What if a Woman starts Bleeding in Early Pregnancy ? P.H.M van de Weijer MD PhD gynaecologist 24 Januari 2010

What if a Woman starts Bleeding in Early Pregnancy ? The clinical problem © PHMvdW 2010 For the woman,

What if a Woman starts Bleeding in Early Pregnancy ? Vaginal bleeding in the first trimester of pregnancy occurs in about 25 % of pregnant women. It is the commonest complication in pregnancy The clinical problem Hasan R et al. Association between first trimester vaginal bleeding and miscarriage. Obstet Gynecol 2009;114: For the woman, © PHMvdW 2010 Community based pregnancy cohort study level II Participants4510 Vaginal bleeding 1204 (27%)

What if a Woman starts Bleeding in Early Pregnancy ? Vaginal bleeding in the first trimester of pregnancy occurs in about 25 % of pregnant women. It is the commonest complication in pregnancy It may be any combination of light or heavy, intermittent or constant, painless or painful bleeding The clinical problem For the woman, © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Vaginal bleeding in the first trimester of pregnancy occurs in about 25 % of pregnant women. It is the commonest complication in pregnancy It may be any combination of light or heavy, intermittent or constant, painless or painful bleeding The occurrence of vaginal bleeding in early pregnancy is very distressing The clinical problem For the woman, © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? in the first trimester of pregnancy occurs in about 25 % of pregnant women. It is the commonest complication in pregnancy It may be any combination of light or heavy, intermittent or constant, painless or painful bleeding. The occurrence of vaginal bleeding in early pregnancy is very distressing Brier N. Grief following miscarriage: a comprehensive review of the literature. J Womens Health 2008;17: © PHMvdW 2010 Review article Descriptions of grief following miscarriage are highly variable but tend to match descriptions of grief used to characterize other types of significant losses

What if a Woman starts Bleeding in Early Pregnancy ? in the first trimester of pregnancy occurs in about 25 % of pregnant women. It is the commonest complication in pregnancy It may be any combination of light or heavy, intermittent or constant, painless or painful bleeding. The occurrence of vaginal bleeding in early pregnancy is very distressing © PHMvdW 2010 Mann JR et al. Predicting depressive symptoms and grief after pregnancy loss. J Psychosom Obstet Gynaecol 2008;29 : Community based pregnancy cohort study level II Risk factors : Age (young); History of mental illness Inverse association: Religious Attendance

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, The clinical problem © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, it is important : - to understand the short- and long-term consequences of early pregnancy bleeding The clinical problem © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, it is important : - to understand the short- and long-term consequences of early pregnancy bleeding - to exclude the presence of serious pathology as soon as possible, The clinical problem © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, it is important : - to understand the short- and long-term consequences of early pregnancy bleeding - to exclude the presence of serious pathology as soon as possible, - to make a definitive diagnosis The clinical problem © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, it is important : - to understand the short- and long-term consequences of early pregnancy bleeding - to exclude the presence of serious pathology as soon as possible, - to make a definitive diagnosis - to stay in touch with new developments in research and management The clinical problem © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Outcome in clinical evident first trimester pregnancy © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Outcome in clinical evident first trimester pregnancy Herbert D; Lucke J; Dobson A. Pregnancy losses in young Australian women: findings from the Australian Longitudinal Study on Women's Health. J. Womens Health Issues; 2009 ; 19: Population cohort study n=9,145 level II-2 baseline yrs follow up 10 years Blohm F, Friden B, Milsom I. Prospective longitudinal population based study of clinical miscarriage in an urban swedisch population. BJOG 2008; 115: Population cohort study n=685 level II-2 baseline 19 yrs follow up 20 years © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Outcome in clinical evident first trimester pregnancy © PHMvdW 2010 Casanova BC et al. Prediction of outcome in women with symptomatic first-trimester pregnancy: focus on intrauterine rather than ectopic gestation. J Womens Health Issues ;18: Retrospective cohort study n=2026 Level II women presenting with bleeding in early pregnancy Hasan R et al. Association between first trimester vaginal bleeding and miscarriage. Obstet Gynecol 2009;114: Retrospective analysis in cohort study n=4510 Level II Miscarriage in women presenting with bleeding in first trimester pregnancy

What if a Woman starts Bleeding in Early Pregnancy ? Ectopic Pregnancy 1.5-2% Miscarriage / non viable pregnancy12-16% Termination 16% Ongoing Intra uterine Pregnancy 65-67% Outcome in clinical evident first trimester pregnancy Overall Herbert D; Lucke J; Dobson A. Pregnancy losses in young Australian women: findings from the Australian Longitudinal Study on Women's Health. J. Womens Health Issues; 2009 ; 19: Blohm F, Friden B, Milsom I. Prospective longitudinal population based study of clinical miscarriage in an urban swedisch population. BJOG 2008; 115: © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Ectopic Pregnancy 1.5-2% % Miscarriage / non viable pregnancy12-16% 46 % Termination 16% n.a. Ongoing Intra uterine Pregnancy 65-67% % Outcome in clinical evident first trimester pregnancy OverallBleeding / Pain © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? about out of has an ectopic pregnancy bleed about one half of those who bleed will loose their pregnancy; compared with non-bleeders this represents a threefold increase The short term consequences of early pregnancy bleeding © PHMvdW

What if a Woman starts Bleeding in Early Pregnancy ? about out of will get a miscarriage about one half of those who bleed will loose their pregnancy; compared with non-bleeders this represents a threefold increase The short term consequences of early pregnancy bleeding © PHMvdW bleed

What if a Woman starts Bleeding in Early Pregnancy ? The short term consequences of early pregnancy bleeding more than one half of those who bleed will loose their pregnancy © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? The short term consequences of early pregnancy bleeding more than one half of those who bleed will loose their pregnancy The long-term consequences of early pregnancy bleeding In ongoing pregnancies, adverse outcomes are reported for - very preterm delivery (< 34 weeks) OR 1.9 ( ) - low birth weight (<2500 g) OR 2.3 ( ) - ante partum haemorrhage OR 1.8 ( ) Van Oppenraay RHF et al. Predicting adverse obstetric outcome after early pregnancy events and complications:.a review Human Reproduction Update 2009;15: © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, it is important : - to understand the short- and long-term consequences of early pregnancy complications - to exclude the presence of serious pathology as soon as possible, and - to make a definitive diagnosis The clinical problem © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? For the clinician, it is important : - to understand the short- and long-term consequences of early pregnancy complications - to exclude the presence of serious pathology as soon as possible, and - to make a definitive diagnosis The clinical problem Ectopic Pregnancy 8 -18% Pre test likelihood in a woman who starts bleeding in early pregnancy 6% of all maternal deaths Barnhart KT. Ectopic Pregnancy NEJM 2009;361: © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? : - - to exclude the presence of serious pathology as soon as possible, and - to make a definitive diagnosis The clinical strategy © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss The clinical strategy © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2010 Assess blood loss

What if a Woman starts Bleeding in Early Pregnancy ? Loss of circulating volume Class(%)ml I0-15<750 II III – 2000 IV> 40> 2000 Tachycardia Tachypnoea, Vasoconstriction Loss of consciousness Life threatening !!! Fall in systolic BP Change in mental status Grady K, Howell Ch, Cox Ch. The MOET Course Manual 2007 edition RCOG press © PHMvdW 2010 Assess blood loss

What if a Woman starts Bleeding in Early Pregnancy ? Suspected / Actual severe blood loss The clinical strategy Grady K, Howell Ch, Cox Ch. The MOET Course Manual 2007 edition RCOG press IV access Replace volume Call for senior assistance Monitor Site 2 large IV cannulae Crossmatch FBC Clotting screen Blood sample Maintain adequate volume replacement (warm fluids) Stop Bleeding Non-invasive blood pressure Pulse oximeter Urinary catheter Surgical Medical © PHMvdW 2010 Assess blood loss

What if a Woman starts Bleeding in Early Pregnancy ? Suspected/actual severe blood loss Assess blood loss Make the diagnosis The clinical strategy © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss History The clinical strategy Make the diagnosis © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? History Date of the last menstrual period - The usual menstrual cycle ? - Method of contraception ? Pregnancy test done? when positive ? - Symptoms of early pregnancy present and still present ? Bleeding - Timing and degree in relation to menstrual cycle. - Associated with pain ? shoulder tip pain ? - Did bleeding occur after intercourse ? Last cervical smear. - Was any tissue passed ? Previous history - ectopic or miscarriage, PID, tubal surgery, SOA, Medication © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss History Examination The clinical strategy Make the diagnosis © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Examination Pulse, blood pressure Abdomen: rebound tenderness, guarding Pelvic examination: Inspection: trauma ?, cervix open / closed ? Bimanual: size, shape, consistency of the uterus, cervical excitation, adnexal mass © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss History Examination Investigations The clinical strategy Make the diagnosis © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? Investigations Transvaginal ultrasound Human chorionic gonadotrophin (hCG) © PHMvdW 2010

Bleed + No Pain >1 wk ovulation < 4 weeks LMP spotting light bleeding Pregtest (+) History Examination Investigations What if a Woman starts Bleeding in Early Pregnancy ? The clinical problem © PHMvdW 2010

Bleed + No Pain >1 wk ovulation < 4 weeks LMP spotting light bleeding Pregtest (+) History Examination Investigations Implantation bleeding What if a Woman starts Bleeding in Early Pregnancy ? days after conception Make the diagnosis © PHMvdW 2010 Implantation bleeding will appear before the woman expects her period and it is mistaken for spotting before the period begins.

Bleed + No Pain >1 wk ovulation < 4 weeks LMP spotting light bleeding Pregtest (+) History Examination Investigations Implantation bleeding What if a Woman starts Bleeding in Early Pregnancy ? The clinical strategy Reassurance Make the diagnosis © PHMvdW 2010

Bleed +Pain ++ No PainBleed + >1 wk ovulation < 4 weeks LMP< 8 weeks spottinguterus normal light bleedingunilateral mass Pregtest (+)Pregtest + History Examination Investigations Implantation bleeding What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2009 The clinical problem

Bleed +Pain ++ No PainBleed + >1 wk ovulation < 4 weeks LMP< 8 weeks spottinguterus normal light bleedingunilateral mass Pregtest (+)Pregtest + History Examination Investigations Ectopic pregnancy Implantation bleed What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2009 Make the diagnosis

Bleed +Pain ++ No PainBleed + >1 wk ovulation < 4 weeks LMP< 8 weeks spottinguterus normal light bleedingunilateral mass Pregtest (+)Pregtest + History Examination Investigations Ectopic pregnancy Implantation bleed What if a Woman starts Bleeding in Early Pregnancy ? Suspected/actual severe blood loss © PHMvdW 2009 Make the diagnosis

Bleed +Pain ++ No PainBleed + >1 wk ovulation < 4 weeks LMP< 8 weeks spottinguterus normal light bleedingunilateral mass Pregtest (+)Pregtest + History Examination Investigations Ectopic pregnancy Implantation bleed What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2009 Make the diagnosis Miscarriage various

Bleed +Pain ++ No PainBleed + >1 wk ovulation < 4 weeks LMP< 8 weeks spottinguterus normal light bleedingunilateral mass Pregtest (+)Pregtest + US scan Quantitative hCG laparoscopy History Examination Investigations Ectopic pregnancy Implantation bleed What if a Woman starts Bleeding in Early Pregnancy ? The clinical strategy Determine Is gestation potentially viable ? if not location should be determined © PHMvdW 2009 Make the diagnosis Miscarriage various

Gestational age (LMP) US findings B-HCG normal IU pregnancy < 5 wks excentrally placed small sac (2-5mm) may be visible within one layer of endometrium> 50 IU/L 5,5 wks yolk sac visible in gestational sac (GS) IU/L 6 wks embryonic pole should be visualized 6,5 wks fetal cardiac activity What if a Woman starts Bleeding in Early Pregnancy ? Is gestation potentially viable ? © PHMvdW 2009 Barnhart KT. Ectopic Pregnancy NEJM 2009;361:379-87

Gestational age (LMP) US findings B-HCG normal IU pregnancy < 5 wks excentrally placed small sac (2-5mm) may be visible within one layer of endometrium> 50 IU/L 5,5 wks yolk sac visible in gestational sac (GS) IU/L 6 wks embryonic pole should be visualized 6,5 wks fetal cardiac activity non-viable IU pregnancy GS > 10 mm; no yolk sac GS > 20 mm; no embryonic pole CRL>5mm; no fetal cardiac activity What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2009 Barnhart KT. Ectopic Pregnancy NEJM 2009;361: Is gestation potentially viable ?

Gestational age (LMP) US findings B-HCG normal IU pregnancy < 5 wks excentrally placed small sac (2-5mm) may be visible within one layer of endometrium> 50 IU/L 5,5 wks yolk sac visible in gestational sac (GS) IU/L 6 wks embryonic pole should be visualized 6,5 wks fetal cardiac activity non-viable IU pregnancy GS > 10 mm; no yolk sac GS > 20 mm; no embryonic pole CRL>5mm; no fetal cardiac activity What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2009 Barnhart KT. Ectopic Pregnancy NEJM 2009;361: Is gestation potentially viable ?

© PHMvdW 2009 What if a Woman starts Bleeding in Early Pregnancy ? B-HCG Barnhart KT. Ectopic Pregnancy NEJM 2009;361: Is gestation potentially viable ?

What if a Woman starts Bleeding in Early Pregnancy ? B-HCG Barnhart KT. Ectopic Pregnancy NEJM 2009;361: Is gestation potentially viable ? © PHMvdW 2010

US findings non-viable IU pregnancy GS > 10 mm; no yolk sac GS > 20 mm; no embryonic pole CRL>5mm; no fetal cardiac activity ectopic pregnancy TVU PPV extrauterine sac + fetal cardiac activity 7%100% extrauterine sac + fetal pole, no cardiac activity 13% adnexal mass with hyperechoic ring around GS 20% adnexal mass separate from ovary 60% 80-90% What if a Woman starts Bleeding in Early Pregnancy ? Location ? Barnhart KT. Ectopic Pregnancy NEJM 2009;361: Is gestation potentially viable ? © PHMvdW 2010

What if a Woman starts Bleeding in Early Pregnancy ? TVU + BhCG The clinical strategy Flowchart BhCG <1500 mIU/ml No IU pregnancy seen Repeat TVU +BhCG 48 hours Viable IU Pregnancy IU pregnancy seen Ectopic No observed mass Adnexal mass © PHMvdW

What if a Woman starts Bleeding in Early Pregnancy ? The clinical strategy Flowchart BhCG rise > 53% Repeat TVU +BhCG 48 hours Ectopic BhCG decline >12%-12%<BhCG < 53% IU pregnancy seenNo IU pregnancy seen Adnexal mass © PHMvdW

What if a Woman starts Bleeding in Early Pregnancy ? The clinical strategy Flowchart BhCG rise > 53% Repeat TVU +BhCG 48 hours Non-viable pregnancy Viable IU Pregnancy Ectopic BhCG decline >12%-12%<BhCG < 53% IU pregnancy seenNo IU pregnancy seen Adnexal mass © PHMvdW %71 %

What if a Woman starts Bleeding in Early Pregnancy ? TVU + BhCG The clinical strategy Flowchart BhCG <1500 mIU/ml No IU pregnancy seen BhCG rise > 53% Repeat TVU +BhCG 48 hours IU pregnancy seen BhCG decline >12%-12%<BhCG < 53% IU pregnancy seenNo IU pregnancy seen No observed mass Adnexal mass © PHMvdW 2010 Non-viable pregnancy Viable IU Pregnancy Ectopic

Bleed +Pain ++Bleed ++ No PainBleed +Pain + >1 wk ovulation < 4 weeks LMP< 8 weeks6-12 weeks spottinguterus normaluterus enlarged light bleedingunilateral massNo adnexal mass Pregtest (+)Pregtest +Pregtest ? US scan Quantitative hCG US scan Quantitative hCG laparoscopy History Examination Investigations Miscarriage various Ectopic pregnancy Implantation bleed What if a Woman starts Bleeding in Early Pregnancy ? Make the diagnosis © PHMvdW 2010

Classification of Miscarriage Miscarriage Abortion Spontaneous Induced Threatened Inevitable Recurrent legal illegal Delayed complete incomplete RCOG guideline no 25 The management of early pregnancy loss. October 2006 Miscarriage Threatened Spontaneous Recurrent Expulsion Delayed / Complete / Incomplete Method Spontaneous Surgical Medical What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2010

Bleed +Pain ++Bleed ++Pregnancy No PainBleed +Pain +symptoms ++ >1 wk ovulation < 4 weeks LMP< 8 weeks6-12 weeks Vaginal bleeding uterus normaluterus enlargedUterus large unilateral massNo adnexal massTheca lutein + Pregtest (+)Pregtest +Pregtest ?hCG ++++ US scan Quantitative hCGsnowstorm laparoscopy History Examination Investigations Miscarriage various Ectopic pregnancy Trophoblastic disease Implantation bleed What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss The clinical strategy Make the diagnosis © PHMvdW 2010

Pregnancy symptoms ++ Vaginal bleeding Uterus large Theca lutein + hCG ++++ snowstorm History Examination Investigations Trophoblastic disease What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss The clinical strategy Make the diagnosis Evacuation Histology of specimen Chest X ray Hb, ABO+Rhesus Thyroid function Serum hCG follow-up Contraception © PHMvdW 2010

Bleed +Pain ++Bleed ++pregnancyspecific No PainBleed +Pain +symptoms ++history >1 wk ovulation < 4 weeks LMP< 8 weeks6-12 weeks Vaginal bleeding uterus normaluterus enlargedUterus largespeculum unilateral massNo adnexal mass Theca luteine + Pregtest (+)Pregtest +Pregtest ?hCG ++++biopsy ? US scan Quantitative hCGsnowstorm PCR / culture ? laparoscopy History Examination Investigations Miscarriage various Ectopic pregnancy Trophoblastic disease Implantation bleed Coincidental What if a Woman starts Bleeding in Early Pregnancy ? Assess blood loss The clinical strategy Make the diagnosis © PHMvdW 2010

specific history speculum biopsy ? PCR / culture ? Coincidental What if a Woman starts Bleeding in Early Pregnancy ?

Bleed +Pain ++Bleed ++pregnancyspecific No PainBleed +Pain +symptoms ++history >1 wk ovulation < 4 weeks LMP< 8 weeks6-12 weeks Vaginal bleeding uterus normaluterus enlargedUterus largespeculum unilateral massNo adnexal mass Theca luteine + Pregtest (+)Pregtest +Pregtest ?hCG ++++biopsy ? US scan Quantitative hCGsnowstorm PCR / culture ? laparoscopy History Examination Investigations Miscarriage various Ectopic pregnancy Trophoblastic disease Implantation bleed Coincidental What if a Woman starts Bleeding in Early Pregnancy ? © PHMvdW 2010

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