Women with a history of multiple high-quality embryo transfers without pregnancy had no greater risk for common pregnancy complications once pregnant than women with single successful embryo transfers, based on data from nearly 300 individuals presented at American Society for Reproductive Medicine (ASRM) 2025.

Although many women with recurrent implantation failure (RIF) go on to have successful live births, data on the potential impact of an RIF history on pregnancy outcomes are lacking, according to Joshua Ewy, MD, a resident at the Hospital of the University of Pennsylvania, Philadelphia, and colleagues.

RIF affects approximately 5% of the population pursuing in vitro fertilization (IVF), Ewy said in an interview. Limited studies have investigated whether a history of RIF affects pregnancy outcomes, including placenta-mediated pregnancy complications (PMPC), he said. PMPC is defined in the literature to include hypertensive disorders of pregnancy, abruption, small for gestational age, preterm birth, and late pregnancy loss, Ewy told Medscape Medical News.

In the current study, the researchers reviewed data from singleton live births to 100 women with RIF and 179 control individuals who had successful pregnancies after a single embryo transfer. The participants were seen at a single center between July 2015 and March 2023. RIF was defined as three or more high-quality blastocysts transferred in two or more embryo transfer procedures that did not result in clinical pregnancy.

The primary outcome was a composite of four PMPCs, including hypertensive disorders of pregnancy, placental abruption, small for gestational age, and preterm birth. The researchers adjusted for factors including age, race, BMI, infertility diagnosis, embryo quality, presence of fibroids, and use of preimplantation genetic testing.

The overall prevalence of the composite outcome was 44.4%, with no significant difference in risk between patients with RIF and control individuals (relative risk [RR], 1.02; adjusted RR [aRR], 0.97; P = .72). When separated by individual outcomes, the risks for preterm birth and hypertensive disorders of pregnancy were similar between the groups. The risk for placental abruption was slightly higher in the RIF group, but did not persist in adjusted analysis (aRR, 2.76; P = .21). Small for gestational age showed a trend toward significance in an adjusted analysis (aRR, 2.78; P = .06). No differences appeared in the risk for vasa previa, placenta previa, or placenta accreta spectrum disorder, the researchers noted.

The study found no increased risk for PMPC in patients with a history of RIF after adjusting for potential confounders, and the lack of increased risk contradicts other published studies that showed an increased risk for preterm birth and abruption in patients with a history of RIF, Ewy told Medscape Medical News.

“To our knowledge, this is the first study to assess the association between RIF and a composite risk of PMPC,” he said. Although data remain limited, the current study is reassuring, he added.

“Some researchers have proposed that RIF is not a true pathologic entity but rather a statistical extreme, and the results of this study do not rule out this possibility,” Ewy noted. “Furthermore, even if RIF represents a true pathologic state, our data suggest that it should be viewed as a heterogeneous condition rather than a uniform, blanket diagnosis,” he said.

The current study was limited by its retrospective, single-institution design, with limited power to measure rare outcomes, said Ewy. “Future research directions include multi-center studies to strengthen the body of literature on pregnancy outcomes following RIF, and additional avenues of research should include the assessment of placental, immunologic, and endometrial markers to identify possible underlying biologic mechanisms of RIF,” he said.

Good News for IVF Patients

“Whether a history of RIF in IVF patients is associated with increased risks of placental complications and adverse perinatal outcomes is an area of significant concern for both clinicians and patients,” said Mark P. Trolice, MD, who was not involved in the study.

Prior literature on the impact of RIF on pregnancy outcomes has been inconsistent, Trolice, professor at the University of Central Florida College of Medicine and founder/medical director of the IVF Center of Central Florida, both in Orlando, Florida, told Medscape Medical News. Although the new study is retrospective, with inherent limitations, the results suggest that a history of RIF does not dramatically worsen the risk for the identified composite complications, he said.

“Individualized counseling and monitoring are appropriate, but overall, patients with RIF who achieve pregnancy can be reassured about their prognosis,” said Trolice. However, larger prospective studies are needed to clarify the association between RIF and specific placental complications and to explore underlying mechanisms such as immunologic, endometrial, or procedural factors, he noted. “There is also a need to define optimal monitoring and intervention strategies for RIF patients who achieve pregnancy, and to further standardize the definition and management of RIF,” Trolice added.

This study received no outside funding. Ewy disclosed no financial conflicts of interest.

Trolice disclosed no financial conflicts of interest.