Value of hormonal treatment in endometrial hyperplasia debated— News from ACOG Annual Clinical and Scientific Meeting 2016.

The John I. Brewer Memorial Lecture on Day 2 of the Annual Clinical and Scientific meeting, ACOG  2016 considered the role of hormones in treatment of Endometrial Hyperplasia vs the common surgery of Hysterectomy.

Debaters were David E. Cohn, MD, professor in the Department of Obstetrics and Gynecology and director of the Division of Gynecologic Oncology at The Ohio State University College of Medicine, and Amanda Nickles Fader, MD, associate professor and director, The Kelly Gynecologic Oncology Service and Johns Hopkins Hospital in Baltimore. They all agreed that when treatment is tailored according to patient need both forms can be beneficial.

Dr. Cohn opined that in patients who are fit for surgery and have completed the family the most effective and definitive way of preventing the transition into endometrial cancer is hysterectomy. He cited the 2006 prospective cohort study in which out of 289 women with atypical endometrial hyperplasia on biopsy or curettage,42.6 percent had endometrial cancer at hysterectomy within 12 weeks of sampling. He also said that hormonal treatment has to be continued for an indefinite period of time vs hysterectomy which is a one-step procedure with much higher success rates.

He also referred to a meta-analysis of 34 observational studies in which progestins were used to treat atypical endometrial hyperplasia. The statistical analysis showed that while 86% of women saw regression, 3.6% of women had ovarian cancer and 1.9% had advanced endometrial cancer.

He further quoted “That’s sobering news about the potential for bad outcomes with progestins.”

He acknowledged the committee opinion from 2015 that says “Progestin treatment was an unproven but commonly used alternative to hysterectomy, but optimal doses and duration of treatment need to be defined and post-hormonal surveillance and frequency is yet to be determined. It is also not determined whether it should be continuous or cyclical. And also lacks the optimal clinical as well as histological measures of response.”

He concluded by seconding the ACOG committee opinion of lots of unanswered questions regarding the use of progestins therapy.

The second debater Dr. Fader argued in favor of progestins therapy and stressed that the surgical option is chosen more out of fear than by evidence, nonetheless ample evidence exists in support of hormonal treatment.

As times have changed in last 15 years and in contemporary times, a number of organ-sparing treatments have become a reality. She further said “Almost all endometrial hyperplasia is sensitive to hormonal treatment and most — including atypical hyperplasia — regresses or remains unchanged without therapy and doesn’t progress to cancer.”

She presented evidence in the form of results of 150 retrospective studies and 12 prospective, in which progestin treatment brings about atypical hyperplasia regression in 75 to 95 percent of cases. 

Additional review of 4 large studies also showed that progestins were associated with regression of hyperplasia due to unopposed estrogens in 90% of patients.

Dr. Fader also said that with 40% of endometrial hyperplasia patients are obese or want to retain fertility, making hormonal treatment a valid choice for them. Endometrial hyperplasia is a public health problem due to increasing demographics of obesity and endogenous estrogen production, with many of the women younger than 45 years of age, which increases the need of exploring life style modifications and treatment beyond surgery a viable option.

Both the debaters agreed upon the impact of obesity on endometrial hyperplasia and the Dr.Cohn pointed out that early data on  bariatric surgery is promising in converting abnormal endometrium into normal endometrium without surgery. 

References:

http://www.acog.org/-/media/Committee-Opinions/Committee-on-Gynecologic-Practice/co631.pdf?dmc=1&ts=20150426T1515499455

http://www.acogdailynews.com/role-of-hormones-in-endometrial-hyperplasia-debated/

Is outpatient preinduction cervical ripening an option at term? News from ACOG Annual Clinical and Scientific Meeting 2016.

Outpatient preinduction cervical ripening has always been debated. With nearly 1 in 4 pregnancies scheduled for induction of labor and  50% of these women having unfavorable cervix interest in this has grown. Those clinician and researchers in favor of it vouch that it offers many advantage like decreased hospitalization time, conserving resources due to decreased labor room staffing, and improving patient satisfaction.  

While clinicians against it advocate its use only in specific, well planned situation with valid indication. The reason behind it is lack of large scale data reporting experience behind it. There are also no large scale trials to back up the regime. Studies found in literature involve term pregnancies of living fetuses with some means of continuous monitoring of uterine activity and the fetal heart rate for the first few hours. Also there exist no studies comparing the mechanical vs various drug therapies for cervical ripening.

Samuel A. Cosgrove Memorial Lecture on May 17, 2016 took a detailed look at doing cervical ripening on an outpatient basis for low-risk patients.

Dr. Anthony C. Sciscione, DO, Christiana Care Health Services, Newark, DE was in favor of outpatient cervical ripening and he mostly shared his experiences with Foleys catheter.

He stressed that outpatient ripening has a very high rate of patient satisfaction and patients were willing to make extra trip to hospital. Studies also showed that in-patients have a very high level of anxiety and outpatients were more stress free.  

A small randomized trial at Christiana care was carried out to see if patients can manage Foleys catheter in outpatient setting.   Women who were low risks, with stable vital signs, adequate amniotic fluid had a catheter placed in and randomized to 2 groups inpatient (n=50) and outpatient (n=61) and observed for 2 hours. The outpatient group was discharged with proper instructions and advised to return next day 6 AM. Dr. Sciscione did not really observed any difference between the two groups. 

While Dr. William F. Rayburn, MD, MBA, University of New Mexico, Albuquerque, NM, scrutinized it because of lack of concrete and meticulous research behind it . He urged the audience that they should not postulate that all outpatient inductions are safe. He argued that Up to Date does not recommend it except in research settings and ACOG practice bulletin and leading textbook do not mention it. A review of literature found less than 10% of literature on this subject.

He quoted “What we all would agree with here, I assume, is that whatever we do with this procedure, we want to add as little, or ideally, no additional risk to the mother and the fetus, so we’ve got to have sufficient experience to really say that.”

In researching for the debate he only found two additional clinical trial to the one conducted by Dr. Sciscione. The total number of patients receiving outpatient balloon cervical ripening was only 141.

While adverse effects were rare, no consensus was reached on what constitutes unacceptable risk. 

The studies found that compared with placebo, PGE2 (vaginal or intracervical) and misoprostol (oral or vagina) are effective. But good benefits were documented with Foleys balloon catheter too.

He also commented on the difficulties faced by patients in transporting to and from hospitals and lack of monitoring at home.

In the end he stressed the need of having large randomized trial or meta-analysis to really exclude excess risk here and determine what works and what does not.

References:

http://www.acogdailynews.com/value-of-outpatient-cervical-ripening-debated/

When and How to Induce Labor in Nulliparous Women-- News from ACOG Annual Clinical and Scientific Meeting 2016.

Induction of labor is a major component of obstetrics practice with nearly one third of multiparous women   and 43 percent of nulliparous women undergoing induction.

Mary Catherine Tolcher, MD, MS, assistant professor of obstetrics, Mayo Clinic Rochester said “Induction of labor is likely to become more common with increasing maternal age, hypertensive disorders and obesity,” at Saturday afternoon Clinical Seminar at the conference.

The leading indications for induction of labor at the Mayo Clinic are late-term pregnancy, fetal indications, PROM, gestational hypertension and diabetes.

She further added that benefits of induced labor are clear, Induced labor avoids maternal and fetal risks of continuing pregnancy, avoids risks of late-term pregnancy, allows the timing of labor to be controlled in cases where delivery in a particular facility is appropriate and may be an alternative to cesarean delivery.

The risks are equally clear too, which means prolonged hospitalization before delivery, increased likelihood of more intrusive interventions, increased risk of postpartum hemorrhage and increased likelihood of cesarean delivery.

Answering the key question of whether induction increases the risks of cesarean section she said that it is like a lot of other things in medicine, and depends on your comparison group. 

Results based on retrospective cohort data show the following conclusions.

Depending upon studies the odds ratio for undergoing a cesarean delivery was somewhere between 1.9 and 3.5 when comparing spontaneous labor and induction. 

But compared to expectant management, induction does not seem to be associated with an increased risk of cesarean delivery. 

The first randomized control trial of induction vs expectant (ARRIVE TRIAL) management is currently recruiting participants and will be completing the data collection at the end of 2016.

Since the inception of induction of labor, many methods have been in use like mechanical ripening by Foleys catheter, pharmacological use of prostaglandins and oxytocin. These are either used alone or in combination with or without amniotomy.    

According to Dr. Tolcher, clinical trials have shown all of them to be effective. Cervical ripening is definitely more effective than oxytocin alone, while prostaglandins and Foleys catheter seems to have the same outcome.  Recent data reported at annual meeting of Society for Maternal-Fetal Medicine in 2016, concluded that time to delivery is shortened by using combination methods than using each of the method alone with no increase in cesarean section rates.

Amniotomy is also effective in augmenting the labor, but when early amniotomy (Cervix < 5 cm dilated) was compared to late amniotomy (Cervix > 5 cm dilated), the latter seemed more appropriate. Early amniotomy does results in shorter labor time but it comes with higher incidences of chorioamnionitis and increased fetal cord compression.

Dr. Tolcher also said that Mayo clinic has its own protocols for induction and the cases scheduled for induction in the coming week are reviewed in a staff meeting on Friday and Labor and Delivery nurse also has a significant say to put a stop to non-indicated cases.

Current indication for inductions include advanced maternal age, cholestasis, diabetes, fetal issues, hypertensive disorders, obesity, preterm premature rupture of membranes, prolonged pregnancy, prior stillbirth and unstable presentation. Depending on the indication, the pregnancy must be in week 37 and later.

Cervical ripening is the initial step, followed by oxytocin as needed and amniotomy at the discretion of physician. A failed induction is 24 hours of oxytocin or 18 hours of oxytocin plus rupture of membranes.

Before the decision for induction is taken, the physician should have a very good discussion with patient about the procedure, the expected time to delivery and slightly higher odds of having a cesarean delivery.

References:

http://www.acogdailynews.com/when-and-how-to-induce-labor-in-nulliparous-women/

http://www.acog.org/Womens-Health/Labor-Induction