Early Pregnancy Problems

1. Early Pregnancy Problems Sarah Bray GPST2

2. Why women’s health? Women-specific health matters including contraception, pregnancy, menopause and disorders of reproductive organs will account for over 25% of your time as a general practitioner (GP)

3. 3.06 Women’s Health • Recognise common signs and symptoms of, and know how to manage, gynaecological disease; be the first port of call for pregnancy, eating disorders and other conditions confined to or more common in women, involving other members of the healthcare team as appropriate • Recognise and intervene immediately when patients present with a gynaecological or obstetric emergency

4. Aims and Objectives • To be able to identify presentations of suspected ectopic pregnancy and know how they are investigated and managed in secondary care • To be able to identify presentations of hyperemesis gravidarum and know how to investigate and manage the condition in primary care, including when to refer to secondary care. • To be aware of the many other (minor) problems that may present in pregnancy.

5. Ectopic Pregnancy

6. Case of SH • 20 year old girl • Periods usually regular but since TOP 6 months ago have been more irregular • 1 other previous TOP • Previous chlamydia infection, recent swabs NAD but partner then tested positive • Not using any contraception • 2 day history of severe RIF pain worse on movement • Irregular heavy PV bleeding for past 2 weeks, last period prior to that a lot lighter 6 weeks ago • Faintly positive PT in GP practice

7. Definition • Fertilised ovum implanted in a tissue other than the endometrial lining of the uterus • Approximately 1% pregnancies • Most occur within one or other of fallopian tubes • Can also occur in cervix, ovaries, abdomen • 10 deaths 2005-2008 • 32,000 cases in the UK in a 3 year period

9. Risk factors • Any tubal pathology • Previous ectopic pregnancy • Previous PID/chlamydia • Previous pelvic surgery including tubal surgery/sterilisation • Smoking • Advanced maternal age • Failed IUCD/failed tubal ligation • IVF/assisted fertilisation

10. Presentation • Pelvic pain, often unilateral • Abnormal vaginal bleeding • Collapse • 5-14 weeks gestation, most present 6-8 weeks post LMP • May be an incidental finding at USS • Less common symptoms: • Shoulder tip pain • Dizzy spells/syncope • Diarrhoea and vomiting (atypical presentation) • Negative PT makes ectopic unlikely but not impossible

11. Investigation How would you manage SH if she presented to you in primary care?

12. Serum β-hCG (sBhCG) • Can be positive within 7-10 days of conception • Doubles approximately every 48 hours in 85% of normal intrauterine pregnancies of 4-6 weeks • In more than 80% of ectopic pregnancies the rise in serum sBhCG is <66% in 48 hrs (in about 13% of ectopics the doubling time is normal – false negatives) • About 15% of normal pregnancies have subnormal doubling time • At levels of 1000 -1500 iu/L (discriminatory zone), an intrauterine gestation sac should normally be seen by high resolution transvaginal ultrasound imaging • Less than 10% of ectopic pregnancies have pseudogestational sac • Normal values of sBhCG: • 5 weeks 20 – 7000 IU/L • 6 weeks 1000 – 56000 IU/L • 7 – 8 weeks 7500 – 230000 IU/L

13. Mean (SE) serum concentrations of human chorionic gonadotrophin (adapted from Braunstein et al 1976)

14. USS • Transvaginal ultrasound shows fetal heart action in normal pregnancy around 37 days from first day of last menstrual period on scanning. • In IVF pregnancies the incidence of heterotopic pregnancy (both intrauterine and ectopic at once) is 1 in 33 – 100. • Possible findings: • Intrauterine pregnancy • Adnexal mass • Free fluid • No abnormality i.e. pregnancy of unknown location

15. Management Options • Surgical Management • Medical Management • Expectant Management

16. Surgical management • If high sBhCG >4000 IU/L or cardiac activity seen within ectopic • Urgent in signs of shock or already ruptured • Salpingostomy or salpingectomy • Laparoscopic vs laparotomy • If sBhCG >1500 IU/L diagnostic laparoscopy may be required

17. Medical management • 1st line if haemodynamically stable, sBhCG <3000 IU/L, measures <3.5cm, absent fetal heart beat, minimal free fluid, minimal symptoms • Methotrexate IM – dose calculated according to weight (50mg/m2) • Monitor with serial sBHCG day 4 and 7 • Some require second dose (if fall in sBhCG between days 4 to 7 <15%) • Avoid SI, adequate fluid intake, reliable contraception 3 months (teratogenic risk)

18. Following methotrexate management • 7% chance of rupture after medical management • Monitoring of sBhCG may take up to 10 weeks • Adverse effects include abdominal pain (75%) following treatment and, more rarely, conjunctivitis, stomatitis, and gastrointestinal upset • Some women with abdominal pain will need to be admitted for observation and assessment, as it can be impossible to distinguish pain due to tubal abortion from pain due to tubal rupture

19. Expectant management • sBhCG <1500 IU/L and no visible intra or extra-uterine pregnancy seen on USS = pregnancy of unknown location • If no or minimal symptoms and no blood in POD – sBhCG in 48 hours • If there is a normal increase in sBhCG (>66%) – repeat USS in 1 week • If there is a subnormal increase in sBhCG (<66%) or clinical deterioration – diagnostic laparoscopy • If there is a fall in sBhCG: • If bleeding – manage as miscarriage i.e. ERPC surgically or medically and send for histology to confirm of miscarriage • If no bleeding – review in 3 days • Serial sBhCG should be monitored until < 20 IU/L

20. Follow up • All rhesus negative patients must have anti-D immunoglobulin within 72 hours of initial assessment. • Advise all patients to return ASAP (or see their GP) if symptoms change. • Follow up histology. • Counsel women regarding the risk of recurrence.

21. Case of SH • Tender RIF with guarding and rebound tenderness, no palpable mass • Right adnexal tenderness but no masses on PV examination • sBhCG 201 • Pain settled with analgesia • USS revealed adnexal mass on right • Repeat sBhCG 140 then 42 • Received expectant management for miscarriage

22. http://www.ectopicpregnancy.co.uk/ • http://www.ectopic.org.uk

24. Hyperemesis Gravidarum

25. Case of AW • 30 years old • First pregnancy • 8 weeks gestation by LMP • Persistent vomiting for past week • Unable to tolerate food or fluids for past 24 hours • Passing little urine • Small sample in GP – ketones 4+

26. Definition • Nausea (70%) and vomiting (60%) common in 1st trimester, peaking at 10/40 • Hyperemesis = fluid and electrolyte imbalance and nutritional deficiency • Persistent and severe vomiting • Less common (3.5/1000) • More severe in: • Multiple gestation • Hydatidiform mole • Without treatment can lead to CNS disturbance, liver and renal failure

27. Presentation • Severe nausea and vomiting • Dehydration • Weight loss • Ketosis • Ptyalism (unable to swallow saliva)

28. Diagnosis • Consider other causes e.g. UTI, gastritis, ketoacidosis, peptic ulceration, Addison’s disease, pancreatitis • Investigations: • FBC (raised haematocrit) • U&E (hyponatraemia, hypokalemia, hypouraemia) • LBP (raised transaminases, found in up to 50% cases) • TFTs (thyrotoxicosis) • Urinalysis and MSU for culture and sensitivity • USS (if not done yet) • Weight

29. Management • If no ketones: • Regular anti-emetics: - Promethazine hydrochloride 25mg QDS or - Cyclizine 50mg TDS or - Prochlorperazine 5-10mg TDS • Reassurance should be given • Dietary advice (small, frequent carbohydrate meals low in fat, avoiding spicy foods, trying cold meals, ginger root, vitamin B6) • Review as appropriate

30. Inpatient Management • IV rehydration • Normal Saline (sodium chloride 0.9%, 150mmol/l Na+) or Hartmann’s solution (sodium chloride 0.6%, 131mmol/l Na+) • Potassium chloride 40mmol/l should be given as required to correct hypokalaemia • DO NOT use 5% dextrose (Wernicke’s encephalopathy may be precipitated) • Thiamine supplementation • In severe cases of hyperemesis (vomiting for more than 2 weeks) : give Thiamine 25-50mg TDS orally or Intravenous thiamine (Pabrinex) injection diluted in 100mls NaCl 0.9% infused over 30min, once weekly.

31. Inpatient Management contd … • Regular anti-emetics • 1st line - Promethazine hydrochloride 25mg QDS IM/PO • 2nd line - Cyclizine 50mg TDS IM/PO • 3rd line - Prochlorperazine 12.5mg TDS IM or suppository 5-10mg TDS or tablets 5 -10mg TDS • 4th line - Metoclopramide 10mg TDS IM/PO • 5th line - Corticosteroids: • 100mg IV Hydrocortisone BD for a maximum of 3 days • Oral therapy: Prednisolone 40mg for 3 days, continue to decrease dose by 5mg every 3 days until 5 mg daily for 3 days. Then decrease by 1 mg every 3 days until 1 mg daily for 3 days. (Total of 36 days of drug therapy max)

32. Further management • Thromboprophylaxis: • TED stockings for all inpatients • LMWH (Fragmin) with TEDs if one of the following factors: • age >35 years old • BMI >35 at booking • Parity >4 • Sickle cell disease • Varicose veins • Personal or family history of thromboembolic disease • Significant dehydration • In patient for more than 4 days • Repeat Investigations: • Urinalysis daily • U&Es alternate days while on intravenous fluids • LBP and TFTs in 4 weeks if abnormal • Weight twice weekly (inpatient only) • Referral to dietician if symptoms not resolved after a week of in-patient treatment • http://www.pregnancysicknesssupport.org.uk/

33. Other (early) pregnancy problems • Back pain • Fatigue • Varicose veins • Constipation • Haemorrhoids • Insomnia • Bloating and reflux • Pruritus gravidarum • Obstetric cholestasis • Red degeneration of fibroids • Urinary frequency

34. References • AGH clinical guidelines • Ectopic Pregnancy • Hyperemesis gravidarum • Green top guidelines • Ectopic Pregnancy : http://www.rcog.org.uk/womens-health/clinical-guidance/management-tubal-pregnancy-21-may-2004 • Oxford Handbook of Obstetrics and Gynaecology (2nd edition 2010) • Mastering the DRCOG, Jamila Groves (2010)