LMWH Does Not Help With Unexplained Recurrent Pregnancy Loss

Troy Brown, RN

May 05, 2015

Low-molecular-weight heparin (LMWH) does not increase ongoing pregnancy or live-birth rates in women with a viable pregnancy and unexplained recurrent pregnancy loss (RPL), according to a new study.

"Our data show that LMWH prescribed to women with unexplained RPL and a viable pregnancy does not increase live-birth rates. Moreover, our data show that any effect LMWH may have is minimal," the researchers write. "Given the burden of daily injection, we do not recommend its use in such women for the purpose of reducing miscarriage rates."

Ekkehard Schleussner, MD, PhD, from Friedrich Schiller University Hospital, Jena, Germany, and colleagues report their findings in an article published in the May 5 issue of the Annals of Internal Medicine.

LMWH can increase live-birth rates in women with recurrent pregnancy loss caused by thrombophilic disorders, but it is unclear whether it can also help women without thrombophilic disorders who have unexplained recurrent pregnancy loss.

The researchers conducted a randomized controlled, open-label multicenter trial from 2006 to 2013. They included 449 women who had experienced at least two consecutive early miscarriages (<12 weeks' gestation) or one late miscarriage (≥12 weeks' gestation) and had a viable singleton pregnancy confirmed by ultrasonography during 5 to 8 weeks' gestation.

The researchers randomly assigned the women to receive either multivitamin pills or multivitamins plus a daily injection of dalteparin-sodium 5000 IU for up to 24 weeks' gestation.

The study's primary outcome was ongoing pregnancy at 24 weeks' gestation. Secondary outcomes included late pregnancy complications and the live-birth rate.

At 24 weeks' gestation, 191 (86.8%) of 220 pregnancies were intact in the intervention group, and 188 (87.9%) of 214 pregnancies were intact in the control group, for an absolute difference of −1.1 percentage points (95% confidence interval [CI], −7.4 to 5.3 percentage points).

The live-birth rates were 86.0% (185 of 215 women) in the intervention group and 86.7% (183 of 211 women) in the control group, for an absolute difference of −0.7 percentage point (95% CI, −7.3 to 5.9 percentage points).

There were three intrauterine fetal deaths, including one in a woman in the intervention group. Nine women developed preeclampsia or hemolysis, elevated liver enzyme level, and low platelet count (HELLP) syndrome (three women had used LMWH), and 11 women developed intrauterine growth restriction or placental insufficiency (five women had used LMWH).

"[A]vailable evidence strongly suggests that clinicians should not prescribe LMWH for women with RPL before 12 weeks' gestation. This will protect patients from LMWH-associated adverse events and unnecessary costs of care," Jean-Christophe Gris, MD, PhD, from University Hospital, Nimes, France, writes in an accompanying editorial. "Schleussner and colleagues should be congratulated for their important findings."

The question of whether or not LMWH has a future in the prevention of RPL is still unanswered, Dr Gris writes.

"It is now time to begin characterizing the various molecular mechanisms behind RPL. We can then start new therapeutic trials focused on homogeneous subcategories of patients who may have the most promising benefits," Dr Gris explains. "Maybe then LMWH and other treatments will find a clearly defined role in the treatment of some women with RPL."

One coauthor reports receiving personal fees from Leo and personal fees from Pfizer during the conduct of the study and personal fees from Leo, Pfizer, and sanofi-aventis outside the submitted work. Another coauthor reports receiving grants from Pfizer Pharma GmbH Germany and nonfinancial support from Merck Selbstmedikation GmbH Germany during the conduct of the study. Another coauthor reports receiving payment for data monitoring from Pfizer during the conduct of the study. Another coauthor reports receiving an unrestricted grant that was used for data monitoring fee from Pfizer during the conduct of the study. The other authors have disclosed no relevant financial relationships. Dr Gris reports receiving grants from drug companies and personal fees from drug companies outside the submitted work.

Ann Intern Med. 2015;162:601-609.

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