Heparin of No Benefit to IVF Patients With Recurrent Implantation Failure

Low-molecular-weight heparin did not improve live birth or pregnancy outcomes for fertility patients who had recurrent implantation failure (RIF), according to the results of a randomized controlled trial.

Fertility patients who received bemiparin after three or more embryo implantation failures did not have improved live birth rates after a single embryo transfer compared with those who received no treatment (15.6% vs 15.2%), reported Johnny Awwad, MD, of the American University of Beirut Medical Center.

The bemiparin cohort also saw no significant differences in pregnancy rate at 8 weeks’ gestation (34.7% vs 39.4%) or 12 weeks’ gestation (28% vs 32.4%). The difference in overall pregnancy rate was 9.3% in favor of the control group (40% vs 49.3%), which was not statistically significant, Awwad said in a virtual presentation during the American Society for Reproductive Medicine annual meeting.

“Using a prospective, randomized controlled design, we could not demonstrate any significant clinical benefit of bemiparin on pregnancy outcomes when used in the luteal phase of IVF/ICSI [in vitro fertilization/intracytoplasmic sperm injection] treatment cycles in women with three or more recurrent IVF failures,” Awwad stated.

His group underscored that in the absence of thrombophilia, routine use of low-molecular-weight heparin in women with three or more unsuccessful fertility treatment cycles is not warranted.

In this trial, Awwad and colleagues investigated outcomes among 165 women with RIF who underwent IVF or ICSI at the American University of Beirut Medical Center from 2016 to 2020. Women included in the trial were ages 18 to 40 (mean age 35), premenopausal, and had at least three consecutive failed cycles.

Women were excluded from the study if their male partner had azoospermia, if they had more than two previous pregnancy losses, or if they had pre-existing illnesses.

Women were randomized to receive luteal progesterone supplementation alone or with a daily injection of bemiparin sodium (3,500 IU) starting on the evening of embryo transfer up until the day of their pregnancy test. If the patient received a positive pregnancy test, bemiparin was continued until they reached 12 weeks of pregnancy.

In the intention-to-treat analysis, 76 patients were included in the heparin group and 73 in the control group. There were no major demographic or clinical differences between the two groups, including anti-Müllerian hormone levels, type of infertility, duration of stimulation, and gonadotropin consumption. The two groups also did not have significant differences in the number of oocytes, the number of embryos transferred, and the day of embryo transfer.

There were no significant differences in maternal adverse events or obstetric complications between the two cohorts, and no significant bleeding events among those who received heparin. There were four preterm births among women in the treatment group. Fetal adverse events included one intrauterine fetal death, as well as three cases of postnatal infant death as a result of prematurity, in the intervention group.

There is a growing need for “proper translational research” based on a deeper understanding of the pathophysiological pathways of RIF, Awwad said. “It follows, and it is our firm belief, that subjecting RIF women to other interventions without pre-selection on the basis of etiology could be nothing more than another wishful fishing expedition,” he said.