Assessment and Management of Infertility Flashcards
Occurrence of infertility?
Common and half of the couples affected conceive either spontaneously or with relatively simple advice/treatment
Some remain sub-fertile and require more complex treatment, e.g: assisted conception techniques
Incidence of inferility increases in?
- Older women (decreased fertility, increased spontaneous abortions)
- Rise in Chlamydia infections (can cause tubule blockage)
- Obesity (less likely to ovulate)
- Change in expectations (same-sex marriage)
- Awareness of treatments
- Male factor infertility
Describe chances of spontaneous pregnancy
Increase over the months until 12 months
Definition of infertility?
Failure to achieve a clinical pregnancy after 12 months/ more of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child
2 types of infertility?
Primary - couple have never conceived
Secondary - couple previously conceived, although the pregnancy may not have been successful, e.g: miscarriage or ectopic pregnancy
Factors that increase the chance of conception?
- Woman <30 years
- Previous pregnancy
- <3 years trying to conceive
- If there is an unexplained cause
- Intercourse during 6 days before ovulation, part. 2 days before ovulation
- Woman’s BMI 20-30
- Both partners non-smokers
- Caffeine intake (<2 cups of coffee daily)
- No use of recreational drugs
Causes of infertility in couple having IVF/ICSI?
Can be:
- Unexplained
- Tubal disease (secondary infertility is more common here)
- Endometriosis
- Uterine factor
- Male factor infertility
- Multiple factors can cause infertility
Each of these have primary and secondary sub-types
What is anovulatory infertility?
The person is infertile and their ovaries do not release an egg
Physiological causes of anovulatory infertility?
Before puberty, pregnancy, lactation and menopause
Gynaecological causes of anovulatory infertility?
Hypothalmic:
- Anorexia/bulimia
- Excessive exercise
Pituitary:
- Hyperprolactinaemia
- Tumours
- Sheehan’s syndrome
Other causes of anovulatory infertility?
Systemic disorder, e.g: chronic renal failure
Endocrine disorder, e.g: testosterone-secreting tumours, CAH and thyroid problems
Drugs, e.g: depo-provera, explanon, OCP
WHO classification of anovulatory disorders?
Group 1 - AKA hypothalamic amenorrhea, inc:
- Stress, excessive exercise, anorexia
- Kallman’s syndrome
- Isolated gonadotrophin deficiency
Group 2 - AKA hypothalamic-pituitary dysfunction; normogonadotrophic-normoestrogenic-anovulation:
• PCOS
Group 3 - AKA ovarian failure, inc. all variants of ovarian failure and resistant ovary
Other causes include hyperprolactinaemia
Success of ovulation induction in the different groups of ovulatory disorders?
Ovulation can be induced in group 1 & 2 but is usually unsuccessful in group 3 (tends to require oocyte donation)
Occurrence of anorexia nervosa?
More common in females; there is an uncertain aetiology
Clinical features of anorexia nervosa?
Low BMI (<18.5)
Loss of hair and increased lanugo (fine hair)
Low pulse and BP
Anaemia
Ix hormone results in anorexia nervosa?
Low FSH, LH and oestradiol, i.e: they develop hypogonadortrophic hypogonadism
Occurrence of polycystic ovary syndrome (PCOS)?
Most common cause of anovulatory infertility; it is an inherited condition but weight gain exacerbates it
Clinical features of PCOS?
Obesity (usually, central so waist : hip ratio is increased)
Acne/oily skin
Hirsutism
Cycle abnormalities and infertility
Ix biochemistry in PCOS?
Biochemical tests (day 2-5):
High testosterone/free androgen index
High LH
Normal oestrogen
Impaired glucose tolerance (higher risk of DM)
What is the diagnosis of PCOS based on?
Score 2 out of 3 in the Rotterdam criteria:
- Chronic anovulation
- Polycystic ovaries (on USS)
- Hyperandrogenism (clinical or biochemical)
USS appearance of polycystic ovaries?
Increased ovarian volume (>10 ml)
>12 follicles, between 2-8 mm in diameter, in a single plane (a necklace pattern) and they tend to be peripherally located; can be unilateral or bilateral
Treatment of PCOS?
1st line treatment:
• Anti-oestrogens - Clomifene citrate OR Tamoxifen
2nd line treatment:
• Aromatase inhibitors - Letrozole (unlicensed)
If this fails, ask the patient to lose weight OR:
- Clomifene citrate + Metformin (to improve sensitivity)
- Gonadotrophin daily injections
- Laparoscopic ovarian diathermy
Use of Clomifene citrate?
Used from days 2-6, for 5 days, with a maximum dose of 150 mcg/day; it induces ovulation in the majority of patients but only 1/2 conceive
Monitored with an ovulation tracking scan and luteal phase serum progesterone
Occurrence of premature ovarian failure?
Occurs <40 years of age, i.e: it is premature menopause (although this term is discouraged)
Can be:
- Idiopathic
- Genetic, e.g: Turner’s syndrome (mosaic, where 1 chromosome is normal and the other is abnormal), fragile X
- Chemo/radiotherapy
- Oophorectomy
Clinical features of premature ovarian failure?
Hot flushes and night sweats
Atrophic vaginitis
Ix hormones in premature ovarian failure?
High FSH and LH
Low oestradiol
What is tubal disease?
Anything that cause blockage
Infective causes of tubal disease?
- Pelvic inflammatory disease, like STIs (e.g: chlamydia, gonorrhoea) and others (e.g: anaerobes, syphilis, TB)
- Transperitoneal spread, e.g: appendicitis (can cause adhesions if rupture occurs), intra-abdominal abscess
- Following procedure, e.g: IUCD insertion, hysteroscopy, HSG
Short-term effects of pelvic inflammatory disease?
- Tubo-ovarian abscess
- Peritonitis
- Fitz-Hugh-Curtis syndrome - liver capsule inflammation leading to the creation of adhesions
Long-term effects of pelvic inflammatory disease?
- Chronic pelvic pain
- Hydrosalpinx (distally blocked fallopian tube filled with fluid) causes infertility; it creates a characteristic sausage-shaped fallopian tube and this must be operated on
- Ectopic pregnancy
Non-infective causes of tubal disease?
- Endometriosis
- Surgical causes (e.g: sterilisation, ectopic pregnancies)
- Fibroids
- Polyps
- Congenital
- Salpingitis isthmica nodosa (diverticulosis of the fallopian tube) - nodular thickening of narrow part of the fallopian tube due to inflammation
Clinical features of pelvic inflammatory disease?
- Abdominal/pelvic pain
- Febrile
- Vaginal discharge and cervical excitation
- Dyspareunia (painful intercourse)
- Menorrhagia (abnormally heavy or prolonged periods) and dysmenorrhea (painful periods)
- Infertility
- Ectopic pregnancy
What is endometriosis?
Presence of endometrial glands outside the uterine cavity; incidence is higher in infertile women and it is assoc. with impaired infertility
Retrograde menstruation is the most likely cause; other inc:
- Altered immune function
- Abnormal cellular adhesion molecules
- Genetic
Clinical features of endometriosis?
Dysmenorrhoea (classically before menstruation) and menorrhagia
Dysparenuia and painful defaecation
Chronic pelvic pain
Ix for endometriosis?
USS may show characteristic ‘chocolate’ cysts on ovary, infertility, asymptomatic; uterus may be fixed and retroverted
Histopathology shows an active, typical glandular endothelium with active proliferation and secretory changes
Laparoscopic view
Why do chocolate cysts occur?
Endometrium wraps around and bleeds into the ovaries
Male causes of infertility?
Hypothalmic pituitary
Testicular disease
Obstruction/transport
Unexplained
Other causes
Endocrine causes of male infertility?
- Hypogonadotropic hypogonadism, e.g:
- Kallmann’s syndrome
- Anorexia
- Testicular failure:
- Klinefelter’s syndrome (47 XXY)
- Chemo/radiotherapy
- Undescended testes
- Idiopathic
- Hyperprolactinaemia (macro/microadenoma)
- Acromegaly
- Cushing’s disease
- Hyper/hypothyroidism
Causes of obstructive male infertility?
Congenital absence e.g: in cystic fibrosis (CF)
Infection
Vasectomy
Clinical features of obstructive male infertility?
Normal testicular volume
Normal secondary sexual characteristics, as sex hormones are normal
Vas deferens (normally,it is fairly muscular and can be palpated) may be absent
Ix hormones in obstructive male infertility?
Normal, LH, FSH and testosterone
Causes of non-obstructive male infertility?
47 XXY
Chemo/radiotherapy
Undescended tested
Idiopathic
Clinical features of non-obstructive male infertility?
Low testicular volume
Reduced secondary sexual characteristics
Vas deferens will be present
Ix hormones in non-obstructive male infertility?
High LH and FSH
Low oestradiol
History questions in infertility presentation?
See as a couple:
- Infertility history
- Gynaecology
- Andrology
- Sexual history
- Social history (illegal drugs/smoking)
- PMH, PSH, POH
Examination of a female with infertility?
BMI
General, assess body hair distribution and galactorrhoea
Pelvic examination (assessment for uterine and ovarian abnormalities/tenderness/mobility)
Examination of a male with infertility?
BMI
General examinaion, assessing size and position of testes
Penile abnormalities
Presence of vas deferens and of any varicoceles
Ix of a female with infertility?
- Endocervical swab for chlamydia
- Cervical smear if due
- Blood for rubella (teratogenic) immunity
- Mid-luteal progesterone level
- For an anovulatory cycle, do an early menstrual hormone profile (day 2-5)
- Test of tubal patency (with hysterosalpingiogram or laparoscopy)
- Others if indicated: e.g. hysteroscopy, USS, endocrine profile and chromosomes
What do regular and irregular cycle suggest and what should be done in each case?
Regular cycles are highly suggestive of ovulation, although some regular cycles are anovulatory; do a mid-luteal progesterone measurement
Irregular cycles usually indicate oligo/anovulation; do an early follicular hormone profile
Treatment of an infertile female who is +ve for Chlamydia?
Azithromycin; if allergic, doxycycline
How to take a mid-luteal progesterone level?
Take it on day 21 of a 28 day cycle OR 7 days prior to the expected period, in prolonged cycles
Progesterone > 30nmol/l suggests ovulation
How to interpret results of blood rubella immunity test?
If rubella antibodies are <10 U/L, the patient is non-immune
What is Rubella syndrome?
AKA congenital rubella - physical symptoms manifest in the fetus due to maternal infection; characteristics inc:
- Rash at birth
- Low birth weight
- Microcephaly (small head size)
- Heart abnormalities, e.g: patent ductus arteriosus (PDA)
- Visual abnormalities, e.g: cataracts
- Bulging fontanelle
Prevention of rubella in a female attempting to conceive?
Rubella vaccine (MMR)
The female must not conceive in the 4 weeks following vaccination
Treatment of tubal disease?
Tubal surgery - success depends on:
- Amount of healthy tube
- If there is both proximal and distal disease
- Condition of tubal wall
- Presence of adhesions
IVF
IVF procedure?
On day 1 , following inseminatin, formation of 2 pro-nuclei indicates normal fertilisation
Division occurs and, on day 4, compaction occurs to form a macula; on day 5, the blastocyst forms
What is a hysterosalpingiogram and when is it used as an Ix?
X-ray used to see if fallopian tubes are patent and if the uterine cavityis normal; it is indicated if there is:
- Suspected tubal/pelvic pathology, e.g: PID, endometriosis, adhesions
- Nil known risk factors
- Laparoscopy contraindicated
When is laparoscopy contraindicated?
Obesity, previous pelvic surgery and Crohn’s disease
When is laparoscopy used?
Possible tubal/pelvic pathology, e.g: PID (pelvic inflammatory disease)
Known previous pathology, e.g: ectopic pregnancy, ruptured appendix, endometriosis
Hx suggestive of pathology, e.g: dysmerrhoea and dyspareunia
Previously abnormal HSG
What is a hysteroscopy and when is it used?
Examinate the uterine cavity; ONLY performed in cases where suspected or known endometrial pathology, i.e: uterine septum, adhesions, polyp
When is a pelvic USS used?
When: • Abnormality on pelvic examination, e.g: enlarged uterus, adnexal mass • Required from other Ix, e.g: possible polyp seen at HSG
Other assessments that can be done if the patient has an anovulatory cycle or infrequent periods?
- Urine HCG (pregnancy test)
- Prolactin
- TSH
- Testosterone and SHBG (sex-hormone binding globulin)
- LH, FSH and oestradiol
Other assessment that can be done if the patient has hirsutes?
Testosterone and SHBG
Other assessments that can be done if the patient has amenorrhea?
• Endocrine profile • Karyotype
Treatment of premature menopause?
Counselling and prevention of osteoporosis
Oocyte donation
Cryopreservation of ovarian tissue (prior to radiotherapy/therapy)
Causes of male factor infertility?
Mostly idiopathic
Obstructive causes
Non-obstructive causes
Hormonal causes
Others: varicocele, chemotherapy, radiotherapy erectile dysfunction, immunological
Obstructive causes of male infertility?
Vasectomy
Infection (e.g: chlamydia/gonorrhoea)
Congenital absence of vas deferens (e.g: CF)
Non-obstructive causes of male infertility?
Undescended testis
Orchitis (e.g: mumps)
Torsion/trauma
Chromosomal, e.g: Klinefelter’s syndrome (47XXY), Kartagener syndrome, Y-chromosome micro deletions
Hormonal causes of male infertility?
- Hypogonadotrophic hypogonadism
- Hypothyroidism
- Hyperprolactinaemia
- Testicular cancer
Ix of a male with infertility?
Semen analysis; this is done twice but over 6 weeks apart:
- If abnormal, do an endocrine profile
- If severely abnormal / azoospermic, do an endocrine profile + chromosome analysis and screen for CF
Normal semen parameters on analysis?
Volume >1.5 ml
pH 7.2-7.8
Concentration >15x10 to the power of 6 /ml
Morphological normal forms of 4%
Motility - >50%
WBC - 1x10 to the power of 6 /ml
What Ix should be done in a male that has an abnormality on genital examination?
Scrotal USS
Treatment of male infertility?
Surgery to obstructed vas deferens
Intra-uterine insemination (in mild disease)
Intra-cytoplasmic sperm injection (ICSI)
Percutaneous Epididymal Sperm Aspiration (PESA), combined with ICSI OR Percutaneous Testicular Sperm Aspiration
Donor sperm insemination
