Investigation of infertility Flashcards
Wat is the definition of Infertility?
- Infertility is the inability to conceive
- A couple is referred for clinical assessment for infertility if, after regular sexual intercourse, they have not conceived in 1yr (NICE CG156, updated 2017)
- “regular” is unprotected sexual intercourse every 2-3 days
What are classifications of Infertility?
- Primary in couples who have never conceived
- Secondary in couples who have previously conceived
What are factors affecting fertility?
- Age
- Endocrine disturbances e.g. thyroid, prolactin
- Obesity, anorexia, excessive exercise
- Alcohol
- Drugs
- Infections (Chlamydia), blocked fallopian tubes, endometriosis
- Low sperm count
- Infertility affects 1:7 couples
- 1/3rd unexplained infertility
What is the recommendation for patient with unexplained infertility?
NICE guidelines recommend that people with unexplained infertility try to conceive naturally for a min of 2 years as new evidence suggests that treatment in these circumstances is no more beneficial than attempting to conceive through intercourse.
How does weight affect fertility?
Meta-analysis (Hum Reprod Update 2012) 21 studies:
Odds ratio (95% confidence interval) for oligospermia or azoospermia:
- 1.15 (0.93-1.43) - underweight (BMI<18.5)
- 1.11 (1.01-1.21) - overweight (BMI 25-29)
- 1.28 (1.06-1.55) - obese (BMI 30-40)
- 2.04 (1.59-2.62) - morbidly obese (BMI >40)
What are investigations for infertility in females?
Infertility investigated after 1 year regular intercourse without contraception (earlier referral if >36 years or known clinical cause)
Investigations:
- Assessing menstrual cycle
- Other hormonal causes of infertility - hypothyroidism, prolactinaemia
- Assessing ovarian reserve
- Structural or other abnormalities
How is menstrual cycle assessed?
Regular menstrual cycles (26-36 days) usually indicative of ovulation
Day 2-5 LH, FSH, oestradiol
- Rule out menopause/premature ovarian failure.
- Rule out pregnancy (hCG)
Day 21 progesterone
- Assess ovulation (progesterone only released from corpus luteum after ovulatory cycle so if >30 consistent with ovulation) N.B. Clinicians frequently use other ranges from >16 up to 30)
What are biochemical markers for different pathologies involving the menstrual cycle?
Hypogonadotropic hypogonadism (10%)
- Low LH, Low FSH, Low oestradiol, normal prolactin
Hypothalamic pituitary dysfunction (85%)
- Abnormal gonadotrophins, normal oestradiol
- Predominantly PCOS
Ovarian failure (5%)
- High LH, High FSH, Low oestradiol
What are features of PCOS?
- Hyperandrogenaemia (usually)
- Serum testosterone high (not normally >5 pmol/l (ref <1.5 nmol/l)), SHBG used to calculate FAI
- FAI (normally <4.5%) = testosterone/SHBG x 100 %
What is Polycystic Ovarian Syndrome?
- Most common cause of anovulatory infertility
- Associated with hirsutism, other features of the metabolic syndrome: hyperinsulinaemia, insulin resistance, dyslipidaemia
- Not all PCOS patients have polycystic ovaries, not all patients with ovarian cysts have PCOS
- Definitions usually include hyperadrogenaemia, anovulation +/- polycystic ovaries
What are other hormonal causes of infertility?
Hypothyroidism (TSH, fT4)
- Estimated that subclinical hypothyroidism occurs in 0.88-11.3% women with ovulation disorders
- Can lead to menstrual and ovulatory disturbance associated with infertility
Hyperprolactinaemia (prolactin)
- Causes galactorrhoea, irregular menstruation and possible infertility
- Raised prolactin found in up to 10% infertile but ovulatory women.
•N.B. NICE suggest testing only if symptomatic
How is Ovarian Reserve assessed?
- Transvaginal ultrasound scan – antral follicle count (AFC) (AFC <4 low)
- Serum AMH (< 5.4 pmol/L low)
- Day 3 FSH (> 8.9 IU/L low): High day 3 FSH correlates with diminished ovarian reserve in women over 35 and is assoc with poor pregnancy rates post ovulation induction; poor pregnancy rates and higher miscarriage post IVF (any age)
What are interpretations for Serum AMH?
- >55: Risk of ovarian hyperstimulation (OHSS) during treatment. (Can be found in PCOS/granulosa cell tumours)
- 34.1 - 55: Optimal ovarian reserve
- 17.1 - 34: Satisfactory
- 2.6 - 17: Low
- <2.6: Very low/undetectable
What are structural or other abnormalities associated with infertility?
Tubal disease accounts for 14% causes of subfertility in women (5% endometriosis)
- Tubal obstruction and pelvic adhesions due to infection (Chlamydia), endometriosis and previous surgery.
- Tests of tubal patency e.g. HSG (hysterosalpinography), laparoscopy with dye
Uterine integrity e.g. fibroids
- Hysteroscopy
What are causes of Azoospermia?
- Hypogonadotropic hypogonadism (<1%)
- Primary testicular failure (non obstructive)
- Obstruction of the genital tract (<2%)
What are investigations of infertility?
Biochemistry (serum):
- FSH 1.5 - 12.4 IU/L – useful to detect primary from secondary testicular failure & to investigate azoospermia
- Testosterone (9am) 8.6 - 29 nmol/L (18-49yrs)
- LH 1.7 - 8.6 IU/L
- Oestradiol 41 - 159 pmol/L (gynaecomastia)
- Prolactin (pituitary disease)
Sperm
- Count
- Motility
- Volume
- pH
- viability
- WBC
Rule out non biochemical causes
- Drugs/alcohol
- Infection (if raised leucocytes treat with antibiotics)
- Impotence/anejaculation
What are biochemical markers for different pathologies involving the male infertility?
Hypogonadotropic hypogonadism
- Low LH, FSH with low testosterone & failure of spermatogenesis
Primary testicular failure
- High FSH, Low testicular volume
Obstruction of the genital tract (eg.CABVD assocCF)
- Normal FSH, normal testis size
- [CABVD= congenital absence of bilateral vas deferens)
What are causes of Primary Testicular failure?
Due to
- Cryptorchidism
- Chromosome disorders (Kleinefelter’s, Y-microdeletions)
- Systemic disease, radio/chemotherapy
66% cause unknown
What is Clomifene?
- Anti-oestrogen; selective oestrogen receptor modulator
- Binds to oestrogen receptors in the hypothalamus, disrupting negative feedback to increase GnRH production, this in turn increases pituitary FSH production, stimulating the ovary so that more follicles develop
- Side effects: Hot flushes, Multiple pregnancy, Abdominal discomfort, Ovarian hyperstimulation
How is Clomifene administered?
- 70% women with anovulatory cycles achieve ovulation on clomifene
- 50-100mg (max 250mg)
- Failure defined as failure to ovulate on 150mg. Clomifene failure assoc with BMI >27.2
- Max 6 cycles of clomifene
- Clomifene + metformin particularly in PCOS
What are treatments for infertility in females?
- Clomifene
- Gonadotrophin (recombinant FSH, recombinant LH, purified urine gonadotrophins)
- Surgical procedures eg laparoscopic ovarian drilling (if identified cause tubal surgery)
What are treatment for infertility in males?
Primary testicular failure
- No effective treatment for infertility
- Testosterone replacement (eg Testogel)
Hypogonadotrophic hypogonadism
- hCG
- Pulsatile GnRH
What requirements for IVF in patients?
- BMI between 19-30 (NICE guidance)
- Smoking cessation (both partners)
- Decrease caffeine; alcohol 1 unit/d
- Woman between 23-39 years
- Priority to couples without children
- Other options for private IVF treatment
- Differences seen in funding for NHS in different areas of UK, in terms of criteria and number of cycles
What are biochemistry tests used during treatment?
- AMH and LH used to inform induction protocol
- hCG for confirmation of pregnancy
- Oestradiol for monitoring IVF induction cycle (very high may indicate OHSS)
What are forms of assisted reproduction?
- IVF
- ICSI (intracytoplasmic sperm injection)
- Egg donation
- Donor insemination
