Investigation of infertility Flashcards

1
Q

Wat is the definition of Infertility?

A
  • 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
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2
Q

What are classifications of Infertility?

A
  • Primary in couples who have never conceived
  • Secondary in couples who have previously conceived
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3
Q

What are factors affecting fertility?

A
  • 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
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4
Q

What is the recommendation for patient with unexplained infertility?

A

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.

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5
Q

How does weight affect fertility?

A

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)
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6
Q

What are investigations for infertility in females?

A

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
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7
Q

How is menstrual cycle assessed?

A

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)
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8
Q

What are biochemical markers for different pathologies involving the menstrual cycle?

A

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
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9
Q

What are features of PCOS?

A
  • 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 %
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10
Q

What is Polycystic Ovarian Syndrome?

A
  • 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
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11
Q

What are other hormonal causes of infertility?

A

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

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12
Q

How is Ovarian Reserve assessed?

A
  • 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)
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13
Q

What are interpretations for Serum AMH?

A
  • >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
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14
Q

What are structural or other abnormalities associated with infertility?

A

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
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15
Q

What are causes of Azoospermia?

A
  • Hypogonadotropic hypogonadism (<1%)
  • Primary testicular failure (non obstructive)
  • Obstruction of the genital tract (<2%)
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16
Q

What are investigations of infertility?

A

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
17
Q

What are biochemical markers for different pathologies involving the male infertility?

A

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)
18
Q

What are causes of Primary Testicular failure?

A

Due to

  • Cryptorchidism
  • Chromosome disorders (Kleinefelter’s, Y-microdeletions)
  • Systemic disease, radio/chemotherapy

66% cause unknown

19
Q

What is Clomifene?

A
  • 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
20
Q

How is Clomifene administered?

A
  • 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
21
Q

What are treatments for infertility in females?

A
  • Clomifene
  • Gonadotrophin (recombinant FSH, recombinant LH, purified urine gonadotrophins)
  • Surgical procedures eg laparoscopic ovarian drilling (if identified cause tubal surgery)
22
Q

What are treatment for infertility in males?

A

Primary testicular failure

  • No effective treatment for infertility
  • Testosterone replacement (eg Testogel)

Hypogonadotrophic hypogonadism

  • hCG
  • Pulsatile GnRH
23
Q

What requirements for IVF in patients?

A
  • 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
24
Q

What are biochemistry tests used during treatment?

A
  • AMH and LH used to inform induction protocol
  • hCG for confirmation of pregnancy
  • Oestradiol for monitoring IVF induction cycle (very high may indicate OHSS)
25
Q

What are forms of assisted reproduction?

A
  • IVF
  • ICSI (intracytoplasmic sperm injection)
  • Egg donation
  • Donor insemination