Abnormal Uterine Bleeding: The Basics

Today we talk through the varied etiologies and a basic workup for a common GYN complaint: abnormal uterine bleeding. ACOG PB 128 makes for good companion reading for women of reproductive age.

The terminology of AUB has changed quite a bit, and you may still hear older terms being used. “Dysfunctional uterine bleeding” or DUB has fallen out of favor, as have terms such as metrorrhagia or menorrhagia, yielding instead to simpler terminology such as prolonged menstrual bleeding and heavy menstrual bleeding, respectively. The terms such as oligomenorrhea (bleeding cycles > 35 days apart) and polymenorrhea (cycles < 21 days apart) are also in use to some degree.

Heavy bleeding is difficult to discern, but for research purposes has been described as >80cc blood loss per cycle. In clinical practice, this is obviously impractical, so we rely on subjective descriptions of heavy bleeding to guide care.

The biggest takeaways from this episode include the PALM-COIEN classification of bleeding by FIGO, as well as the common culprits of bleeding by age group. Remember also the criteria for working up for disorders of coagulation, which we’ve put here (though contained in the practice bulletin).

Stay tuned for future episodes about the treatments of these various etiologies, or check out our friends at The OBG Project for excellent summaries of guidelines and new literature!

ACOG PB 128

ACOG PB 128

ACOG PB 128

Cervical Cancer Screening and Prevention

Today we discuss one of the basic screening tools of the OB-GYN office: the Pap smear. Named for Georgios (George) Papanikolau, credited for its creation around 1923, it is a test that has singlehandedly changed the face of cancer screening. With its widespread use, the incidence of cervical cancer in the US has dropped from 14.8 / 100k women in 1975, to 6.7 / 100k women in 2011. The converse also demonstrates the importance of this routine test: 50% of those diagnosed with cervical cancer have never had Pap screening, and 10% have not had screening within the preceding 5 years.

We also now know and can test for the presence of oncogenic strains of human papilloma virus, or HPV. Types 16 and 18 account for over 70% of cervical cancer worldwide, and 12 other strains account for the remaining majority of cases. Ongoing trials are looking at whether HPV screening may ultimately supplant cytology as the preferred 1st test, but HPV screening has added another excellent tool to help OB-GYNs discuss risk and prevent cancer in their patients.

Follow along with ACOG PB 168!

So what are the screening guidelines?
In the immunocompetent patient, they are as follows:

  • < 21 years: Screening should not be performed, even in the presence of behavior-related risk factors.

    • Only 0.1% of cervical cancer cases occur before age 20.

    • Women younger than 21 with no immunocompromising conditions generally clear HPV infection between 8-24 months after exposure. 

    • This population should have discussion about safe sex practices to avoid exposure to STIs including HPV, and strong consideration for HPV vaccination.

  • 21 - 29 years: Screening should be performed using cytology alone every 3 years.

    • Annual screening is discouraged in this group, as it exposes patients to a much more significant number of unnecessary procedures for minimal improvement in outcomes. 

    • HPV co-testing is not recommended in this group; however, HPV reflex testing in the event of an ASC-US Pap smear may be considered to determine need for colposcopy.

  • 30 - 65 years: Screening should be performed with cytology alone every 3 years, or cytology with HPV co-testing every 5 years. 

    • In this population, with a negative cytology and negative HPV test, the risk of developing CIN 2 or 3 in the next 4-6 years is extremely low, based on large database studies (approximately 0.08% risk over 5 years). The risk is higher, but also quite low, with cytology alone (0.26% over 5 years). This is the rationale for the screening interval being extended.

    • RCTs have demonstrated in this population that cotesting has a number of distinct advantages:

      • Cotesting has a higher detection rate of high-grade dysplasia in first round of screening, and decreases risk of CIN3 or cancer in subsequent screening.

      • Cotesting likely has a better pickup rate for cervical adenocarcinomas (vs. squamous cell) than cytology alone.

  • > 65 years, or post-benign hysterectomy: Screening should be discontinued, provided that:

    • There has been no history of CIN2, CIN3, or AIS in the preceding 20 years, and:

    • There are adequate negative prior results:

      • 3 consecutive negative cytology results within last 10 years, or

      • 2 consecutive negative cotest results within the last 10 years, with the most recent test performed within the past 5 years.

    • Women in this age group do get cervical cancer; however, the majority of these cases occur in women who are not screened, or in those who are underscreened.

    • The changes of menopause may also cause false positive Pap tests in this group, leading to likely unnecessary additional and invasive testing and procedures.

Behavioral risks, such as cigarette smoking, new or multiple sexual partners, or early sexual debut, may increase risk of HPV acquisition or persistence, but do not alter screening recommendations.

However, two particular conditions do merit changes to screening:

  • In utero diethylstilbestrol (DES) exposure:

  • DES was an estrogen that was manufactured and prescribed in the US during the 1930s until 1971. It was thought that the medication helped with premature birth or history of miscarriage, though by the 1950s it had been demonstrated to be ineffective.

  • ACOG states that annual cytology is reasonable in women exposed to DES in utero, as cohort studies have demonstrated a much higher incidence of clear cell adenocarcinoma of the vagina in women born to mothers who took DES or similar medications. DES has also been associated with other health problems in both men and women.

  • You can find a list of DES and related medications online at the CDC, and there is an interactive tool for patients to use to determine if they may be at risk.

  • HIV or immunocompromising conditions:

    • Women infected with HIV or with other immunocompromising conditions are less readily able to clear HPV infections. Thus, the recommendations in this population differ:

  • Screening should begin within 1 year of sexual activity, and no later than age 21.

  • In women less than 30, If the first screen is negative, it should be repeated in 12 months. If three consecutive annual screens are normal, screening may be spaced to regular intervals (i.e., q3 year cytology). HPV cotesting is not recommended.

  • In women older than 30, three annual tests should be normal, before moving to cytology alone or co-testing. Screening intervals should be every 3 years in this population, regardless of the method chosen. 

  • Screening should continue for the lifetime of the woman, and not stop at age 65.

What about HPV vaccination?

HPV vaccination has been an incredible advance for primary prevention of cancer. Currently available include a bivalent vaccine, a quadrivalent vaccine, and a 9-valent vaccine. All of these cover HPV types 16 and 18. The 9-valent vaccine covers up to 50% additional cases of cervical cancer versus the bivalent vaccine. The 9-valent vaccine should be given to boys and girls ages 9-26. 

  • For those receiving their first dose before age 15, only two doses given 6 months apart are needed. 

  • For those receiving it after age 15, 3 doses given at 0, 1-2, and 6 months apart are recommended. 

HPV vaccination is not recommended during pregnancy, but also hCG screening is not necessary prior to initiating the dose. If pregnancy interrupts the schedule, it should be resumed postpartum without need for redosing. Studies are ongoing to determine the safety of HPV vaccination during pregnancy. 

In June 2019, the CDC’s advisory council on immunization practices (ACIP) updated its HPV vaccination recommendations, to extend recommendation for vaccination for all persons up through age 45, after the FDA approved this in October 2018. While this hasn’t made it into official ACOG practice guidance yet, it’s safe to say that this is forthcoming!

Further Reading from the OBG Project:

USPSTF Releases Final Cervical Cancer Screening Guidelines – Including ‘HPV Only’ Option
Screening for Cervical Cancer in the Woman at Average Risk
What is the Most Efficient Method for Cervical Cancer Screening?
Cervical Cytology and HPV Screening in the HIV Positive Woman

Cervical Cancer Screening Strategies and Cost-Effectiveness: Which is the Best?

Care of the Transgender Patient

Today we sit down with Dr. Beth Cronin, clinical associate professor and assistant program director at Brown / Women and Infants of Rhode Island. Dr. Cronin has become a national expert in the care of LGBTQ patients, and is a fixture at ACOG and other venues, and we are lucky enough today to have her break down the need-to-know essentials for the OB/Gyn.

Definitions are an excellent place to start, and set the stage for this conversation:

  • Sex is what we do in the delivery room - defining “male” or “female” based on the presence of external genitalia.

  • Gender is a social construct, comprising attitudes, feelings, or behaviors associated to “male” or “female” by a culture.

  • Gender identity is a person’s internal sense of their gender:

    • Cisgender the biological sex and gender identity align

    • Transgender the biological sex and gender identity are opposite:

      • Transgender woman biological sex male, identity female

      • Transgender man biological sex female, identify male

    • Gender should be viewed along a spectrum, with varying definitions for terms such as gender fluid, gender queer, or nonbinary.

About 1.4 million adults and 150,000 youth aged 13-17 are estimated to identify as transgender or gender non-binary in the United States. This population has much higher risks of experiencing discrimination, violence, and sexual assault. Additionally, these patients are likely to have poor experiences in healthcare settings. These patients really need access to care, and OB/Gyns are in perfect position to be safe and welcoming environments for the transgender/gender non-binary community.

For your office and daily practice, it is important to be inclusive, and there are myriad resources to get this started. Staff training and education to promote inclusivity is also important. Inclusive forms and medical record systems that elicit gender identity are important to make available, including documentation of preferred pronouns.

Dr. Cronin also took time today to discuss some clinical care aspects. UCSF and WPATH each have excellent protocols and guidelines for clinical care, including for initiating or maintaining transition care. Modifications of usual care, and care in the midst of hormonal transition, is discussed in great detail at these resources. ACOG also has excellent online modules for OB/Gyns for transgender healthcare, in addition to more primary reading at CO 512, CO 685, and additional ACOG-approved resources for clinicians.

Dr. Cronin easily explains it as “screen the parts that are present” per usual care guidelines, including with respect to things such as breast and cervical cancer screening, contraceptive methods, and pregnancy and abortion care.

Intimate Partner Violence and Gun Violence

Today we are spending some time on IPV/DV and gun violence. These are topics every OB/GYN should be familiar with; IPV accounts for 250,000 hospital visits, 2,000 deaths, and $8 billion in direct care costs annually on a conservative estimate. 1 in 3 American women is victimized by IPV during their lifetimes, and 1 in 5 report being the victim of sexual assault.

ACOG CO 518 serves as essential reading for our conversation today. Important points from the reading and today’s episode include:

Finally, check out ACOG’s stance and legislative priority list surrounding gun violence. Be active and get involved today — this is our lane!

Management of an Early Unlocated Pregnancy

Today we’re bringing back Dr. Erin Cleary one more time before she transitions to her new role as an MFM fellow at the Ohio State University! Dr. Cleary today talks with us on early pregnancy of unknown location - a common problem in the office or the emergency department/triage.

Women presenting to the ED with first trimester bleeding, pain, or both, have had a demonstrated prevalence rate of ectopic pregnancy up to 18% in some studies. Ruptured ectopic is a leading cause of pregnancy-related mortality in the first trimester, accounting for 2.7% of pregnancy-related deaths overall in 2011-2013. Proper identification and management of early, unlocated pregnancy is life-saving!

Dr. Cleary was kind enough to put together her high points from this episode for our blog post today:

H&P:

  • Any patient with an unlocated pregnancy should be considered to have a potential ectopic pregnancy.

    • Women with prior ectopic, regardless of method of treatment, are at risk for ectopic in a subsequent pregnancy (three- to eightfold higher compared with other pregnant women).

    • If pregnancy is present while IUD is in place, risk of ectopic is 1 in 2 pregnancies for the levonorgestrel IUD and 1 in 16 pregnancies for the copper IUD.

    • Women with a history of PID have an approximately threefold increased risk of ectopic pregnancy

  • Pelvic exam. THIS MUST BE DONE.

Beta-HCG

  • The threshold for a positive qualitative β-hcg test is 20-50 milli-int units, depending on test. For quantitative serum tests, the threshold is 5-10 milli-int units, and 1-2 milli-int units, for ultrasensitive tests.

  • The β-hcg concentration doubles every 29 to 53 hours during the first 30 days after implantation of a viable, intrauterine pregnancy.

  • When ectopic pregnancy is on the differential, a qualitative test is not sufficient. A serum quantitative value is essential to:

    • 1. Interpret imaging (“discriminatory zone”)

    • 2. Have a baseline in the event the β-hcg must be trended

The Discriminatory Zone

  • Definition: A concept that there is a quantitative β-hcg level above which the landmarks of a normal intrauterine pregnancy (yolk sac and embryo) should be visible on ultrasound.

    • Therefore, the absence of a gestational sac when β-hcg level is above the DZ is strongly suggestive of nonviable pregnancy, with 50-70% being ectopic.

  • Pelvic ultrasound is the gold standard first line imaging modality in early pregnancy and for evaluation of suspected ectopic pregnancy

  • Imaging results will fall into 1 of 5 main categories

    • IUP with normal adnexa. Normal pregnancy!

    • IUP with abnormal adnexa. Although rare, must evaluate for heterotopic pregnancy, or presence of both an intra and extra-uterine pregnancy.

    • No IUP, extra-uterine mass with YS/FP. Confirms ectopic pregnancy.

    • No IUP, adnexal mass without YS/FP. Suspicious for ectopic pregnancy

    • No IUP, normal adnexa. Differential includes normal but early IUP, failed IUP, or unidentified ectopic.

  • A patient with a confirmed ectopic requires evaluation and counseling by an OBGYN to evaluate candidacy for medical or surgical evaluation.

Management:

  • Expectant management: serial quantitative β-hcg level assessment ~q 48 hours, only for stable patients.

    • Scenario A: The β-hcg level rises appropriately (doubles approximately every 2 days).

    • Scenario B: The β-hcg level falls precipitously.

    • Scenario C: The β-hcg level neither rises appropriately nor drops precipitously. Now we should be MORE concerned about ectopic pregnancy, but abnormal IUP is also on the differential.

  • Repeat pelvic imaging is very helpful

  • Every patient who is stable and an appropriate candidate to trend β-hcg levels will eventually declare herself, with either a located IUP, a failed IUP/SAB, or a confirmed or presumed ectopic pregnancy.

We will cover ectopics for surgical and medical management in a future episode, so stay tuned!