Biochemistry Pregnancy and Fertility Flashcards
Definition of sub-fertility →
Cumulative conception rates:
- 4 Months 65%
- 9 Months 82%
- 12 Months 85%
Causes of Subfertility →
- Ovulatory failure 21%
- Tubal damage 14%
- Endometriosis 6%
- Mucus defect 3%
- Sperm defects 24%
- Other male 2%
- Coital failure 6%
- Unexplained 28%
- Others 11%
Assessment of Ovulation →Progesterone (nmol/L)
> 30 ovulation (not sub-fertile)
<30 reduced conception rate
Low level repeat next cycle
“day 21” progesterone
7 days before menses
Note → Variability in period together → change in follicular phase not luteal phase.
Timing
“day 21” progesterone
7 days before menses
Note → Variability in period together → change in follicular phase not luteal phase.
Primary Ovarian Failure →
- Impaired follicular development >
a. Low oestradiol
b. High LH/FSH (better marker) – PCOS or irregular ovulation – can alter LH levels.
→ No negative feedback to hypothalamus.
Causes of Ovarian Failure
➢ Premature ovarian Failure ➢ Post menopausal ➢ Autoimmune damage ➢ Surgery ➢ Irradiation (late effects of childhood or early adult cancer) ➢ Dysgenesis (Turners Syndrome)
Secondary Ovarian Failure
➢ Impaired LH/FSH production
➢ Low LH/FSH – not completely suppressed *
➢ Impaired follicular development > low estradiol
Causes of secondary Ovarian Failure
- LHRH deficiency (Kalmann’s syndrome)
- Pituitary tumours (prolactinoma)
- Secondary hypopituitarism e.g. irradiation, infiltrative and vascular disorders
- Function – weight loss, stress, exercise, starvation
- Systemic disease – e.g. thyroid, adrenal
Kallmann’s Syndrome:
- Absent sense of smell
2. Won’t go into puberty
Polycystic Ovarian Syndrome → Epi
87-90% oligomenorrhea, 26-37% amenorrhoea
Polycystic Ovarian Syndrome → Diagnosis
- Ultrasound → 15 cysts arranged around cortex, echogenic stromal compartment.
- Or Endocrine studies (less time consuming)
Polycystic Ovarian Syndrome → Characteristic features of PCOS
- Obesity
- Insulin resistance – independent from obesity contribution
- Increased cardiovascular risk
- Hirsutism
- Oestrogenisation – from multiple follicles
Polycystic Ovarian Syndrome → Serum Levels
LH increased
FSH normal
LH:FSH ratio abnormal
Testosterone increased (free testosterone is a better discrimination
Polycystic Ovarian Syndrome → Abnormal
Not all patients show the pattern
LH 12.6 93.1-26.0) 1-10 iu/L
• Sensitivity (positivety in disease)-60%
• Specificity (negativity in health)-94%
Hormonal Assessment of the infertile male:
Semen Analysis
Abnormal
Testicular Problem
Semen Analysis
Normal – no endocrine tests
Abnormal
Abnormal
LH/FSH, prolactin testosterone
• Testicular problem
• Hypothalamic pituitary
Testicular Problem
Normal endocrinology
Abnormal endocrinology
Hypergonadotrophic hypogonadism (testicular failure)
serum levels
Low Testosterone
High LH
High FSH
Isolated germinal compartment failure serum levels
Normal testosterone Normal LH (acting on Leydig) High FSH (abnormal sertoli cell function)
Non-Endocrine – impaired sperm serum levels
Obstructive azoospermia Retrograde ejaculation → Normal Testosterone → Normal LH → Normal FSH
Hypogonadotrophic hypogonadism → serum levels
Low Testosterone, LH, FSH
Chemical
Increases – Alk phos, hormone binding proteins
Decreases – Albumin, creatinine, urea
Physiological
Increases – plasma volume, cardiac output, weight gain, GFR early pregnancy
Deceases – Fasting BG early pregnancy, renal threshold for glucose
Endocrine
Increase – Oestrogen, progesterone, prolactin, hCG
Decrease – LH and FSH
Gestational diabetes → Epi
1-2% women develop gestational diabetes
Gestational diabetes → Diagnostic problem
15% women develop g;ycosuria
No accepted reference ranges
Gestational diabetes → Diagnostic tests
Blood glucose, random/fasting
GTT (glucose tolerance)
Gestational diabetes → Risk Factors for gestational diabetes
- BMI >30 kg/m2
- Previous macrosomic baby weighing >4.5 kg
- Previous gestational diabetes
- Family history diabetes (first degree relative)
- Family origin with a high prevalence of diabetes
Gestational diabetes → Diagnostic tests
Blood tests: U and E, urate, urine protein, clotting, LFT
HELLP
Gestational diabetes → HELLP
Haemolysis, Elevated Liver enzymes, low Platelets
Gestational diabetes → HELLP diagnosis
Abnormality seen with raised ALT/AST
Gestational diabetes → Urate in gestational diabetes
Independent raise in pregnancy not explained by the change in renal function associated with pregnancy
Increase urate = worse prognosis
Pregnancy related liver disease “Big 5”
- Pre-eclampsia
- HELLP
- Hyperemesis Gravidarum
- Acute Fatty Liver of Pregnancy
- Obstetric Cholestasis
Pregnancy Unrelated Liver Disease
- Pre-existing liver disease
7. Liver disease co-incident with pregnancy
Obstetric Cholestasis → Definition
Usually occurs in the 3rd trimester
Significant peri-natal mortality and maternal morbidity
Obstetric Cholestasis → Cardinal feature
Generalised puritis (not specific)
Obstetric Cholestasis → Biochemical tests
Serum bile acids (sensitive but not specific)
ALT and AST often raised
Alkaline phosphatase and bilirubin – no significant contribution
Second Trimester
Triple or quadruple test which provides the current standard of a detection rate above 75% and a false-positive rate of less than 3%
New Guidance First trimester
The “combined test” (nucal translucency, hCG, pregnancy associated plasma protein A) should be offered between 11-13 weeks 6 days
Down’s Syndrome Screening Markers – 2nd Trimester
AFP hCG Free-beta hCG Alpha hCG Unconjugated estriol (uE3) Inhibin – A
Down’s Syndrome Screening Markers – 1st Trimester
Pregnancy associated plasma protein A nuchal translucency
