Obstetric Lacerations: Repair and Prevention

Here’s the RoshReview Question of the Week!

After a forceps delivery of a 9 lb neonate, a perineal laceration is noted with both the external anal sphincter and internal sphincter torn. During the repair, a glistening white fibrous structure is sutured together in a continuous, nonlocking fashion. What tissue is this?

• Anal mucosa

• External anal sphincter

• Internal anal sphincter

• Transverse perineal muscle

Check out if your answer is correct and enter the Qualifying Exam QBank Giveaway at the links above!

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Anatomic Review

• Perineal body anatomy – most common site of injury

  • This is the fibromuscular mass in the middle line of the perineum at the junction between the urogenital triangle and the anal triangle  

    • Bulbospongiosus 

    • Superficial transverse perineal muscle 

    • Deep transverse perineal muscle 

  • Below this = anal sphincter complex 

    • External anal sphincter – voluntary control; provide squeeze pressure of the anal canal 

    • Internal anal sphincter – involuntary (autonomic) control and provides up to 80% of resting pressure of the anal canal. Very important for continence 

So how often do obstetric lacerations occur? 

• Varying numbers, but about 53-79% of women will sustain some type of lac during delivery 

• Types 

  • First Degree – injury to perineal skin only 

  • Second Degree – involves perineal muscles but not involving anal sphincter 

  • Third Degree – injury involves the anal sphincter complex 

    • 3a: <50% of external anal sphincter thickness torn 

    • 3b: >50% of external anal sphincter thickness torn 

    • 3c: Both external and internal anal sphincter torn 

  • Fourth Degree – injury involves anal sphincter complex and anal epithelium 

    • Studies show (obviously) that women with 4th degree lacs are at highest risk of reporting bowel symptoms at 6 months postpartum 

    • Report bowel control 10x worse than women with third degrees 

• What about episiotomies? 

  • Surgical enlargement of the posterior aspect of the vagina by incision to the perineum to facilitate the second stage of labor 

  • Rates have decreased since 2006 

    • However, 12% of vaginal births include episiotomies based on 2012 data 

  • Difficult to separate contribution of vaginal birth, operative delivery, episiotomy, and OASIS to pelvic floor function and anatomy 

  • Systematic review showed that routine episiotomy offered no immediate or long-term maternal benefit in perineal laceration severity, pelvic floor dysfunction, or pelvic organ prolapse 

    • In other reviews though, episiotomy has been associated with increased risk of postpartum anal incontinence; seen in one meta-analysis: increased risk of anal incontinence even if no extension into anal sphincter complex 

  • Routine episiotomy did not improve self-reported sexual function outcomes; more likely to have pain with intercourse in months after pregnancy and slower to resume intercourse than women whom episiotomy use was restricted 

  • So… there is a time and place for episiotomies, but don’t routinely cut them 

What are the risks for higher order lacerations, ie. OASIS? 

• Operative deliveries 

  • Forceps (OR 5.50), VAVD (OR 3.98) 

• Midline episiotomy (OR 3.82)  

• Increased fetal birth way (mean difference 192.88g) 

• Midline episiotomy + forceps substantially increases the risk of 3rd and 4th degree laceration 

• Other ones that are less modifiable: 

  • Primiparity 

  • Asian ethnicity (problematic)

  • Labor induction 

  • Labor augmentation 

  • Epidural use 

  • Persistent OP 

Ok, so now that we’ve talked about all the scariness, how do we prevent them? 

• Antepartum or intrapartum perineal massage 

  • Thought is to decrease perineal muscle resistance and reduce likelihood of lacs 

    • In studies that compared antenatal perineal massage to no-massage, digital massage from 34 weeks gestation on was associated with modest reduction in perineal trauma that required suture repair (RR 0.91), and decreased episiotomy 

    • Perineal massage during second stage of labor may reduce 3rd and 4th degree lacs when compared with “hands off” methods but was not associated with significant changes in rate of birth with intact perineum 

  • Perineal support: data is so-so 

    • Meta-analysis with >6600 women – did not demonstrate protective effect for OASIS 

    • However, three nonrandomized studies showed significant reduction 

    • But techniques of support not well described 

• Warm compress 

  • Meta-analysis with 1525 women 🡪 randomized to warm compress or no in second stage of labor 🡪 did reduce 3rd and 4th degree lacs 

  • Did not increase rate of women having intact perineums 

• Birthing position 

  • Upright or lateral birth position compared with supine or lithotomy associated with fewer episiotomies and operative deliveries, but higher rates of second-degree lacs (overall low quality data) 

  • Meta-analysis of five randomized trials showed no clear benefit 

  • Recent randomized trial: lateral birth position with delayed was compared with lithotomy positions 🡪 lateral positive with delayed pushing more likely to deliver with intact perineum 

• Delayed pushing – no difference in lacerations

How do we manage obstetric lacerations?

• Periclitoral, periurethral, labial lacerations 

  • Small tears of the anterior vaginal wall and labia are relatively common 

  • If superficial and no bleeding – can be left unrepaired 

  • However, if bleeding or distort anatomy, should repair and also consult experts if you do not feel comfortable with it 

• First and second degree 

  • Insufficient evidence exists to recommend surgical or nonsurgical repair of first or second degree lacs 

  • A lot of data does not include long-term outcomes 

  • Use clinical judgement about repair 

    • Continuous suturing is preferred over interrupted suture 

    • Associated with less pain up to 10 days postpartum, less analgesia used, and lower risk of having suture material removed postpartum 

    • Use absorbable synthetic suture like polyglactin (ie. Vicryl) 

• OASIS injuries 

  • Overt OASIS reported in 4% of women in the US

    • Occult OASIS may be later identified by endoanal ultrasonography, but have no clinical findings – occur in 27% of women after first vaginal delivery 

  • The first thing to do: really look! If you suspect, do a digital rectal exam. Examine the perineal body and also the vaginal mucosa. See if you can start to see fibers of the internal and external anal sphincter 

    • SIM has been shown to be helpful in helping providers identify and repair these 

  • How to repair for OASIS 

    • Anal mucosa – expert opinion varies on technique and suture material 

      • Subcuticular running repair that uses a transvaginal approach and interrupted sutures with knots tied in the anal lumen have been described 

      • Suggest using 4-0 or 3-0 polyglactin or chromic 

      • No comparative trials have been done 

    • Internal/external anal sphincter 

      • Identify the area of the internal and external anal sphincter 

      • Because of retraction, we will usually place an Allis on either side of the external anal sphincter muscle to bring them together. Can cross the Allis’s and do a rectal to see if you are bringing the right muscles together 

      • Suture fascial sheath as well as muscle! 

      • Methods: End-to-end and overlap repair 

        • Remember: overlap requires full thickness disruption and 1-1.5 cm torn muscle on either end, so don’t use it for 3a or partial thickness 3b sphincter injuries 

        • Expert opinion: use 3-0 or 2-0 polyglactin suture

        • Meta-analysis of six randomized controlled studies showed no difference between two techniques at 12 months of perineal pain, dyspareunia, or flatal incontinence, but there were lower incidence of fecal urgency and lower anal incontinence scores in women with overlap repair 

        • No significant difference in quality of life or anal incontinence symptoms 36 months after repair  

      • We tend to do end-to-end because of visualization; PISA technique

• Antibiotics for OASIS 

  • Wound complications (ie. Infection, breakdown) are decreased when intrapartum antibiotics are administered 

  • So single dose of antibiotics (studies looked at single dose of second gen cephalosporin) is reasonable. Further research is needed to determine whether severe perineal lacerations warrant routine postpartum partum antibiotics to prevent complications 

Complications from severe perineal trauma 

• First six weeks 

  • After OASIS, 25% of women experience wound breakdown, 20% experience wound infection 

  • Those with complications will have more pain than women with normal healing 

  • Possible to have fistulas (9% of rectovaginal fistulas in the US are associated with OB trauma) 

• How to care for them? 

  • Pain control, avoid constipation, and evaluate for urinary retention 

  • In one study, use of oral laxative was associated with significantly less pain and earlier bowel movement 

  • Monitored frequently for wound healing 

  • Pelvic floor exercise + biofeedback physiotherapy has been suggested 

What about next pregnancies? 

• Increased risk of OASIS in the next pregnancy, but absolute risk is low (3%) 

• Can have elective cesarean 

  • But there is no difference when there is vaginal delivery or elective cesarean in fecal urgency, anal incontinence, or bowel-related quality of life 

Thrombocytopenia in Pregnancy

Here’s the RoshReview Question of the Week!

A 23-year-old primigravid woman at 25 weeks gestation presents to the prenatal appointment to follow up on lab results. Her platelet count is noted to be 77,000/μL, decreased from 205,000/μL in the first trimester. She reports no abnormal bruising or bleeding. What is the most likely reason for her thrombocytopenia?

• Autoimmune process

• Consumptive coagulopathy

• Deficient von Willebrand factor-cleaving protease

• Hemodilution

Check your answer and enter the QE Exam Giveaway at the links above!

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Practice Bulletin 207 is our companion reading this week!

Introduction 

• Evaluation of thrombocytopenia in pregnancy can be difficult because there are many things that could cause it - not all of them are related to pregnancy 

• Definition: when platelets are <150,000/microL 

• So what is normal? 

  • Recall in our very first few episodes that pregnancy can lead to increased plasma volume and not necessarily an equal increase in blood components 

  • This can lead to what appears to be some dilutional effects 

  • In the National Health and Nutrition Examination Survey (NHANES), the mean plt count in pregnancy is as follows: 

    • Non pregnant: 273k 

    • 1st trimester: 251k

    • Second trimester 230k

    • Third trimester 225k 

    • Delivery 217 k 

    • Postpartum (7 weeks) 264k  

• Definitely suggests that some decrease in platelet count could be expected in pregnancy

What are the causes of thrombocytopenia in pregnancy?

• Gestational thrombocytopenia - benign and self limited; may even occur in the first trimester, but usually is more common as pregnancy continues; frequency is 5-10% at the time of delivery

  • But remember this is a diagnosis of exclusion! It’s acceptable if there is mild thromboctyopenia, but again, you should look if Plt <100k  

•  Immune Thrombocytopenia (ITP) - 1-3/10,000 pregnancies, but really low plts only affect a small portion of these

  • ITP is more frequent in pregnancy than in the general adult population but may be because of recognition (checking more frequent CBCs in preg) 

  • Autoimmune condition where antiplatelet antibodies interfere with platelet production and causes destruction of circulating platelets

    • Diagnosis based on exclusion of other causes of thrombocytopenia  

• Preeclampsia/HELLP Syndrome

  • Remember that it is very rare <24 weeks, and there are usually other signs and symptoms as well like elevated BP, headache, vision changes, etc. As well as other hematologic abnormalities like anemia due to hemolysis (high LDH), and may have abnormal LFTs 

  • We won’t go too much into preeclampsia since we discuss it elsewhere, but always something to keep in mind 

• Less likely things, but still things to keep in mind 

  • DIC - Disseminated intravascular coagulation

    • There is usually an underlying cause of this such as placental abruption, sepsis, etc 

    • Patients will have bleeding and oozing at IV sites for example 

    • Usually will have low fibrinogen and elevated PT and PTT labs as well  

  • Acute fatty liver of pregnancy 

  • Thrombotic thrombocytopenic purpura (either immune or hereditary)

    • Will usually present with purpura, can have neurological changes, fever, kidney injury, can have elevated BPs and may be confused with PEC 

    • Will have reduced activity of ADMATS13, but this may be a send out lab in most places and will not come back for some time 

    • Will have schistocytes on smear 

  • Lupus 

  • Infection

  • Inherited platelet disorders

So… when should we start to worry?

• When platelets are: 

  • If platelets are between 100k-150k if there are risk factors present (but usually, do not need work up and can be attributed to gestational thrombocytopenia) 

  • At any point <100k (usually this is beyond the lower end of gestational thrombocytopenia)

    • Plts of <100k only occur in 1% of uncomplicated pregnancies 

    • Remember that there is increased risk of spontaneous bleeding if Plt <20k 

    • Some institutions have cut offs for platelets for ability to give neuraxial analgesia - some places are 70-80k, some places are 100k. Please check with your institution and your patients, because this may require treatment or your patient won’t get an epidural! 

Ok, so that’s a lot of causes… how do I go about figuring out what to do? 

• Evaluation of the patient

  • Get a good history and physical - this can sometimes help you determine what it is not

    • If patient is well appearing, with no pain, vaginal bleeding, elevated blood pressure or other complaints, it’s usually not going to be something like AFLP, DIC, TTP, or preeclampsia  

    • Look through the patient’s chart: what were their platelets before? What other medical problems? What about new medications? 

    • Any history of lupus, TTP, liver disease, anemia

    • You have the CBC - did the lab do a smear? Are there abnormalities on the smear, like schistocytes? 

    • Most of the time, if you have someone who is sitting in the clinic and appears well, you may have some time  

• The asymptomatic patient with Plt >100k

  • Usually, plts between 100-150k without other cytopenis or other major clinical findings can be attributed to gestational thrombocytopenia 

  • The other major cause could be ITP, but minor ITP with plt >100k also does not need treatment 

  • Our practice is to check plts monthly to make sure they do not drop below 100k, or below threshold for neuraxial analgesia 

• The asymptomatic patient with Plt <100k 

  • Review the CBC - make sure there are no other cytopenias; ask for a smear 

  • Evaluate for HIV (usually already done in pregnant patients), as this could also lead to thrombocytopenias 

  • Obtain other coagulation panel like PT, PTT, fibrinogen level 

  • Also obtain CMP - evaluate kidney and liver function 

  • If no obvious signs, it is ok to get hematology involved early

  • More likely to be ITP if <100k, and patients can be treated with steroids or even IVIG in refractory cases if needed 

  • This is to make sure that the platelets do not drop further so that they cannot get neuraxial analgesia or so that they don’t drop too low as to cause issues with bleeding 

• What if they are symptomatic and <100k?

  • A lot of this is going to depend on their history and physical again - we are usually pretty good at evaluating for preeclampsia - get their vital signs and do your exam

    • Do they have fever? Purpura? 

  • Labs: CBC, CMP, coag panel, HIV, LDH, urinalysis, bilirubin 

  • If you are suspicious of TTP (ie. fevers, kidney injury, neurological changes) 

    • Make sure to get CT head to rule out bleed 

    • ADAMTS13 

    • Hematology consult 

  • Ok to get MFM and hematology involved early 

Management 

• Treatment for bleeding or severe thrombocytopenia 

  • If Plt are <10k or <20k, there is increased risk of spontaneous bleed 

  • If Plt <20k and severe bleed (ie. intracranial), you should give platelets regardless of the underlying cause of thrombocytopenia (yes, even in ITP if it will get consume)

• Some platelet thresholds to consider in delivery 

  • Vaginal delivery: 20-30k 

  • C/S: 50k 

  • Neuraxial anesthesia: institution based; ours is 80k; most institutions will have a count between 50-80k 

• Other considerations 

  • Operative vaginal deliveries are relatively contraindicated if there is severe maternal thrombocytopenia 

  • This is because there is concern that there could also be fetal thrombocytopenia (ie. immune mediated or hereditary) 

  • However, if you must perform an operative delivery, forceps is favored over vacuum 

  • Remember: Just because someone has ITP does not mean they can’t have an operative delivery 

• Treatment of specific disorders 

  • ITP - steroids or IVIG 

    • Dosing of steroids: prednisone 1mg/kg/day for two weeks followed by gradual taper; may need 2 weeks to see peak effect (usually 1-4 weeks for peak) 

    • IVIG should be given at least 1 week in advance to allow for maximal efficacy and platelet count retesting if trying to raise platelet counts for epidural 

    • If refractory, other methods in pregnancy are not well studied, and you should have a conversation with your MFM and hematology colleagues 

  • TTP - plasma exchange

  • Preeclampsia or DIC due to abruption: delivery! 

• What about fetal testing of platelets?

  • There isn’t really evidence to suggest we should test fetal platelets (ie. either via PUBS or from fetal scalp during labor

  •  We won’t discuss fetal/neonatal thrombocytopenia here, but just some brief reasons to test neonatal platelets: 

    • Maternal ITP 

    • Neonatal thrombocytopenia in previous pregnancy (concern for NAIT, though this is usually not associated with maternal platelet issues) 

    • Congenital anomalies associated with thrombocytopenia 

    • Bleeding or petechia on the infant 

    • Neonatal infections (ie. CMV, rubella) 

Soft Markers for Aneuploidy

Here’s this week’s RoshReview Question of the Week!

A 38-year-old G1P0 woman at 20 weeks gestation presents to the clinic for her anatomy ultrasound examination. She underwent a first-trimester screen, which showed a borderline nuchal translucency of 3.1 mm. Which one of the following isolated ultrasound findings confers the greatest risk for trisomy 21?

• Atrial septal defect

• Echogenic bowel

• Echogenic intracardiac focus

• Thickened nuchal skin fold

Check out the links above to see if you answered correctly. Also, you can enter for a chance to win a Rosh Review Qualifying Exam (“written boards”) QBank!

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Check out the SMFM Consult Series 57 for excellent companion reading!

What are the ultrasound soft markers, and why do we care? 

• In the era of cell-free DNA, you might ask: what is the utility of soft markers? Aren’t they poor predictors of aneuploidy?

  • Originally introduced to improve the detection of Down syndrome over that of just age-based or serum-based screening 

  • While it is true that each isolated soft marker may be poor predictors, if we see multiple soft markers, that does improve sensitivity  

  • There may also be some misunderstanding of soft markers seen on ultrasound, and so the purpose here is to review some of these soft markers in the setting of cfDNA and discuss next steps 

• Remember: patient’s baseline risk should not limit screening options, and cfDNA should be offered to all per ACOG and SMFM 

What are the first steps when you see a soft marker?

• Make sure that the soft marker is truly isolated - look for other soft markers, fetal growth restriction, or other anomalies 

  • If you feel that your office is not equipped to do this, can refer to MFM to have a level II ultrasound performed - this is of course a discussion with the patient, and not all patients will want further evaluation 

• Look at the patient’s history: 

  • What is their baseline risk? (age, family history, history of aneuploidy) 

  • What are their previous aneuploidy screening results? Did they have any? 

• Ok, so I see one of the soft markers, what do I do next?

  • First of all, have they had cfDNA?

    • Most of the time, there is not much to do after that (again: ISOLATED soft marker) 

    • This is because with cfDNA, the posttest probability of a common aneuploidy (ie. Trisomy 21) of negative cfDNA is very low - it is lowered by 300x for trisomy 21

      • Per the consult series, the residual risk of a 35-yo woman, whose age related risk of Down syndrome is 1/356 is reduced to <1/50,000 after a negative cfDNA result  

  • But what if they didn’t have cfDNA? 

    • If they have had negative serum screening, also ok, no need to do further testing at this time 

      • The detection rate of serum screening test for Down is still high, about 81%-99% depending on the test 

    • If no screening at all, counsel about noninvasive aneuploidy testing - not all patients will want screening 

  • Remember: there isn’t an established cut off residual risk when there is recommendation to do diagnostic testing 

    • Many labs will establish a cutoff of 1:250 or 1:300 

  • SMFM does not recommend diagnostic testing for aneuploidy only for evaluation of isolated soft marker following negative serum or cfDNA screening result 

The Soft Markers (all photo credit to Radiopedia)

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Tubal Ectopic Pregnancy Management

Here’s the RoshReview Question of the Week!

A 24-year-old G2P1 woman presents to the emergency department with right-sided pelvic pain and vaginal spotting. She has been trying to conceive and her last menstrual period was 8 weeks ago. The patient reports her left fallopian tube was removed 3 years ago due to hydrosalpinx. Her beta-human chorionic gonadotropin is 6,700 mIU/mL. On ultrasound, there is no intrauterine pregnancy identified. Fetal heart tones are detected in the right fallopian tube. There is a minimal amount of free fluid noted in the posterior cul-de-sac. What is the most indicated intervention at this time?

• Methotrexate

• Salpingectomy

• Salpingostomy

• Surveillance

Check to see if you got it right at the links above!

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While we have reviewed the workup of the early unlocated pregnancy and diagnosis of ectopic pregnancy previously with Dr. Cleary, and talked about the unusual problem of cesarean ectopic pregnancy before on the show, somehow we missed the management of the regular tubal ectopic! 

ACOG PB 191 is a great resource for all things ectopic pregnancy and important companion reading for the podcast today.

Background Info

• Ectopic pregnancy represents about 2% of reported pregnancies, but this is likely an undercall as not all ectopic pregnancies are reported.

• Ruptured ectopic accounts for a significant cause of maternal morbidity and mortality - 2.7% of maternal deaths in 2011-2013 were attributable to ruptured ectopics. 

• Fallopian tube is the most common location for an ectopic (90%), but as we’ve talked about before, these can be anywhere – abdomen (1%), cervix (1%), ovary (1-3%), and cesarean scar (1-3%). 

  • Can also co-occur with an intrauterine pregnancy – heterotopic pregnancy.

    • Naturally conceived: 1 in 4,000 to 1 in 30,000

    • IVF: as high as 1 in 100

Risk Factors for Ectopic Pregnancy

• 50% of those who receive a diagnosis don’t have any known risk factor. 

• Risk factors that can be present include:

  • Prior ectopic - recurrence risk is about 10% after 1 prior, 25% after 2 prior

  • Prior fallopian tube surgery / damage

  • History of PID or ascending pelvic infection

  • ART - tubal infertility, multiple embryo transfer, infertility in general

  • Cigarette smoking

  • AMA > 35yo

• Contraception and ectopic risk:

  • Those using IUDs are at lower risk overall of ectopic because IUDs are highly effective at preventing pregnancy in general.

    • However, in those who do become pregnant with an IUD in place, up to 53% of these pregnancies are ectopic.

  • OCP use, emergency contraceptive failure, previous pregnancy termination, pregnancy loss, and cesarean delivery have not been associated with increased risk of ectopic pregnancy. 

Confirming a Diagnosis of Ectopic Pregnancy

• We covered this pretty extensively in our episode with Dr. Cleary - there we do a great job of talking you through the “pregnancy of unknown location” workup, especially when you see a patient in ED/triage with bleeding/pain and early pregnancy. 

• We won’t go through it all again today, as we want to focus primarily on management, but a few big points:

  • Trending bHCG every 48 hours helps to determine if the pregnancy is normal or abnormal.

    • If a bHCG is higher than the DZ and you don’t see anything - that’s a good indicator of an abnormal pregnancy, with 50-70% being ectopic. 

  • Transvaginal ultrasound to assess the uterus and adnexae will help you identify any unusual mass that might be an ectopic.

• So let’s start from the point of abnormally rising bHCG, so we know our suspicion is for an abnormal IUP versus ectopic. What options are available?

  • Expectant Management

    • We can continue to trend bHCG in a stable patient, particularly in the case of highly desired pregnancy or low bHCG values that may need more time to declare itself.

    • These patients should be counseled strongly about presenting for care should they experience significant bleeding, severe pain, or other symptoms worrisome for ectopic rupture. 

  • Uterine Aspiration

    • If we are reasonably certain the pregnancy is abnormal, a uterine aspiration can be done to determine if the pregnancy is intrauterine or not.

      • The aspirate can be sent to pathology or floated to quickly identify chorionic villi – if found, then you know it was an IUP.

      • If villi are not found, then hCG should be measured again at 12-24 hours after aspiration.

        • If the hCG drops at least 10-15%, it was likely successful aspiration of a failed IUP; however, drops of 50% or greater are more indicative. 

          • Serial hCG should be followed to zero in these patients since no pathology was identified.

        • If the hCG is plateaued or rising, then the pregnancy is ectopic, and the patient will need additional treatment. 

  • Proceeding Directly to Treatment

    • The PB mentions there is debate whether aspiration is necessary before treating an abnormal pregnancy with methotrexate.

      • On one hand, confirmation of the diagnosis with the procedure helps avoid unnecessary exposure to MTX.

      • On the other hand though, the procedure adds at least 12-24 hours of additional time (and potential ectopic rupture) before giving treatment.

    • ACOG notes that the risk of rupture during this time period overall is low, and that presumptive treatment with MTX doesn’t confer cost savings

      • However, it reserves the choice for patients and their physicians after discussion of risks and benefits.

Medical Treatment of Ectopic Pregnancy

• The standard, as we’ve mentioned, is methotrexate.

  • Folate antagonist binding to catalytic site of dihydrofolate reductase → inhibits synthesis of nucleotides and amino acids, thus inhibiting DNA synthesis, cell repair, and cell replication.

  • MTX affects all rapidly-proliferating cells because of it – marrow, mucosa, cancers, and trophoblasts. 

    • This is helpful to keep in mind to thinking about side effects of MTX:

      • Nausea, vomiting

      • Stomatitis 

      • Abdominal pain

      • Alopecia (rare)

      • Pneumonitis (rare)

    • There are no recommended alternatives to MTX for medical therapy.

• Contraindications to MTX:

  • Absolute:

    • Intrauterine pregnancy

    • Chronic liver or kidney disease

    • Bone marrow dysfunction (anemia, blood dyscrasia, thrombocytopenia, leukopenia).

    • Active GI disease (i.e., PUD) or respiratory disease.

    • Breastfeeding

    • Hemodynamically unstable patient.

    • Inability to participate in follow up. 

  • Relative:

    • Cardiac activity in the ectopic pregnancy

    • High hCG concentration (>5000 mIU/mL)

      • Reviews demonstrate a failure rate of 14.3% or higher at this concentration (vs 3.7% when under 5000 mIU/mL)

    • Ectopic size greater than 4cm on TVUS

    • Refusal to accept blood transfusion

• MTX Regimens:

  • ACOG in the PB 191 mentions three primary regimens: single-dose, two-dose, and fixed multi-dose.

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• Single-dose is the simplest but may require additional dose in up to 25% of patients.

• Two-dose has high success rate with similar monitoring to single-dose regimen.

  • A recent review article suggested the two-dose protocol was more successful while also exposing patients to only minimal, transient side effects versus single dose, and has higher success rates with higher hCG levels.

• Multi-dose fixed regimen requires up to 8 days of treatment with alternating MTX and folinic acid for rescue and minimization of MTX side effects.

• What about surveillance / labs for MTX?

  • Before administration (day 1), you should obtain:

    • bHCG

    • CBC

    • CMP

  • Patients should be counseled about side effects of MTX, and should avoid medications, foods, and supplements that may worsen efficacy

    • Have them stop prenatal vitamins at this time, so the folate doesn’t counteract the MTX!

      • Folate-rich foods and NSAIDs may also decrease the efficacy of MTX.

      • Narcotics, alcohol, and gas-producing foods should also be avoided so as not to mask or be confused with signs of rupture.

      • Patients should also avoid vigorous activity and sex until confirmation of resolution so as not to induce ectopic rupture. 

  • With single and two-dose protocols, you’ll evaluate bHCG again on days 4 and day 7.

    • Success in these protocols is noted with a 15% or more decline between days 4 and 7. 

      • If the decline is less than that, or bHCG increases, then an additional dose of MTX should be administered on day 7. 

      • With repeat doses of MTX, it’s reasonable to consider repeat laboratories to evaluate for any toxicity. 

    • bHCG should continue to decline to zero, and should be followed at least weekly once the initial 15% decline is noted.

      • Resolution can take up to 8 weeks, though average:

        • Two dose: 25.7 +/- 13.6 days

        • One dose: 31.9 +/- 14.1 days

  • Finally, patients should consider avoiding pregnancy for at least 3 months after the last dose of MTX.

    • Studies have found MTX still detectable in cells up to 116 days past exposure. 

    • However, limited evidence also suggests that anomalies and pregnancy loss is not elevated in those who become pregnant shortly after MTX exposure.

  • MTX does not have a measurable effect on fertility.

Surgical Therapy

• For patients who do not desire MTX or are not candidates, surgical therapy is the other option. Surgical therapy is also needed for the patient with hemodynamic instability or symptoms of rupture/intraperitoneal bleeding. 

  • Can also be reasonably considered in stable patients with an indication for another procedure, like salpingectomy for sterilization or hydrosalpinx removal. 

• Surgeries available include salpingectomy (removal of the tube) or salpingostomy (opening the tube).

  • These are generally accomplished laparoscopically – laparotomy is reserved for unstable patients or patients with large bleeding and compromised laparoscopic visualization. 

• Surgery may be more effective than medical therapy and requires less follow up, but does expose patient to surgical risk. 

• Salpingectomy is technically easier to perform, and that’s likely how most of us have trained.

  • Salpingostomy can be considered in patients with desired fertility and damage to the contralateral fallopian tube, and would require ART for future pregnancy.

  • To perform, typically you make an incision along the long axis of the tube over the ectopic, and resect the pregnancy tissue. 

    • Achieving hemostasis is rather tricky in these cases, and may additionally cause damage to the tube. The tube is usually left to heal on its own and not sutured as this may crimp the tube and cause further damage. 

    • Because you may not resect all of the pregnancy tissue at salpingostomy, bHCG monitoring after salpingostomy is needed to ensure complete resolution.

    • MTX may also be given prophylactically if incomplete resection is considered. 

Expectant Management

• We bet you weren’t expecting this one… but ACOG does mention there may be a role for expectant management of ectopic.

• They note that candidates for EM should be:

  • Asymptomatic

  • Objective evidence of resolution (i.e., plateau or decreasing bHCG)

  • Accepting of potential risks after counseling, including tubal rupture, hemorrhage, emergent surgery.

    • EM should be abandoned if hCG insufficiently decreases or begins to rise or with any suspicion for tubal rupture. 

• If initial hCG is under 200 mIU/mL, 88% of patients will have spontaneous resolution.

• In a single small RCT of patients with hCG < 2000 mIU/mL, EM was not associated with lower treatment success than single dose MTX (59% vs 76%).