Clinical Review

2023 Update on obstetrics

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New considerations on which patients might benefit from progesterone therapy to prevent preterm birth, management strategies for IVF pregnancies, and tips for assessing and treating pregnant and postpartum patients with acute or secondary headache



In the musical Hamilton, there is a line from the song “The Election of 1800” in which, after a tumultuous time, Thomas Jefferson pleads for a sense of normalcy with, “Can we get back to politics?”

Trying to get back to “normal,” whatever that is, characterized the year 2022. Peeking out from under the constant shadow of the COVID-19 pandemic (not really gone, definitely not forgotten) were some blockbuster obstetrical headlines, including those on the CHAP (Chronic Hypertension and Pregnancy) trial and the impact of the Dobbs v Jackson Supreme Court decision. As these have been extensively covered in both OBG Management and other publications, in this Update we simply ask, “Can we get back to obstetrics?” as we focus on some straightforward patient care guidelines.

Thus, we offer updated information on the use of progesterone for preterm birth prevention, management of pregnancies that result from in vitro fertilization (IVF), and headache management in pregnant and postpartum patients.

Society guidance and FDA advisement on the use of progesterone for the prevention of spontaneous preterm birth

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins–Obstetrics. Prediction and prevention of spontaneous preterm birth. ACOG practice bulletin no. 234. Obstet Gynecol. 2021;138:e65-e90.

EPPPIC Group. Evaluating Progestogens for Preventing Preterm birth International Collaborative (EPPPIC): meta-analysis of individual participant data from randomised controlled trials. Lancet. 2021;397:1183-1194.

This is not déjà vu! Progesterone and spontaneous preterm birth (sPTB) is a hot topic again. If you wonder what to tell your patients, you are not alone. Preterm birth (PTB) continues to pose a challenge in obstetrics, with a most recently reported overall rate of 10.49%1 in the United States—a 4% increase from 2019. Preterm birth accounts for approximately 75% of perinatal mortality and more than half of neonatal morbidity.2

What has not changed

A recent practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) notes that some risk factors and screening assessments for PTB remain unchanged, including2:

  • A history of PTB increases the risk for subsequent PTB. Risk increases with the number of prior preterm deliveries.
  • A short cervix (<25 mm between 16 and 24 weeks’ gestation) is a risk factor for sPTB.
  • The cervix should be visualized during the anatomy ultrasound exam (18 0/7 to 22 6/7 weeks’ gestation) in all pregnant patients regardless of prior birth history. If the cervix length (CL) appears shortened on transabdominal imaging, transvaginal (TV) imaging should be performed.
  • Patients with a current singleton pregnancy and history of sPTB should have serial TV cervical measurements between 16 0/7 and 24 0/7 weeks’ gestation.2

EPPPIC changes and key takeaway points

In a meta-analysis of data from 31 randomized controlled trials, the EPPPIC (Evaluating Progestogens for Preventing Preterm birth International Collaborative) investigators compared vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control or with each other in women at risk for PTB.3 Outcomes included PTB and the associated adverse neonatal and maternal outcomes.

The EPPPIC study’s main findings were:

  • Singleton pregnancies at high risk for PTB due to prior sPTB or short cervix who received 17-OHPC or vaginal progesterone were less likely to deliver before 34 weeks’ gestation compared with those who received no treatment.
  • There is a benefit to both 17-OHPC and vaginal progesterone in reducing the risk of PTB, with no clear evidence to support one intervention’s effectiveness over the other.
  • There is benefit to either 17-OHPC or vaginal progesterone for CL less than 25 mm. The shorter the CL, the greater the absolute risk reduction on PTB.
  • In multifetal pregnancies, use of 17-OHPC, when compared with placebo, was shown to increase the risk of preterm premature rupture of membranes. Neither 17-OHPC nor vaginal progesterone was found to reduce the risk of sPTB in multifetal pregnancies.3

What continues to change

While the March 30, 2021, statement from the Society for Maternal-Fetal Medicine (SMFM), “Response to EPPPIC and consideration for the use of progestogens for the prevention of preterm birth” (https://www ement-response-to-epppic-and-consider ations-of-the-use-of-progestogens-for-the -prevention-of-preterm-birth), stands, ACOG has withdrawn its accompanying Practice Advisory on guidance for integrating the EPPPIC findings.

In August 2022, the US Food and Drug Administration (FDA) granted a hearing on the Center for Drug Evaluation and Research’s proposal to withdraw approval for Makena (hydroxyprogesterone caproate injection, 250 mg/mL, once weekly) on the basis that available evidence does not demonstrate that it is effective for its approved indication to reduce the risk of PTB in women with a singleton pregnancy with a history of singleton sPTB.4

The key takeaway points from the FDA hearing (October 17–19, 2022) were:

  • A better designed randomized controlled confirmatory trial is needed in the most at-risk patients to determine if Makena is effective for its approved indication.
  • Makena and its approved generic equivalents remain on the market until the FDA makes its final decision regarding approval.4

For now, the decision to use intramuscular progesterone in women with a prior sPTB should be based on shared decision-making between the health care provider and patient, with discussion of its benefits, risks, and uncertainties. SMFM currently recommends that women with a singleton pregnancy and a short CL (<25 mm) without a history of prior sPTB be offered treatment with a progesterone. While 17-OHPC and vaginal progesterone appear to offer benefit to women with a singleton pregnancy and either a short CL or a history of sPTB, the greatest benefit and least risk is seen with use of vaginal progesterone. In multifetal pregnancies, there is not enough evidence to recommend the use of progesterone outside of clinical trials.

Although in our practice we still offer 17-OHPC to patients with the counseling noted above, we have focused more on the use of vaginal progesterone in women with singleton pregnancies and a history of sPTB or short CL.

Continue to: Managing pregnancies that result from IVF...


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