Meta-analysis identifies interventions, techniques that affect embryo transfer outcomes

Researchers identified techniques and interventions implemented in embryo transfer that affect clinical pregnancy rates, and they specifically advised against post-embryo transfer bed rest.

“IVF is becoming a common fertility treatment helping thousands of couples to start their family life worldwide,” senior author Bassel H. Al Wattar, MD, PGD, MRCOG, PhD, a clinical research associate at the University College London Institute for Women’s Health and National Institute for Health Research, told Healio. “IVF involves several integrated stages from stimulating the ovaries to obtain several eggs, to fertilizing them in order to form embryos in the lab, and finally, transferring an embryo back to the mother’s womb. The process of embryo transfer is particularly delicate as optimal conditions need to be in place to maximize the chances of embryo implantation and pregnancy.”

There are several interventions meant to improve the chances of achieving a pregnancy after an embryo transfer, but “evidence of their effectiveness varied, leading to uncertainty,” Al Wattar said.

Defining inclusion criteria

Al Wattar and colleagues identified 188 randomized controlled trials (RCTs) for inclusion through their electronic database review from inception to March 2021. The RCTs evaluated 38 total interventions within the 24 hours before and after embryo transfer in 59,530 women undergoing IVF or intracytoplasmic sperm injection (ICSI).

The primary outcome was clinical pregnancy, which the researchers defined as viable pregnancy confirmed by ultrasound following embryo transfer.

In their analysis of the RCTs, Al Wattar and colleagues determined there was a low risk for randomization and attrition bias, although there was a significant risk for publication bias.

Embryo transfers occurred most often on day 2 or 3 during the cleavage stage (40.4%), and most transfers were fresh (51.1%).

Pregnancy rates with interventions

Clinical pregnancy rates were higher with ultrasound guidance compared with clinical touch (24 studies; RR = 1.265; 95% CI, 1.151-1.391), hyaluronic acid compared with routine care (nine studies; RR = 1.457; 95% CI, 1.197-1.261) and soft catheters compared with hard catheters (27 studies; RR = 1.122; 95% CI, 1.028-1.224).

Other interventions that were associated with greater chances of achieving clinical pregnancy were granulocyte colony-stimulating factor (four studies; RR = 1.774; 95% CI, 1.252-2.512), atosiban (seven studies; RR = 1.493; 95% CI, 1.184-1.882) and human chorionic gonadotropin, or hCG (17 studies; RR = 1.232; 95% CI, 1.099-1.382)

“Prolonged bed rest (for more than 20 minutes after the embryo transfer) actually reduced the chances of pregnancy by about 15% and should therefore be avoided,” Al Wattar said. “Instead, women should continue their routine activity post embryo transfer.”

The researchers found no significant benefits with interventions such as prophylactic antibiotics, inflammatory drugs and acupuncture.

Implications for practice

Al Wattar was clear about the clinical implications of the findings.

“Our findings should be translated directly into clinical practice to help couples undergoing IVF maximize their chances of achieving a pregnancy,” he said. “Similarly, we highlighted interventions that remain of uncertain effect pending future research. Couples should avoid paying for such experimental interventions unless clinically indicated.”

Specifically, Al Wattar noted that the drug atosiban and the pregnancy hormone hCG have shown potential, but more studies are needed.

“We need more research to show just how effective these inventions are, and we call on major health funders to urgently invest in IVF research to help couples in need to help them start a family,” he said.