ICL 14.3: Spontaneous Abortion, Ectopic Pregnancy and Pregnancy Complications

Question 1

where is β-hCG produced? what does it do?

Answer 1

β-hCG is produced by the developing syncytiotrophoblast of the blastocyst

it helps maintain the corpus luteum for progesterone production and helps support the pregnancy until the placenta is well-established

Question 2

what does it mean if β-hCG levels fall early on in a pregnancy?

Answer 2

if they fall in the first 8 weeks it predicts a failing pregnancy

they should rise for 8-10 weeks then drop after that

Question 3

what is the trend of β-hCG levels with ectopic pregnancies?

Answer 3

weirdly enough, 21% of ectopic pregnancies display normal rising β-hCG levels initially so you need to be wary!

Question 4

how should β-hCG levels be changing throughout a normal pregnancy?

Answer 4

they have an expected minimal increase in level every 48 hours based on the starting β-hCG levels

it should be a 49% increase for an initial β-hCG of <1500 mIU/mL

40% increase for an initial β-hCG of 1500-3000

33% increase for an initial β-hCG of 3000+

it used to be that they’re supposed to double every 48 hours but it was just because we were fearful of missing an ectopic or missing a pregnancy that could’ve progressed to a full term intrauterine pregnancy

99% of normal intrauterine pregnancies will have a β-hCG pattern with rate of increase more than these

Question 5

at what levels of β-hCG should you be able to see an intrauterine pregnancy?

Answer 5

1500-3500

1500 is pretty darn low though and most people don’t use this to rule out an intrauterine pregnancy

Question 6

what is an intrauterine pregnancy?

Answer 6

a gestational sac WITH yolk sac and/or embryo

in the absence of a yolk sac, you cannot diagnose an IUP based on a presumed gestational sac

a pseudo sac is something that can happen with an ectopic pregnancy that is a sac in the uterus with fluid in the middle but no yolk sac or embryo so it’s not an IUP even though you might think it looks like it!

Question 7

how can you tell if there is an ectopic pregnancy based on US?

Answer 7

presence of an intrauterine pregnancy virtually rules out ectopic

but absence of an intrauterine pregnancy virtually confirms an ectopic pregnancy….

Question 8

what does fetal cardiac activity indicate?

Answer 8

90-96% of pregnancies with fetal cardiac activity, even in the presence of vaginal bleeding,, result in a viable infant!

Question 9

what are the risks associated with 1st trimester bleeding?

Answer 9

1st trimester bleeding increases risk of preterm birth

prior 1st trimester bleeding is predictive of recurrence in future pregnancies

Question 10

what do progesterone levels indicate about eh prognosis of a pregnancy?

Answer 10

progesterone <10 is predictive of poor pregnancy outcome

progesterone >20 is predictive of favorable pregnancy outcomes

progesterone levels 11-19: equivocal

doesn’t help determine site of pregnancy though

Question 11

27 year old G1P0 present with vaginal bleeding yesterday with continued spotting today

LMP 7 weeks ago with normal menstrual cycle and no hormone use in the past year

taking prenatal vitamins for past 6 months and denies cramping/pain in lower abdomen

β-hCG = 3200

TV US: intrauterine pregnancy with cardiac activity noted

what do you advise?

Answer 11

where is the pregnancy located? look at the hCG and get an US and maybe do a pelvic exam too to make sure there aren’t other reasons for her to be bleeding outside of pregnancy

no hormones in the past year is important because she may have breakthrough bleeding from OCPs or other contraception so this way we know the dating is accurate for her last LMP

so she’s fine because there’s an intrauterine pregnancy with cardiac activity! you’d only really refer to hCG levels if the US showed an empty uterus

so for this girl she will probably have a healthy pregnancy because of the cardiac activity on the US which is THE most important part!!!

Question 12

27 year old G1P0 present with vaginal bleeding yesterday with continued spotting today

LMP 7 weeks ago with normal menstraul cycle and no hormone use in the past year; taking prenatal vitamins for the past 6 months; denies cramping/pain

β-hCG = 1100

TV US: no intrauterine structure visualized, no adnexal masses

progesterone = 15

what do you advise?

Answer 12

midrange progesterone and empty uterus and low hCG….

probably should tell her to come back in 48 hours to check her hCG levels to see if it’s increasing and we want to see a 49% increase since her initial hCG was less than 1500

we also have to keep in mind she could totally have an ectopic pregnancy since the US came back with an empty uterus so we also need to tell her the warning signs like worsening pelvic pain or vaginal bleeding from an ectopic rupture that could cause hemorrhagic shock and in these cases she should come back before 48 hours

Question 13

27 year old G1P0 present with vaginal bleeding yesterday with continued spotting today

LMP 7 weeks ago with normal menstraul cycle and no hormone use in the past year; taking prenatal vitamins for the past 6 months; denies cramping/pain

β-hCG = 1100

US: no intrauterine structure visualized, no adnexal masses

progesterone = 15

patient returns after 2 days with β-hCG = 1500, US shows no intrauterine contents, no adnexal masses but patient is having some lower abdominal pain on the right side more than the left

Answer 13

?

Question 14

27 year old G1P0 present with vaginal bleeding yesterday with continued spotting today

LMP 7 weeks ago with normal menstraul cycle and no hormone use in the past year; taking prenatal vitamins for the past 6 months; denies cramping/pain

β-hCG = 1100

US: no intrauterine structure visualized, no adnexal masses

progesterone = 15

patient returns after 2 days with β-hCG = 2500, US shows no intrauterine contents, no adnexal mass

Answer 14

hCG did go up 49% in 48 hours which is what’s supposed to happen for an initial hCG less than 1500

so since she isn’t having any pain and hCG is rising appropriately but we don’t realyyyy know what’s going on, you should assume the positive side and maybe it’s just an early IUP! but also still just tell them this doesn’t rule out an ectopic, just that we’re leaning towards an IUP and probably redo the US and hCG in another 48 horus

Question 15

27 year old G1P0 present with vaginal bleeding yesterday with continued spotting today

LMP 7 weeks ago with normal menstraul cycle and no hormone use in the past year; taking prenatal vitamins for the past 6 months; denies cramping/pain

β-hCG = 1100

US: no intrauterine structure visualized, no adnexal masses

progesterone = 15

patient returns after 2 days with β-hCG = 700, US shows no intrauterine contents, no adnexal masses

Answer 15

this is a failing pregnancy since hCG is falling but it doesn’t tell us if it was in the uterus or ectopic

if hCG falls or plateaus before 8-10 weeks then it’s a failing pregnancy

Question 16

27 year old G1P0 present with lower abdominal pain that started yesterday but has gotten much worse today

LMP 7 weeks ago with normal menstrual cycle and no hormones used in the past year and taking prenatal

no bleeding reported

β-hCG = 4000

US shows right adnexal mass that’s 1.2 cm with no intrauterine pregnancy identified

what are your treatment options?

Answer 16

shared decision making model with the patient

you shouldn’t make a diagnosis based on location but that, combined with hCG and TVUS, it sounds like it’s an ectopic pregnancy

1. so you could say laparoscopy to look for a diagnosis and treatment but if you dont see anything then you have an IUP that isn’t going to be successful, an IUP that isn’t visible or an ectopic that isn’t in the tube it’s actually abdominal
2. you could also offer methotrexate but ectopic could still rupture – it works on rapidly proliferating cells which is why it works on the placenta but it would also effect GI and BM etc. and it’s a folate antagonist – also get creatinine levels because that’s where it’s cleared – must come back at day 4, 7 and then weekly until the hCG drops till it’s under 5
3. uterine aspiration and if you find chorionic villi then you’ve ruled out an ectopic! this way you avoid the OR and methotrexate

Question 17

27 year old G1P0 present with vaginal bleeding yesterday with continued spotting today
LMP 7 weeks ago with normal menstrual cycle and no hormone use + prenatal vitamins

denies cramping or pain in lower abdomen

β-hCG = 105,000

US reveals complex structure within the uterus with absence of fetal heart tones

Answer 17

hCG are SUPER high but there’s no fetal heart sounds on the US

so this is probably gestational trophoblastic disease aka abnormal trophoblasts cells grow inside the uterus after conception

Question 18

what is gestational trophoblastic disease?

Answer 18

abnormal trophoblast (placenta) cells grow inside the uterus after conception

types:
1. hydatidiform mole

2. invasive mole
3. choriocarcinoma
4. placental-site trophoblastic tumor

Question 19

what is a hydatidiform mole?

Answer 19

molar pregnancy that looks like a bunch of grapes – can be complete or partial

it’s not cancer but can develop into cancer form of gestational trophoblastic disease (GTD)

so it’s a benign tumor of the uterus that develops following abnormal fertilization of the ovum –> can be complete (fertilization of an empty egg that does not carry any chromosomes; tumor does not contain any fetal or embryonic parts) or partial (fertilization of a normal egg with two sperms; tumor contains fetal or embryonic parts)

Question 20

what is a complete hydatidiform mole?

Answer 20

a gestational trophoblastic disease where 1 or 2 sperm cells fertilize an egg with no nucleus/DNA so no fetal tissue results

it’s completely paternal chromosomes!! typically 46XX when a haploid sperm duplicates in an empty egg but can sometimes rarely by 46XY –> 46YY is non-viable

swollen villi are present because there is no fetal tissue to drain villi

can initially present as a normal pregnancy because they’re often uterine sized but will present on US as a “snowstorm” appearance

Question 21

what is a partial hydatidiform mole?

Answer 21

a gestational trophoblastic disease where 2 sperm fertilize a single normal egg so the GTD will contain some fetal tissue mixed with trophoblastic tissue

there are some maternal chromosomes present!

69XXX or 69XXY is the result

villi are less swollen due to some fetal tissue

Question 22

what is the clinical presentation of a complete hydatidiform mole?

Answer 22

1. US: snowstorm appearance
2. hyperemesis gravidarum
3. extremely high hCG levels
4. theca lutein cyst due to ovarian stimulation by hCG
5. preeclampsia in first 20 weeks
6. hyperthyroidism since very high hCG can drive TSH receptors in the thyroid

Question 23

what is an invasive mole?

Answer 23

a type of gestational trophoblastic disease where a hydatidiform mole grows into the muscle layer of the uterus

complete moles become invasive more often but partial moles can as well

there’s an increased risk if there is 4+ months between LMP and treatment and also if the women is 40+ years old

can metastasize…

Question 24

what is a choriocarcinoma?

Answer 24

the malignant form of gestational trophoblastic disease where sheets of malignant cytotrophoblasts and syncytiotrophoblasts with no identifiable villi form

can start as a spontaneous abortion, induced abortion, tubal pregnancy or molar pregnancy

most present due to metastatic disease symptoms and they often metastasize to the lungs –> since they so commonly metastasize and cause non-gynecological symptoms, all women of reproductive age should have a pregnancy test done for any unusual signs or symptoms

Question 25

what is a placental-site trophoblastic tumor?

Answer 25

rare form of gestational trophoblastic disease that develops where placenta attaches to the uterine lining

can develop after normal pregnancy or abortion

Question 26

how do you treat gestational trophoblastic disease?

Answer 26

for nonmetastatic and metastatic GTN with good pronogisis:
1. methotrexate or actinomycin D

2. hysterectomy is an option especially for older women due to higher risk of choriocarcinoma after molar pregnancy

for metastatic GTN with poor prognosis:
1. bagshaw regimen = 6 drug chemotherapy

for brain or liver metas, radiation may be used

2. surgical resection for chemo resistant disease like a hysterectomy or pulmonary lesion

can cute 50-70% of patients (:

Question 27

can an ectopic pregnancy spontaneously resolve?

Answer 27

yeah maybe

there are patients who have decreasing hCG levels that indicate that the pregnancy is resolving but it never goes down to zero for ever and there was never an IUP so it’s probably an ectopic that resolved….

Question 28

why do we track hCG levels back to less than 5?

Answer 28

because molar pregnancies can occur!!! which these can then become choriocarcinomas and you don’t want to miss them