Counselling about risk in Gyanecology

Presenting information on risk :

 

Term	Numerical ratio	Colloquial description
Very common	1/1 to 1/10	A person in family
Common	1/10 to 1/100	A person in street
Uncommon	1/100 to 1/1000	A person in village
Rare	1/1000 to 1/10 000	A person in small town
Very rare	Less than 1/10 000	A person in large town

 

 

 

 

RCOG Consent Advice 9 - Perineal Tears Following Childbirth :

 

Serious risks -

1. Incontinence of stools and/or flatus - 
 Common

1/10 to 1/100

A person in street

 
2. Delivery by caesarean section in future pregnancies may be recommended if symptoms of incontinence persist or investigations suggest abnormal anal sphincter structure or function.

Uncommon:

1/100 to 1/1000

A person in village

  
 3. Haematoma. 
 4. Consequences of failure of the repair requiring the need for further interventions in the future such as secondary repair or sacral nerve stimulation.

Rare:

1/1000 to 1/10 000

A person in small town

5.  Rectovaginal fistula.

Very rare:

Less than 1/10 000

A person in large town

 

 

RCOG Consent Advice 10 - Surgical evacuation of the uterus :

 

Serious risks include:

• Uterine perforation, up to five in 1000 women (uncommon-A person in village)
• Significant trauma to the cervix (rare-A person in small town)

Frequent risks include:

• Bleeding that lasts for up to 2 weeks is very common but blood transfusion is uncommon (1–2 in 1000 women)
• Need for repeat surgical evacuation, up to five in 100 women (common)
• Localised pelvic infection, three in 100 women (common).

RCOG Consent Advice 12 - CS for placenta previa :

 

In all women with placenta praevia:

• Emergency hysterectomy, up to 11 in 100 women (very common)
• Massive obstetric haemorrhage, 21 in 100 women (very common).
• Need for further laparotomy during recovery from the caesarean, 75 in 1000 women (common)
• Thromboembolic disease, up to three in 100 women (common)
• Bladder or ureteric injury, up to six in 100 women (common)
• Future placenta praevia, 23 in 1000 women (common)

Links for cancer information

For detailed & well-presented information about cancers -
 Must read  -  
 Cervical cancer
 Endometrial cancer

Anorexia nervosa

• Onset typically before the age of 25 years
• One of the most important causes of secondary amenorrhoea in adolescents
• Amenorrhoea frequently pre-dates weight loss

• Weight loss >25% original body weight
• Distorted body image with implacable attitude towards eating

• Exclude medical illness that could cause weight loss
• Exclude other psychiatric disorders

• Associated with lanugo hair, bradycardia , hypotension, constipation, hypothermia, vomiting (may be self-induced) and periods of over-activity

• Psychiatric referral required  

• May occur in adolescents and present with primary amenorrhoea

• FSH and LH levels are low and may be undetectable

• Oestradiol and progesterone low. Progesterone challenge test typically negative

• Cortisol elevated

• Prolactin normal

• TSH and T4 levels are normal but T3 and reverse T3 are elevated

• Changes revert to normal with weight gain but 30% remain amenorrhoeic

• Response to GnRH is regained at ~15% below the ideal body weight and occurs before the resumption of menses

Causes of azoospermia

1) Hypothalamic-pituitary failure: (Hypogonadotrophic hypogonadism)

2) Primary testicular failure (nonobstructive azoospermia)

3) Obstruction of the genital tract (obstructive azoospermia)

4) Anejaculation 

5) Retrograde ejaculation

WHO reference values for semen analysis - Year 2010

Semen volume: ≥ 1.5 ml

 pH: ≥ 7.2  

Sperm concentration: ≥ 15 million spermatozoa per ml

Total sperm number: ≥ 39 million spermatozoa per ejaculate 

Total motility (percentage of progressive motility and non-progressive motility): ≥ 40% motile or ≥ 32% with progressive motility

Vitality: ≥ 58% live spermatozoa 

Sperm morphology (percentage of normal forms): ≥ 4% 

(Please note : Older values, year 2002 are different)

Causes of azoospermia - 4

4) Anejaculation: 
    - total failure of seminal emission into the posterior urethra. 
    - Rare

5) Retrograde ejaculation: 
  - substantial propulsion of seminal fluid from the posterior urethra into the bladder. 
  - Accounts for 0.3–2.0% of male fertility problems

(4) and (5) may result from:

1. Spinal cord injury
2. Transurethral prostatectomy – only 7% of men retain ejaculation
3. Retroperitoneal lymph node dissection
4. Diabetes mellitus
5. Transverse myelitis
6. Multiple sclerosis
7. Psychogenic / idiopathic disorders

Causes of azoospermia - 3

3) Obstruction of the genital tract (obstructive azoospermia): 

Prevalence < 2%

Diagnosis is based on normal testis size and normal serum FSH levels.
Causes include :
Congenital bilateral absence of vas deferens 
(associated with cystic fibrosis mutations or renal tract abnormality)

Causes of azoospermia - 2

2) Primary testicular failure (nonobstructive azoospermia): 

The diagnosis is based on reduction in testicular size and elevation of serum FSH levels. 

It is the most common cause of male infertility due to oligozoospermia. 

May be due to:

• Cryptorchidism
• Torsion
• Trauma
• Orchitis
• Chromosome disorders (Klinefelter’s syndrome, Y-chromosome microdeletions)
• Systemic disease
• Radiotherapy or chemotherapy
• Idiopathic (66%)

There is no effective treatment. 

Men undergoing treatments that cause infertility should be offered the opportunity to cryopreserve semen.

Causes of azoospermia - 1

1) Hypothalamic-pituitary failure: (Hypogonadotrophic hypogonadism). 

 Accounts for < 1% of male factor fertility.

 It results in a deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which is associated with -

failure of spermatogenesis and testosterone secretion.

Kallman Syndrome

 - X-linked recessive disease
- Reduced or complete absence of the sense of smell (anosmia-caused by the absence of the olfactory bulbs),  
- underdeveloped genitalia  - infertility
- lack of secondary sexual characteristics, 
- gynaecomastia, 
- short 4th metacarpal bone
- Males affected (1 in 10,000). 

- Presents at puberty

- Normal life-span 

- reduced or absent GnRH, with hypogonadotrophic hypogonadism. 

 - Hypothalamus is also affected

Anovulation in hyperprolactinemia

Hyperprolactinemic anovulation -

- 5-10% anovulation. 

- Anovulatory because hyperprolactinemia inhibits gonadotropin and therefore estrogen secretion. 

- Most have oligomenorrhea or amenorrhea. 

- Their serum gonadotropin concentrations are usually normal or decreased. 

- Hyperprolactinemia should always be confirmed by several measurements of serum prolactin. 

- An MRI of the head should be done in whom the cause is not obvious (eg, neuroleptic drug therapy, primary hypothyroidism).

WHO Group 3 ovulation disorders

Hypergonadotropic hypoestrogenic anovulation -

 - 10-30% cases of anovulation. 

- Primary causes :

1. POF (absence of ovarian follicles due to early menopause) or 
2. ovarian resistance (follicular form). 

- Many, but not all, of these women have amenorrhea.

- They usually do not respond to therapy for anovulation.

WHO Group 1 ovulation disorders

Hypogonadotropic hypogonadal anovulation -
(Hypothalamic pituitary Failure)

- 5 to 10 % of anovulation, usually amenorrhea 
(although a range of gonadal compromise can be seen)

- Low or low-normal FSH and low serum estradiol due to decreased hypothalamic secretion of GnRH or pituitary unresponsiveness to GnRH
(Low gonadotrophins
Normal prolactin
Low oestrogen)

- Causes of hypothalamic amenorrhea include :

1. stress-or exercise-related amenorrhea, 
2. anorexia nervosa, and 
3. Kallman's syndrome (isolated gonadotropin deficiency); approximately 5 to 10 percent have hypopituitarism. 

- Reversing the lifestyle factors that contribute to the anovulation (low weight, heavy exercise) should be attempted before considering intervention with medications.

Infertility & HIV

HIV: To prevent Male to female transmission :

1) Sperm washing is used to reduce the viral load in prepared sperm to a very low or undetectable level followed by IUI, IVF of ICSI

However, alternatives to sperm washing are now being proposed.

2) HAART treatment to reduce viral load to undetectable levels followed by timed intercourse – may be equally effective, less invasive and more cost effective for a specific cohort of patients. 

- Not appropriate in situations where any form of female infertility is diagnosed or suspected

• Where the man is HIV positive, the risk of HIV transmission to the female partner is negligible through unprotected sexual intercourse when all of the following criteria are met:

a)    The man is compliant with highly active antiretroviral therapy (HAART)

b)    The man has had a plasma viral load of less than 50 copies/ml for more than 6 months

c)    There are no other infections present

d)    Unprotected intercourse is limited to the time of ovulation

Infertility & HIV

HIV: 

To prevent Female to male transmission -

Use of assisted reproductive techniques (ART), such as IUI or IVF

Luteal phase defect

- Luteal-phase defect is a defect of progesterone secretion by the corpus luteum or a defect in endometrial response to hormonal stimulation, resulting in an inadequate endometrium for implantation

- Affects 3–20% of the infertile population and 23–60% of women with recurrent miscarriage

- Its role as a cause of infertility has been questioned and the benefit of treatment on pregnancy rates has not been established

- Women should not be offered an endometrial biopsy to evaluate the luteal phase as part of the investigation of fertility

WHO Group 2 ovulation disorders

Hypothalamic pituitary dysfunction (Normogonadotrophic-normoestrogenic)

Characterised by

• Gonadotrophin disorder
• Normal oestrogen

 

• Accounts for ~ 85% of ovulatory disorders
• Results in anovulatory oligo/amenorrhea, predominately involving women with polycystic ovaries.
• Polycystic ovaries are present in about 80–90% of women with oligomenorrhoea and 30% of women with amenorrhoea.
• In women with polycystic ovaries and clinical symptoms (menstrual disturbances, obesity and hyperandrogenism), this combination is referred to as PCOS.
• About 30% of the PCOS population is of normal weight

• The diagnosis of a polycystic ovary requires the presence of at least 12 follicles measuring 2–9 mm in diameter and/or an ovarian volume in excess of 10 cm3

The diagnosis of PCOS requires the presence at least two of the following three criteria

1. Oligo- and/or anovulation
2. Clinical and/or biochemical hyperandrogenism
3. Polycystic ovaries, with the exclusion of other aetiologies.

WHO classification of ovulation disorders

Patients are classified as :

WHO-1  - hypo-gonadotropic, hypo-estrogenic, (15%)

WHO-2  - normo-gonadotropic, normo-estrogenic, (80%) and 

WHO-3 - hyper-gonadotropic, hypo-estrogenic (5%)


( Class 1 has hypothalamic-pituitary failure
  Class 2 has hypothalamic-pituitary-ovarian axis dysfunction
  Class 3 has ovarian failure )



 The WHO criteria for classification of anovulation include :
the determination of -
- oligomenorrea (menstrual cycle >35 days) or 
- amenorrhoea (menstrual cycle > 6 months) in combination with -concentration of prolactin, follicle stimulating hormone (FSH) and estradiol (E2). 

  The vast majority of anovulation patients belong to the WHO-2 group and demonstrate very heterogeneous symptoms ranging from anovulation, obesity, biochemical or clinical hyperandrogenism and insulin resistance.

Assessing ovarian reserve

• Female fertility is related to the ovarian reserve. Ovarian reserve declines from before birth until the menopause.
• The rate of embryo implantation decreases while the rate of pregnancy loss increases with age. There is a decline in IVF success rates from around age 35 years.
• A woman’s age is therefore the most readily measured surrogate for ovarian reserve and should be used as an initial predictor of her overall chance of success through natural conception or with IVF

The following can be used to predict the likely ovarian response to gonadotrophin stimulation in IVF:

1. Total antral follicle count measured by TV scan on day 3 of cycle ≤ 4 for a low response and > 16 for a high response
2. Anti-Müllerian hormone of ≤ 5.4 pmol/l for a low response and  ≥ 25.0 pmol/l for a high response
3. FSH > 8.9 IU/l for a low response and < 4 IU/l for a high response

The following should not be used on their own to predict any outcome of fertility treatment:

1. Ovarian volume
2. Ovarian blood flow
3. Inhibin B
4. Oestradiol levels

Nonobstructive azoospermia

Primary testicular failure

The diagnosis is based on reduction in testicular size and elevation of serum FSH levels. 

It is the most common cause of male infertility due to oligozoospermia. 

May be due to:

• Cryptorchidism
• Torsion
• Trauma
• Orchitis
• Chromosome disorders (Klinefelter’s syndrome, Y-chromosome microdeletions)
• Systemic disease
• Radiotherapy or chemotherapy
• Idiopathic (66%) 

Obstructive azoospermia

Obstruction of the genital tract

• Prevalence < 2%
• Diagnosis is based on normal testis size and normal serum FSH levels.
• Causes include : Congenital bilateral absence of vas deferens (associated with cystic fibrosis mutations or renal tract abnormality).
  

Drugs affecting fertility in males

Male

• Cimetidine and sulphasalazine and long term-daily use of androgens can affect semen quality and cause oligozoospermia.

The effect is reversible after three months following withdrawal of medication

• Beta-blockers and psychotropic drugs may lead to impotence
• Chemotherapy can induce azoospermia, which is permanent in most cases
• The use of drugs such as anabolic steroids and cocaine can adversely affect semen quality.

Infertility - Effect of occupation

Occupation

• A specific enquiry about occupation should be made to people who are concerned about their fertility and appropriate advice should be offered.

• Men should be informed that there is an association between elevated scrotal temperature and reduced semen quality, but that it is uncertain whether wearing loose-fitting underwear improves fertility

Males

• Heat exposure (increased scrotal temperature): Abnormal sperm parameters
• X-ray exposure (radiotherapists): Azoospermia and reduced sperm count which may be reversible
• Exposure to vibration (engine drivers): Oligozospermia and asthenozospermia
• Chemicals
• Dibromochloropropane (pesticide – agriculture workers): Oligozospermia, azoospermia which are generally reversible; reduced fertilisation rates
• Ethylene dibromide (pesticide): Abnormal sperm parameters
• Lead, Cadmiun, Manganese (metal workers, smelters, battery factory workers): reduced fertility
• Acetone, Carbon disulphide, Glycol ethers (Chemists, lab workers, painters): Abnormal sperm parameters, reduced fecundability, oligozoospermia

Infertility - Effect of BMI

BMI

• Women who have a BMI ≥30 should be informed that they are likely to take longer to conceive. 
•  Women who have a BMI ≥30 and who are not ovulating should be informed that losing weight is likely to increase their chance of conception. 

Participating in a group programme involving exercise and dietary advice leads to more pregnancies than weight loss advice alone.

• In women, weight loss of > 15% of ideal body weight is associated with menstrual dysfunction with secondary amenorrhoea when > 30% of body fat is lost.
• Restoration of body weight may help to resume ovulation and restore fertility.
• Men who have a BMI ≥30 should be informed that they are likely to have reduced fertility

Infertility - Facts & statistics

- In a woman of reproductive age who is having regular unprotected vaginal intercourse two to three times per week, failure to conceive within 12 months should be taken as an indication for further assessment and possible treatment.

- The prevalence of infertility in European countries is around 14% (1 in 7 couples)

- Ovulation usually takes place 12 to 16 days before the start of the next period
 
- For a woman with a 28-day menstrual cycle, ovulation takes place around day 14
 
- After ovulation, the egg usually lives for up to 24 hours
 
- After ejaculation, sperm can survive for up to 7 days in the genital tract
 
- In the general population, 84% of women would conceive within 1 year of regular unprotected intercourse. 

This rises to 92% after 2 years and 93% after 3 year
 
- A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner.
 
- A woman of reproductive age who is using artificial insemination to conceive should be offered further clinical assessment and investigation if she has not conceived after 6 cycles of treatment, in the absence of any known cause of infertility. 
 

Premature ovarian failure - Aetiology

Aetiology -

• Unknown in most cases

• Genetic - up to 40% of cases. 

Karyotypic abnormalities -commonest being 45X and 47XXY followed by mosaiciams and structural abnormalities of sex chromosomes

• More common in families with fragile X syndrome

• Auto-immune disorder in some cases and associated with increased risk of other auto-immune diseases such as thyroid disease and pernicious anaemia

• Infections - mumps

• Irradiation / chemotherapy

Premature ovarian failure - Pathophysiology

• Definition - Ovarian failure before the age of 40 years

• Incidence ~1% and 0.1% between the ages of 15-29 years

• Usually caused by accelerated follicular atresia rather than absence of primordial follicles

• Associated with increased risk of cardiovascular disease and osteoporosis but not ovarian cancer

Secondary amenorrhoea - causes

• Auto-immune diseases such as 

1. Addison's disease, 
2. thyroid disease and 
3. diabetes mellitus 

are associated with premature ovarian failure. 

In addition, any severe endocrine disorder can cause amenorrhoea
• The Down's syndrome female has ovaries containing a reduced number of smaIl follicles, which have a greatly increased rate of atresia
• Bulimia & anorexia nervosa associated with secondary amenorrhoea
  (Androgen insensitivity syndrome associated with primary amenorrhoea)

OHSS - complications

Complications  -

• Hypo-albuminaemia - the ascites fluid is an exudate

• Electrolyte imbalance - hyponatraemia with hyperkalaemic acidosis

• Increased thrombogenesis - due to haemo-concentration and immobility. 
 Arterial, venous and intra-cerebral thrombosis occurs

• Cardio-respiratory failure - effusions, ascites and ARDS

• Pre-renal failure and multiple organ failure

• Ovarian torsion

OHSS - Risk factors

1. Young age
2. Low body weight
3. PCOS
4. High dose of gonadotrophins (rare with oral ovulation induction)
5. Large number of oocytes retrieved
6. High oestradiol levels on the day of HCG administration
7. Pregnancy

Metformin in PCOS

• Weight not significantly altered by metformin treatment

• Blood pressure - both systolic and diastolic blood pressure significantly reduced with metformin compared to placebo
• Fasting insulin significantly reduced
• Total cholesterol unchanged but LDL cholesterol significantly reduced. HDL cholesterol and triglycerides unaffected

• GI side-effects more common with metformin, particularly nausea and vomiting.

Bromocriptine

Side-effects -

1. Nausea, 
2. vomiting, 
3. headache, 
4. postural hypotension, 
5. constipation, 
6. dizziness, 
7. drowsiness, 
8. Raynaud's phenomenon, 
9. psychiatric symptoms especially aggression, 
10. pleural effusion, 
11. retro-peritomeal fibrosis

Commence treatment with small dose taken at night with food to minimise side-effects.

Pituitary micro-adenoma

• Carbegoline - long-acting dopamine agonist, better side-effect profile compared to bromocriptine

-Prolactin levels fall within a few days of therapy and a reduction in tumour volume occurs within 6 weeks

• Interpretation of serum prolactin levels in pregnancy is difficult

• In women with micro-adenomas, risk of symptoms in pregnancy 2-5%

Hyperprolactinemia

Psychotrophic agents - diazepam, phenothiazines, tricyclic anti-depressants, opiates, haloperidol
Anti-hypertensives - methyldopa, reserpine, propranolol
Hormones - oestrogen, COCP, TRH
Anti-emetics - metoclopramide, sulpiride

(L-dopa is a dopamine agonist which would inhibit prolactin release)

Turner's syndrome

• 45X0


• Associated with increased nuchal transluscency, coarctation of the aorta, atrial septal defects, cystic hygroma, fetal hydrops.


• There is -

1. short stature with no adolescant growth spurt, 
2. webbed neck, 
3. wide carrying angle, 
4. hypoplasia of the nails and short fourth metacarpals, 
5. broad chest with widely spaced nipples and 
6. a low hair line
7. peripheral lymphoedema in 40% of cases.

• Streak ovaries with primary amenorrhoea (menstruation may occur in some and pregnancy has been reported).


• Increased risk of systemic hypertension and Hashimoto's thyroiditis.


• Normal intellectual development.

Primary amenorrhoea

In a 16 year old woman with primary amenorrhoea but normal breast, pubic and axillary hair development  -
- possible causes can be -
1. Uterine agenesis
2. CAH

Not - Androgen insensitivity syndrome & Kallman's syndrome

• Androgen insensitivity syndrome - absent / scanty pubic and axillary hair, short blind-ending vagina, absent uterus and cervix
• Kallman's syndrome is characterised by hypogonadism and infantile sexual development

Androgen activity in females

• 85% of testosterone is bound to sex hormone binding globulin and is metabolically inactive. 

10-15% bound to albumin and 1-2% free 

- free and albumin-bound testosterone are biologically active
• Testosterone is converted to the biologically active dihydrotestosterone by 5-alpha reductase 

- increased activity of this enzyme may result in the manifestations of androgen excess
• 2/3rd daily female testosterone production is of ovarian origin 

(total = 0.35mg/day - of which -
 0.1mg = direct ovarian production; 
 0.2mg = peripheral conversion of androstendione; 
 0.05mg = peripheral conversion of DHEA).

Tamoxifen

Side-effects -

1. hot flushes, 
2. abnormal vaginal bleeding, 
3. GI disturbance, 
4. headache, 
5. visual disturbance, 
6. VTE, 
7. altered liver enzymes

Finasteride

Side-effects -
 

1. breast tenderness, 
2. hypersensitivity reactions, 
3. decreased libido

Cyproterone acetate

Side effects -

1. Fatigue, 
2. SOB,
3. hepatotoxicity including jaundice

PCOS

1) Decreased sex hormone binding globulin production by the liver with a resultant increase in free, biologically active androgens and oestradiol

2) About 50% of women with PCOS have elevated levels of DHEA-S, an adrenal androgen

3) Raised androgens - testosterone / androstendione - ovarian hypersecretion

PCOS - Long-term consequences

1. Increased incidence of multiple pregnancy following ovulation induction
2. Increased incidence of gestational diabetes
3. Increased incidence of pregnancy induced hypertension
4. Increased risk of endometrial cancer -5-fold
5. Cardiovascular disease -mortality is not significantly increased although women with PCOS have abnormal lipid profiles
6. Increased risk of adult onset diabetes mellitus ~ 40% risk of NIDDM by the age of 40 years

PCOS - infertility Rx

• Both recombinant FSH and human menopausal gonadotrophin (hMG) are effective ovulation induction agents in women with clomiphene resistant PCOS (about 20-30% of women with PCOS).
• No advantage in routinely using GnRH analogues in conjunction with gonadotrophins in these women - no increase in pregnancy rate and their use may be associated with an increased risk of ovarian hyperstimulation.
• Risk of first trimester miscarriage is increased and this is not reduced by supression of LH hypersecretion

PCOS - Diagnosis

• PCOS is a biochemically and clinically heterogeneous condition
• Women with clinical or biochemical evidence of PCOS but with normal ovarian morphology on ultrasound scan should be considered as having hyperandrogenic chronic anovulation
• Women with PCOS may have normal LH:FSH ratio and a normal body mass index

• Rapidly progressive virilisation would indicate an androgen-secreting tumour

PCOS - hormones

- LH hypersecretion is found in 40% of women with PCOS and is associated with a reduced chance of conception and increased risk of miscarriage 
- TSH unaffected. 

- Typically presents with secondary amenorrhoea
- About 50% of women with PCOS have elevated levels of DHEA-S, an adrenal androgen

Contraceptive vaginal ring - contents

NuvaRing delivers -
        15 µg of ethinyl estradiol  and  
        120 µg of etonogestrel (a progestin) each day of use.

Combined contraceptive patch - contents

- Releases 20 µg/day of ethinyl estradiol and  
                 150 µg/day of norelgestromin.

- Only currently available patches are - Ortho Evra in US & Evra in UK

Yuzpe regimen

- 100 mcg Ethinyl estradiol + 500 mcg levonorgestrel  

- two doses -12 hours apart

- Licensed in 1984
- Now replaced with POEC (Progesterone only emergency contraception)

Down's syndrome & maternal age

A woman's risk of having a baby with chromosomal abnormalities increases with her age.  

Down syndrome is the most common chromosomal birth defect, and a woman's risk of having a baby with Down syndrome is:

• At age 25 -  1 in 1,250
• At age 30 - 1 in 1,000
• At age 35 - 1 in 400
• At age 40 - 1 in 100
• At age 45 - 1 in 30
• At age 49 - 1 in 10

Monozygotic twins - Types

Various types of chorionicity and amniosity (how the baby's sac looks) in monozygotic (one egg/identical) twins as a result of when the fertilized egg divides  :  (From wikipedia)


 

Read chart near the diagram in wiki  

Good site about Congenital heart anomalies

Good site about Congenital heart anomalies


A pdf about perinatal medicine

SLE

Infections in SLE :

- Patients with SLE may be functionally asplenic and at risk from encapsulated bacterial infections like meningococcemia.
- Immunosuppred patients are at increased risk of sepsis
- Infection can mimic a lupus flare
- ESR and CRP may be raised. CRP changes more acutely, and the ESR lags behind disease changes.
- Measurement of complement may be useful as C3 and C4 levels are reduced in patients with active SLE due to consumption by immune complex–induced inflammation.

Raynaud's phenomenon

- Diagnostic criteria for primary Raynaud phenomenon :

1. Attacks triggered by exposure to cold and/or stress
2. Symmetric bilateral involvement
3. Absence of necrosis
4. No detectable underlying cause
5. Normal inflammatory markers and negative antinuclear factors.

Raynaud's phenomenon

Raynaud phenomenon:

- Recurrent vasospasm of the fingers and toes usually in response to stress or cold exposure.

- Characterised by 3 phases of change:

1. White (vasoconstriction), followed by
2. Blue (cyanosis), and then
3. Red (rapid blood reflow)

- Raynaud disease (primary Raynaud phenomenon) is characterised by the occurrence of the vasospasm alone, with no association with another illness

- Secondary Raynaud phenomenon is vasospasm associated with another illness, usually an autoimmune disease – typically systemic sclerosis, SLE and mixed connective tissue disease

- Diagnostic criteria for primary Raynaud phenomenon :

1. Attacks triggered by exposure to cold and/or stress
2. Symmetric bilateral involvement
3. Absence of necrosis
4. No detectable underlying cause
5. Normal inflammatory markers and negative antinuclear factors.

- Young women with Raynaud phenomenon alone for more than 2 years and no additional manifestations are at low risk for developing an autoimmune disease.

SLE - Challenges in management in pregnancy

1. Differentiating signs and symptoms of normal pregnancy from those of exacerbations SLE
2. Differentiate malar rash from chloasma
3. Differentiate proteinuria secondary to preeclampsia from proteinuria due to lupus nephritis. Lupus nephritis is often associated with proteinuria and cellular casts whereas only proteinuria is seen in patients with preeclampsia.
4. Differentiating renal disease secondary to an exacerbation of SLE from preeclampsia.
5. Differentiating thrombocytopenia in pregnancy from thrombocytopenia of SLE exacerbation

SLE

Pulmonary features of SLE

• Pleurisy with pleuritic chest pain +/- pleural effusions is the commonest feature
• Pulmonary embolism, lupus pneumonitis, chronic lupus interstitial lung disease, pulmonary hypertension, alveolar hemorrhage and infection are other complications

GI features

• Abdominal pain in active SLE may be due to peritonitis, pancreatitis, mesenteric vasculitis or bowel infarction

Cardiac features

• Pericarditis is the most common cardiac feature, presenting with positional chest pain that is relieved on leaning forward.
• Myocarditis and pulmonary hypertension can present with breathlessness and chest pain
• Coronary artery disease presents with angina

Pulmonary embolism - recommended investigations

RCOG Guidelines

1. Where there is clinical suspicion of acute PE a chest X-ray should be performed. 

2. Compression duplex Doppler should be performed where chest X-ray is normal. 

3. If both tests are negative with persistent clinical suspicion of acute PE, a ventilation–perfusion (V/Q) lung scan or a computed tomography pulmonary angiogram (CTPA) should be performed. 

4. Alternative or repeat testing should be carried out where V/Q scan or CTPA and duplex Doppler are normal but the clinical suspicion of PE is high. 

Anticoagulant treatment should be continued until PE is definitively excluded.

SLE - Rx & effects

Maternal effects :
- Treatment with cyclophosphamide may lead to premature ovarian failure and infertility

- Increased risk of hypertensive disorders: Pre-eclampsia occurs in ~15% of women and may be difficult to distinguish from lupus nephritis

- Increased risk of UTI

- Increased risk of gestational diabetes

- VTE – risk especially increased in women with anti-phospholipid antibodies. 

1. Women already on warfarin should be switched to therapeutic LMWH as soon as the pregnancy is recognized. 
2. Women with antiphospholipid syndrome but no previous VTE should be treated with prophylactic LMWH and low-dose aspirin during subsequent pregnancies. 
3. Women with SLE + antiphospholipid antibodies but no past morbidity can be managed with low-dose aspirin +/- hydroxychloroquine.

SLE - preconceptional counselling

Preconception management :

1. Assess disease activity from history, examinations and investigations

2. Risk assessment by checking for antiphospholipid antibodies (for a risk of fetal loss) and for anti-Ro and anti-La antibodies (for a risk of neonatal lupus) should be performed before pregnancy.

3. If active disease, advise to defer pregnancy and continue effective contraception

4. Discuss effect of SLE on pregnancy management and outcome. 

5. Women with anti-phospholipid antibody syndrome will require more frequent monitoring than those with SLE alone

6. Discuss effect of pregnancy on SLE

7. Discuss terratogenic effects of drugs such as methotrexate, cyclophosphamide and mycophenolate. 
Due to long half-lives, these drugs should be stopped at least 3 months before the planned conception.

8. Women should use contraception while on immunosuppressive disease-modifying drugs such as mycophenolate and cyclophosphamide. 
 Cyclophosphamide is absolutely contraindicated during pregnancy.

9. Discuss drugs that need to be stopped as soon as pregnancy is detected, such as warfarin.

10. Discuss general measures including folic acid supplementation, screening for rubella immunity

LMWH & regional anasthesia

Regional techniques should not be used until 12 hours after prophylactic & 24 hours after therapeutic dose of LMWH.

Catheter should not be removed within 10-12h of the most recent injection. 

Delivery by C/S -

Prophylactic dose LMWH day before surgery, 
omit morning dose on day of surgery and 
administer prophylactic dose by 3 hours post-op or 4h after insertion or removal of catheter

Cardiac murmur in pregnancy

• Systolic murmurs are common 
- prevalence over 90% 
- vast majority are flow murmurs. 
- Over 90% of patients have normal cardiac structure and function on ECHO
• Left sternal border area is most frequently the area of maximal intensity

• Diastolic mumurs are uncommon and should be considered abnormal as should pansystolic and long and loud systolic murmurs

Acute cortical necrosis

• Characterised by renal cortical cell death with sparing of the medullary portion of the kidney

• Rare complication and almost always associated with pregnancy especially in association with placental abruption in older multiparous women

• If the entire renal cortex is involved, renal failure is irreversible

• Renal failure from acute tubular necrosis is more common (75% of acute renal failure) and is reversible

Medical disorders in pregnancy

• Sickle cell disease - complications are more common in pregnancy and ~35% of pregnancies will develop crises
• Eisenmenger's syndrome - atrial or ventricular septal defect with pulmonary hypertension and right-to-left shunt.

- Cyanotic heart disease with ~50% mortality in pregnancy
• Multiple sclerosis is less likely to present for the first time and less likely to relapse during pregnancy

Anticoagulation in pregnancy

- LMWH should be given daily in two subcutaneous divided doses (in view of recognised alterations in the pharmacokinetics of dalteparin and enoxaparin during pregnancy) titrated against the woman’s booking or most recent weight. 
 
- Tinzaparin may be administered once daily. 

- Routine measurement of peak anti-Xa activity for patients on LMWH is not recommended except in women at extremes of body weight (< 50 kg and > 90 kg) or with other complicating factors (for example with renal impairment or recurrent VTE) putting them at high risk. 

- Peak anti-Xa (3 hours post-injection) should be 0.5–1.2 units/ml.

- Routine platelet count monitoring should not be carried out (unless unfractionated heparin has been given).

Pulmonary embolism - Investigations

Chest X-ray - may identify other pulmonary disease such as pneumonia, pneumothorax or lobar Collapse. 

If the X-ray is abnormal with a high clinical suspicion of PE, CTPA should be performed.

If the X-ray is normal, bilateral Doppler ultrasound leg studies should be performed. 

A diagnosis of DVT may indirectly confirm a diagnosis of PE and, since anticoagulant therapy is the same for both conditions, further investigation may not be necessary.

This would limit the radiation doses given to the mother and her fetus.

The choice of technique for definitive diagnosis (V/Q scan or CTPA) will depend on local availability and should be made after discussion with a radiologist.

(RCOG recommendations)

D-dimers

D-dimers are elevated in normal pregnancy and post-partum and also in complications of pregnancy such as pre-eclampsia. 

However, low level in pregnancy decreases index of suspicion of VTE

Previous VTE with No thrombophilia:

• Low molecular weight heparin for 6 weeks after delivery is recommended


• Value of antenatal thromboprophylaxis is controversial.


• However, if the previous VTE was oestrogen-related (pregnancy or OCP) or high BMI, antenatal thromboprophylaxis should be considered


• Women with more than one VTE, one VTE plus VTE in a first degree relative or VTE in an unusual site(e.g. - axillary) should receive antenatal thromboprophylaxis continued for 6 weeks post-partum


• Most VTE occurs antenatally but the risk per day is greatest in the weeks immediately following delivery


• Previous VTE is not contra-indication to regional anaesthesia in labour

Pituitary micro-adenomas

• Tumour less than 10mm diameter

• Microadenomas enlarge during pregnancy but <2% of women will develop signs / symptoms - headache usually preceeds visual disturbance
• Serum prolactin levels are not useful in assessing tumour size in pregnancy
• Bromocriptine can safely be used in the first trimester. 

• Breast-feeding is permitted without fear of stimulating tumour growth

Immune diseases & pregnancy

• Rheumatoid arthritis typically improves in pregnancy
• Sarcoidosis is unaffected or may improve during pregnancy
• Asthma may improve, worsen (typically severe disease) or remain unchanged

• Eczema often, but not invariably improves in pregnancy