OB Module

First Trimester Bleeding

Philip Trangmar, MD

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Case Study – at home call

Diana is a 34 year old, G1 P0Diana did not have a period for 5 weeks and so had a pregnancy test at home which was positive.She was very happy with the news.That was two days ago. She now phones you at 2am when you are at home on outpatient call. She tells you that she has seen spotting. She has mild abdominal cramping which causes her some discomfort rather than pain. However, she is very anxious and is crying.

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What you should be thinking now

Does Diana need to be seen tonight; or can you go back to sleep, telling her to just turn up at the clinic in the morning?

What differential diagnoses are you thinking about? Try to name at least three!

Clinic ER

List of dif dx

Does the patient need to be seen tonight?

Bleeding in the first trimester can be a medical emergency! Even spotting can be enough to warrant a visit to the ER. If Diana had not had a positive pregnancy test, then it would not be considered first trimester bleeding; just a late period. However, that is not the case here. HOWEVER, it can be a judgment call if there is no pain and the patient has only very mild spotting.Best practice is to play it safe and send her for an exam tonight. Particularly given her disposition – she is anxious.

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What differential diagnoses are you thinking about for 1st Trimester bleeding?

1. Abortion Requires positive pregnancy test and usually some bleeding. May or may not be accompanied by pain This includes threatened, inevitable, or missed abortions

click here for a description of the different types

2. Ectopic pregnancy A pregnancy which is not contained in the uterus Any bleeding is usually accompanied by pain – either moderate or severe This subject is covered later in the module

3. Molar pregnancy This is now referred to as Gestational Trophoblastic Disease This term encompasses several disease processes that originate in the placenta These include complete and partial moles, placental site trophoblastic tumors,

choriocarcinomas, and invasive moles Patients usually present with elevated hCG levels Click here for a web page with more information on hydatidiform moles

4. Infection STDs and particularly PID can cause vaginal bleeding

5. Trauma Sexual acts can cause abrasions to the vaginal wall which can result in bleeding

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Abortion terminologySpontaneous

It is defined as a clinically recognized pregnancy (eg, by blood test, ultrasound) which is then lost before 20 weeks' gestation.

They are sub-classified into:threatened, inevitable, incomplete, complete or missed

It is the most common complication of pregnancy

Elective Either medical or surgical termination of the pregnancy

Therapeutic This is where an elective abortion is given for the medical benefit of the

mother.

Septic A spontaneous or elective abortion complicated by a pelvic infection Could be the result of a non-medical/home abortion attempt

Miscarriage This term is normally only used ‘medically’ where the termination occurs at

greater than 20 weeks. However, when talking to patients it can be used instead of abortion as

abortion carries with it harsh overtones!

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Sub categories of spontaneous abortionsThreatened

Vaginal bleeding during early pregnancy represents a threatened abortion, On vaginal examination, the cervical os is closed and no tissue is found.

Inevitable Vaginal bleeding is accompanied by dilatation of the cervix. Bleeding usually is more severe than with threatened abortion and often is

associated with abdominal pain. Incomplete

Vaginal bleeding usually is intense and accompanied by abdominal pain. The cervical os is open and products of conception are being passed. Ultrasound shows some products of conception are still present in the

uterus. Complete

Patients usually present with a history of bleeding, abdominal pain, and tissue passage.

By the time abortion is complete, bleeding and pain usually have subsided. Diagnosis is confirmed by observation of the aborted fetus +/- vacant

uterus on U/SMissed

In utero death of the fetus with retained products of conception. Also known as blighted ovum, anembryonic pregnancy, or fetal demise.

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Case Study – in the ER

Diana goes to the ERIt is 3.45am and she gives the ER doctor her history as stated on the ‘phone to the on-call resident.She has no further spotting and only mild crampingShe still appears tearful and anxious

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After confirming she is pregnant, what should the next step be?

a. Bi-manual pelvic exam b. Sterile speculum examc. Order an Ultra-soundd. Send her home as the bleeding seems to have resolved

Case Study - next steps

Answer b is correct: Sterile speculum exam

Diana needs to have her bleeding assessed now She may not be spotting but she may be actively bleeding This needs to done use a sterile speculum to visualize the cervix Only then can you assess at what stage is this threatened

abortion

Do a G/C test and wet prep whilst you’re in there! There may be a reversible cause for her bleeding (infection).

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This would now be a good time to think about lab work.What labs would you order for Diana?

Labs necessary to orderSerum hCG

This should be done now. We know she is pregnant but it will help correlate with the ultrasound exam

and again in 48 hours - this second draw is done to ensure that the pregnancy is progressing

Click here to see expected hCG levels Progesterone levels. If <10, highly correlated with abnormal

pregnancy (ectopic or miscarraige). If>25, correlated with normal pregnancy.

CBC and type We need to see if Diana lost any significant amount of blood and ascertain her blood group to see if she is Rh negative

STDs I hope that you did this as part of the pelvic exam as you should have

got Gonorrhea and Chlamydia swabs, as well as a wet prep!

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hCG levels

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Weeks of pregnancy hCGafter period

Week 3 (ie 7d post period) 0 to 5

Week 4 (ie 14d post period) 5 to 426

Week 5 18 to 7340

Week 6 1,080 to 56,500

Weeks 7 to 8 7,650 to 229,000

Weeks 9 to 12 25,700 to 288,000

Weeks 13 to 16 13,300 to 254,000

Weeks 17 to 24 4,060 to 165,400

Weeks 25 to birth 3,640 to 117,000

4/6 weeks post Less than 5

NB – Because of the variation, this is less useful to pinpoint likely dates. hCG is more useful for ultrasound correlation.

Ref:http://www.birth.com.au/class.asp?class=6620&page=8

Case Study – patient outcome

Her CBC is normal and she is A pos This rules out severe blood loss and no Rhogram required

Diana’s hCG levels are 900 This will enable you to assess what should be seen on ultrasound

Micro Her wet prep was negative for Trich and fungal infections and

she has no clue cells Her G & C test will not come back until tomorrow

A 2002 study showed clinical judgment is not an alternative to ultrasoundNOW you can order a stat ultra sound

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What would the ultra sound show at this stage? - 4 weeks and a few days

Ultrasound findings in 1st trimester

Trans-vaginal findingsWeeks from

LMP β-HCG (mIU/ml)

Gestational sac (25 mm) 4.5-5 1000

Yolk sac 5-5.5 1500-2500

Fetal pole 5-6 2000-5000

Fetal cardiac activity 5.5-6.5 4000-17000

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The β-hCG level at which an intra-uterine pregnancy (IUP) should be visualized by transvaginal ultrasound, with near 100% sensitivity, is 1000-2000 mIU/mL.

The level for transabdominal sonography is less certain but has been suggested to be between 4000 and 6500 mIU/mL.

Click for view

Click for view

Click for view

Gestational Sac - TVUS

Gestational sac is visible at 4-5 weeks. The fetal pole is barely visible

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Yolk Sac - TVUS

Yolk sac is seen within the gestational sac, and is visible at 5-6 weeks

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Fetal pole - TVUS

Fetal pole is seen below the yolk sac

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Case study - current diagnosis

Diana has a closed cervix and no additional blood visualized in the vaginal vault. It was too early to show any IUP evidence of a yolk sac. What type of abortion would you consider classifying Diana W at this stage? Place cursor over your choice

Complete Incomplete Inevitable Missed Threatened

Click here if you want to see the definitions again

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Sub categories of spontaneous abortionsThreatened

Vaginal bleeding during early pregnancy represents a threatened abortion, On vaginal examination, the cervical os is closed and no tissue is found.

Inevitable Vaginal bleeding is accompanied by dilatation of the cervix. Bleeding usually is more severe than with threatened abortion and often is

associated with abdominal pain. Incomplete

Vaginal bleeding usually is intense and accompanied by abdominal pain. The cervical os is open and products of conception are being passed. Ultrasound shows some products of conception are still present in the

uterus. Complete

Patients usually present with a history of bleeding, abdominal pain, and tissue passage.

By the time abortion is complete, bleeding and pain usually have subsided. Diagnosis is confirmed by observation of the aborted fetus +/- vacant

uterus on U/SMissed

In utero death of the fetus with retained products of conception. Also known as blighted ovum, anembryonic pregnancy, or fetal demise.

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Case Study – patient outcome

Diana’s bleeding and cramping was most likely a threatened abortion

however, the word abortion is not a word which should be used with patients

the better understood word for patients is potential miscarriage, but it is really too early to tell

You tell her that you are going to send her home she should take Tylenol for her pain and cramping and start prenatal vitamins if she has not done so already

You advise her to take it easy no strenuous activity or heavy lifting or exercise for the next 7 days to follow up with a hCG serum level in two days to ensure that the

levels are doubling every 48 hours Doubling hCG levels are a sign of well being in early pregnancy

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Case Study – patient’s questions

Diana does have several questions for you

1. What is the chance of her having an actual miscarriage/abortion?

2. What risk factors are there for spontaneous abortions?

3. What causes an abortion?next

Abortion Epidemiology

You should tell Diana that:Spontaneous abortions occur in 20-30% of pregnancies 2/3 of first trimester spontaneous abortions have chromosomal abnormalities

i.e. these are inevitable as the abnormalities are not compatible with life

First trimester bleeding is also common: about 25% of pregnancies50% of these go on to have a normal course of pregnancy

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Click here to see epi statistic slide

You can therefore tell Diana that abortions/miscarriages are far from unusual and that there is a good chance that this will carry to term

Epidemiology of Abortions

Frequency In the US: Up to an estimated 30% of pregnancies are terminated spontaneously before the

first missed menstrual period and, therefore, usually are not clinically recognized. Spontaneous abortions occur in an estimated 10-20% of known pregnancies. They usually occurs between the 7th and 12th weeks of pregnancy

Vaginal bleeding occurs in approximately 25% of all pregnancies during the first 2 trimesters.

About 50% these cases progress to an actual abortion/miscarriage. Age:

Age and increased parity affect a woman's risk of a miscarriage. In women younger than 20 years, miscarriage occurs in an estimated 12% of pregnancies; in women older than 20 years, miscarriage occurs in an estimated 26% of pregnancies.

Mortality/Morbidity: Surveillance data from the US between 1987 and 1990 revealed a total of 1459

pregnancy-related deaths. Spontaneous and induced abortions accounted for 5.6% of these deaths.

Race: Surveillance data for pregnancy-related deaths between 1987 and 1990

demonstrated that more black mothers died after abortions, both spontaneous (14%) and induced (7%), than white mothers (8% and 4%, respectively).

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Risk factors associated with Abortions

You should tell Diana that the following items cause increased risk of abortions:Cigarette smoking increases risk of abortion

Over 14 Cigarettes per day doubles risk over non-smokers Relative Risk increases 1.2x for each 10 cigs/day

Alcohol abuse increases risk of abortion Abortion risk doubled for twice weekly alcohol Abortion risk tripled for daily alcohol use*

Illicit drug use Uterine surgeries or anomalies Incompetent cervix (usually second trimester)IUDs

Ref: http://www.fpnotebook.com/OB9.htm

* Somewhat controversial statement but is the basis for the ACOG saying not to drink in pregnancy

BackApart from smoking, drugs and alcohol, there are no real risk factors

which Diana can influence

Causes of early miscarriageGenetic or fetal causes  

Trisomy; Polyploidy or aneuploidy; translocations  Environmental or maternal causes,

Smoking, alcohol, drugs Congenital uterine anomalies; Leiomyoma    Intrauterine adhesions (Asherman's syndrome) 

Endocrine    Progesterone deficiency (luteal phase defect)   Diabetes mellitus (poorly controlled);  Hypothyroidism Luteinizing hormone hypersecretion   

Immunologic    Autoimmunity: antiphospholipid syndrome, lupus    

Infections    Toxoplasma gondii, Listeria monocytogenes Chlamydia trachomatis,

Ureaplasma urealyticum, Mycoplasma hominis, Herpes simplex, Treponema pallidum, Borrelia burgdorferi, Neisseria gonorrhoeae

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You can inform Diana of the main causes

– and try to see if any may apply at this stage?

Case Study – return visit

Diana returns to visit you in clinic three weeks later She is 6 weeks post LMP

Looking at her history you note that her hCG had doubled on a second lab visit

and therefore you had told her that at that time her pregnancy was progressing well

However, she is now experiencing increased abdominal pain in the right side and is bleeding The bleeding is described as more than spotting – a cupful.

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What differential diagnoses do you have now?

Differential diagnosis of pain and bleeding at 7 weeks

– the same as 4 weeksAbortion

click here for review of different types

Molar pregnancy link to web site

Trauma

Infections

And of course ….

Ectopic pregnancy

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What is the next step?

Sub categories of spontaneous abortions - 3Threatened

Vaginal bleeding during early pregnancy represents a threatened abortion, On vaginal examination, the cervical os is closed and no tissue is found.

Inevitable Vaginal bleeding is accompanied by dilatation of the cervix. Bleeding usually is more severe than with threatened abortion and often is

associated with abdominal pain. Incomplete

Vaginal bleeding usually is intense and accompanied by abdominal pain. The cervical os is open and products of conception are being passed. Ultrasound shows some products of conception are still present in the

uterus. Complete

Patients usually present with a history of bleeding, abdominal pain, and tissue passage.

By the time abortion is complete, bleeding and pain usually have subsided. Diagnosis is confirmed by observation of the aborted fetus +/- vacant

uterus on U/SMissed

In utero death of the fetus with retained products of conception. Also known as blighted ovum, anembryonic pregnancy, or fetal demise.

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Ectopic work up

Since Diana has unilateral pain, your thought process is directed towards a possible ectopic pregnancy

This means an emergency ultrasound in the ER

Remember on her first visit to the ER the ultrasound was unable to visualize an Intra-uterine Pregnancy

This was because it was too early

We now do a serum hCG and get 7000

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What are the likely findings?

Diana’s findings

Remember back to the table on the correlation between hCG and ultrasound findingsAt a hCG level of 7000 you should be able to find, using a transvaginal ultrasound

a fetal pole and cardiac activity

If there is no IUP, then you would be looking at a potential ectopic or recent complete abortion

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Click here to see hCG table again

Ultrasound findings in 1st trimester

Trans-vaginal findingsWeeks from

LMP β-HCG (mIU/ml)

Gestational sac (25 mm) 4.5-5 1000

Yolk sac 5-5.5 1500-2500

Fetal pole 5-6 2000-5000

Fetal cardiac activity 5.5-6.5 4000-17000

The β-hCG level at which an intra-uterine pregnancy (IUP) should be visualized by transvaginal ultrasound, with near 100% sensitivity, is 1000-2000 mIU/mL.

The level for transabdominal sonography is less certain but has been suggested to be between 4000 and 6500 mIU/mL.

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Ectopic work up using ultrasound

Diagnostic of IUP “Double” gestational sacIntrauterine fetal pole or yolk sacIntrauterine fetal heart activity

Diagnostic of Ectopic Gestation Ectopic fetal heart activity orEctopic fetal pole

Suggestive of Ectopic Gestation Moderate or large cul-de-sac fluid without IUPAdnexal mass † without IUP

Indeterminate Empty uterusNonspecific fluid collectionsEchogenic materialAbnormal sacSingle gestational sac

* Modified from Dark RG: Role of pelvic ultrasonography in evaluation of symptomatic first trimester pregnancy, Ann Emerg Med 33:310–320, 1999.† Complex mass most suggestive of ectopic pregnancy, but cyst can also be seen with ectopic pregnancy.

Click here to see Ultrasound pictures

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Click here to see Tubal ectopics

Ultrasound of ectopic pregnancy

Same imagesUterus outlined in red, uterine lining in green, ectopic pregnancy yellow.

Fluid in uterus at blue circle - sometimes called a "pseudosac" Click here for magnified image

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Magnified ultrasound image of ectopic

Same imagesTubal pregnancy circled in red, 4.5 mm fetal pole (between cursors) in

green, pregnancy yolk sac blue. Back

Ectopic pregnancies

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Laparoscopic view of ectopic

Uterus with fallopian ectopic

Management of ectopic pregnancy

Medical Methotrexate

It has a very good success rate, but does carry risk and therefore is generally managed by ob/gyn.

only used in early pregnancy where the patient is hemodynamically stable

Otherwise it is off to:

Surgery Laparoscopic approach

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Methotrexate in Ectopic Pregnancy

The antifolate drug - methotrexate is widely used to treat ectopic pregnancies without surgery

Methotrexate, 50 mg/m2 intramuscularly

Misoprostol is not used for ectopic pregnancy. It is a prostaglandin used to empty the uterus. It is used after methotrexate for early medical TABs that are intrauterine only.

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Surgical treatment Ectopic pregnancy

Salpingectomy by laparotomy has long offered almost a 100 percent cure. More recently laparoscopic salpingostomy and laparoscopic partial salpingectomy are thus rapidly replacing laparotomy. Laparotomy should be performed only when a laparoscopic approach is too difficult, the surgeon is not trained in operative laparoscopy, or the patient is hemodynamically unstable.Approximately 95 percent of laparoscopic salpingostomies are successful (i.e., no additional procedures are needed).Of the 93 women evaluated in one study, 86 percent were later shown to have patent oviducts; 66 percent of 430 women who were followed subsequently became pregnant, with 23 percent of those pregnancies being ectopic.i.e there is a high risk for future Ectopics

Ref: Seifer DB, Gutmann JN, Doyle MB, et al: Persistent ectopic pregnancy following laparoscopic linear salpingostomy. Obstet Gynecol 76:1121, 1990.

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Ultrasound exam of Diana

On a transvaginal ultrasound you find Gestational sac in utero Fetal pole at 2cm No cardiac activity

Cardiac activity should become visible and begin once the fetal pole reaches 5mm. No cardiac activity at this stage means:

a non-viable fetus

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Pelvic exam of Diana

On doing a Pelvic exam you find blood in vaginal vault Cervix is partially open No tissue is seen

What type of abortion would you consider classifying Diana at now? Place your curser over your choice

Complete Incomplete Inevitable Missed Threatened

Click here if you want to see the definitions again

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Sub categories of spontaneous abortionsThreatened

Vaginal bleeding during early pregnancy represents a threatened abortion, On vaginal examination, the cervical os is closed and no tissue is found.

Inevitable Vaginal bleeding is accompanied by dilatation of the cervix. Bleeding usually is more severe than with threatened abortion and often is

associated with abdominal pain. Incomplete

Vaginal bleeding usually is intense and accompanied by abdominal pain. The cervical os is open and products of conception are being passed. Ultrasound shows some products of conception are still present in the

uterus. Complete

Patients usually present with a history of bleeding, abdominal pain, and tissue passage.

By the time abortion is complete, bleeding and pain usually have subsided. Diagnosis is confirmed by observation of the aborted fetus +/- vacant

uterus on U/SMissed

In utero death of the fetus with retained products of conception. Also known as blighted ovum, anembryonic pregnancy, or fetal demise.

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Management of inevitable (or incomplete or missed) abortion

Medical Misoprostol

Surgical Dilation and curettage

Manual or Standard Vacuum Curettage Dilation and evacuation

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So which would you offer for Diana?

Misoprostol in Missed abortion

The antifolate drug methotrexate is not needed for a missed AB as it is used to stop growth of a pregnancy and this pregnancy is already non-viable.Misoprostol can be used to empty the uterus at this point: vaginal misoprostol 800 μg, can be repeated at 24 hours if the patient had not aborted. Statistics:

Fifty-three percent aborted after the first dose of misoprostol

an additional 15 percent after the second dose a total of 92 percent aborted by 35 days

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Surgical treatment in Missed or incomplete abortion

Technique for Manual Vacuum Procedures After examination to determine uterine position and to be sure that pregnancy is 7 weeks or less, the cervix is exposed with a speculum, infiltrated with local anesthetic, and grasped with a tenaculum placed vertically at 12 o'clock. Four- and 5-mm-diameter cannulas are passed through the cervical canal as dilators, and then a 6-mm cannula is inserted and attached to the evacuated 50-ml syringe to establish suction. The 4- and 5-mm cannulas are not large enough to dependably evacuate the uterus in pregnancy, but are useful as atraumatic dilators and for endometrial biopsies in the nonpregnant state. The 6-mm cannula is rotated and pushed in and out with gentle strokes, taking care to rotate the cannula only on the outstroke so as to avoid twisting off the flexible tip by rotating it when it is pressed against the uterine fundus. When no more tissue comes through, the cannula is withdrawn, its tip cleared in a sterile fashion, and it is reinserted and vacuum reestablished for a final, check curettage to

Technique for Standard Vacuum CurettageStandard vacuum curettage applies essentially the same technique as manual vacuum, but uses larger cannulas, from 7 to 12 mm, with an electric vacuum pump. After establishing a paracervical block as above, the operator dilates the cervical canal, using serial insertion of tapered rods that increase progressively in size. Dilatation is continued to a diameter 1 mm less than the estimated length of gestation in menstrual weeks and then a vacuum cannula of that same outside diameter is inserted. After aspiration is complete, we gently insert a sharp curette and use it as a finger to gently explore the cavity and prove it empty. Finally, the suction cannula is reintroduced for a final few seconds to remove any additional tissue remaining.

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Diana’s case

The first choice would be medical - Misoprostol Or watch and wait. Some women may

choose to remain at home for a miscarraige, unless bleeding becomes heavy or concerning.

Only if Diana failed medical treatment would you need to offer the surgical route

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Case study – procedure

Diana decided to go thought with a trial of misoprostol

She was advised that if it did not work, she would likely require a D&C in any event

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Case study – bleeding

On the third day Diana passed clots and plenty of blood.

As this was her first early abortion, there was no need to have the fetus analyzed for chromosomal abnormalities.

This would be an indication for a D&C in other patients.

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Patient Questions

Diana asks you: What are the chances of having a

successful next pregnancy?

What if she was 37 YO or she had a history of previous abortions?

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Answers

In women with an unknown etiology of prior pregnancy loss, the probability of achieving successful pregnancies is 40-80%.

As stated earlier, increased age increases chances of spontaneous abortion.

This is also the case with patients who have three or more previous abortions

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Click here to see epi statistic slide

Epidemiology of Abortions

Frequency In the US: Up to an estimated 30% of pregnancies are terminated spontaneously before the

first missed menstrual period and, therefore, usually are not clinically recognized. Spontaneous abortions occur in an estimated 10-20% of known pregnancies. They usually occurs between the 7th and 12th weeks of pregnancy

Vaginal bleeding occurs in approximately 25% of all pregnancies during the first 2 trimesters.

About 50% these cases progress to an actual abortion/miscarriage. Age:

Age and increased parity affect a woman's risk of a miscarriage. In women younger than 20 years, miscarriage occurs in an estimated 12% of pregnancies; in women older than 20 years, miscarriage occurs in an estimated 26% of pregnancies.

Mortality/Morbidity: Surveillance data from the US between 1987 and 1990 revealed a total of 1459

pregnancy-related deaths. Spontaneous and induced abortions accounted for 5.6% of these deaths.

Race: Surveillance data for pregnancy-related deaths between 1987 and 1990

demonstrated that more black mothers died after abortions, both spontaneous (14%) and induced (7%), than white mothers (8% and 4%, respectively).

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Follow up with Diana

Lastly you should address any relevant psychiatric issues concerning the loss of a baby and look for potential depression beyond normal grief. IMPORTANT: reassure her that she did nothing to cause the miscarriage (unless drugs or alcohol are involved).Make a follow up appointment sooner rather than later if you have any concerns on this point .Some parents need closure, even with a very pre-term fetus and wish to see the aborted fetus, following a D&C. Some parents may also wish to bury the fetus to aid with closure.

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OB Module – First Trimester BleedingReferences

1. Ultrasound in pregnancyChristopher Moore, MD, RDMS, RDCS Susan B. Promes, MD, FACEP Emergency Medicine Clinics of North AmericaVolume 22 • Number 3 • August 2004Copyright © 2004 W. B. Saunders Company http://home.mdconsult.com/das/journal/view/40844780-4/N/14936568?ja=432625&PAGE=1.html&sid=299459631&source=

2. Table on U/S modified from Dart RG: Role of pelvic ultrasonography in evaluation of symptomatic first trimester pregnancy Ann Emerg Med 33:310–320, 1999.

3. Threatened miscarriage in general practice: diagnostic value of history taking and physical examination. Authors Wieringa-de Waard M, Bonsel GJ, Ankum WM, Vos J, Bindels PJ Source British Journal of General Practice Date of publication 2002 Oct Volume 52 Issue 483 Pages 825-9

4. The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis (Structured abstract)NHS Centre for Reviews and DisseminationOriginal article: Mol B W, Lijmer J G, Ankum W M, van der Veen F, Bossuyt P M. The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis. Human Reproduction. 1998. 13(11). 3220-3227.

5. Interventions for tubal ectopic pregnancyHajenius PJ, Mol BWJ, Bossuyt PMM, Ankum WM, Van der Veen FDate of most recent substantive amendment: 24 October 1999This review should be cited as: Hajenius PJ, Mol BWJ, Bossuyt PMM, Ankum WM, Van der Veen F. Interventions for tubal ectopic pregnancy (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.

6. The medical management of ectopic pregnancy: a meta-analysis comparing 'single dose' and 'multidose' regimens (Provisional record)NHS Centre for Reviews and DisseminationOriginal article: Barnhart K T, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing 'single dose' and 'multidose' regimens. Obstetrics and Gynecology. 2003. 101(4). 778-784.

7. http://www.emedicine.com/emerg/topic5.htm

8. http://home.mdconsult.com/das/book/41051225-2/view/1007

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Family MedicineOB Module

First Trimester Bleeding

THE END