For Physicians. By Physicians.™

FREE weekly ObG Insider NewsletterClick here

Do the New Guidelines for Diagnosing Nonprogressing Labor Actually Reduce Cesarean Deliveries?


  • Wood et al. (AJOG, 2023) assessed whether adoption of new guidelines for diagnosing nonprogressing labor reduced cesarean delivery rates


  • Cluster randomized controlled trial
    • 26 Canadian hospitals
    • Province of Alberta
    • REDucing the utilization of CEsarean delivery for dystocia (REDUCED trial)
  • Participants
    • Nulliparous
    • Vertex presentation
    • In labor at term
  • Intervention
    • Intervention sites: 2014 guidelines for nonprogressing labor
    • Control sites: Operated under usual care
  • Old guidelines (2012)
    • First stage arrest: ≥6 cm dilation with rupture and no cervical change for ≥4 hours with adequate contractions or ≥6 hours with inadequate contractions
    • Second stage arrest: No progress for ≥4 hours in nulliparous with epidural or ≥3 hours in nulliparous without epidural
  • New guidelines (2014)
    • First stage: Prolonged latent stage (e.g., ≥20 hours in nulliparous) should not be considered an indication for cesarean | Slow but progressive labor should not be indication for cesarean
    • Second stage: Specific maximum time at which point women should undergo operative delivery has not been established | Allow at least 3 hours pushing in nulliparous | Longer times may be indicated on individualized basis
  • Study design
    • Data from all sites from the baseline (2015–2017) and follow-up (2017–2020) periods
    • Intention to treat approach
    • Cesarean delivery rates assessed using repeated measures mixed effects logistic regression applied to individual births
  • Primary outcome
    • Rate of cesarean delivery
  • Secondary outcomes
    • Spontaneous vaginal birth
    • Maternal and neonatal safety


  • Deliveries at intervention sites: 45,193 | Deliveries at control sites: 43,725
  • There was no evidence of a decrease in the rate of cesarean delivery when the new 2014 guidelines were implemented
    • Baseline-adjusted odds ratio 0.94 (95% CI, 0.85 to 1.05) | P=0.259
  • The rate of spontaneous vaginal delivery increased slightly
    • Baseline-adjusted odds ratio 1.10 (95% CI, 1.01 to 1.18) | P=0.024
  • There were no differences in adverse maternal or neonatal outcomes


  • Randomized implementation of 2014 guidelines for diagnosing nonprogressing labor did not reduce cesarean deliveries
    • Hospitals that implemented the intervention did experience increased spontaneous vaginal deliveries
  • Implementation of the guidelines did not have adverse effects
  • The authors state

Furthermore, this trial was conducted in a setting where midpelvic forceps deliveries are performed more often than cesarean deliveries. Therefore, if the intervention had been tested in a setting where this is rarely done, the cesarean delivery rate may have been more substantially reduced

Learn More – Primary Sources:

The REDUCED trial: a cluster randomized trial for Reducing the utilization of Cesarean delivery for dystocia

Secondary Analysis of the ANODE Trial: Does the Benefit of Antibiotics Following Operative Birth Depend on Presence of Episiotomy?


  • The ANODE trial (see ‘Related ObG Topics’ below) showed that prophylactic antibiotics reduced infection burden following operative delivery
    • However, episiotomy rates were high and infections remained high even in the treatment group
  • Humphreys et al. (AJOG, 2022) sought to determine whether the effectiveness of the prophylactic antibiotic at reducing infection was independent of perineal trauma


  • Secondary analysis of ANODE RCT
  • Population
    • Forceps or vacuum assisted birth at ≥36 weeks
    • Exclusion: Missing data or withdrew consent
  • Primary interventions
    • IV prophylactic amoxicillin and clavulanic acid
    • Placebo
  • Study design
    • Received intervention/placebo as soon as possible immediately after delivery to ≤6 hours
  • Primary outcome
    • Consistency of the prophylactic antibiotics in preventing infection across the exposure subgroups


  • 3225 women
    • Episiotomy alone: 66.5%
    • Episiotomy and a tear: 22.5%
    • Tear alone: 8.6%
    • Neither episiotomy nor tear: 2.4%
  • Among women who experienced perineal trauma, amoxicillin and clavulanic acid administration were protective against infection in all subgroups
  • The following were associated with higher risk of infection 
    • Episiotomy: Adjusted risk ratio (aRR) 2.94 (95% CI, 1.62 to 5.31) 
    • Forceps (vs vacuum extraction): aRR 1.37 (95% CI, 1.12 to 1.69)  
    • Primiparity: aRR 1.34 (95% CI, 1.05 to 1.70) 
    • Prophylactic antibiotic use: aRR 0.60 (95% CI, 0.51 to 0.72) 
    • BMI of 25.0 to 29.9 kg/m2: aRR 1.21 (95% CI, 1.00 to 1.47) 
    • BMI of ≥30 kg/m2: aRR 1.22 (95% CI, 0.9 to 1.52) 
  • Each 15-minute increment between birth and antibiotic administration was associated with a 3% higher risk of infection
    • aRR 1.03 (95% CI, 1.01 to 1.06)


  • Prophylactic antibiotics reduce the risk of infection after operative birth, regardless of type of perineal trauma 
  • The following were associated with increased risk of infection after operative birth
    • Episiotomy | Forceps birth | Primiparity | Overweight
  • The authors state

This study has found no evidence to suggest that prophylactic amoxicillin and clavulanic acid administration is less protective against confirmed or suspected infection after OVB with perineal trauma in the absence of episiotomy, which provides reassurance of the benefit of prophylactic antibiotic in settings where the episiotomy rate is lower

Importantly for clinical practice, the burden of infection may be further reduced by timely administration of the antibiotic to all women irrespective of the state of their perineum

Learn More – Primary Sources:

Factors associated with infection after operative vaginal birth—a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth

Hysteroscopy Guidelines


Hysteroscopy can be performed either in the operating room or the office.  When planning a hysteroscopic procedure, the joint ACOG/AAGL recommendations include the following

  • Preoperative consultation
    • Discuss risks/ benefits/ alternatives
    • Review medical history
    • Exclude pregnancy if appropriate
  • If cervical stenosis is present
    • Consider misoprostol (off label) 200 to 400 mcg buccal/ sublingual/ intravaginal the night before surgery
  • Optimize visualization
    • Perform during follicular phase of cycle, after menses | Secretory phase may mimic polyps: Irregular menses may be scheduled at any time
    • Actively bleeding “may not undergo the procedure” due to decreased visibility
    • Pretreatment with progestins or combined OCP may further optimize visualization by thinning the endometrial lining
  • Antibiotic prophylaxis not recommended
  • Pain management
    • Multiple pharmacologic approaches described, but evidence insufficient to recommend any particular analgesic regimen | No regimen has been shown to be superior to placebo
      • NSAIDS | Topical anesthetic | Acetaminophen | Benzodiazepines (anti-anxiety medications) | Opiates | Intracervical and/or paracervical block
    • Non-pharmacologic
      • <5 mm diameter hysteroscopes | Flexible hysteroscopes | Vaginoscopic approach
  • Cervical Ripening
    • “Insufficient evidence to recommend routine cervical ripening before diagnostic or operative hysteroscopy”
      • Consider if risk of cervical stenosis or increased procedural pain
    • Misoprostol (off label)
      • 200 to 400 micrograms oral or intravaginal the night before surgery (12 hours prior to procedure)
      • Postmenopause: 25 micrograms vaginal estrogen 14 days prior to procedure plus misoprostol 12 hours prior to procedure
    • Osmotic dilators
      • Data to support use | Requires additional office visit | Must be removed if procedure is cancelled
    • Vasoconstrictors (epinephrine or vasopresessin)
      • Potential benefits: Less bleeding | Reduce fluid absorption | Improve potency of local anesthesia | Reduce force needed to dilate cervix
      • Risks (rare): Bradycardia | Hypotention or increased BP | Cardiac arrest
      • No evidence for optimal dose
      • One regimen cited in literature (see ‘Learn More – Primary Sources’ below): 20 mL dilute vasopressin solution (4U of 0.05 U/mL in 80 mL normal saline)


  • Office hysteroscopy
    • Diagnostic or minor operative
    • Should be considered for the treatment of endometrial polyps
  • Operating room hysteroscopy
    • Use for patients with
      • Cervical stenosis
      • Medical comorbidities (e.g., cardiopulmonary disease)
      • Significant uterine pathology
      • High levels of anxiety
      • Previously failed or not tolerated office hysteroscopy


  • Known pregnancy
  • Active herpetic infection
  • Genital tract infection
  • Known advanced stage cervical/ uterine malignancy

Distention Medium

CO2 gas

  • Clear view of cavity and easy equipment maintenance
  • Limit flow to 100 mL/min
  • Maintain intrauterine pressure to <100 mm Hg
  • Use hysteroscopic (not laparoscopic) insufflator

Electrolyte poor fluids

  • Glycine 1.5% | Sorbitol 3% |Mannitol 5%
  • Use for
    • Operative hysteroscopy
    • Monopolar devices
    • Radio-frequency energy devices
  • Caution: Excessive absorption associated with
    • Hyponatremia | Decreased serum osmolality | Hyperammonemia
    • Can lead to seizures and mortality
    • Note: Mannitol 5% is iso-osmolar and while may cause hyponatremia, should not decrease serum osmolality

Electrolyte-containing fluids

  • Normal saline | Lactated Ringer’s solution
  • Use for
    • Diagnostic cases
    • Laser | Bipolar | Mechanical energy
  • Less risk of hyponatremia/ decreased osmolality


Polyps, synechiae, Mullerian abnormalities, leiomyomata and retained foreign bodies can often be diagnosed and treated successfully with hysteroscopy.  Visualization of the endometrial cavity allows biopsy of abnormal areas and can optimize the diagnosis of hyperplasia or malignancy




  • Signs and symptoms
    • Hypotention | Bradycardia
    • Sweating | Pallor | Loss of conciousness |  Nausea and vomiting
  • Management
    • Assess: Vitals | Airway, Breathing, Circulation
    • Place patient in Trendelenberg or raise legs
    • If bradycardia does not resolve
      • Atropine: Single dose 0.5 mg IV q3 to 5 minutes (total dose 3 mg)

Fluid Overload and Hyponatremia 

  • Prevention
    • Strictly monitor both IV hydration and hysteroscopic fluid deficit
    • Electrolyte poor fluids maximal deficit: 1000 mL (in healthy individuals)
      • Consider stopping procedure at 750 mL deficit
    • Electrolyte-containing fluids maximal deficit: 2500 mL (in healthy individuals)
      • Consider stopping procedure at 2000 mL deficit
    • Consider lower thresholds for elderly, cardiovascular or renal comorbidity or when laboratory services/ acute care options are limited
  • Management
    • Hypertonic saline solution and diuretics (e.g., furosemide)
    • Increase serum sodium levels by 1 to 2 mEq/L/h
    • Caution: Do not increase by more than 12 mEq/L in the first 24 hours
    • Transfer to an urgent care facility and further consultation may be required


  • Management
    • Apply electrosurgical coagulation if bleeding sites identified
    • Inject vasopressin into the cervix
    • Use Foley catheter balloon tamponade or manual uterine compression
    • Surgical approach as a last resort includes
      • Laparoscopic suturing of perforation
      • Hysterectomy
      • Uterine artery embolization

Uterine Perforation

  • Prevention
    • Perform careful pelvic exam prior to hysteroscopy
    • Use ultrasound guidance as needed
    • If flexible hysteroscope available, insertion may be performed prior to using dilators
  • Management
    • Midline perforation is seldom morbid unless laser or electrosurgery is used
    • Lateral perforations carry risk for retroperitoneal hematomas
    • Discontinue hysteroscopy if perforation occurs
    • Consider laparoscopy to
      • Identify any bowel/ bladder injury
      • Check for hematomas

Air/CO2 Embolization

  • Prevention
    • Purge and flush air from tubing prior to procedure and whenever bags are changed | Avoid repetitive instrument insertions | Limit intrauterine pressure
  • Worrisome symptoms include
    • Dyspnea | Chest pain | Decreased O2 saturation | ‘mill wheel’ heart murmur | Hypotension | Cardiac arrhythmia (e.g., tachycardia/bradycardia)
  • Management
    • Terminate procedure
    • Deflate uterine cavity
    • Eliminate sources of fluid and gas
    • Position in left lateral decubitus with Trendelenburg position (Durnat’s maneuver)

Learn More – Primary Sources:

ACOG Committee Opinion 800: The Use of Hysteroscopy for the Diagnosis and Treatment of Intrauterine Pathology

The Effect of Dilute Vasopressin Solution on the Force Needed for Cervical Dilatation: A Randomized Controlled Trial

ACOG Opinion on Expanded Carrier Screening


ACOG has published two committee opinions on carrier screening. Committee Opinion 691 reviews the recommendations based on disorders. Committee Opinion 690 addresses the issues related to use of screening strategies such as expanded gene panel testing.

Key Highlights

  • Spinal Muscular Atrophy (SMA) has joined cystic fibrosis (CF) as a recommendation for all women who are pregnant or considering pregnancy
  • Hemoglobinopathies
    • Test all patients for CBC and RBC indices as part of antepartum care (ideally preconception)
    • Add Hgb electrophoresis if
      • Increased risk based on ethnicity:  African, Middle Eastern, Southeast Asian, West Indian and Mediterranean ancestry
      • MCV is less than 80 fL with normal iron studies
  • Ashkenazi Jewish Testing (central and Eastern Europe descent)
    • Recommended testing remains for 4 disorders
      • Canavan; CF; Familial dysautonomia; Tay Sachs Disease
    • Additional tests to ‘consider’ has been expanded to the following
      • Usher syndrome, Familial hyperinsulinism, Joubert and Maple syrup urine disease in addition to Bloom/Gaucher/Fanconi anemia/ML4/Neimann-Pick disease
  • Tay Sachs Disease
    • In addition to Ashkenazi Jews, offer if either partner is French-Canadian descent or Cajun
    • Screening can be performed using DNA-based testing (mutation analysis) or hexosaminidase enzyme in serum or leuckocytes (leukocyte only with oral contraceptives)
    • Enzyme testing picks up approximately 98% of carriers regardless of ethnicity
    • Mutation analysis is highly effective in at risk populations – detection rate is limited in other populations
  • Committee Opinion 690 reviews expanded carrier screening, including a discussion on counseling and what disorders should be included | Important summary statements include the following

Ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening. Each obstetrician–gynecologist or other health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening.

Expanded carrier screening does not replace previous risk-based screening recommendations. If obstetrician–gynecologists or other health care providers do not offer expanded carrier screening in their practice, screening recommendations for individual disorders should follow guidelines for carrier screening as outlined in Committee Opinion No. 691, Carrier Screening for Genetic Conditions.

Note: ACMG has published a document on preconception and prenatal carrier screening that includes a tiered approach to the selection of disorders | For the summary and links see ‘Related ObG Topics’ below)

Learn More – Primary Sources:

ACOG Committee Opinion 690: Carrier Screening in the Age of Genomic Medicine

ACOG Committee Opinion 691 Carrier Screening for Genetic Conditions

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist: SMFM

FDA Withdraws Makena Approval for US Market

FDA approval for Makena, a drug used to reduce risk for preterm birth, has been formally withdrawn. The withdrawal also includes all generics (17-alpha hydroxyprogesterone caproate [17-OHPC]). Regarding any current medication in distribution, the FDA states that “Patients who have questions should talk to their healthcare provider.” Both ACOG and SMFM have addressed the situation.


Intramuscular 17-OHPC is not recommended for the primary prevention of preterm birth in patients with a history of spontaneous preterm birth

In summary, at this time, the body of evidence is equivocal regarding the effectiveness of 17-OHPC, and the referenced FDA action will limit access to 17-OHPC for patients


We agree with the FDA determination and discourage continued prescribing of 17-OHPC, including through compounding pharmacies

We agree with the FDA that there is no evidence of benefit with continued treatment

Patients currently receiving 17-OHPC can be counseled that the FDA’s Center for Drug Evaluation and Research (CDER) has not identified evidence of harm from discontinuation prior to 37 weeks of gestation


The authors of the PROLONG trial (Progestin’s Role in Optimizing Neonatal Gestation) reported on the use of 17α-hydroxyprogesterone caproate (17-OHPC) for the treatment of preterm birth (PTB)

In this study population, 250 mg 17-OHPC did not decrease recurrent PTB and was not associated with increased fetal/early infant death

On October 29, 2019, the FDA advisory committee recommended that the drug be withdrawn from the market (9 to 7 vote). On October 5, 2020, the Center for Drug Evaluation and Research (CDER) proposed that Makena be withdrawn from the market. At that time, the decision was made to hold further meetings and discussions. Based upon further follow-up, the CDER briefing materials for the Advisory Committee meeting (October 17-19, 2022) states

Makena has not been shown to improve neonatal outcomes from premature birth, is no longer shown to be effective for its approved use, and has known risks

The 1,708-person confirmatory trial designed to verify Makena’s clinical benefit instead failed to show that Makena has any benefit to newborns. Data from this trial, taken together with other evidence, also fail to show that Makena reduces the risk of recurrent preterm birth

For these and other reasons detailed herein, Makena should be withdrawn from the market

Background to PROLONG Trial

  • A previous study, on behalf of the NICHD, demonstrated success of IM 17-OHPC in preventing PTB (see ‘Learn More – Primary Sources)
    • Meis et al. (NEJM, 2003): 250 mg IM 17-OHPC reduced recurrent preterm birth (PTB) in women with a prior spontaneous PTB (SPTB)
      • Relative risk [RR] 0.66 (95% CI, 0.54–0.81)
  • The current PROLONG study was a ‘confirmatory trial’, performed with FDA input as a requirement for the FDA accelerated approval pathway


  • Double-blind randomized controlled trial (RCT)
  • Participants
    • ≥18 years
    • Singleton pregnancy
    • Currently 16w0d to 20w6d
    • Previous history of singleton SPTB (birth between 20w0d and 36w6d following preterm labor or PROM)
  • Groups (IM injection 1 in upper outer quadrant of the gluteus maximus) weekly until delivery or 36 weeks
    • 17-OHPC (250 mg)
    • Placebo
  • Stratified by
    • Study site
    • GA at randomization
  • Primary outcomes
    • PTB < 35 weeks
    • Composite neonatal morbidity and mortality index


  • PTB < 35w0d (p=0.72)
    • 17-OHPC: 11.0%
    • Placebo: 11.5%
    • Relative risk (RR) 0.95 (95% CI, 0.71–1.26)
  • Neonatal composite index (p=0.73)
    • 17-OHPC 5.6%
    • Placebo 5.0%
    • RR 1.12 (95% CI, 0.70–1.66)
    • Note: No differences seen in any of the individual components that were part of the composite index


Sibai et al. Obstet Gynecol, 2020

Meis Trial

  • Well designed and conducted
  • Highly statistically significant results
    • Prespecified criterion threshold of alpha=0.015 was met regarding benefit of 17-OHPC
    • Preterm birth <37 weeks: Relative risk (RR) 0.66 (95% CI, 0.54 to 0.81; P<.001)
    • Preterm births <35 weeks: RR 0.67 (95% CI, 0.48 to 0.93)
    • Preterm birth <32 weeks: RR 0.58 (95% CI, 0.37–0.91)
  • Subgroup analysis: Number of prior preterm birth | Race | Marital status | Smoking or substance use
    • Confirmed generalizability

Prolong Trial

  • Population studied was very different from that of the Meis trial (non-US)
  • Trial is underpowered based on observed event rates
    • For 90% power, PROLONG required 3,600 women for preterm birth <35 weeks and 6,000 women for neonatal composite outcome
  • PROLONG not powered for subgroup analysis, but Meis et al. did look at US subgroup and found that while not statistically significant
    • Direction and magnitude of effect <32 weeks and neonatal composite index were similar to the Meis trial

Authors’ Conclusion

We assert PROLONG was underpowered, based on substantially lower observed preterm birth rates than anticipated, and therefore was a false-negative study, rather than the Meis trial being a false-positive study

Careful assessment of these two trials is critical as removal of 17α-hydroxyprogesterone caproate from the U.S. marketplace may have substantial effects on public health

Learn More – Primary Sources:

FDA Commissioner and Chief Scientist Announce Decision to Withdraw Approval of Makena

ACOG Practice Advisory: Updated Clinical Guidance for the Use of Progesterone Supplementation for the Prevention of Recurrent Preterm Birth

SMFM Special Statement: Response to the Food and Drug Administration’s withdrawal of 17-alpha hydroxyprogesterone caproate

17-OHPC to Prevent Recurrent Preterm Birth in Singleton Gestations (PROLONG Study): A Multicenter, International, Randomized Double-Blind Trial

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. (NEJM, 2003)

Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee Meeting Announcement: MAKENA supplemental new drug application

FDA (October 2020): CDER proposes withdrawal of approval for Makena

Re-examining the Meis Trial for Evidence of False-Positive Results (Sibai et al. Obstetrics & Gynecology, 2020)

FDA Briefing Materials for Withdrawal of Makena Approval (2022)

FDA: UPDATED INFORMATION: October 17 – 19, 2022: Hearing Announcement involving the Obstetrics, Reproductive, and Urologic Drugs Advisory Committee

NIH COVID-19 Treatment Guidelines

NOTE: The FDA has addressed the use of bebtelovimab among nonhospitalized patients in light of an increase in subvariants. Due to resistance, bebtelovimab is not currently authorized for emergency use in any US region. Information and guidelines may change rapidly. Check in with listed reference in ‘Learn More – Primary Sources’ to best keep up to date.


NIH has released guidance on the diagnosis, management and treatment of COVID-19. A Panel was convened to develop recommendations, with the understanding that there is still much that is unknown and the guidelines will be updated as additional data become available

Critical Care Treatment

Infection Control When Caring for Patients with COVID-19

  • Aerosol-generating procedures
    • Use fit-tested respirators (N-95 respirators) or powered air-purifying respirators rather than surgical masks
    • The above masks should be used in addition to other PPE (gloves, gown, and eye protection such as a face shield or safety goggles)
  • Endotracheal intubation
    • Should be done by healthcare professionals “with extensive airway management experience, if possible”
    • Intubation should be done with video laryngoscopy, if possible

Hemodynamic Support

  • First-choice vasopressor: Norepinephrine
  • To assess fluid responsiveness
    • Use dynamic parameters, skin temperature, capillary refilling time, and/or lactate levels vs static parameters
  • Acute resuscitation of adults with COVID-19 and shock
    • Use buffered/balanced crystalloids over unbalanced crystalloids
    • Panel recommends against initial use of albumin
  • Septic shock and steroids
    • IV hydrocortisone 200 mg per day administered either as an infusion or in intermittent doses
    • Duration of hydrocortisone is typically a clinical decision
    • Patients who are receiving corticosteroids for COVID-19 are receiving sufficient replacement therapy such that they do not require additional hydrocortisone

Ventilatory Support for Patients with COVID-19

  • Oxygen saturation (SpO2) target
    • Optimal goal is uncertain
    • A target SpO2 of 92% to 96% “seems logical”
    • Experience suggests that SpO2 <92% or >96% may be harmful
  • Prone position
    • Appropriate candidate for awake prone positioning: Patients who can adjust their own position independently and tolerate lying prone
    • Awake proning should not be used as a substitute for intubation and invasive mechanical ventilation in patients with refractory hypoxemia who otherwise meet the indications for these interventions
    • Pregnancy: Acceptable and can be done in left lateral decubitus or fully prone
  • Refractory hypoxemia in patients who otherwise require intubation and mechanical ventilation
    • Panel recommends against using awake prone positioning as a rescue therapy to avoid intubation 
  • Acute hypoxemic respiratory failure despite conventional oxygen therapy
    • Options for providing enhanced respiratory support include high-flow nasal cannula (HFNC), NIPPV, intubation and invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)
    • Use HFNC oxygen rather than noninvasive positive pressure ventilation (NIPPV)
    • If HFNC is unavailable and there is no indication of intubation: Use a closely monitored trial of NIPPV
  • For patients on supplemental oxygen
    • Monitor closely for worsening of respiratory status
    • If respiratory status worsens, the Panel recommends early intubation by an experienced practitioner in a controlled setting
  • For patients mechanically ventilated with ARDS
    • Use low tidal volume (VT) ventilation (VT 4 to 8 mL/kg of predicted body weight) vs higher tidal volumes (VT >8 mL/kg)
    • If refractory hypoxemia despite optimized ventilation, the Panel recommends prone ventilation for 12 to 16 hours per day over no prone ventilation
    • In the setting of hypoxemia and severe ARDS despite optimized ventilation and other rescue strategies, a trial of inhaled pulmonary vasodilators is recommended as a rescue therapy| Taper if there is no rapid improvement in oxygenation

Inpatient Pharmacologic Management

Note: For patients who are hospitalized for reasons other than COVID-19 and who are found to have mild to moderate COVID-19 and a high risk of disease progression, the Panel recommends following its recommendations for treating nonhospitalized patients with COVID-19 (section below)

The following applies to individuals admitted for the treatment of COVID-19

Therapeutic Management of Hospitalized Adults With COVID-19 Based on Disease Severity

Tap picture below to view Therapeutic Management Tables for Hospitalized Adults with Covid-19


  • Recommended for use in hospitalized patients who require supplemental oxygen
    • 200 mg IV once, then RDV 100 mg IV once daily for 4 days or until hospital discharge
    • If the patient progresses to more severe illness, complete course


  • Found to improve survival in hospitalized patients who require supplemental oxygen
    • Greatest effect observed in patients who require mechanical ventilation
    • The Panel recommends against using dexamethasone among patients who do not require supplemental oxygen
  • Primary immunomodulator for all patients who require high-flow nasal canula oxygen, noninvasive ventilation, mechanical ventilation, or ECMO
  • Dose
    • 6 mg IV or PO once daily for up to 10 days or until hospital discharge
    • If dexamethasone is not available, an equivalent dose of another corticosteroid may be used


  • Humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)
    • FDA approved to treat inflammatory diseases
  • Dose
    • 8 mg/kg actual body weight (up to 800 mg) administered as a single IV dose
    • In clinical trials, a third of the participants received a second dose of tocilizumab 8 hours after the first dose if no clinical improvement was observed
  • Avoid tocilizumab for the following
    • Significant immunosuppression | Alanine transaminase >5 times the upper limit of normal | High risk for gastrointestinal perforation | Uncontrolled, serious bacterial, fungal, or non-SARS-CoV-2 viral infection | Absolute neutrophil count <500 cells/µL | Platelet count <50,000 cells/µL


  • Oral Janus kinase (JAK) inhibitor that is selective for JAK1 and JAK2
    • FDA approved to treat rheumatoid arthritis
  • Dose
    • Baricitinib dose is dependent on eGFR; duration of therapy is up to 14 days or until hospital discharge
    • eGFR ≥60 mL/min/1.73 m2: Baricitinib 4 mg PO once daily
    • eGFR 30 to <60 mL/min/1.73 m2: Baricitinib 2 mg PO once daily
    • eGFR 15 to <30 mL/min/1.73 m2: Baricitinib 1 mg PO once daily
    • eGFR <15 mL/min/1.73 m2: Baricitinib is not recommended


  • Oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis
  • Dose
    • 10 mg PO twice daily for up to 14 days or until hospital discharge
    • Use as an alternative immunomodulatory drug if baricitinib is not available or not feasible to use (BIIa)
    • eGFR <60 mL/min/1.73 m2: Tofacitinib 5 mg PO twice daily


  • Humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)
    • FDA approved to treat rheumatoid arthritis
  • Dose
    • Use the single-dose, prefilled syringe (not the prefilled pen) for SQ injection
    • Reconstitute sarilumab 400 mg in 100 cc 0.9% NaCl and administer as an IV infusion over 1 hour
    • Use as an alternative immunomodulatory drug if tocilizumab is not available or not feasible to use

Therapeutic Management of Nonhospitalized Adults With COVID-19

Tap picture below to view Therapeutic Management Tables for Nonhospitalized Adults with Covid-19

NIH refers to the CDC guidance to determine at increased risk for progression | See ‘Learn More – Primary Care’ for reference

In Order of Preference

  • Paxlovid (for more information, see ‘oral antivirals below’)
    • Orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥12 years and weighing ≥40 kg
  • Remdesivir
    • 200 mg IV on Day 1, followed by remdesivir 100 mg IV daily on Days 2 and 3, initiated as soon as possible and within 7 days of symptom onset in those aged ≥12 years and weighing ≥40 kg 

Alternative Therapies to be used ONLY if none of the preferred therapies are available, feasible to deliver, or clinically appropriate (listed in alphabetical order)


800 mg orally twice daily for 5 days, initiated as soon as possible and within 5 days of symptom onset in those aged ≥18 years ONLY when none of the above options can be used

Note: BQ.1 and BQ.1.1 subvariants appear to be resistant to bebtelovimab and as of 11/30/2022, bebtelovimab is not currently authorized for emergency use in any US region | The Panel continues to recommend Paxlovid, followed by remdesivir for treatment of mild to moderate COVID-19 in nonhospitalized adults who are at high risk for progression

More on Oral Antivirals

  • Ritonavir-Boosted Nirmatrelvir (Paxlovid)
    • Nirmatrelvir
      • Orally bioavailable protease inhibitor
      • Works by inhibiting viral protease MPRO (protease that plays an essential role in viral replication)
      • Active against all coronaviruses known to infect humans
    • Packaged with ritonavir (as Paxlovid)
      • Ritonavir is a cytochrome P450 (CYP) 3A4 inhibitor and pharmacokinetic boosting agent
      • Boosts nirmatrelvir concentrations to the target therapeutic ranges

Note: Review other medications to assess drug interactions including OTCs and herbal supplements | University of Liverpool has a site with COVID-19 Drug Interactions (included in the NIH Panel guidelines – see “Learn More – Primary Resources’ below)

  • Molnupiravir
    • Oral prodrug of beta-D-N4-hydroxycytidine (NHC)
    • NHC is a ribonucleoside with antiviral activity against RNA viruses
    • NHC uptake by viral RNA-dependent RNA-polymerases results in viral mutations and lethal mutagenesis

Note: Pregnancy and COVID-19 Oral Antivirals

  • Paxlovid
    • SMFM supports the use of Paxlovid in pregnancy as indicated (see ‘Primary Sources – Learn More’ below)
  • Molnupiravir
    • Although FDA concluded that there is a low risk for genotoxicity, due to concern regarding mutagenesis, the FDA EUA recommends against use during pregnancy
    • The NIH Panel states “However, when other therapies are not available, pregnant people with COVID-19 who are at high risk of progressing to severe disease may reasonably choose molnupiravir therapy after being fully informed of the risks, particularly those who are beyond the time of embryogenesis (i.e., >10 weeks’ gestation). The prescribing clinician should document that a discussion of the risks and benefits occurred and that the patient chose this therapy”


Serologic or Antibody Testing for Diagnosis of SARS-CoV-2 Infection

The Panel does not recommend using serologic testing as the sole basis for diagnosing acute SARS-CoV-2 infection 

  • Serologic or antibody tests can detect recent or prior SARS-CoV-2 infection
  • It may take ≥21 days after symptoms for seroconversion to occur (i.e., IgM and/or IgG antibodies to SARS-CoV-2)
  • NAATs and antigen tests for SARS-CoV-2 occasionally yield false negative results
    • Serologic tests have been used in some settings as an additional diagnostic test for patients who are strongly suspected to have SARS-CoV-2 infection
    • Using a serologic test in combination with a NAAT to detect IgG or total antibodies 3 to 4 weeks after symptom onset maximizes the sensitivity and specificity to detect past infection

Concomitant Medications in Patients with COVID-19

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs) and Statins (HMG-CoA Reductase Inhibitors)

  • Continue taking these medications as prescribed
  • The Panel recommends against the use of ACE inhibitors or ARBs for the treatment of COVID-19 outside of the setting of a clinical trial

Chronic Corticosteroids

  • For patients on oral corticosteroid therapy used prior to COVID-19 diagnosis for another underlying condition (e.g., rheumatological diseases)
    • Corticosteroids should not be discontinued
    • Supplemental or stress-dose steroids: Determine use on a case-by-case basis
  • Asthma and chronic obstructive pulmonary disease for control of airway inflammation (daily use)
    • Should not be discontinued

Pregnancy Considerations

  • Betamethasone and dexamethasone cross the placenta and are therefore used for fetal benefit to decrease the risk of RDS in the setting or threatened preterm delivery
  • The Panel recommends “using dexamethasone in pregnant women with COVID-19 who are mechanically ventilated or who require supplemental oxygen but who are not mechanically ventilated”

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

  • Continue taking NSAIDs for a co-morbid condition as previously directed by physician
  • “The Panel recommends that there be no difference in the use of antipyretic strategies (e.g., with acetaminophen or NSAIDs) between patients with or without COVID-19”

Coagulopathy Considerations

Antithrombotic Therapy for Nonhospitalized Patients without VTE

  • The Panel recommends against the use of anticoagulants and antiplatelet therapy (aspirin or P2Y12 inhibitors) for the prevention of VTE or arterial thrombosis unless the patient has other indications for the therapy or is participating in a clinical trial
  • The Panel recommends against routinely continuing VTE prophylaxis for patients with COVID-19 after hospital discharge, except in a clinical trial 
  • For patients who are at high risk for VTE and low risk for bleeding, there is insufficient evidence to recommend either for or against continuing anticoagulation after hospital discharge unless another indication for VTE prophylaxis exists

General Considerations for Hospitalized Patients

  • The Panel recommends against using anticoagulant or antiplatelet therapy to prevent arterial thrombosis outside of the usual standard of care for patients without COVID-19 
  • In hospitalized patients, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) is preferred over oral anticoagulants, because these 2 types of heparin have shorter half-lives and the effect can be reversed quickly, can be administered intravenously or subcutaneously, and have fewer drug-drug interactions 
  • When heparin is used, LMWH is preferred over UFH

Hospitalized, Nonpregnant Adults Who Require Low-Flow Oxygen and Are Not Receiving Intensive Care Unit Level of Care

  • Use therapeutic-dose heparin for patients who have a D-dimer above the upper limit of normal and have no increased bleeding risk
  • LMWH is preferred over unfractionated heparin
  • Contraindications for therapeutic anticoagulation for COVID-19 due to an increased bleeding risk
    • Platelet count <50 x 109/L
    • Hemoglobin <8 g/dL
    • Need for dual antiplatelet therapy
    • Known bleeding within the last 30 days requiring an emergency room visit or hospitalization
    • Known history of a bleeding disorder
    • Inherited or active acquired bleeding disorder
  • If no VTE
    • Continue therapeutic treatment for 14 days or until hospital discharge, whichever comes first
  • The Panel recommends using prophylactic-dose heparin (LMWH or unfractionated heparin) for patients who are not administered therapeutic heparin unless a contraindication exists 


  • There is insufficient evidence for the Panel to recommend either for or against the use of a therapeutic dose of apixaban for VTE prophylaxis or the prevention of COVID-19 progression.
  • The Panel recommends against the use of a therapeutic dose of rivaroxaban for VTE prophylaxis or the prevention of COVID-19 progression
  • There is insufficient evidence for the Panel to recommend either for or against the use of thrombolytic agents for the treatment of COVID-19
  • The Panel recommends against the use of antiplatelet therapy to prevent COVID-19 progression or death in noncritically ill patients 

Hospitalized, Nonpregnant Adults Who Are Receiving ICU Level of Care (Including Patients Who Are Receiving High-Flow Oxygen)

  • Use prophylactic-dose heparin as VTE prophylaxis unless a contraindication exists 
  • The Panel recommends against the following except in a clinical trial
    • Use of intermediate-dose (e.g., enoxaparin 1 mg/kg daily)
    • Therapeutic-dose anticoagulation for VTE prophylaxis
  • For patients who start on therapeutic-dose heparin while on low-flow oxygen due to COVID-19 and then transfer to the ICU
    • Switch from therapeutic to prophylactic-dose heparin unless a VTE is confirmed 
  • There is insufficient evidence for the Panel to recommend either for or against antiplatelet therapy in critically ill patients with COVID-19

Pregnant Adults

  • The Panel recommends that pregnant patients who are receiving anticoagulant or antiplatelet therapies for underlying conditions continue these medications after they receive a diagnosis of COVID-19
  • Use prophylactic-dose anticoagulation for pregnant patients hospitalized for manifestations of COVID-19 unless otherwise contraindicated
  • Because pregnant patients have not been included in most clinical trials evaluating therapeutic anticoagulation in the setting of COVID-19, there is currently insufficient evidence to recommend either for or against therapeutic anticoagulation for pregnant patients with COVID-19 in the absence of a known VTE

Influenza and COVID-19

Vaccine Considerations

  • It is important to ensure that vaccination programs to protect against influenza continue during the pandemic
  • Patients with COVID-19 can receive inactivated influenza vaccine
  • Moderately or Severely Ill with SARS-CoV-2
    • Consider deferring influenza vaccination until the patients have completed the COVID-19 isolation period and are no longer moderately or severely ill
  • Asymptomatic or not moderately or severely ill with SARS-CoV-2
    • Influenza vaccination can be given when infected individual no longer require isolation
    • Vaccinate sooner if they are in a health care setting for other reasons

Note: Influenza vaccine and a COVID-19 vaccine may be administered concurrently at different injection sites

Testing for Influenza

  • Test for both viruses in all hospitalized patients with acute respiratory illness 
  • The Panel recommends influenza testing in addition to SARS-CoV-2 testing in outpatients with acute respiratory illness if
    • Results will change the clinical management strategy for the patient such as initiating antiviral treatment for influenza 
  • Consider testing patients for other pathogens based on their specific clinical circumstances
    • Additional testing is especially important for patients with influenza who have a high risk of acquiring bacterial superinfections

Treatment for Influenza

  • Antiviral treatment of influenza is the same in all patients with or without SARS-CoV-2 coinfection 
  • Hospitalized patients with suspected influenza
    • Start on empiric treatment for influenza with oseltamivir as soon as possible 
    • Do not wait for influenza test results 
    • Stop antiviral treatment for influenza when influenza has been ruled out by nucleic acid detection assay
      • Nonintubated: Negative report for upper respiratory tract specimens
      • Intubated: Negative report for both upper and lower respiratory tract specimens

Learn More – Primary Sources:

NIH: Coronavirus Disease 2019 (COVID-19) Treatment Guidelines

Underlying Medical Conditions Associated with Higher Risk for Severe COVID-19: Information for Healthcare Providers (

NIH: Paxlovid Drug-Drug Interactions | COVID-19 Treatment Guidelines

Liverpool COVID-19 Interactions (

SMFM: FDA Issues EUA for the Treatment of Mild-to-Moderate COVID-19 (Paxlovid)

CHEST: Antithrombotic therapy in arterial thrombosis and thromboembolism in COVID-19

Do Proton Pump Inhibitors Increase the Risk for CVD in Patients with Type 2 Diabetes?


  • Proton pump inhibitors (PPIs), used for treating gastric-acid related diseases, have been linked with cardiovascular disease (CVD)
    • How PPI use affects type 2 diabetes (T2D) patients, who are more likely to use PPIs and more likely to develop CVD, is unclear
  • Geng et al. (Journal of Clinical Endocrinology & Metabolism, 2022) evaluate the associations of PPI use with risks of CVD and all-cause mortality in patients with T2D


  • Secondary analysis of prospective cohort study
  • Population
    • Patients in the UK Biobank with preexisting T2D
  • Exposure
    • PPI use
  • Primary outcomes
    • Coronary artery disease (CAD)
    • Myocardial infarction (MI)
    • Heart failure (HF)
    • Stroke
    • All-cause mortality


  • 19,229 adults with T2D
    • Median follow up: 10.9 to 11.2 years
  • PPI use was significantly associated with higher risks of
    • CAD: HR 1.27 (95% CI, 1.15 to 1.40)
    • MI: HR 1.34 (95% CI, 1.18 to 1.52)
    • HF: HR 1.35 (95% CI, 1.16 to 1.57)
    • All-cause mortality: HR 1.30 (95% CI, 1.16 to 1.45)
  • The results were consistent in the subgroup analyses stratified by factors including
    • Indications of PPI | Antidiabetic medication use | Antiplatelet drug use
  • Analyses in a 1:1 propensity score-matched cohort of PPI users vs nonusers yielded similar results


  • PPI use among patients with T2D is associated with an increased risk of CVD events, compared to non-use
  • The authors state

The benefits and risks of PPI use should be carefully balanced among patients with T2D, and monitoring of adverse CVD events during PPI therapy should be enhanced

Learn More – Primary Sources:

Proton Pump Inhibitor Use and Risks of Cardiovascular Disease and Mortality in Patients with Type 2 Diabetes

ACOG Committee Opinion on Delayed Cord Clamping


For both ‘vigorous’ term and preterm infants, ACOG recommends waiting at least 30 to 60 seconds after birth before clamping the umbilical cord. The committee opinion provides a comprehensive literature and evidence review. ACOG states

In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes

Delayed umbilical cord clamping is associated with significant neonatal benefits in preterm infants, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage

Benefits include

  • Term infants
    • Increased hemoglobin levels and iron stores
  • Preterm infants
    • Improved transitional circulation
    • Better establishment of RBC volume
    • Decreased blood transfusion
    • Lower risk of NEC and IVH

Note: There was no evidence for increased risk of PPH

Caution: The committee opinion notes that there may be a small risk for jaundice requiring phototherapy in term infants and therefore the delivery center should have the necessary infrastructure to monitor and treat, if necessary

Immediate Umbilical Cord Clamping

When is delayed cord clamping not appropriate?

  • Maternal reasons
    • Hemorrhage
    • Hemodynamic instability
    • Abnormal placentation (e.g., previa, abruption etc.)
  • Fetal / Neonatal reasons
    • Need for immediate resuscitation
    • Placental circulation not intact
      • abruption
      • previa
      • cord avulsion
      • IUGR with abnormal cord Doppler

NOTE: ACOG states

Maternal hemodynamic instability or the need for immediate resuscitation of the newborn on the warmer would be an indication for immediate umbilical cord clamping

Cord Milking

  • Based on the latest evidence (see ‘Learn More – Primary Sources’ below) that found a higher risk of IVH in preterm infants (23 to 27 weeks) following cord milking, ACOG states

…cord milking should not be used for extremely preterm infants (less than 28 weeks of gestation)

…there is insufficient evidence to either support or refute umbilical cord milking in infants born at 32 weeks of gestation or more, including term infants

Learn More – Primary Sources:

ACOG Committee Opinion 814: Delayed Umbilical Cord Clamping After Birth

Eclampsia and Role of Magnesium Sulfate


Eclampsia is a severe, life-threatening manifestation of preeclampsia.  While long-term neurologic damage is rare, there is risk of maternal hypoxia and death. Most women will experience signs such as headaches or visual changes prior to a seizure.


  • Defined as convulsions during pregnancy and/or postpartum
    • Tonic-clonic, focal, or multifocal
    • New onset
    • Unexplained by other neurologic pathology
  • Consider other underlying cerebral conditions when
    • Seizures occur 2 to 3 days postpartum
    • Patient on magnesium sulfate

Note: Not all women will demonstrate classic features of preeclampsia (hypertension, proteinuria)

Magnesium Sulfate – Seizure Prophylaxis  

  • Magnesium sulfate is the treatment of choice for seizure prophylaxis (ACOG recommended dosing) 
    • Loading dose of 4–6 g of magnesium sulfate administered per infusion pump over 20–30 minutes (i.e., slowly) followed by a maintenance dose of 1-2 g per hour as a continuous intravenous infusion  
    • Continue 24 hours postpartum
  • Recurrent seizures
    • Additional dose of 2-4 g can be infused over 5 minutes
  • Refractory seizures
    • Sodium amobarbital: 250 mg IV in 3 minutes
    • Thiopental or phenytoin: 1,250 mg IV at a rate of 50 mg/minute
    • Patient should be managed in ICU
    • Consider neuroimaging
  • IM option
    • 10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
    • Use if IV access limited
    • Mix with 1 mL xylocaine 2% to alleviate pain

Note: Magnesium sulfate should not be considered an antihypertensive agent

Magnesium Sulfate – When to Use

  • Severe features of preeclampsia 
    • Administer to all women 
  • No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg 
    • There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
    • ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy” 

Delivery and Postpartum 

  • Vaginal delivery
    • Continue infusion 24 hours postpartum
  • Cesarean
    • Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
    • Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended

 Prevention of Magnesium Sulfate toxicity 

  • Place Foley to monitor renal function (hourly output)  
  • Confirm normal serum creatinine  
  • Serial evaluation of patellar deep tendon reflexes 
  • Monitor respiratory rate  
  • Serum magnesium levels not routinely required
    • Monitor serum magnesium levels in setting of renal dysfunction and/or absence of patellar reflexes 
    • Maintain serum concentrations 5 to 9 mg/dL (4–7 mEq/L) range  
  • Predictive symptoms of magnesium sulfate toxicity  
    • Loss of deep tendon reflexes >9 mg/dL (greater than 7 mEq/L)  
    • Respiratory depression >12 mg/dL (greater than 10 mEq/L) 
    • Cardiac arrest >30 mg/dL (greater than 25 mEq/L) 

Pending toxicity 

  • Notify appropriate health care provider  
  • Discontinue magnesium infusion  
  • Administer supplemental oxygen  
  • Obtain a serum magnesium level  
  • Reverse magnesium 
    • 10 mL of 10% calcium gluconate IV (1 g total) and over 3 min (i.e., slowly) to avoid hypotension and/or bradycardia 
    • Calcium effect (competitively inhibits magnesium at neuromuscular junction) can wear off if magnesium level stays high 
    • Furosemide may help increase urinary excretion
  • Respiratory arrest: Intubation and assisted ventilation as indicated

Other Prophylactic Agents

  • Magnesium sulfate is superior to diazepam, phenytoin and lytic cocktail (chlorpromazine, promethazine, pethidine) in reducing significantly the risk of seizure recurrence  
    • Cochrane Review 2010: Magnesium sulfate reduced eclampsia compared to phenytoin (relative risk 0.08, 95% CI 0.01 to 0.60)   
  • Morbidity related to pneumonia, mechanical ventilation and admission to an intensive care unit are significantly reduced with the use of magnesium sulfate compared with phenytoin  
  • Magnesium sulfate does not cause maternal or newborn CNS depression 
    • Diazepam or lorazepam does stop or shorten seizures, but risk of maternal apnea and/or cardiac arrest
  • Diazepam and phenytoin may be considered if
    • Patient on these medications to treat epilepsy
    • Magnesium sulfate is contraindicated
      • Myasthenia gravis | Hypocalcemia | Moderate-to-severe renal failure | Cardiac ischemia | Heart block | Myocarditis

Learn More – Primary Sources:

National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period 

ACOG Practice Bulletin 222: Gestational Hypertension and Preeclampsia

Management of pre-eclampsia: issues for anaesthetists 

Acute pulmonary oedema in pregnant women 

Cochrane Review: Magnesium sulphate and other anticonvulsants for women with pre-eclampsia 

HPV Vaccine Recommendations Including Guidance for Ages 27 to 45


The most recent evidence-based HPV vaccine recommendations address when to administer the vaccine and dosing.  One area that has elicited more recent guidance focuses on whether to offer the HPV vaccine to individuals over the age of 26.

  • The FDA (October 2018) extended approval of HPV vaccine to individuals age 27 to 45 years
  • ACIP (June 2019) voted to
    • Expand routine and catch-up HPV vaccination in males through 26 years of age who are inadequately vaccinated
    • Offer HPV vaccine to individuals age 27 to 45 years who have not been adequately vaccinated based on shared clinical decision making
  • ACIP published their final recommendations (August 2019) in the CDC’s Morbidity and Mortality Weekly Report

Children and adults aged 9 through 26 years: HPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be given starting at age 9 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated.

Adults aged >26 years: Catch-up HPV vaccination is not recommended for all adults aged >26 years. Instead, shared clinical decision-making regarding HPV vaccination is recommended for some adults aged 27 through 45 years who are not adequately vaccinated. HPV vaccines are not licensed for use in adults aged >45 years.

These recommendations for children and adults aged 9 through 26 years and for adults aged >26 years apply to all persons, regardless of behavioral or medical risk factors for HPV infection or disease.

For persons who are pregnant, HPV vaccination should be delayed until after pregnancy; however, pregnancy testing is not needed before vaccination.

Persons who are breastfeeding or lactating can receive HPV vaccine. Recommendations regarding HPV vaccination during pregnancy or lactation have not changed.

  • ACIP suggests considering the following points for shared-decision making with adults who are 27 to 45 years of age
    • HPV is very common, usually transient and asymptomatic
    • Although typically acquired in young adulthood, some adults are at risk for acquiring new HPV infection
    • A new sex partner is a risk factor, while those in long-term, mutually monogamous partnerships are not likely to acquire a new HPV infection
    • HPV types: Sexually active adults will likely have been exposed to some HPV types, but not all HPV types are vaccine targets
    • There is no antibody test to determine immunity
    • HPV vaccine has high efficacy in young persons not yet exposed to vaccine-type HPV
    • Lower vaccine effectiveness may be expected in those with HPV risk factors
      • Multiple lifetime sex partners | Previous infection with vaccine-type HPV | immunocompromising conditions
    • HPV vaccines are prophylactic only and can’t prevent infection progression, improve time to clearance or treat HPV-related disease
  • In summary, the CDC states

For adults aged 27 years and older, clinicians can consider discussing HPV vaccination with people who are most likely to benefit. HPV vaccination does not need to be discussed with most adults over age 26 years

CDC Dosing Schedule 

  • <15 years: 2 doses spaced 6 to 12 months apart
  • ≥15 years: 3-dose schedule
    • Initial dose
    • Second dose at 1 to 2 months after initial 
    • Third dose at 6 months after initial 

Updated ACOG HPV vaccine recommendations 

  • Routine HPV vaccination is recommended for females and males 
  • Target age is 11 to 12 years but can be given through age 26
    • Can be given from age of 9 
  • Do not test for HPV DNA prior to vaccination
    • Vaccinate even if patient was tested and is HPV DNA positive
  •  If not vaccinated between 11 to 12 years
    • Vaccinate between 13 to 26 years (catch up period)
  • Women 27 to 45 years and not previously unvaccinated
    • Use shared clinical decision making
  • ACOG “does not recommend that an individual who received the quadrivalent HPV vaccine be revaccinated with 9-valent HPV vaccine, including those aged 27–45 years who previously completed some, but not all, of the vaccine series when they were younger”
  • Pregnancy
    • HPV vaccine is not recommended during pregnancy
    • Pregnancy testing prior to HPV vaccination not recommended
    • If vaccination schedule is interrupted by pregnancy, resume postpartum with the next dose
    • HPV vaccine can and should be given to breastfeeding women ≤26 who have not been vaccinated
  • Counsel to expect mild local discomfort and that this is not a cause for concern
    • Watch adolescents for at least 15 minutes following vaccination due to risk of fainting in this population


  • The AAP  has also endorsed the CDC HPV recommendations
    • The HPV vaccine should be normalized as a standard of care
    • Recommendation should be clear and unambiguous 
    • AAP provides multiple strategies (see ‘Learn More – Primary Sources’ below) to engaging with patients including focusing on cancer prevention benefits for all children 


  • The ACS endorses ACIP CDC guidance regarding HPV guidance except for the approach to take with individuals who are 27 to 45 years and not adequately vaccinated

The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit

Adjuvant HPV Vaccine to Prevent CIN Recurrence 

  • ACOG recommends considering adjuvant HPV vaccine for unvaccinated individuals 27 to 45 years who are undergoing treatment for CIN 2+

Learn More – Primary Sources:

FDA approves expanded use of Gardasil 9 to include individuals 27 through 45 years old

Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices (MMWR)

CDC: HPV Vaccination Schedules & Recommendations

ACOG Committee Opinion 809: Human Papillomavirus Vaccination

ACOG Practice Advisory: Adjuvant Human Papillomavirus Vaccination for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia 2+

AAP: How Pediatricians Can Recommend HPV Vaccination to Parents and Caregivers

CDC Frequently Asked Questions about HPV Vaccine Safety

CDC: HPV Educational Materials For Clinicians

ACS: Human papillomavirus vaccination 2020 guideline update

Transvaginal Ultrasound in the Evaluation of Postmenopausal Bleeding


Postmenopausal uterine bleeding needs to be evaluated quickly and transvaginal ultrasound can play an important role in the initial work-up.

Endometrial Thickness  

  • Measure the maximum anterior-posterior thickness on a long-axis transvaginal view 
  • Transvaginal ultrasound is appropriate for the initial evaluation  
  • Thin endometrial echo  
    • Defined as ≤4mm   
    • Endometrial fluid should not be included in measuring endometrial thickness
    • >99% NPV for endometrial cancer 
    • Cannot exclude all pathology, including endometrial cancers such as uterine papillary serous, mucinous, clear cell  
  • Thickened endometrium is not diagnostic of a particular pathology  

Recommended Management 

  • Transvaginal ultrasound  
    • Should only be used as an initial evaluation if there is low prior probability for cancer or hyperplasia   
    • Additional evaluation is required if persistent/recurrent bleeding  
    • Either transvaginal ultrasound or endometrial sampling are ‘reasonable’ alternatives as first line – both not required if low risk
    • Proceed to endometrial sampling if abnormal endometrium is seen on transvaginal ultrasound  
  • Endometrial sampling  
    • First-line test if clinical risk factors are present (see ‘Endometrial Cancer: The Basics’ in ‘Related ObG Topics’ below) or clinical presentation is suspicious  
    • Outpatient endometrial sampling using disposable device is method of choice  
    • NOTE: Proceed to hysteroscopy with D&C if persistent or recurring bleeding and blind sampling is negative for endometrial hyperplasia or malignancy 


  • If transvaginal ultrasound image inadequate proceed to following options  
    • Sonohysterography | Office hysteroscopy | Endometrial sampling   
  • If insufficient tissue on endometrial sampling 
    • Transvaginal ultrasound can be used to further evaluate and if a thin echo is seen and bleeding has stopped, no further work-up is necessary  
    • Persistent/recurrent bleeding needs a histologic evaluation even in the presence of a thin echo 
  • Postmenopausal women who are not bleeding 
    • Transvaginal ultrasound should not be used as a screening tool for endometrial cancer in this population  
    • If an endometrial echo >4mm is found incidentally, this is not an automatic ‘trigger’ for further evaluation but rather should be placed in context and “individualized … based on patient characteristics and risk factors”  

Learn More – Primary Sources:  

ACOG Committee Opinion 734: The Role of Transvaginal Ultrasonography in Evaluating the Endometrium of Women With Postmenopausal Bleeding