Gestational Trophoblastic Disease

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On today’s podcast, we welcome Jenna Emerson, MD, the current 3rd year fellow in gynecologic oncology and alumnus of the residency at Brown University / Women and Infants! Jenna takes us today through the often confusing world of GTD (or GTN, or GTT).

GTD encompasses several distinct disease entities, including complete and partial molar pregnancy, invasive moles, gestational choriocarcinoma, and placental-site trophoblastic tumors (PSTT).

Molar Pregnancies are a form of non-invasive GTD, and will be encountered by the general OB/GYN. It’s estimated 1:600 TABs will pathologically be molar pregnancies. 20% will lead to malignant GTD and require treatment, with complete moles more often leading to malignancy than partial moles.

The distinction of complete versus partial moles make for great test questions, though the management is the same. There are two main distinctions:

  • Karyotype – partial is triploid, complete is diploid

  • Clinical features – complete is completely weird, while partial only partially weird. Though the ACOG PB 53 has since been retired, this table is helpful in going over the main differences:

ACOG PB 53

Moles generally present with first trimester bleeding or characteristic US findings (“snowstorm appearance”). Initial management requires a number of steps for evacuation or hysterectomy. Be sure to check out the NCCN guidelines (membership required, but free!) for review.

Malignant GTD occurs post-molar if bHCG plateaus, increases, or is persistently positive. This ultimately requires staging per FIGO criteria:

NCCN / FIGO

NCCN / FIGO

If disease is low risk and local disease only, management is hysterectomy vs repeat D&C. A second curettage for low risk cures 40% of patient, and avoids need for chemotherapy. This is a change from traditional teaching, based on a prospective trial published in 2016.

If this surgical management is unsuccessful while following bHCG, then it’s time to move to chemotherapy. Low risk disease is treated with single agent chemo (MTX or Actin-D). Per GOG174, Actin-D has a higher complete response rate, but is more toxic than MTX. High risk disease is treated with EMACO. Check out the NCCN guidelines for more information on these regimens. 

Choriocarcinoma and Placental Site Trophoblastic Tumor

  • Choriocarcinoma can follow term pregnancies (50%), moles (25%), or non-term histologically normal pregnancies (25%). They have early systemic mets, and require chemotherapy. The staging system is the same as above to decide single vs. multi-agent therapy. These are very vascular, so the classic CREOG answer is that you should not biopsy a suspected choriocarcinoma!

  • PSTT, epithelioid trophoblastic tumor – both of these are very rare and can follow any pregnancy. These should be referred to specialized centers, and are most commonly treated with hysterectomy.

Diagnostic Dilemmas

We reviewed a number of scenarios that can pose diagnostic challenges. In brief:

  • Malignant GTD following non-molar pregnancies

    • In the case of persistent AUB for > 6weeks after pregnancy, a bHCG should be checked to rule out new pregnancy or GTD

  • Choriocarcinoma as malignancy of unknown primary 

    • Mets have been reported in pretty much every body site.

    • Serum beta (which will almost certainly be above discriminatory zone) and pelvic US to r/o pregnancy allow for diagnosis.

  • Phantom hCG – heterophile antibodies

    • Positive serum hCG testing can result due to relatively non-specific circulating antibodies which bind to secondary antibody in a sandwich assay (antigen 🡪 primary antibody detects antigen-labeled secondary antibody, which detects primary antibody and has detectable indicator).

    • Several ways to identify: pos serum with neg urine (antibodies aren’t shed in the urine but bHCG glycoprotein is), value doesn’t decrease with serial dilutions, or can send to a separate lab which may use separate secondary assay.

  • Postmenopausal hCG

    • Baseline small amount of hCG produced by the pituitary – rises in peri- and post-menopausal, during chemo. Typically beta is 5 or less but can occasionally be higher. Confirm by checking LH – if LH is consistent with menopause, this confirms pituitary source.

Trial of Labor after Cesarean (TOLAC)

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In 2016, the US cesarean delivery rate was 31.9%. With ever increasing volumes of cesarean delivery, TOLAC has become a popular option for patients desiring vaginal delivery. On today’s episode, we examine TOLAC and share some counseling pointers in thinking about your patient. ACOG PB 205 is the requisite reading for the topic.

While there are no RCTs comparing TOLAC to planned cesarean, the relative benefits are easy to see: there is less recovery time, the patient avoids major surgery, and the potential sequelae of complications from major surgery — worsened bleeding, more opportunity for infection, more risk of complications requiring additional procedures. However, TOLAC is not without risk. We primarily counsel with respect to uterine rupture. Evaluations of “rupture” though have varied in the literature; it’s important to keep a discerning eye, as what is classified as rupture in some series is very different than what is in others. ACOG suggests the rate of uterine rupture in a patient with one low transverse cesarean delivery is around 0.5 - 0.9 %. Otherwise, maternal risks are fairly equal. Neonatal risks are also considered fairly equal, though with some increased risk associated with TOLAC.

ACOG PB 205

ACOG PB 205

We can think about patients who should be counseled against TOLAC:

  • Those at high risk of uterine rupture: ie. those with classic uterine incision, T-incision, prior uterine rupture, or extensive prior uterine fundal surgery like a myomectomy.

  • Women who are not otherwise candidates to have vaginal deliveries: ie. previa.

  • Women who desire homebirth: While ACOG does not definitely say that you cannot TOLAC in this instance, if you don’t access to emergency cesarean delivery, it is recommended that these patients have a discussion regarding the hospitals resources and possibly referral to a hospital that does have access to emergency cesarean delivery.

We can also consider patients for whom there may be a question of whether TOLAC is appropriate:

  • Low vertical incision? 

    1. Few studies, but those that have looked at them have shown similar rates of vaginal deliveries as low transverse. Can consider TOLAC!

  • Twins? 

    1. Studies show similar rates of successful VBAC in twins as in singleton gestations 

  • Obesity 

    1. Unfortunately, higher BMI seems to have an inverse relationship with success of VBAC. 85% of normal weight women achieve VBAC while only 65% of morbidly obese women do. However, morbidly obese women also can have more complications with an elective repeat cesarean, so counseling should be individualized

  • Induction and augmentation of labor 

    1. Mechanical dilation can be used - ie. cervical foley 

    2. Misoprostol has been shown to have increased risk of uterine rupture, so should not be used in term patients who have had c/s or other major uterine surgery for induction 

    3. However, in women undergoing second trimester labor inductions (ie. for missed abortion, induction of labor for stillbirths), use of prostaglandins have shown similar results in women who have had scars on their uterus and those without; so these women can still have prostaglandins, especially because no fetal considerations 

  • What if they’ve had a uterine rupture? 

    • If the site of rupture or dehiscence is in the lower part of the uterus, their risk of uterine rupture in labor is 6%. If it is in the upper segment of the uterus, the rate of dehiscence in labor is up to 32%. While there is no high quality data to guide this, recommendations are generally for subsequent pregnancies to be delivered by cesarean between 36-37 weeks.

Counseling should be individualized, and the MFMU has excellent calculators to help guide you and your patients to a decision about TOLAC:

(not in labor) https://mfmunetwork.bsc.gwu.edu/PublicBSC/MFMU/VGBirthCalc/vagbirth.html

(at admission) https://mfmunetwork.bsc.gwu.edu/PublicBSC/MFMU/VGBirthCalc/vagbrth2.html

#MedEd: How to Give Feedback

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We’re starting into a new miniseries at CREOGs Over Coffee that will be devoted to topics specific to medical education! To help us kick this off, we’ve invited Dr. Dayna Burrell, assistant professor and OB/GYN residency program director at Brown / Women and Infants, as well familiar voice Liz Kettyle, CNM, clinical instructor at Brown / Women and Infants. Now well into a new academic year, the dreaded topic on the front of everyone’s minds is delivering feedback. The word ‘feedback’ itself probably conjures up a lot of negative emotion, and Dr. Burrell and Liz are here to help change the spin on that and set you up to both receive and give feedback effectively.

For the website today, we’ll devote space to their seven tips for effective feedback:

  1. Define the time: Plan in advance. Set expectations that feedback will happen on a regular basis - after each procedure, after each delivery, on a weekly basis - whatever makes the most sense for that learning environment. When people know what to expect, and time is defined, both the person giving feedback and the person receiving it will be less anxious, and it will be more likely to have an impact.

  2. Create a positive learning environment: Setting the stage for a positive learning environment can really optimize your ability to give and the learner’s ability to receive the feedback that’s coming.  If possible, try to find a private space away from the direct clinical area. Try to pay attention to the learner’s needs -- has he been in the OR all day? Would it help to get water, coffee, a sandwich before the feedback session?  Pay attention to the small talk you’ve had with him. Do you remember any relevant details in his world? How’s that patient from yesterday doing? Is your baby sleeping through the night yet? Are you getting settled into your new place? You are demonstrating that you care about the learner as a person. You are providing feedback because you care! You are invested in his development and really want him to be successful! 

  3. Define that this is feedback happening now: When Dayna started as an APD, she was given the advice to start defining the feedback, by starting each meeting with, “This is your feedback session.” At her program, this immediately improved the perception of the quantity and quality of feedback given. It seems silly, but meetings with someone who is senior to you can be stressful and anxiety provoking and the messaging can be lost in that stress. Take the time, acknowledge the purpose of the meeting in a relaxed manner and move forward. 

  4. Allow the learner to self assess: Having the learner tell you about what she thinks went well and what could be improved upon lends tremendous insight that can make your ability to deliver feedback much more impactful.  If your views align, it can be mutually rewarding, thereby strengthening your relationship. You can validate her observations which in turn strengthens her confidence. If there is a discrepancy, a deeper dive will be required to understand how, where and why you perceive the performance differently and this may guide how you decide to approach your delivery.  

  5. The feedback sandwich, or your food analogy of choice:

    1. The traditional sandwich: positive - area for improvement - positive. A great place to start when you are giving feedback- it is very concrete. 

      • So what is the content? Start with a positive, and roll into an area for improvement- remember you aren’t trying to criticize, you are aiming to provide specific information to reinforce or change a behavior. And you can’t change someone’s personality! Focus on behaviors that you can impact. End with a positive, or a goal to accomplish. 

      • The sandwich is getting a bad wrap per the literature of being overused, and students complaining about it being predictable. So spice it up. Add condiments, maybe some dill pickles, maybe some pesto!

    • The sushi roll: the sushi rice on the outside represents the background/the positive, the tougher nori represents the area for improvement, the spicy tuna on the inside represents the end goals, the part of the bite that makes it all come together

    • The sundae: the ice cream represents that background/the positive- comes in many flavors! The toppings represent areas for improvement- also many varieties- some small and concise(sprinkles), some more wide spread (hot fudge). The whipped cream and cherry are the bonuses on top- the plans, the goals. 

  6. Engage in a dialogue: Now we need to close the loop and ask about barriers she perceives with respect to accomplishing the identified objectives. Listening openly to her perspectives on how her learning and performance can be optimized is crucial. Be prepared, the dialogue may include feedback on your institution and teaching style. 

  7. Set Goals: This is it. Arguably the most important part of the whole feedback session. Set goals to improve! How do you meet those goals, what tools do you need for success, how do you measure success. As the person giving feedback- make sure you follow up. Recognize when someone is meeting those goals, or acknowledge their effort to get there, for the sake of positive reinforcement. 

 

Considerations for Planned Singleton Breech Vaginal Delivery

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Today’s episode dives more into the realm of expert opinion rather than hard science, and we hope some of our listeners will share their own experiences and criteria for offering planned breech labor!

ACOG CO 745, in addition to PB 161 on external cephalic version, deal with this topic, but there is much variation in the literature available. In particular, international guidelines on this topic are rather variable. The ObG Project has a great summary and links to these varying resources that is worth checking out.

There are particular risks to breech labor, and experienced provider hands are necessary, which is why almost 90% of planned term breech birth in the USA is performed by cesarean section. The 2000 Term Breech Trial, a multicenter randomized trial, noted perinatal morbidity and mortality was overall reduced with planned cesarean delivery than with planned vaginal delivery of term breech (1.6% vs 5.0%), with no differences in reported maternal morbidity or mortality. Follow up studies to the Term Breech Trial, however, have noted no differences in maternal or neonatal outcomes at 2 years.

Additional studies performed since this time have been mixed. While some prospective studies demonstrated excellent maternal and neonatal outcomes, both short- and long-term, they utilized very strict criteria and protocols for the selection of candidates offered a trial of breech labor. Cohort studies of breech birth in general populations demonstrates at least short-term risk of neonatal morbidity, including birth injury, nerve injury, and need for assisted ventilation. This risk is present with any trial of breech labor, including if intrapartum cesarean is performed, versus planned cesarean delivery.

Below is a sample protocol based on some of these studies with stricter inclusion criteria. We recognize there is likely some significant debate to be had on these criteria, and in particular clinical scenarios, so be sure to discuss with experienced obstetricians in your area as well as check your hospital’s own breech birth protocol.

(c) CREOGs over Coffee, 2019. Adapted from Hofmeyr/UpToDate, 2019.

Finally, intrapartum management should proceed according to usual obstetric practice. However with breech presentations, providers should closely consider a number of factors outlined below. Notably, these factors are largely based on expert opinion and guidelines from international societies.

  • Avoidance of early amniotomy, and preference for spontaneous rupture of membranes.

  • The progress of labor in the active phase, and progress of descent during active pushing. 

    • Cesarean delivery should be recommended with a protracted labor course, particularly in the active phase, as this may be indicative of fetopelvic disproportion. 

    • Use of oxytocin in the active phase of labor is discouraged.

    • With the achievement of full cervical dilation, the breech should reach the pelvic floor.

    • Passive descent should not be permitted for more than 90 minutes after achieving full cervical dilation.

    • With onset of active pushing, delivery by cesarean should be considered if the infant has not delivered within 30-60 minutes.

Cardiac Arrest in Pregnancy

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Today we discuss a topic that we hope you never encounter, but want every OB, EM, and really any other person or medical professional to be prepared for cardiac arrest in pregnancy. The American Heart Association (AHA) Scientific Statement on Cardiac Arrest in Pregnancy can be found here and is essential companion reading.

(c) AHA

In preparation for a maternal cardiac event, a cesarean delivery kit should be available as part of the adult code cart. This at minimum should have a scalpel (#10 blade), betadine splash prep, clamps for cutting the umbilical cord, sponges, absorbable suture, and additional clamps and/or retractors if feasible. A neonatal resuscitation cart should accompany the adult cart if a maternal code is ongoing.

BLS is not different from standard for any other adult resuscitation, except for one key component: leftward displacement of the uterus. This allows for improved venous return to the right heart via the inferior vena cava, which may be compressed to some degree as early as 12 weeks gestation. Otherwise hand positioning, compression technique, and ventilation considerations in the BLS portion do not have any differences.

The ACLS algorithm also proceeds as usual, with the notable exception being performance of resuscitative hysterotomy (aka, peri-mortem cesarean section) at 4 minutes of pulseless arrest. This should be performed at any gestation above 20 weeks (i.e., fundal height at or above the umbilicus). It serves the dual purpose of improving maternal venous return, as well as protecting the fetus from consequences of prolonged anoxia.

Otherwise, ACLS algorithms use the same medications and doses, the same indications for shocks, and actually many times the same etiologies for arrest. However there are some pregnancy-specific considerations all physicians should recall, in a simple mnemonic:

(c) Society of Obstetric Anesthesia and Perinatology