O+G Flashcards
Common symptoms in pregnancy
Nausea Heartburn Constipation SOB Diizziness Swelling Backache Abdominal discomfort
NB: These are generally due to physiological adaptations but may be due to an underlying serious cause
Main risks of smoking during pregnancy
FGR
Preterm labour
Placental abruption
Intrauterine foetal death
When should the booking visit have taken place by?
10 weeks
Antenatal risks associated with increased BMI in pregnancy
Difficulty accurately assessing growth and anatomy of foetus
Increased risk of GDM
Hypertensive disorders of pregnancy; increased risk of chronic hypertension, gestational hypertesnion and pre-eclampsia
Increased risk of VTE
Intrapartum risks of increased BMI during pregnancy
Difficulty with analgesia (epidurals and spinal) and GA if needed
Diffuclty with monitoring in labour
Increased instrumental delivery rate
Increase C-section rate
Postnatal risks of increased BMI during pregnancy
VTE risk
Wound breakdown and infeciton
Postnatal depression
Risks to foetus of increased BMI during pregnancy
Increased congenital malformations: if BMI>40, risk of neural tube defects is three times that of a woman with BMI < 30
Macrosomia and associated complications (e.g. shoulder dystocia)
Foetal growth restriction and associated complications
Miscarriage: overall miscarriage risk is 20%, which increases to 25% if BMI>30
Stillbirth risk doubled
Increased risk of childhood obesity and diabetes later in life
RCOG dietary and exercise advide during pregnancy
Do NOT eat for two - maintain your normal portion size and try and avoid snacks
Eat fibre-rich foods such as oats, beans, lentils, grains, seeds, fruit and vegetables as well as whole grain bread, brown rice and pasta
Base your meals on starchy foods such as potatoes, bread, rice and pasta, choosing whole grain where possible
Restrict intake of fried food, drinks and confectionary high in added sugars, and other foods high in fat and sugar
Eat at least 5 portions of a variety of fruit and vegetables each day
Dieting in pregnancy is NOT recommended but controlling weight gain in pregnancy is advocated
Aerobic and strength conditioning exercises in pregnancy are considered beneficial and safe
May help recovery following delivery, reduce back and pelvic pain during pregnancy and contribute to overall wellbeing
Avoid contact sports
Pelvic floor exercises during pregnancy may reduce the risk of urinary and faecal incontinence in the future
It is safe to resume exercise after delivery once the woman feels comfortable
WHO recommendations for breastfeeding after pregnancy
Initiation of breastfeeding within an hour of birth
Exclusive breastfeeding for first 6 months of age
Continued breastfeeding beyond 6 months at least up to 2 years
Home Birth pros and cons
ADVANTAGES: familiar surroundings, no interruption of labour to go to hospital, no separation from family members, continuity of care
DISADVANTAGES: 45% of first-time mothers are transferred to hospital, poor perinatal outcome is twice as likely for home births, limited analgesic options
Midwifery units or birth centre pros and cons
ADVANTAGES: continuity of care, fewer interventions, convenient location
DISADVANTAGES: 40% of nulliparous women require transfer to a hospital birth centre, limited access to analgesic options
Hospital birth centre pros and cons
Midwives provide care during labour but doctors are available should the need arise
DISADVANTAGES: lack of continuity of care, greater likelihood of intervention
What are the risks of asymptomatic bacteriuria in pregnancy?
Increased risk of preterm prdelivery
Increased risk of pyelonpehritis during pregnancy
An MSU should be sent for culture and sensitivity at the booking visit as a screening test
What is urine screened for at every antenatal visit?
Protein- detect renal disease or pre-eclampsia
Persistent glycosuria- pre-existing diabetes or GDM
Nitrites- detect UTIs (If nitrites are detected, an MSU is sent for MC+S to detect asymptomatic bareiuria. Treatment will be initiated if a positive culture is found)
What happens to blood pressure during pregnancy?
BP falls a small amount in the first trimester, and will rise to pre-pregnancy levels by the end of the second trimester
Measurement of BP in first trimester also allows identification of previously undiagnosed chronic hypertension- this allow early initiation of treatment (antihypertensives and aspirin)
Booking tests in pregnancy
FBC MSU Blood group and anitbody screen Haemoglobinopathy screening Infection screen Dating scan and first trimester screening
FBC antenatal screening
Allows identification of anaemia
NOTE: anaemia in pregnancy is defined as:
FIRST trimester < 110 g/L
SECOND and THIRD trimesters < 105 g/L
POSTPARTUM < 100 g/L
If anaemia is detected, MCV should be examined to identify the likely cause
Additional investigations include B12, folate or iron studies
If iron deficiency anaemia, a trial of oral iron should be considered (an increase in Hb at 2 weeks suggests positive response)
Women with a known haemoglobinopathy should have serum ferritin checked and offered oral supplements if ferritin < 30 mcg/L
FBC may show low platelets (may be due to ITP)
Gestational thrombocytopaenia rarely present in the first trimester
NOTE: it’s more common > 28 weeks
So, a low platelet count in the first trimester warrants further investigation
A baseline platelet count is also useful later in pregnancy if the patient is suspected of having developed pre-eclampsia or HELLP syndrome
Blood group antenatal screening
Mainly to identify Rhesus D-negative women
These women should be informed about the risks of rhesus isoimmunisation and sensitisation from a RhD-positive baby
Anti-D immunoglobulin is administered (ideally < 72 hours) in cases of potential sensitising events (e.g. CVS, amniocentesis, trauma)
In pregnancies < 12 weeks, anti-D prophylaxis is only indicated if:
Ectopic pregnancy
Molar pregnancy
Therapeutic TOP
Uterine bleeding that is repeated, heavy or associated with abdominal pain
Minimum dose of anti-D = 250 IU Women who are RhD-negative are offered prophylactic anti-D at 28 weeks This can be done as a single large dose at 28 weeks Or two doses at 28 and 34 weeks RhD-negative mothers will receive anti-D postpartum once the baby has been confirmed as being RhD-positive on cord blood testing
Gestational diabetes antenatal screening
Women with previous GDM should be offered a glucose tolerance test or random blood glucose in the first trimester- this hopes to identify pre-existing diabetes that may have developed since the previous pregnancy
What is the mode of inheritance of thalassemia?
Autosomal recessive
What chromosome encodes alpha chains of haemoglobin?
Four genes, two on each chromosome 16
Severity if disease depends on the number of alpha globin genes that are mutated
Which chromosome encodes beta globin chains?
Beta chains are produced by 2 genes, one on each chromosome 11
Who is offered screening for thalassemia?
ALL pregnant women at the booking visit using the Family Origin Questionnaire and/or FBC results. Those deemed at high risk will be referred to a foetal medicine unit to discuss options for more invasive testing
Sickle cell antenatal screen
Carrier rate of sickle cell trait (HbAS) is 1 in 10 in Afro-Caribbean people
Carrier frequency of haemoglobin C trait is around 1 in 30
HbSS is the most serious form with patients suffering chronic haemolytic anaemia and acute sickle cell crises
People with HbSC have a milder features but are still at risk of sickle cell crises
Partners should also be tested if at high risk
Which diseases are screened for in the first trimester infection screen?
Rubella (screening programme has stopped due to MMR. If a woman is idenitifed as not being immune, they should be advised to avoid conact with individuals known to be currently infected. They should be offered the MMR vaccination following delivery)
Syphilis
Hepatitis B
Hepatitis C (not routinely screened- may be offered to women at high risk e.g. IVDU, HIV)
HIV
What are the risks of syphilis to the pregnancy?
Can cause miscarriage or stillbirth
Routinely screened for in pregnancy
What interventions are in place if a abby is born to a woman with active Hepatitis B?
Hepatitis B vaccine
One dose of hep B immunoglobulin within 12 hours
This confers 95% protection. Additional doses of Hepatitis B vaccine will be needed at 1 and 6 months.
What interventions are in place to minimise transmission of HIV to the foetus?
Initiation of ART by 24 weeks if naive
Planned C-section if viral load > 400 copies/ml at 36 weeks
Exclusive formula feeding from birth
Women who decline initial screening should be offered screening again at 28 weeks
Treatment for women at high-risk of developing pre-eclampsia
NICE recommends that women at high risk of pre-eclampsia should be given 75mg aspirin form early in pregnancy (12 weeks) to delivery
All women should be screened at every antenatal visit for pre-eclampsia by measurement of blood pressure and urinalysis for protein
Women at high risk of dveloping pre-eclampsia:
Hypertensive disease during previous pregnancy
Chronic kidney disease
Autoimmune diseases such as SLE and antiphospholipid syndrome
Diabetes mellitus
Chronic hypertension
Women at moderate risk of developing pre-eclampsia:
Primiparity Advanced maternal age (>40 years) Pregnancy interval of more than 10 years BMI>35 at booking visit Family history of pre-eclampsia Multifoetal pregnancy
Women with 2 or more moderate risk factors should start aspirin
Women at risk of preterm birth:
Previous preterm birth
Previous late miscarriage
Multifoetal pregnancies
Cervical surgery (e.g. cone biopsy)
These women may be offered serial cervical length screening (with or without monitoring foetal fibronectin)
Foetal growth measurements
NICE recommends that SFH measurements should be performed at every antenatal appointment form 24 weeks
If there are cocnerns of slow or arrested foetal growth, an ultrasound scan should be performed
Typically, a dating scan is offered at the end of the first trimester and an anomaly scan at 20-22 weeks, but no further growth assessment unless clinically indicated
Vitamin D screening in pregnancy
NOt routinely screened
Those at risk (e.g. skin colour, obesity) may be given vitamin D supplementation (oral cholecalciferol or ergocalciferol)
NICE recommends that ALL pregnant and breasfteeding women should be advised to take 10micrograms of vitamin D supplements daily
When is the anomaly scan carried out?
20-22 weeks
Which conditions can be identified in the anomaly scan?
Spina bifida
Major congenital abnormalities
Diaphragmatic hernia
Renal agenesis
Risk factors for gestational diabetes mellitus
Previous GDM Previous macrosomia Raised BMI First-degree relative with diabetes Asian, black Caribbean or Middle-Eastern origin
If risk factors are present, the woman should be offered a 2-hour 75g oral glucose tolerance test at 24-28 weeks
Women with previous history of GDM should have an OGTT at 16-18 weeks and then a repeat should be performed at 24-28 weeks
Triple test for Down syndrome
Nuchal translucency
PAPP-A
BetahcG
What are the risk factors for twin pregnancy?
Advanced maternal age
Antiretroviral therapy
IVF
Family history
Treatment for twin-twin transfusion syndrome
Foetoscopic laser ablation
How does the mirena coil work?
Hormone in mirena reduces heavy menstrual bleeding by controlling the monthly development of the womb, making the lining thinner
Thickens cervical mucus
In some cases, it stops ovulation
What is Barker hypothesis?
This showed that there is an association between reduced foetal growth and increased susceptibility to several adult diseases (e.g. coronary heart disease, stroke and diabetes)
Small for gestational age
Foetus <10th centile
Many SGA foetuses may be constitutionally small, but many have failed to reach their full growth potential (FGR): this is associated with increased risk of perinatal morbidity and mortality. Growth-restricted foetuses are at increased risk of intrauterine hypoxia/asphyxia, so they are more likely to be stillborn or have features of HIE (e.g. seizures, multi-organ failure). Other complications that they are at increased risk of in the neonatal period: Hypoglycaemia Hypothermia Infection Necrotising entercolitis
Complications of foetal hyperinsulinaemia
Results in foetal macrosomia and excessive fat deposition, which can lead to:
Shoulder dystocia
Stillbirth
Neonatal hypoglycaemia
Chromosomal disorders which cause FGR
Patau syndrome (trisomy 13) Edward's syndrome (trisomy 18)
Genes from which parent encourage growth?
Evidence suggests that geners that are paternally expressed promote growth, whereas maternally expressed genes suppress growth
Maternal influences on foetal growth
Maternal height
Pre-pregnancy weight
Age
Ethnicity
Increasing parity (associated with increased birthweight)
Teenage pregnancy (associated with FGR)
Smoking, alcohol and recreational drug use (LBW)
Cocaine (associated with spontaneous preterm birth, LBW and small head circumference (placental abruption is also associated with cigarette smoking and recreational drug use)
Chronic maternal disease (e.g. hypertension, CF, cyanotic heart disease, maternal thrombophilia)
Placental influences on foetal growth
Causes of placental insufficiency:
Poor maternal uterine artery blood flow
Thicker placental trophoblast barrier
Abnormal foetus villous development
Placental infarction
Acute premature separation (e.g. in placental abruption)
Antepartum haemorrhage
What are the four shunts that ensure that oxygenated blood from the placenta is delivered to the foetal brain?
Umbilical circulation
Ductus venosus
Foramen ovale
Ductus arteriosus
Umbilical circulation
Carries foetal blood to and from the placenta for gas and nutrient exchange
Umbilical arteries arise from the caudal end of the dorsal foetal aorta
They carry deoxygenated blood from the foetus to the placenta
The umbilical vein returns oxygenated blood from the placenta to the foetal liver
Usually there are:
2 x foetal arteries
1 x foetal vein
A small proportion of blood is used to oxygenate the liver, but most of it will bypass the liver via the ductus venosus and joins the IVC
The ductus venosus is a narrow vessel with high blood velocities within it
The streaming of the ductus venosus blood, along with a membranous valve in the right atrium (crista dividens), prevents mixing of the well-oxygenated blood in the ductus venosus with the desaturated blood of the IVC
The ductus venosus stream will pass through the foramen ovale into the left atrium
The blood then passes through the mitral valve into the left ventricle
It is them pumped into the aorta, from which 50% goes to the head and upper extremities
The remainder will pass down the aorta and mix with blood of reduced oxygen saturation from the right ventricle (via the ductus arteriosus)
Deoxygenated blood returning from the foetal head and lower body flows through the right side of the heart into the pulmonary artery
It will then bypass the lungs and enter directly into the descending aorta via the ductus arteriosus
This means that deoxygenated blood from the right ventricle will pass down the aorta and enter the umbilical arterial circulation to be returned to the placenta for oxygenation
Why is the ductus arteriosus patent before birth?
Production of prostaglandin E2 and prostacyclin
What can cause premature closure of the ductus arteriosus?
COX inhibitors
Cardiopulmonary changes at birth
Cessation of umbilical blood flow causes cessation of flow into the ductus venosus, leading to a fall in the pressure in the right atrium –> closure of the foramen ovale
Ventilation of the lungs opens the pulmonary circulation, causing a rapid fall in pulmonary vascular resistance –> increasing pulmonary circulation
Ductus arteriosus closes within a few days of birth
Persistent foetal circulation
Sometimes, the transition from foetal to adult circulation is delayed, usually because the pulmonary vascular resistance fails to fall despite adequate breathing = persistent foetal circulation, which results in left-to-right shunting of blood from the aorta through the ductus arteriosus into the lungs.
The baby will be cyanosed and can suffer from life-threatening hypoxia
This delay in closure of the ductus arteriosus is most commonly seen in preterm infants (<37 weeks) and results in congestion of pulmonary circulation and a reduction in blood flow to the Gi tract and brain (also implicated in the pathogenesis of necrotising enterocolitis and intraventricular haemorrhage)
Failure of closure of what results in neural tube defects?
The CNS begins as a simple neural plate that folds to form a groove then a tube (initially open at each end). Failure of closure of these open ends leads to neural tube defects.
Later development of the foetal brain involves elaborate folding of the neurocortex (mainly in the second half of pregnancy).
There is a rapid increase in grey matter in the last trimester.
Respiratory system in utero
The lungs first appear as an outgrowth from the primitive foregut at about 3-4 weeks post-conception
By 4-7 weeks, epithelial tube branches and vascular connections are forming
By 20 weeks, the conductive airway tree and parallel vascular tree is well developed
By 26 weeks, type I and type II epithelial cells are beginning to differentiate
By 30 weeks, surfactant production has started
Up to delivery, dilatation of the airspaces, alveolar formation and maturation of surfactant continues
In utero the foetal lungs are full of fluid
What changes happen to the lungs at birth?
Production of flung fluid ceases
Fluid is absorbed
Adrenaline appears to play a major role in this process
The clearance of fluid and onset of breathing leads to a fall in pulmonary pressure and a rise in pulmonary blood flow
A consequent increase in left atrial pressure causes closure of the foramen ovale
What is the main constituent element of surfactant?
Surfactant prevents the collapse of small alveoli during expiration by lowering surface tension
The main phsopholipid in surfactant is phosphatidylcholine (lecithin)
Production of lecithin is enhanced by cortisol, growth restriction, prolonged rupture of membranes
Surfactant production is delayed in maternal diabetes mellitus
Acute complications of RDS
Hypoxia/asphyxia
Intraventricular haemorrhage
Necrotising enterocolitis
How can the incidence and severity of RDS be minimised?
Administration of steroids antenatally to mothers at risk of preterm delivery: the steroids will cross the placenta and stimulate premature release of stored foetal pulmonary surfactant in the foetal alveoli
What is the purpose of foetal breathing movements (FBM)?
Several intermittent FBM occur in utero especially during REM sleep
These movements help maintain a high level of lung expansion that is essential for normal lung growth and maturation
During the apnoeic episodes in between FBM, active laryngeal constriction opposes lung recoil by preventing the escape of lung liquid via the trachea
Prolonged absence or impairment of FBM is likely to result in reduced mean lung expansion and can lead to hypoplasia of the lungs. What are some other causes of pulmonary hypoplasia?
Oligohydramnios
Decreased intrathoracic space (e.g. diaphragmatic hernia)
Chest wall deformities
What does the foregut endoderm later give rise to?
Oesophagus Stomach Proximal duodenum Liver Pancreas
What does the midgut endoderm give rise to?
Distal half of duodenum Jejunum Ileum Caecum Appendix Ascending colon Transverse colon
Between weeks 5-6, due to a rapidly enlarging liver and elongation of the intestines accompanied by a lack of space in the small abdomen, the midgut extrudes into the umbilical cord as a physiological hernia
Whilst herniated, the gut will undergo rotation and then re-enter the abdominal cavity by 12 weeks gestation
What does the hindgut endoderm give rise to?
Descending colon
Sigmoid colon
Rectum
What can failure of the midgut to re-enter the abdominal cavity result in?
Omphalocele (exomphalos)
Malrotation can result in what?
Volvulus
Bowel obstruction
Atresia
When a segment of bowel has a lumen that is not patent.
Usually occur in the upper GI tract
The foetus continuously swallows amniotic fluid, so an obstruction that prevents passage of the amniotic fluid through the GI tract will cause polydramnios
Meconium in the amniotic fluid is associated with:
Post-term pregnancies
Foetal hypoxia
Aspiration of the meconium-stained liquor by the foetus at birth can cause meconium aspiration syndrome or RDS
Why are preterm infants at increased risk of low weight?
In the last trimester, water content decreases and glycogen and fat stores increase about fivefold. Consequently, preterm infants have virtually no fat and have a reduced ability to withstand starvation
This can be compounded by poor sucking, uncoordinated swallowing mechanisms, delayed gastric emptying and poor absorption
Growth-restricted foetuses also have reduced glycogen stores–> more prone to hypoglycaemia (glycogen is stored in small quantities in the liver from the 1st trimester and peaks in 3rd trimester)
Indications for expectant management in ectopic pregnancy
Low bhCG
No symptoms
Tubal ectopic pregnancy measuring <35mm
No heartbeat
Indications for methotrexate in ectopic pregnancy
Small (<35mm) unruptured pregnancy No visible heartbeat Serum bhCG<1500 No intrauterine pregnancy No pain
Patient must be able to attend follow-up
Methotrexate is an anti metabolite chemotherapeutic drug. It interferes with DNA synthesis and disrupts cell multiplication, thus preventing the pregnancy from forming.
Indications for surgical management of ectopic pregnancy
Laparoscopic salpingectomy (or salpingotomy if there is a risk of infertility)
Larger than 35mm
Causing severe pain
BhCG>1500
Risk of infertility if remaining Fallopian tube is problematic in the future
In utero, what performs the normal functions of the liver? (metabolic)
Placenta (e.g. unconjugated bilirubin from haemolysis in the foetus is transferred to the mother rather than being conjugated in the foetus)
What may cause physiological jaundice?
The foetal liver is less able to conjugate bilirubin than the adult liver because of deficiencies of enzymes (e.g. UGT)
After birth, loss of placenta and this immature ability to conjugate bilirubin (especially in prematuer infants) may result in transient unconjugated hyperbilirubinaemia
What causes pelvic kidney?
Failure of normal migration (as the foetus develops, the torso elongates and the kidneys rotate and migrate upwards within the abdomen causing the length of the ureters to increase)
What causes duplex kidneys?
Abnormal development of the collecting duct system can result in duplications such as duplex kidneys
What is the danger with severe ureteric obstruction in utero?
Can lead to hydronephrosis and renal interstitial fibrosis
Why are preterm infants at increased risk of acid-base homeostasis issues, even though the structures of the urinary system are already in place at 32-36 weeks?
The excretory and concentrating ability of foetal kidneys develops gradually and continues after birth –> preterm infants may experience abnormal water, glucose, sodium and acid-base homeostasis
What is a posterior urethral valve?
An obstructing membrane in the posterior male urethra
Renal agenesis results in what?
Oligohydramnios (foetal urine forms much of the amniotic fluid)
Bilateral renal agenesis causes Potter’s syndrome, which is associated with:
Widely-s[aced eyes Small jaw Low set ears Secondary oligohydramnios Renal failure (and death) Pulmonary hypoplasia
Preterm babies have no vernix (which is what the periderm sloughs off as) and thin skin:
This leads to insensible fluid loss
They also have poor thermal control due to having a large surface area to body weight ratio and little insulation
They also have immature vascular tone meaning that they cant use peripheral vasoconstriction to limit heat loss
When is lanugo hair shed?
Usually shed before birth
Why are there more Treg cells in the second trimester than at any other point in life?
It is important in the induction of tolerance
IgM or IgA in the newborn without IgG: what is this suggestive of?
Foetal infection
(much of the IgG in the foetus will be from the mother.
The foetus produces small amounts of IgA and IgM)
When is the switch from foetal to adult haemoglobin?
28-34 weeks
HbF has a higher affinity for oxygen. Infants also have a higher haemoglobin concentration which enhances transfer of oxygen across the placenta
Growth-restricted foetuses exist in a state of relative hypothyroidism
May be a compensatory measure to decrease metabolic rate and oxygen consumption
Foetal movements 7-8 weeks
These will begin as discernible movements, and progress to startles, movements of arms and legs and breathing movements
By 12 weeks, yawning, sucking and swallowing can be seens
Four foetal behavioural states
1F- quiescence (like non-REM sleep in a neonate)
2F- frequent and periodic gross body movements with eye movements (like REM sleep)
3F- no gross body movements but eye movements (like quiet wakefulness)
4F- vigorous continual activity with eye movements (like active wakefulness)
What is thought to be the importance to choriodecidual function?
Thought to be important in the initiation of labour by the production of prostaglandins E2 and F2a
How is amniotic fluid removed after 16 weeks?
Foetal swallowing
Quantity of amniotic fluid at - weeks gestation
10 weeks = 30ml
20 weeks = 300ml
30 weeks = 600ml
38 weeks = 1000ml
40 weeks = 800ml
42 weeks = 350ml
Functions of amniotic fluid
Protect the foetus form mechanical injury
Permit the movement of the foetus while preventing limb contracture
Prevent adhesions between foetus and amnion
Permit foetal lung development in which there is two-way movement of fluid into the foetal bronchioles (absence of amniotic fluid in the second trimester is associated with pulmonary hypoplasia)
Causes of oligohydramnios
Renal agenesis
Cystic kidneys (PCKD)
FGR
Causes of polyhydramnios
Congenital neuromuscular disorders
Anencephaly
Oesophageal/duodenal atresia (prevents swallowing of amniotic fluid)
How is GnRH released?
The hypothalamus secretes GnRH in a pulsatile manner to stimulate pituitary secretion of LH and FSH
Outline what occurs in the pituitary following release of GnRH by the hypothalamus
GnRH stimulates basophil cells in the anterior pituitary gland which synthesise FSH and LH. This is modulated by oestrogen and progesterone.
Low oestrogen has an inhibitory effect on LH, but high oestrogen will increase LH production (increases concentrations of GnRH receptors)
The high oestrogen levels in the late folicular phase act via a positive feedback to generate a periovulatory LH surge
Low progesterone has a positive feedback effect on pituitary LH and FSH secretion, high progesterone will inhibit LH and FSH production (by increasing sensitivity to GnRH in the pituitary)
Progesterone can only have these effects on gonadotrophic hormone release after priming by oestrogen
COCP maintains a constant serum oestrogen level that is within the negative feedback range, thereby preventing an LH surge
Outline the hormonal changes that occur during the follicular phase in the ovaries
If LH and FSH are absent, follicular development will fail at the preantral stage and follicular atresia will occur
FSH rises in the first days of the menstrual cycle whilst oestrogen, progesterone and inhibin levels are low
The FSH rise will stimulate a cohort of small antral follicles to grow, within which there are theca cells (LH stimulates productions of androgens from cholesterol) and granulosa cells (convert androgens from theca cells into oestrogens via the process of aromatisation under the influence of FSH)
As follicles grow, oestrogen secretion increases, which has a negative feedback effect on FSH leading to a decrease in FSH- this assists in the selection of the dominant follicle (smaller follicles will undergo atresia)
Inhibin is secreted by the granulosa cells and downregulates FSH release and enhances androgen synthesis
Activin is produced by granulosa cells and the pituitary and acts to increase FSH binding on the follicles
IGF-1 and 3 also act as paracrine regulators, as do kisspeptins
Outline the hormonal changes that occur during ovulation
FSH induces LH receptors on the granulosa cells to compensate for lower FSH levels and prepare for ovulation
Production of oestrogen increases until it reaches a threshold to exert positive feedback on the hypothalamus resulting in an LH surge (this happens over 24-36 hours)
LH-induced luteinisation of granulosa cells in the dominant follicle cause progesterone to be produced, which exerts more positive feedback for LH secretion and causes a small rise in FSH
The LH surge also stimulates the resumption of meiosis
The physical ovulation occurs after breakdown of the follicular wall under the influence of LH, FSH, proteolytic enzymes and prostaglandins
NB: inhibition of prostaglandin production can affect ovulation, therefore women wanting to become pregnant should avoid taking PG synthetase inhibitors (e.g. aspirin, ibuprofen)
Outline the hormonal changes that occur during the luteal phase
After release of the oocyte, the remaining granulosa and theca cells form the corpus luteum
It undergoes extensive vascularisation to supple granulosa cells with a rich blood supply for continued steroid production (aided by local VEGF production)
Ongoing pituitary LH secretion and granulosa activity provides a supply of progesterone, which stabilises the endometrium in preparation of pregnancy
The progesterone also suppresses FSH and LH to prevent further follicular growth
The luteal phase lasts 14 days
In the absence of B-hCG produced by the implanitng embryo, the corpus luteum will regress via luteolysis
The mature corpus luteum will produce less progesterone, which will eventually result in menstruation
A reduction in progesterone, oestrogen and inhibin feeding back to the pituitary cause increased FSH secretion, so new preantral follicles will be stimulated and the cycle begins again
What changes occur to the endometrium during the proliferative phase?
Glandular and stromal growth begins
The epithelium will change from a single layer of columnar cells to pseudostratified epithelium with frequent mitoses
When does the proliferative phase of the endometrium begin?
Immediately after menstruation
What changes occur to the endometrium during the secretory phase?
After ovulation, there is a period of secretory activity
After the LH surge, the oestrogen-induced proliferation is inhibited so that the endometrium does not get any thicker
The endometrial glands, however, become more tortuous, spiral arteries will grow and fluid is secreted into the glandular cells and uterine lumen
Progesterone induces the formation of a temporary layer (decidua) in the endometrial stroma
Apical membrane projections of epithelial cells (pinopodes) appear after day 21-22 which makes the endometrium receptive for implantation
What changes occur in the endometrium during menstruation?
Shedding of dead endometrium
A fall in oestrogen and progesterone at the end of the luteal phase leads to a loss of tissue fluid, vasoconstriction of spiral arterioles and distal ischaemia, leading to tissue breakdown and loss of upper layers
What are the three layers present in the endometrium immediately before menstruation?
Basalis - lower 25% which remains throughout the menstrual cycle
Stratum spongiosum - oedematous stroma and exhausted glands
Stratum compactum - upper 25% with prominent decidualised stromal cells
Why do wpatients on HRT or COCP have a withdrawal bleed on their pill-free week?
Lack of oestrogen or progesterone
How does haemostasis differ in the uterus?
It does not involve clot formation and fibrosis
What initiates the physical changes seen in puberty?
Oestrogen produced by the ovaries (GnRH pulses increase in amplitude and frequency around 8-9 years, leading to an incerase in FSH and LH, which triggers follicular growth and steroidogenesis)
Leptin plays a permissive role in puberty
What is the mean age of menarche?
12.8 years
What is noteworthy about the first few periods?
May take several years before the menstrual cycle establishes a regular pattern
Initial cycles are anovulatory and may be unpredictable and irregular
What tool helps to describe pubertal staging?
Tanner Staging
Define precocious puberty
Onset of puberty before 8 in a girl, or before 9 years of age in a boy
Classification of precocious puberty
Central (gonadotrophin dependent)
Peripheral (gonadotrophin independent): ALWAYS patholigcal. May be caused by exogenous ingestion of oestrogen or hormone-producing tumour
Define delayed puberty
When there are no signs of secondary sexual characteristics by age of 14 years
Causes of delayed puberty
Central defect (hypogonadotrophic hypogonadism) Anorexia nervosa Excessive exercise Chronic illness Kallmann's syndrome
Gonadal failure (hypergonadotrophic hypogonadism)- does not respond to gonadotrophins:
Turner’s (45 XX)
XX gonadal dysgenesis
Premature ovarian failure: can be secondary to autoiummunity, metabolic disorders, chemo/radiotherapy, idiopathic
Main clinical features of Turner’s syndrome
Short stature
Webbing of neck
Wide carrying angle
Associated medical conditions with Turner’s syndrome
Coarctation of the aorta IBD Sensorineural and conduction deafness Renal anomalies Endocrine dysfunction (e.g. thyroid disease)
What is the name given to gonads in Turner’s syndrome
Streak gonads
DO not function to produce oestrogen or oocytes
When is the diagnosis of Turner’s made?
At birth
As the gonads do not produce oestrogen, the physical changes of puberty do not happen
Management of Turner’s syndrome
Focus on growth during childhood
Focus on induction of puberty during adolescence
Pregnancy only possible with ovum donation
In girls with mosaicism, they may undergo normal puberty and menstruation may occur
46 XY gonadal dysgenesis
The gonads do not develop into testis
May be due to SRY gene mutation
In complete gonadal dysgenesis (Swyer syndrome), the gonad remains as a streak and does not produce any hormones
The absence of anti-Mullerian hormone, the Mullerian structures (uterus, vagina and Fallopian tube) will develop normally
The absence of testosterone means the foetus does NOT virilise
The baby is phenotypically FEMALE but has an XY chromosome
The gonads do NOT function and the patient will present with delayed puberty
The dysgenetic gonad has a high malignancy risk and should be removed when the diagnosis is made
Puberty must be induced with oestrogen
Pregnancy may be possible with a oocyte donor
In mixed gonadal dysgenesis, both functioning ovarian and testicular tissue can be present (this is known as ovotesticular DSD)
The anatomical findings depend on the function of the gonads
Complete androgen insensitivity/ 46XY DSD
Most common cause is complete androgen insensitivity
In this condition, virilisation of the external genitalia does NOT occur due to partial or complete inability of the androgen receptor to respond to androgen stimulation
In these patients, testes form normally due to action of the SRY gene
The testes will secrete anti-Mullerian hormone leading to regression of the Mullerian ducts (so they do NOT have a uterus)
Testosterone is also produced BUT the androgen receptors does NOT respond so the external genitalia does NOT virilise and instead undergoes female development
The baby is born with:
Normal female external genitalia
Absent uterus
Testes found somewhere in the line of descent
Presentation is usually at puberty with primary amenorrhoea
NOTE: the testes could cause a hernia
Initial diagnosis should be accompanied by:
Psychological support
Full disclosure of the XY karyotype
Information about infertility
Gonadectomy is recommended because of the small long-term risk of testicular malignancy
Long-term HRT will be required
The vagina may need to be lengthened to be suitable for penetrative intercourse (vaginal dilatation)
In partial androgen insensitivity, the patient may be partially virilised and the baby may be diagnosed at birth with ambiguous genitalia
5-alpha reductase deficiency
The foetus is XY and has normal functioning testes that both produce testosterone and AMH, but the foetus cannot convert testosterone to DHT and so cannot virilise normally
Presentation is usually with ambiguous genitalia
It may also present with increasing virilisation of a female child at puberty
46XX DSD
Most common cause is congenital adrenal hyperplasia (CAH)
Causes virilisation of the female foetus
Enzyme deficiency in the corticosteroid synthesis pathway (mainly 21-hydroxylase - converts progesterone to deoxycorticosterone and 17-hydroxyprogesterone to deoxycortisol) leads to shunting of precursors into the androgen synthesis pathway
Reduced negative feedback due to low output of cortisol leads to adrenal hyperplasia
Physical Changes due to Virilisation:
Enlarged clitoris
Fused labia (scrotal in appearance)
Upper vagina joins the urethra and opens as one common channel into the perineum
2/3 with 21-hydroxylase deficiency will have a salt-losing variety due to inadequate aldosterone production (can cause a salt-losing crisis soon after birth)
Affected individuals require lifelong steroid replacement
Surgical treatment of the genitalia may be considered
Define amenorrhoea
Absence of menstruation for more than 6 months in the absence of pregnancy in a woman of fertile age
Define primary and secondary amenorrhoea
Primary: when a girl fails to menstruate by 16 years of age
Secondary: absence of menstruation for >6 months in a normal female of reproductive age that is not due to pregnancy, lactation or menopause
Define oligomenorrhoea
Irregular periods at intervals of more than 35 days, with only 4-9 periods per years
Causes of ameno/oligomenorrhoea
Hypothalamic (hypogonadotrophic hypogonadism):
Excessive exercise, weight loss, stress
Hypothalamic lesins (craniopharyngioma, glioma)
Head injuries
Kallman’s syndrome (genetic condition causing lack of GnRH)
Systemic disorders (sarcoidosis, TB)
Drugs (progestogens, HRT, dopamine antagonists)
Pituitary (hypogonadotrophic hypogonadism):
Adenomas (prolactinoma is most common)
Pituitary necrosis (e.g. Sheehan’ syndrome)
Iatrogenic (surgery, radiotherapy)
Congenital failure of pituitary development
Ovarian (hypergonadotrophic hypogonadism):
PCOS
Premature ovarian failure= cessation of periods <40 years of age
Endometrial:
Mullerian defects in genital tract (e.g. absent uterus) causing haematocolpos
Secondary amenorrhoea may be due to scarring of the endometrium (Asherman syndrome)
Investigations of ameno/oligomenorrhoea
Pregnancy test if sexually active
Blood for hormone levels: Raised LH+testosterone= PCOS Raised FSH= POF Raised prolactin = prolactinoma Thyroid function if clinically indicated
Ultrasound would be useful to visualise polycystic ovaries
MRI could be used to visualise pituitary gland
Hysteroscopy- Asherman, cervical stenosis
Karyotyping - Turner’s and other chromosomal abnormalities
Management of amenorrhoea/oligomenorrhoea
Low BMI - Dietary advice and support
Hypothalamic lesions (e.g. glioma) - surgery
Hyperprolactinaemia/prolactinoma - Dopamine agonist (e.g. carbergoline or bromocriptine) or surgery if medication falls
POF - HRT or COCP
PCOS - COCP, clomiphene
Asherman’s - Adhesiolysis and IUD insertion at time of hysteroscopy
Cervical stenosis - Hysteroscopy and cervical dilation
Cardinal features of PCOS
Hyperandrogenism
Polycystic ovarian morphology
Which conditions does PCOS predispose to an increased risk of?
T2DM
Cardiovascular events
Clinical features of PCOS
Oligo/amenorrhoea due to chronic anovulation in 75% Hisutism Subfertility in up to 75% Obesity in at least 40% Acanthosis nigricans May be asymptomatic
How is the diagnosis of PCOS made?
Rotterdam consensus criteria - must have 2/3 of these features:
Amenorrhoea/oligomenorrhoea
Clinical or biochemical hyperandrogenism
Polycystic ovaries on ultrasound (12 or more subcapsular follicular cycts < 10mm in diameter and increased ovarian stroma)
Will also have a high LH
Management of PCOS
COCP to regulate menstruation (increases sex hormone-binding globulin which helps to relieve androgenic symptoms)
Cyclical oral progesterone (regulate the withdrawal bleed)
Clomiphene (induces ovulation if subfertility is an issue. SERM.)
Lifestyle advice (dietary modification and exercise if at increased risk of developing T2DM and cardiovascular disease)
Weight reduction
Ovarian drilling (destroys the ovarian stroma and may prompt ovulatory cycles)
Treating hirsutism/androgenic symptoms: Topical efrlonithine cream Crypoterone acetate (antiandrogen) Metformin GnRH analogues (reserved for women intolerant of other therapies) Surgical (laser or electrolysis)
Define PMS
Occurrence of cyclical somatic, psychological and emotional symptoms occurring in the luteal phase
Clinical features of PMS
Bloating Cyclical weight gain Mastalgia Abdominal cramps Fatigue Headache Depression Irritability
Management of PMS
Conservative: Stress reduction Alcohol and caffeine limitation Exercise Vitamins St. John's wort
Medical:
COCP- Bi/tricycling packets is effective (recommended that low-dose progesterone also given)
Transdermal oestrogen- reduces symptoms by overcoming the fluctuations in a normal cycle
GnRH analogues for severe PMS- turn off ovarian activity. HRT should also be administered to prevent osteoporosis
SSRIs for severe PMS
CBT for depression
Surgical (last-resort):
Hysterectomy with bilateral salpingo-oophorectomy (only if all other measures fail)
Mnemonic to categorise gynaecological pathology
PALM COEIN
Polyps Adenomyosis Leiomyoma Malignancy Coagulopathy Ovulatory disorders Endometrial Iatrogenic Not classified
Define menorrhagia
Blood loss > 80ml per period
Difficult to quantify, so has changed to whatever the patient regards as abnormally heavy
Common causes of menorrhagia
Fibroids Adenomyosis Endometrial polyps Coagulation disorders (e.g. vWD) PID Thyroid disease Drug therapy (e.g. warfarin) IUDs Endometrial/cervical carcinoma
Key features of a menorrhagia history
Heaviness of period
Extent to which it disrupts the womans life and causes anaemia
Did the HMB start at menarche or has it changed since?
Regularity of the menstrual cycle
Symptoms associated with HMB and related pathologies
Endometrial or cervical polyp or other cervical abnormality: Irregular bleeding, IMB, PCB
Coagulation disorder: Excessive bruising/bleeding elsewhere, history of PPH, excessive postoperative bleeding, excessive bleeding with dental extractions, family history of bleeding problems
PID: Unusual vaginal discharge
Fibroids: Urinary symptoms, abdominal mass or fullness
Thyroid disease: weight change, skin changes, fatigue
Investigations for HMB
FBC
Coagulation screen if HMB since menarche or FHx of coagulation defects
Pelvic ultrasound scan (if Hx suggests structural/histological problem e.g. PCB, IMB, pain/pressure symptoms, enlarged uterus/vaginal mass)
High vaginal or endocervical swabs
TFTs
Endometrial biopsy indications:
Only if risk factors (e.g. >45 years, treatment failure)
PMB and endometrial thicnkess on TVUSS > 4mm
HMB > 45 years
HMB associated with IMB
Treatment failure
Prior to ablative techniques
Outpatient hysteroscopy with guided biopsy if:
Endometrial biopsy fails
Endometrial biopsy sample is insufficient
TVUSS is inconclusive
Abnormality of TVUSS is amenable to treatment
GA may be needed if outpatient treatment not tolerated
medical management of HMB
Blood loss may be normal
LNG-IUS, Mirena
- Requires long-term use (at least 12 months)
- Reduces mean blood loss
- Should be considered in the majority of women as an alternative to surgical treatment
- NOT suitable in women wishing to conceive
Tranexamic acid
- antifibrinolytic that reduces blood loss by 50%
- Taken during menstruation
- Mefenamic acid inhibits prostaglandin synthesis and redcues blood loss by 30%
- COCP induces slightly lighter periods
Norethisterone
- 15mg daily in a cyclical pattern from day 6-26 of the menstrual cycle
GnRH agonists
- Act on pituitary and stop the production of oestrogen resulting in amenorrhoea
- Used only in the short-term because hypo-oestrogenic state predisposes to osteoporosis
- May be used preoperatively to shrink fibroids or suppress the endometrium to enhance visualisation on hysteroscopy
For whom may surgical management of HMB be considered?
Usually only considered in women for whom medical treatment has failed
Women contemplating surgery must be certain that their family is complete
Surgical management of HMB
Endometrial ablation
- Ablation to a sufficient depth to prevent regeneration
- Suitable for women with a uterus <10 weeks size and with fibroids <3cm
- Methods: impedance controlled endometrial ablation, thermal uterine balloon therapy, microwave ablation
- 80% will have markedly reduced menstrial bleeding or become amenorrhoeic
Uterine artery embolisation
- Useful for HMB associated with fibroids
Myomectomy
- Useful for women with HMB secondary to large fibroids with pressure symptoms who wish to conceive
Transcervical resection of fibroid
- Used for resection of large submucosal fibroids
- May reduce HMB and is appropriate for women wishing to conceive
Hysterectomy
- Surgical removal of the uterus
- Considered in women with HMB associated with large fibroids with pressure symptoms
Management of acute heavy menstrual bleeding
Require stabilisation, examination to exclude cervical abnormalities and pelvic masses
Medications are needed to arrest bleeding and correct anaemia
Admit
Pelvic examination
FBC, coagulopathy screen, biochemistry
IV access and fluid resuscitation
Tranexamic acid oral or IV
TVUSS
High-dose progestogens to arrest bleeding
Consider suppression with GnRH or ulipristal acetate
Longer-term plan when diagnosis has been made
What is the difference between primary and secondary dysmenorrhoea?
Primary= painful periods since the onset of menarche (unlikely to be associated with pathology)
Secondary= painful periods that have developed over time and usually have a secondary cause
Important to distinguish between menstrual pain that precedes the period and pain that only occurs with bleeding
Causes of secondary dysmenorrhoea
Endometriosis or adenomyosis
PID
Cervical stenosis and haematometra (rare)
May be associated with dysapreunia or AUB (abnormal uterine bleeding)
Additional examination findings for dysmenorrhoea
Pelvic mass - endometriosis? Fixed uterus - adhesions? Endometriotic nodule Enlarged uterus - fibroids? Abnormal discharge and tenderness - PID
Investigations for dysmenorrhoea
High vaginal and endocervical swabs
TVUSS is useful to detect endometriomas and adenomyosis
Diagnostic laparoscopy - to investigate secondary dysmenorrhoea
- when the history suggests endometriosis
- when swabs and ultrasound scans are normal but symptoms persist
- when the patient wants a definitive diagnosis or wants reassurance
Management of dysmenorrhoea
NSAIDs
COCP
- Widely used but may not be effective
- Progestogens may be useful to cause anovulation and amenorrhoea
LNG-IUS
- Effective treatment for underlying causes (e.g. endometriosis and adenomyosis)
Lifestyle changes: exercise and dietary (vegetarian) changes may help
Heat
GnRH analogues
- Useful in short term to manage symptoms if awaiting hysterectomy
Surgery
When does successful implantation occur?
When the oocyte is fertilised in the Fallopian tube and implants in the endometrium around 7 days after ovulation
How is the corpus luteum saved from luteolysis during implantation?
The implanted blastocyst secretes hCG which acts on the corpus luteum to rescue it from luteolysis to maintain progesterone secretion, prevent menstruation and support the early conceptus
What is the main source of progesterone to the implanted blastocyst after 8 weeks?
The corpus luteum supports the pregnancy for about 8 weeks
After this, the early placental tissue becomes the main supply of progesterone
What is a biochemical pregnancy?
A positive pregnancy test will detect hCG in the urine 1-2 days before the expected date of menstruation
This transiently positive hCG is a result of pregnancy failure during the early stages of implantation = biochemical pregnancy
When is the foetal heartbeat present on ultrasound?
A TVUSS can detect an early intrauterine gestational sac at around 5 weeks
The foetal heartbeat is visible as early as 6 weeks gestation
Define miscarriage
Pregnancy that ends spontaneously before 24 weeks gestation
Clinical presentation of miscarriage
Vaginal bleeding
Threatened miscarriage
Intrauterine preganncy on USS (with foetal heartbeat)
Vaginal bleeding and abdominal pain
Cervical os closed
Managed supportively
Inevitable miscarriage
Intrauterine pregnancy on USS (no foetal heartbeat)
Vaginal bleeding and abdominal pain
Cervical os open
Expectant, medical or surgical management
Incomplete miscarriage
Retained products of conception
Vaginal bleeding and abdominal pain
Cervical os open, products of conception located in cervical os
Remove pregnancy tissue at time of speculum if possible
Expectant, medical or surgical management
Complete miscarriage
Empty uterus (need serum hCG to exclude ectopic pregnancy if no previous USS identifying intrauterine pregnancy)
Pain and bleeding has resolved
Cervical os closed
Supportive management
Missed miscarriage
Intrauterine pregnancy (no foetal heartbeat)
Asymptomatic
Often diagnosed at booking USS
Expectant, medical or surgical management
Risk factors for miscarriage
Maternal age Chromosomal abnormalities Uterine abnormalities Infections Drugs/chemicals
Investigations for miscarriage
ABCDE
Abdomino-pelvic examination
Address psychological symptoms
TVUSS (can daignose if no pregnancy in uterine cavity)
Haemoglobin and group and save (or cross-match if severely compromised): measure to assess degree of vaginal loss and rhesus status
Management of miscarriage
Threatened Miscarriage
- If the woman has vaginal bleeding and a confirmed intrauterine pregnancy with a foetal heart beat:
- Return for further assessment if the bleeding gets worse or persists beyond 14 days
- Continue routine antenatal care if the bleeding stops
Expectant Management
- Use expectant management for 7-14 days as FIRST LINE in women with confirmed miscarriage
- Explore other options if:
- Increased risk of haemorrhage (e.g. late first trimester)
- Previous adverse/traumatic event associated with pregnancy
- Increased risk from effects of haemorrhage (e.g. unable to have blood transfusion)
- Evidence of infection
- Offer medical management if expectant management is not acceptable
- If bleeding and pain resolves within 7-14 days of starting expectant management, advise taking a pregnancy test after 3 weeks and returning to see the doctor if it is positive
- Offer repeat scan if after the period of expectant management the bleeding and pain:
- Has not started (suggests miscarriage has not begun)
- Persisting and/or increasing (suggesting incomplete miscarriage)
Medical Management
- Do NOT offer mifepristone for miscarriage
- Offer vaginal misoprostol (oral preparation can also be used depending on patient preference)
- If the bleeding has NOT started within 24 hours of treatment, contact a healthcare professional
- Offer pain relief and anti-emetics to all patients undergoing medical management of miscarriage
- Inform patient about what to expect: vaginal bleeding, pain, diarrhoea and vomiting
- Advise taking pregnancy test 3 weeks after medical management
- NOTE: medical management has a 10% failure rate
Surgical Management
- Manual vacuum aspiration under local anaesthetic
- Surgical management in theatre under general anaesthetic
- Vaginal or sublingual misoprostol if often used to ripen the cervix to facilitate cervical dilatation for suction insertion
- Offer anti-D prophylaxis to all Rhesus-negative women undergoing surgical management of miscarriage
Define recurrent miscarriage
Loss of three or more consecutive pregnancies
Risk factors for recurrent miscarriage
Advancing maternal and paternal age Obesity Balanced chromosomal abnormalities Uterine structural anomalies Antiphospholipid syndrome
Causes of recurrent miscarriage
Antiphospholipid syndrome Cervical abnormalities Foetal chromosomal abnormalities Uterine malformations Thrombophilia
Investigations for recurrent miscarriage
Screen for antiphospholipid syndrome
- Lupus anticoagulant
- Anti-cardiolipin antibodies
- DIAGNOSTIC: 2 positive results at least 12 weeks apart)
Cytogenetic analysis
- Of products of conception in the last miscarriage
- Of both partners peripheral blood
TVUSS to assess for uterine anomalies
Screen for inherited thrombophilia (e.g. factor V leiden)
Management of recurrent miscarriage
Antiphospholipid syndrome
- Low-dose aspirin + LMWH in future pregnancy reduces risk of miscarriage by 54%
- NB: steroids and IVIG have no proven benefit
If abnormal parental genetics are found, refer to a clinical geneticist
Cervical issues may be treated with cerclage
Define ectopic pregnancy
Implantation of a pregnancy outside the normal uterine cavity
What is the most common location for an ectopic pregnancy to implant?
Over 98% of ectopic pregnancies will implant in the Fallopian tube
Rare sites: interstitium of the tube, ovary, cervix, abdominal cavity, C-section scars
Who is at greater risk of heterotopic pregnancies? (simultaneous development of two pregnancies, one within and one outside the uterine cavity)
Incidence is higher in patients receiving IVF
Aetiology of ectopic pregnancy
Fallopian tube damage due to pelvic infection, previous ectopic pregnancy and previous tubal surgery
Functional alterations in the Fallopian tube due to smoking and increased maternal age
Previous abdominal age
Subfertility
IVF
Use of intrauterine contraceptive devices
Endometriosis
Conception on oral contraceptive/morning after pill
Clinical presentation of ectopic pregnancy
Abdominal pain and/or vaginal bleeding in early pregnancy
Rarely, patients will present very acutely with rupture of the ectopic pregnancy and massive intraperitoneal bleeding
- The free blood in the peritoneal cavity can cause diaphragmatic irritation and shoulder tip pain
- Signs of acute abdomen and hypovolaemic shock with a positive pregnancy test
Investigations for ectopic pregnancy
ABCDE
Abdominopelvic examination
TVUSS
- Identification of intrauterine pregnancy excludes ectopic pregnancy (except heterotopic pregnancy)
- Ectopic pregnancy will appear as an empty uterus with an adenxal mass
- Presence of moderate to significant free fluid on TVUSS is suggestive of a rupture ectopic pregnancy
Serum hCG
- SHould double every 48 hours in a normal pregnancy, but this rise is suboptimal in an ectopic
- Serial measurements 48 hours apart may show this
Haemoglobin and G+S (or cross-match is severely compromised)
- Measure to assess degree of intra-abdominal bleeding and Rhesus status
Pregnancy of unknown location
- IN 40% of women with ectopic pregnancy, the diagnosis is not made on first attendance and are labelled as having pregnancy of unknown location (PUL)
- TVUSS shows an empty uterus with no evidence of an adnexal mass in a patient with a positive pregnancy test
- Investigate with consecutive measurement of serum hCG
- Endometrial biopsy may be useful if hCG levels are static
Management of ectopic pregnancy
Expectant
- Based on the assumption that a significant proportion of ectopic pregnancies will resolve without treatment
- Suitable for patients who are haemodynamically stable and asymptomatic
- The patient should have serial hCG measurements until the levels are undetectable
Surgical and Medical
- Provide advice on how to contact a healthcare professional if needed and when to get help in an emergency
- Offer IM METHOTREXATE as 1st line if able to attend follow-up and provided that all of the following criteria are fulfilled:
- No significant pain
- Unruptured ectopic pregnancy with adnexal mass < 35 mm with no visible heartbeat
- Serum b-hCG < 1500 iU/L
- No intrauterine pregnancy (confirmed by USS)
- FOLLOW-UP
- Take 2 serum hCG measurements at days 4 and 7
- Take 1 serum hCG per week until a negative result is obtained
- Avoid sexual intercourse during treatment
- Avoid conceiving for 3 months after methotrexate
- Avoid alcohol and prolonged exposure to sunlight
- Offer SURGERY as 1st line if unable to return for follow-up or any of the following:
- Significant pain
- Adnexal mass > 35 mm
- Ectopic pregnancy with a foetal heartbeat visible on ultrasound scan
- Serum b-HCG > 5000 iU/L
SURGERY
- Laparoscopic where possible
- Offer salpingectomy unless there are other risk factors for infertility
- Consider salpingotomy if there are risk factors for infertility or contralateral tubal damage
- WARNING: 1 in 5 women who have salpingotomy need further treatment (methotrexate and/or salpingectomy)
- FOLLOW-UP for Salpingotomy: 1 serum hCG at 1 weeks, then 1 serum hCG per week until negative result is obtained
- FOLLOW-UP for Salpingectomy: urine pregnancy test at 3 weeks
Offer a CHOICE of either methotrexate or surgery if b-hCG 1500-5000 iU/L and:
- No significant pain
- Unruptured ectopic with adnexal mass < 35 mm with no visible heartbeat
- No intrauterine pregnancy identified on USS
- IMPORTANT: methotrexate carries a greater risk of urgent re-admission
Anti-D Prophylaxis
- Offer anti-D prophylaxis (250 iU) to all RhD-negative women who have a SURGICAL management of ectopic pregnancy or miscarriage
- Do NOT do Kleihauer test
- Do NOT offer anti-D prophylaxis if:
- Solely medical management
- Threatened miscarriage
- Complete miscarriage
- Pregnancy of unknown origin
Gestational trophoblastic disease
Risk factors:
- Previous molar pregnancy
- Persistently raised hCG levels after miscarriage
Clinical presentation:
- US features of intrauterine vesicles (‘cluster of grapes)
- Persistently raised hCG levels after miscarriage
Management:
- Uterine evacuation by suction curettage (without misoprostol
- Serial hCG measurements
- Avoid oestrogens
Hyperemesis gravidarum
Risk factors:
- Multiple pregnancies
Clinical presentation:
- Excessive nausea and vomiting, often accompanied by dehydration
Management:
- Antiemetics
- Fluid and electrolyte replacement
- Multivitamin
- Thromboprophylaxis
Which contraceptives prevent ovulation?
Combined hormonal methods (pill, patch, vaginal ring) Progesterone-only injectables Progesterone-only implant (Nexplanon) Oral emergency contraception Lactational amenorrhoea
Which contraceptives work to prevent sperm reaching the oocyte?
Female and male sterilisation
Which contraceptives work to prevent an embryo implanting in the uterus?
cu-IUD
LNG-IUS
What is the definition of LARC in the UK/
A method of contraception that requires administration less than once per month (e.g. implant, injectable, IUD)
MEC category 4 (absolute contraindication to COCP)
Age >35 and smoking BP >160/100 Hypertension with vascular disease DVT, current or past MI, current or past Cerebrovascular accident, current or past Multiple serious risk factors for cardiovascular disease Known thrombogenic mutations Current breast cancer
Which medications induce liver enzymes, and may reduce the efficacy of hormonal methods of contraception?
Anticonvulsants
Antifungals
Antibiotics
Antiretrovirals
If a woman using enzyme-inducing medication wants to use hormonal methods of contraception, consistent use of condoms is also advised
Alternatively, they could consider methods that are unaffected by enzyme induction, such as Cu-IUD, LNG-IUS, or the progesterone-only injectable
Effectiveness of the COCP is not affected by administration of most broad-spectrum antibiotics
Common side-effects amongst all hormonal methods of contraception
Unexpected bleeding
- if it does not settle with time, changing the contraceptive or using a different dose may help
- If bleeding continues for >3 months, investigations to exclude other causes (e.g. polyps, chlamydia infection) should be considered)
Weight gain (IMPORTANT) - There is no evidence that hormonal methods (except the progesterone-only injectable) causes weight gain
Headaches
- If women using COCP experience headaches in the pill-free week, they may benefit from continuing packets of pills to avoid the hormone-free interval
- If headaches occur during the use of the hormonal method that are severe, frequent or migraine, changing the method of contraception is advisable
Mood swings
Loss of libido
What women need to know before starting a method of contraception
How to use the method and what to do when misused (e.g. missed pill) Typical failure rates Common side-effects Health benefits Fertility returning on stopping When she requires review
Formulations available of combined hormonal contraception
Oral pill
Transdermal patch
Vaginal ring
How does combined hormonal contraception work?
Inhibits ovulation via negative feedback of oestrogen and progestogen on the pituitary with suppression of FSH and LH
COCP
Most commonly used COCPs contain ethinyl oestradiol (15-35 mcg)
Some newer pills contain oestradiol valerate or oestradiol hemihydrate
Most preparations contain 21 pills followed by a 7-day pill-free interval (or 7 placebo tablets)
Some preparations will contain 24 pills with a shorter pill-free interval
Preparations are usually monophasic (same dose of hormones throughout)
The 21 days on 7 days off regimen usually results in a withdrawal bleed during the pill-free interval
IMPORTANT: there is no reason why women cannot take the pill continuously
Women with dysmenorrhoea or headaches during the pill-free interval are advised to avoid recurrence of symptoms by tricycling (taking 3 packets without a break)
Progestogens in the pills are categorised as follows:
- 2nd Generation: levonorgestrel, norethisterone
- 3rd Generation: gestodene desogestrel
- 4th Generation: drospirenone, dienogest
- IMPORTANT: 2nd generation progestogens are recommended because 3rd and 4th generation progestogens are associated with an increased risk of venous thrombosis
Combined hormonal patch
Combined hormonal transdermal patch releases 33.9 mcg ethinyl oestradiol per day and norelgestromin 203 mcg/day
It is applied to the skin of the lower abdomen, buttock or arm for 7 days
Usually involves application of patches for a total of 21 days followed by a 7-day hormone free interval
Continued use (tricycling) is also possible
Problems include patch adherence or skin sensitivity
Combined hormonal ring
Flexible ring of 54 mm diameter that releases 15 mcg ethinyloestradiol and 120 mcg etonorgestrel daily
This is lowest dose combined hormonal method
The ring is inserted and worn in the vagina for 21 days followed by a 7-day hormone free period during which withdrawal bleeding occurs
Women should not feel discomfort from the ring
If one pill has been missed (more than 24 hours and up to 48 hours late)
The missed pill should be taken as soon as it is remembered
The remaining pills should be continued at the usual time
Emergency contraception is not usually required but may need to be considered if pills have been missed earlier in the packet or in the last week of the previous packet
If two or more pills have been missed (more than 48 hours late)
The most recent missed pill should be taken as soon as possible
The remaining pills should be continued at the usual time
Condoms should be used or sex avoided until seven consecutive active pills have been taken. This advice may be overcautious in the second and third weeks, but the advice is a backup in the event that further pills are missed
- If pills are missed in the first week (pills 1-7), emergency contraception should be considered if unprotected sex occurred in the pill-free interval or in the first week of pill taking
- If pills are missed in the second week (pills 8-14), no indication for emergency contraception if the pills in the preceding 7 days have been taken consistently and correctly (assuming the pills thereafter are taken correctly and additional contraceptive precautions are used)
- If the pills are missed in the third week (pills 15-21), omit the pill-free interval by finishing the pills in the current pack (or discarding any placebo tablets) and starting a new pack the next day
Length of action of contraceptives
Oral CHC and progestogen - 24 hours Transdermal CHC - 7 days Vaginal ring CHC - 21 days Progestogen-only injectable -14 weeks Progestogen-only implant - 3 years Cu-IUD - 3, 5, 10 years or more LNG-IUS - 3, 5 years or more
Cancer risks among COCP users
12% reduced risk of any cancer
Reduced risk of colorectal, endometrial and ovarian cancer
Increased risk of breast cancer during use
Increased risk of cervical cancer
Protection from endometrial and ovarian cancer seems to persist for more than 15 years after stopping the pill
The risk of breast cancer is increased during use, but will decrease to the same as women who have never used the pill after 10 years
VTE and arterial disease in COCP users
CHC increases the tendency to thrombosis
The absolute risk of thrombosis is very small and much less than that associated with pregnancy
Risk is greatest within the first year of use
Women should be asked about personal or family history of VTE (contraindications)
WOmen > 35 years who smoke are not eligible for CHC because of an increased risk of arterial disease
It is also contraindicated in women who have migraine with aura as this condition is associated with cerebral vasospasm and women may be at increased risk of stroke if they use a CHC
Formulations of progestogen-only contraceptive methods available
Oral
Injectable
Implant
Intrauterine system
How do progestogen-only contraceptives work to prevent pregnancy?
The injectable, implant and desogestrel-containing progestogen-only pill inhibit ovulation
All progestogen-only contraceptives thicken cervical mucus thereby reducing sperm penetrability
and transport
The LNG-IUS has little effect on ovarian activity but causes marked endometrial atrophy meaning that implantation is not possible
Progestogen-only pill
Needs to be taken continuously
Medium-dose pills (e.g. desorgestrel) inhbit ovulaiton in 99% of cycles
Lower-dose pills inhibit ovulation less frequently and rely on thickening of cervical mucus for its contraceptive effect
Side-effects of progestogen-only pill
Irregular bleeidng
Persistent ovarian follicles (simple cysts)
Acne
If missed, the woman should continue taking POP and use extra precautions (e.g. condoms) for the next 48 hours
If unprotected sex occurs during this time, emergency contraception is recommended
How can PPROM be prevented in high risk women?
Vaginal progesterone
Cervical cerclage
If pooling of amniotic fluid is not observed on examination of a woman with suspected PPROM, which other test could be conducted?
IGF binding protein-1
Placental alpha microglobulin-1
Which organisms are likely implicated in PPROM?
GBS
E.coli
How would a patient with PPROM but no signs of infection be managed?
Monitor for signs of infection
Offer oral erithromycin 250mg QDS for a maximum of 10 days or until the patient is in established labour
Do NOT use tocolysis (increases risk of infection)
Decision to deliver depends on risk of prematurity and risk of maternal/foetal infection if delivery is delayed
What is the first line antiemetic used in hyperemesis gravidarum?
Antihistamine (e.g cyclizine)
Phenothiazine (e.g. promethazine)
2nd line: metoclopramide or ondansetron
Thromboprophylaxis
Thiamine supplementation
What is the currently available option for progestogen-only implant?
Single rod (Nexplanon) containing progestogen etonorgestrel
How long does Nexplanon provide protection for
Provides contraception for 3 years
How is Nexplanon inserted?
Nexplanon is inserted subdermally 8cm above the medial epicondyle in the non-dominant arm under local anaesthesia
The implant is not visible but should be easily palpable
It shows up on X-rays
When should Nexplanon patients be reviewed?
Once inserted, there is no need for follow-up until the device is due for removal
When can a patient with progestogen-only implant expect to regain fertility?
Immediately after removal
