Pregnancy Of Unknown Pregnancy Of Unknown Location (PUL)Location (PUL)Dr Kamel ElbadryDr Kamel Elbadry

MD (Sheffield University), FRCOGMD (Sheffield University), FRCOGConsultant Obstetrician and Consultant Obstetrician and

GynaecologistGynaecologist

●●The term PUL is used whenever there is The term PUL is used whenever there is no sign of either intra or extrauterine no sign of either intra or extrauterine pregnancy or retained products of pregnancy or retained products of conception on transvaginal ultrasoundconception on transvaginal ultrasound

● ● A pregnancy site will not be visualised in A pregnancy site will not be visualised in 8-10% of early pregnancy scan in EPAU, 8-10% of early pregnancy scan in EPAU,

up to 31% in other units up to 31% in other units

AssessmentAssessment

Whenever a woman presents with a positive Whenever a woman presents with a positive pregnancy test but no evidence of pregnancy test but no evidence of pregnancy on TVS, clinical assessment pregnancy on TVS, clinical assessment and serum B hCG should be carried out.and serum B hCG should be carried out.

hCG and Ultrasound:hCG and Ultrasound:

Using a discriminatory zone of hCG has Using a discriminatory zone of hCG has been widely evaluated.been widely evaluated.

An intrauterine pregnancy should be visible An intrauterine pregnancy should be visible on ultrasound if hCG ranges from 1000-on ultrasound if hCG ranges from 1000-2400 iu/l2400 iu/l

In multiple pregnancy, hCG levels should be In multiple pregnancy, hCG levels should be interpreted with caution as they are little higher, interpreted with caution as they are little higher, requiring an extra 3 days for the sacs to be requiring an extra 3 days for the sacs to be visible.visible.

If hCG level above the discriminatory level with If hCG level above the discriminatory level with no intrauterine gestational sac on ultrasound. no intrauterine gestational sac on ultrasound. Determine whether the pregnancy is ectopicDetermine whether the pregnancy is ectopic

The diagnosis of ectopic pregnancy should The diagnosis of ectopic pregnancy should be based on the identification of an be based on the identification of an extrauterine sac, and indirect signs such extrauterine sac, and indirect signs such as a complex adnexal mass or fluid as a complex adnexal mass or fluid collection rather than empty uterus on collection rather than empty uterus on scan. scan. The combination of the above scan The combination of the above scan findings has a positive predictive value of findings has a positive predictive value of 93.5%-100% for diagnosing ectopic. 93.5%-100% for diagnosing ectopic.

Trans-vaginal colour Doppler has not been Trans-vaginal colour Doppler has not been shown to increase the detection rates of shown to increase the detection rates of ectopic when compared with 2D ectopic when compared with 2D ultrasound but may be useful in showing ultrasound but may be useful in showing enhanced trophoblastic flow.enhanced trophoblastic flow.

The discriminatory level of each unit should The discriminatory level of each unit should be based on :be based on :

hCG assay technique in usehCG assay technique in use

Quality of ultrasound equipmentQuality of ultrasound equipment

Operator experienceOperator experience

Progesterone:Progesterone:

Serum progesterone levels are elevated, Serum progesterone levels are elevated, indicating the viability of corpus luteum, indicating the viability of corpus luteum, but decrease if the pregnancy fails.but decrease if the pregnancy fails.

Progesterone level < 25 nmol/l, associated Progesterone level < 25 nmol/l, associated with nonviable pregnancy (viable in 0.3%)with nonviable pregnancy (viable in 0.3%)

Progesterone < 20 nmol/l predicts failing Progesterone < 20 nmol/l predicts failing pregnancy with a positive prediction value pregnancy with a positive prediction value > 95%> 95%

Levels > 25 nmol/l are associated with Levels > 25 nmol/l are associated with pregnancies. pregnancies.

Levels > 60 nmol/l are strongly associated Levels > 60 nmol/l are strongly associated with intrauterine pregnancy (2.6% ectopic)with intrauterine pregnancy (2.6% ectopic)

hCG pattern after 48 hours:hCG pattern after 48 hours:

●● Rise of hCG by 66%, predicts an Rise of hCG by 66%, predicts an intrauterine pregnancy (predictive value intrauterine pregnancy (predictive value 96.5%)96.5%)

●● Fall of hCG by at least 15%, most likely Fall of hCG by at least 15%, most likely outcome failing pregnancyoutcome failing pregnancy

When the rise or fall in hCG is suboptimal, When the rise or fall in hCG is suboptimal, the most likely diagnosis is ectopic.the most likely diagnosis is ectopic.

Management of PULManagement of PUL

Conservative management:Conservative management:

According to the Association of Early According to the Association of Early Pregnancy Units guidelines, if no Pregnancy Units guidelines, if no intrauterine or ectopic pregnancy or intrauterine or ectopic pregnancy or retained products of conception are seen retained products of conception are seen on TVS and the woman is asymptomatic on TVS and the woman is asymptomatic she can be managed conservatively.she can be managed conservatively.

Expectant management of PUL has been Expectant management of PUL has been shown to be safe and to reduce the need shown to be safe and to reduce the need for unnecessary surgical intervention and for unnecessary surgical intervention and is not associated with any serious adverse is not associated with any serious adverse outcomes.outcomes.

Unfortunately, multiple visits to EPAU are Unfortunately, multiple visits to EPAU are necessary before diagnosis can be made.necessary before diagnosis can be made.

Clinical outcome of PUL:Clinical outcome of PUL:

1- Failing PUL (44-69%)1- Failing PUL (44-69%)

2- Intrauterine pregnancy2- Intrauterine pregnancy

3- Ectopic pregnancy3- Ectopic pregnancy

4- Persistent PUL4- Persistent PUL

Persistent PUL:Persistent PUL:

Those in which the serum hCG levels fail to Those in which the serum hCG levels fail to decline and there is no evidence of decline and there is no evidence of trophoblastic disease and the location of trophoblastic disease and the location of pregnancy can not be identified.pregnancy can not be identified.

Usually hCG are low (<500 iu/l) and have Usually hCG are low (<500 iu/l) and have reached to a plateau (2% of PUL) reached to a plateau (2% of PUL)

Medical Management:Medical Management:

Methotrexate, 50 mg/m2 has been used Methotrexate, 50 mg/m2 has been used successfully in persistent PUL (90% successfully in persistent PUL (90% effective)effective)

Surgical Management:Surgical Management:

Laparoscopy/ laparotomy is indicated if the Laparoscopy/ laparotomy is indicated if the woman is symptomatic or if an ectopic is woman is symptomatic or if an ectopic is visualised. visualised.

Laparoscopy has false negative rate 3-4% (if Laparoscopy has false negative rate 3-4% (if done too early) and false positive 5% done too early) and false positive 5% because of retrograde uterine bleeding.because of retrograde uterine bleeding.

CurettageCurettage

Not a usual practice in UK, although Not a usual practice in UK, although common in USAcommon in USA

No clinical evidence to change our practice.No clinical evidence to change our practice.

ConclusionConclusion

Asymptomatic PUL should be managed Asymptomatic PUL should be managed conservatively as none of the methods to conservatively as none of the methods to predict the clinical outcome of PUL is predict the clinical outcome of PUL is 100% accurate.100% accurate.

Follow up with hCG and ultrasound until the Follow up with hCG and ultrasound until the pregnancy is located or intervention pregnancy is located or intervention become necessarybecome necessary

Medical management should be reserved for Medical management should be reserved for women with asymptomatic persisting PULwomen with asymptomatic persisting PUL

Surgery is indicated if the woman is Surgery is indicated if the woman is symptomatic symptomatic

Thank YouThank You