Low libido (and other hypogonadal symptoms)/ Infertility/ Osteoporosis
What are the causes of hyperprolactinaemia?
Prolactinoma Pituitary stalk compression Pregnancy and breastfeeding Medications (dopamine antagonists) PCOS Hypothyroidism
What happens to sex chromosomes in Klinefelter’s?
Extra X chromosome (47 XXY)
How does Klinefelter’s present?
Tall stature Low facial and chest hair Infertility (up to 3%) Mildly impaired IQ Breast development Small penis and testes Narrow shoulders Wide hips Low bone density Female like pubes
What should you include when taking history for an infertile man?
Duration, previous children, pubertal milestones, associated symptoms (eg. T deficiency, PRL symptoms, CHH features), medical & surgical history, family history, social history, medications/drugs
How should you examine an infertile man?
BMI, sexual characteristics, testicular volume, epididymal hardness, presence of vas deferens, other endocrine signs, syndromic features, anosmia
How is male infertility investigated
Semen Analysis
Blood tests- LH, FSH, fasting testosterone, SHBG, albumin, iron, karyotyping
Microbiology- urine test, chlamydia swab
Imaging
What is the WHO criteria for normal semen analysis?
Volume: 1.5ml
Sperm Conc. : 15 mil/ml
Total motility: 40%)
What do we look for in a male infertility blood test?
LH, FSH, PRL
Morning Fasting Testosterone
Sex Hormone Binding Globulin (SHBG)
Albumin, Iron studies
Also Pituitary/Thyroid profile
Karyotyping
What do we look for in a male infertility microbiology?
Urine test
Chlamydia swab
What lifestyle changes are advised for infertile males?
Optimise BMI
Smoking cessation
Alcohol reduction/cessation
What treatment is available for infertile males?
Dopamine agonist for hyperPRL
Gonadotrophin treatment for fertility (will also increase testosterone)
Testosterone
(for symptoms if no fertility required – as this requires gonadotrophins)
Surgery
(eg. Micro Testicular Sperm Extraction (micro TESE))
Whats primary amenorrhea?
No period ever and >16 yrs old
Whats secondary amenorrhea?
Irregular periods, start but stop for 3-6 months
What would LH/FSH and oestradiol levels be in premature ovarian insufficiency?
LH-high
FSH-high
Oestradiol-low
What are symptoms of premature ovarian insufficiency (POI)?
Same as menopause
What are causes of POi
Autoimmune, genetic (fragile X or turner’s syndrome), cancer therapy (radio/chemo in past)
What would LH/FSH and oestradiol levels be in anorexia nervosa induced amenorrhea?
LH-low
FSH-low
Oestradiol-low
What are Gnrh, LH, FSH, oestradiol levels in infertile females when the problem arises due to the hypothalamus?
All low
What are LH, FSH, oestradiol levels in infertile females when the problem arises due to the anterior pituitary?
All low
What are LH, FSH, oestradiol levels in infertile females when the problem arises due to the ovary?
LH/FSH high
Oestradiol low
What is the epidemiology of PCOS?
Most common cause of female infertility and most common female endocrine disorder
Affects 5-15% of women of reproductive age
Frequent family history
How is PCOS diagnosed?
2/3 out of:
Oligo/anovulation- assessed by menstrual frequency:
<21d or >35d cycles
<8-9 cycles/y
>90d for any cycle
OR proven by lack of progesterone rise or US
Hyperandrogenism- acne, hirsutism, alopecia, high androgens (testosterone)
Polycystic ovaries:
≥20 follicles OR ≥10ml either ovary on TVUS (8 MHz)
How is PCOS amenorrhea treated?
Oral contraceptive pill
Metformin
How is PCOS increased insulin resistance treated?
Metformin
How is PCOS hirsutism treated?
Creams/wax/laser, anti androgens
How does turners present and in what gender?
Females: Short Low hairline Webbed neck Coarctation of aorta Underdeveloped reproductive tract Brown nevi Short 4th metacarpal Small finger nails Wide spaced nipples Poor breast development Amenorrhea
How should you take a history for an infertile female?
Duration, previous children, pubertal milestones, breastfeeding,
Menstrual History: oligomenorrhoea or 1/20 amenorrhoea, associated symptoms, medical & surgical history, family history, social history, medications/drugs
How should you examine an infertile female?
BMI, sexual characteristics, hyperandrogenism signs, pelvic examination, other endocrine signs, syndromic features, anosmia
What are the main investigations for infertile females?
Blood test
Pregnancy test
Microbiology
Imaging
Describe the difference between Klinefelters, Kallmanns, Turner’s and fragile x syndrome
Klinefelter’s- congenital primary testicular failure, extra x chromosome
Kallmann’s- congenital hypogonadotrophic hypogonadism (due to problems in the pituitary)
Turner’s- congenital female condition where they are partially missing an x chromosome
Fragile X- congenital condition affecting x chromosome leading to developmental problems, intellectual disability etc
What is the most common cause of infertility in a couple?
Female factor (30%)
Male and female factor (30%)
Male factor (30%)
Unknown (10%)
How many couples are affected by infertility?
Affects 1 in 7 couples (14%)
But half will conceive in next 12 months (at 24 months ~7 couples)
What percentage of infertile couples will seep help?
55%
Positive association with socioeconomic status
What are other causes of male infertility outside of the HPG axis?
Androgen receptor deficiency (rare)
Hyper/Hypothyroidism (reduces bioavailable testosterone)
What are GnRH, FSH, LH and T levels in Kallmann syndrome?
Low GnRH (not detectable)
Low FSH/LH
Low T
How is hyperprolactinemia treated?
Dopamine agonist (cabergoline)
Surgery
DXT
What imaging is done for male infertility?
Scrotal US/Doppler
(for varicocoele/obstruction, testicular volume)
MRI Pituitary
(if low LH/FSH or high PRL)
What’s the first thing to check for if a female presents with infertility symptoms?
Check they are not pregnant or breastfeeding
What is amenorrhea?
- No periods for at least 3-6 months.
- or up to 3 periods per year.
What is oligomenorrhea?
- Irregular or Infrequent periods >35 day cycles
- or 4-9 cycles per year.
How do we diagnose primary ovarian insufficiency?
High FSH >25 iU/L (x2 at least 4wks apart
How is hirsuitism assessed?
Ferriman- Gallwey score
How is alopecia assessed?
Ludwig score
What should you not use to assess Polycystic ovaries?
Do not use US until 8y post-menarche (due to high incidence of multi-follicular ovaries at this stage)
How is infertility in PCOS treated?
Clomiphene
Letrozole
IVF
What is a risk with PCOS and how is it treated?
Increase endometrial cancer risk (2-6)
Treat with progesterone cause
What blood tests are done for female infertility?
LH, FSH, PRL
Oestradiol, Androgens
Foll phase 17-OHP, Mid- Luteal Prog
Sex Hormone Binding Globulin (SHBG)
Albumin, Iron studies
Also Pituitary/Thyroid profile
Karyotyping
What type of pregnancy test do we do for female infertility?
Urine or serum HCG
What microbiology tests are done for female infertility?
Urine test
Chlamydia swab
What imaging is done for female infertility?
US (transvaginal)
Hysterosalpingogram
MRI Pituitary
(if low LH/FSH or high PRL)
