Infertility Flashcards
What is infertility?
failure to achieve a clinical pregnancy after ≥12 months of regular unprotected sexual intercourse
What is primary infertility?
have not had a live birth previously
What is secondary infertility?
have had a live birth >12 months previously
How common is infertility?
Affects 1 in 7 of couples.
half will conceive within the next 12 months
55% will seek help, positive association with socio-economic status
What is the most common cause of infertility in a couple?
Male, Female and combination factors.
What are the pre-testicular causes of infertitility?
Congenital & Acquired Endocrinopathies
Klinefelters 47XXY
Y chromosome deletion
HPG, T, PRL
What are the testicular causes of infertility?
(Congenital)
Cryptorchidism
Infection STDs
Immunological Antisperm Abs
Vascular Varicocoele
Trauma/Surgery
Toxins
Chemo/DXT/Drugs/SmokingWhat are the post testicular causes of infertility?
Congenital Absence of vas deferens in CF
Obstructive Azoospermia
Erectile Dysfunction Retrograde Ejaculation Mechanical Impairment Psychological
Iatrogenic Vasectomy
What is cryptorchidism?
Undescended testis (90% in inguinal canal)
What are the ovarian causes of infertility?
40%
- Anovulation (Endo)
- Corpus luteum insufficiency
What are the tubal causes of infertility?
30% Tubopathy due: -Infection -Endometriosis -Trauma
What are the Uterine causes of infertility?
10% Unfavourable endometrium due: -Chronic endometritis (TB) -Fibroid -Adhesions (Synechiae) -Congenital malformation
What are the cervical causes of infertility?
5%
Ineffective sperm penetration due:
-Chronic cervicitis
-Immunological (antisperm Ab)
What are the pelvic causes of infertility?
- Endometriosis
- Adhesions
What percentage of infertility is unexplained?
10%
What is endometriosis?
Presence of functioning endometrial tissue outside the uterus
- 5% of women
- Responds to oestrogen
What are the symptoms of endometriosis?
↑ Menstrual pain
Menstrual irregularities
Deep dyspareunia
Infertility
What is the treatment for endometriosis?
Hormonal (eg continuous OCP, prog)
Laparascopic ablation
Hysterectomy
Bilateral Salpingo-oophorectomy
What are Fibroids?
Benign tumours of the myometrium
- 1-20% of pre-menopausal women (increases w age)
- Responds to oestrogen
What are the symptoms of Fibroids?
Usually asymptomatic ↑ Menstrual pain Menstrual irregularities Deep dyspareunia Infertility
What is the treatment for Fibroids?
Hormonal (eg continuous OCP, prog, continuous GnRH agonists)
Hysterectomy
What are 2 non-endocrine causes of female infertility?
Fibroids, Endometriosis
Describe the HPG axis in regards to fertility
Kisspeptin neurons secrete Kisspeptin that activate kisspeptin receptors on GnRh neurons. GnRh neurons secrete GnRh in local circulation that arrive at Gonadotrophs in the anterior pituitary, which are activated to produce LH &FSH, these pass to the gonads stimulating testosterone/oestrogen secretion. Negative feedback loop.
What would happen to LH/FSH/T in hyperprolactinaemia?
All down
What pattern would you see for LH/FSH/T in primary testicular failure e.g. Klinefelters Syndrome?
LH/FSH increase
T down
What can shut down your hypothalamus?
Congenital Hypogonadotrophic Hypogonadism
-Anosmic (Kallmann Syndrome) or NormosmicAcquired Hypogonadotrophic Hypogonadism
-Low BMI, XS exercise, Stress
Hyperprolactinaemia
What are Pituitary causes for infertility?
Hypopituitarism
-Tumour, Infiltration, Apoplexy, Surgery, Radiation
What are gonadic causes for infertility?
Congenital Primary Hypogonadism
- Klinefelters 47XXY
Acquired Primary Hypogonadism
- Cryptorchidism, Trauma, Chemo, Radiation
What are some other causes of male infertility?
Androgen receptor deficiency - Rare
Hyper/Hypothyroidism reduction in bioavailable testosterone.
What is Kallmann’s syndrome?
Failure of migration of GnRH neurons.
Hypogonadotrophic
Hypogonadism
Anosmia (loss/change in smell)
What are the reproductive features of Kallmann’s syndrome?
Cryptorchidism Failure of puberty -Lack of testicle dvlpt -Micropenis -Primary amenorrhoea Infertility
How does Hyperprolactinaemia inhibit kisspeptin neurons?
Axis flooded with Prolactin, Binds to prolactin receptors on Kisspeptin neurons, inhibit kisspeptin release.
What is the presentation of hyperprolactinaemia?
Female - Oligo/Amenorrhea
Male - Low libido
Infertility, Osteoporosis
What is the treatment for Hyperprolactinaemia
Dopamine agonist (cabergolin) Surgery
Describe Klinefelter’s syndrome?
47XXY
Hypergonadotrophic
Hypogonadism
Infertility, micropenis, breast development, narrow shoulders, reduced chest hair, Mildly impaired IQ, Wide hips, Low bone density
How do you assess a male patient for infertility in the clinic?
including duration, previous children, pubertal milestones, associated symptoms (eg. T deficiency, PRL symptoms, CHH features), medical & surgical history, family history, social history, medications/drugs
What are the examinations for male infertility?
including BMI, sexual characteristics, testicular volume, epididymal hardness, presence of vas deferens, other endocrine signs, syndromic features, anosmia
What investigationsh should be carried out to assess male infertility?
Blood Tests; LH, FSH, PRL, Morning Fasting Testosterone
Sex Hormone Binding Globulin (SHBG), Albumin, Iron studies, Also Pituitary/Thyroid profile, Karyotyping.
Semen analysis; 1.5ml volume, 15million/ml conc, 40% motility.
Microbiology; Urine test, Chlamydia swab.
Imaging; Scrotal US/Doppler (for varicocoele/obstruction, testicular volume), Pituitary MRI ( if low FSH/LH or high PRL).
What are the lifestyle treatments for male infertility?
Reduce BMI
Smoking cessation
Alcohol reduction/ cessation
What are the specific treatments for male infertility?
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))
What is premature ovarian insufficiency?
same symptoms as menopause, 20% chance of conception. Diagnosis is High FSH>25iU/L (x2 at least 4 weeks apart)
What are the causes of Premature ovarian insuffieciency?
Autoimmune
Genetic - Fragile X syndrome, turners syndrome.
Cancer therapy
What happens in Polycystic Ovarian Syndrome?
Most common endocrine disorder in women 5-15%
Most common cause of female infertility
How do you diagnose Polycystic ovarian syndrome?
Rotterdam PCOS Diagnostic criteria 2/3
What are the criteria in the Rotterdam PCOS Diagnostic criteria?
Oligo or Anovulation
Clinical +/- Biochemical Hyperandrogenism
Polycystic Ovaries
What is the criteria for Oligo or Annovulation?
Normally assessed by menstrual frequency as oligomenorrhoea:
<21d or >35d cycles
<8-9 cycles/y
>90d for any cycle
If necessary anovulation can be proven by:
Lack of progesterone rise or US
What is the criteria for Clinical +/- Biochemical Hyperandrogenism?
CLINICAL
Acne, hirsutism (Ferriman-Gallwey score), alopecia (Ludwig score)
BIOCHEMICAL Raised androgens (eg Testosterone
What is the criteria for Polycystic Ovaries?
≥20 follicles OR ≥10ml either ovary on TVUS (8 MHz)
Do not use US until 8y post-menarche (due to high incidence of multi-follicular ovaries at this stage
What is the treatment for Polycystic Ovarian syndrome?
Depends on what you are treating;
Irregular menses/amenorrhea - Oral Contraceptive, Metformin
Insulin resistance - Metformin, Diet & Lifestyle
Hirsutism - Anti-androgens, Creams, waxing, laser
Endometrial cancer risk - Progesterone courses
What are the symptoms for turners syndrome (45X0)?
Short stature, low hairline, shield chest, wide spaced nipples, short 4th metacarpal, webbed neck, coarctation of the aorta, poor breast development, amenorrhea, underdeveloped reproductive tract,
1;2500 live births
What extras would you ask about in a female history taking?
Beastfeeding, Menstrual history
What extra examination would you carry out for a female?
hyperandrogenism signs, pelvic examination.
What extra blood tests would you do in a female, if you are examining fertility?
Oestradiol, Foll phase OHP (rare problem causing hyerandrogenism), Mid luteal Prog(helps us tell if there has been ovulation.
What does it indicate if progesterone rises in the luteal phase?
Acorpus luteum has formed, egg has come out of a follicle to form the corpus luteum, ovulation has taken place.
