Early Pregnancy Problems Feras Izzat Consultant Gynaecologist – EGU/EPAU Lead University Hospitals Coventry & Warwickshire NHS Trust

Introduction Ectopic Pregnancy Bleeding in early pregnancy and miscarriage Gestational Trophoblastic Disease

Ectopic Pregnancy

Definition Pregnancy occurring outside uterine cavity Approx 11/1000 of pregnancies – rate increasing Maternal mortality in 1/2500 ectopic pregnancies (11 deaths in most recent report)

Site Tubal Non Tubal Ovary Abdominal cavity Cervix CS Scar Interstitial 2.4% Isthmic 12% Ampullary 70% Fimbrial 11.1% Non Tubal Ovary Abdominal cavity Cervix CS Scar

Risk factors Previous PID Previous ectopic pregnancy Previous tubal surgery (e.g. sterilisation, reversal) Pregnancy in the presence of IUCD POP ART (IVF)

Symptoms Acute Chronic (Atypical) Low abdominal pain – peritoneal irritation by blood Vaginal bleeding – shedding of decidua Shoulder tip pain – referred from diaphragm Fainting - hypovolaemia Chronic (Atypical) Asymptomatic, gastrointestinal symptoms

Signs Abdominal tenderness Adnexal tenderness / mass Shock – tachycardia, hypotension, pallor None

Diagnosis Ultrasound Serum βhCG & Progesterone Laparoscopy Empty uterus, adnexal mass, free fluid, occasionally live pregnancy outside of uterus Serum βhCG & Progesterone Laparoscopy

Ultrasound

Ultarsound Trans-Vaginal Ultrasonography Sensitivity 100%, specificity 98.2%. The positive predictive value 98%, and the negative predictive value was 100% FH seen in 23% Timor-Tritsch et al, 1990 Am J Obstet Gynecol.

Left Ectopic on laparoscopy

Management Conservative Medical Surgical - Laparoscopy hCG <1000 , Progesterone < 5 stable, success 70% Medical Methotrexate – hCG <4000 mass < 3cm, success 84%. Susequent IUP 54% recurrent EP 8% Surgical - Laparoscopy Salpingectomy, IUP 38.3%, EP 9.8 Salpingotomy, IUP 61.1%, EP 15.5 Yao et al, Fertility Sterility 1997

PUL Pregnancy of unknown location (PUL) - positive pregnancy test with no signs of intra- or extrauterine pregnancy on transvaginal sonography (TVS). 15-20% of all EPAU scans Management should be expectant if stable with an initial serum progesterone (<20) and a hCG ratio 0h/48h of <0.87 Condous et al, Ultrasound Obstet Gynecol 2006

Bleeding in Early Pregnancy & Miscarriage

Definitions Threatened miscarriage Vaginal bleeding at < 24 weeks gestation Delayed (silent) miscarriage Gestational sac with/without fetus present (but no FH) Recurrent miscarriage 3 or more consecutive miscarriages (with or without a known cause)

Miscarriage Approximately 30% of pregnant women will experience bleeding in early pregnancy At least 50% of women with threatened miscarriage will have continuing pregnancy Miscarriage occurs in 15-20% of clinically diagnosed pregnancies

Causes of miscarriage Genetic abnormalities 85% Maternal illness e.g. diabetes, Thyroid disease Phospholipid / Lupus – 15% recurrent miscarriages Uterine abnormalities ‘Cervical incompetence’ Progesterone deficiency?

History LMP When? Amount? Pain? Timing of Pain

Examination ABC (vital signs) Abdominal Vaginal (speculum) Cx state Amount of bleeding

Cusc’o speculum Sim’s speculum

Investigations Ideally in dedicated ‘Early Pregnancy Assessment Unit’ Ultrasound Measurement of serum βhCG Determination of blood & Rhesus group FBC, G&S and admit if significant bleeding Psychological support

Ultrasound Expect to see viable fetus from around 6.5 weeks transabdominally, 5.5 weeks transvaginally Diagnosis can be made on TVS only CRL ≥ 7mm Empty GS with a mean diameter ≥ 25 mm

Gestational sac

Very early..

Normal 8-9 wk pregnancy

Empty sac

Measurement of βhCG Not necessary if diagnosis unequivocal on scan Useful as part of investigations to diagnose / exclude extrauterine pregnancy Doubling time approx 2 days in viable pregnancy Halving time 1-2 days in complete miscarriage Should see fetal pole with βhCG of 1500-2000

Management of incomplete miscarriage Conservative 76% success Medical mifipristone & misoprostol – 82% success Nielsen et al, BJOG 1999 Surgical (ERPC) No difference in satisfaction rate than medical – 95% Chipchase et al, BJOG 1995

Recurrent miscarriage Loss of 3 or more consecutive pregnancies Affects 1% of women in reproductive age group Investigations can identify up to 50% with a cause Women aged <=30 years have a subsequent miscarriage rate of 25% which rises to 52% in women aged >=40 years. The risk of a subsequent miscarriage is 29% after 3 miscarriages, this rises to 53% in 6 or more previous miscarriages Clifford et al, Human Reproduction 1997

Gestational Trophoblastic Disease

GTD The abnormal proliferation of gestational trophoblast tissue Spectrum of disease Pre-Malignant Partial Molar Pregnancy Complete Molar Pregnancy Malignant Invasive mole Choriocarcinoma Placental site trophoblastic tumours

Molar Pregnancy 1 in 1000 live births Partial Complete Partial moles are triploid with 2 sets of paternal and 1 set of maternal chromosomes An embryo often present that dies at 8-9 weeks 0.5% need chemotherapy for invasive disease Complete No fetal pole, diplod chromosomes paternally derived – androgenetic No embryo Chemo therapy rate 8-20%

Presentation Vaginal bleeding Excessive N&V ‘Hyperemesis gravidarum’ Uterus large for dates

Diagnosis Ultrasound Histology after surgical evacuation

Complete mole at hysterectomy

Follow-up Monitor via regional centre – London, Sheffield, Dundee CM – 8-20% risk of invasive disease PM – 0.5% Choriocarcinoma may follow any subsequent pregnancy – miscarriage, TOP, term delivery Choriocarcinoma is curable Monitor βhCG levels to check resolution – for 6 months to 2 years