Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices

This review sought to evaluate the evidence for embryo formation during intrauterine device (IUD) use, to articulate how often embryo loss occurs in well-designed studies, and to comment on other bodies of literature suggestive of postfertilization mechanisms of action of IUDs.

The MEDLINE, EMBASE, and Ovid databases were searched for English-language studies of markers of pregnancy in IUD users in May 2018. Studies of human chorionic gonadotropin (hCG) were subjected to quality assessment based on the US Preventive Services Task Force quality tool. Bias of studies assessing pregnancy in other ways was assessed on a study-to-study basis.

In all, 1,073 studies were identified and 138 were read in detail. Twenty-three studies of β-hCG, 4 studies of direct observation of embryos in fallopian tubes, 2 studies of pregnancy-specific binding globulin (PSBG), and 1 study of heat-shock protein 10 (Hsp10) or chaperonin 10 were included. In all studies considered together, 7.3 percent of IUD users had evidence of fertilization and pregnancy failure. In good-quality studies, 4.5 percent had evidence of fertilization and pregnancy failure.

There are no randomized trials of embryo formation and loss in IUD users compared with noncontracepting controls. Studies of β-hCG span a large spectrum of quality, but several good-quality studies exist, which support embryo formation and loss in IUD users. Evidence of embryos found in tubes is moderate and evidence of PSBG and Hsp10 elaboration was limited, but these are also concerning for embryo formation and loss.

There is good-quality evidence of embryo formation and loss in IUD users. Studies are inconsistent, and the stated conclusions of several papers inaccurately diminish postfertilization evidence of embryo formation. To better assess the rate of embryo loss in IUD users compared with non-users, future research should include well-designed prospective trials and less subjective assessments of embryos in fallopian tubes.

SUMMARY: A systematic review was carried out examining the English-language literature in the MEDLINE, EMBASE, and Ovid databases for evidence of embryo formation and loss during IUD use. In all, 1,073 studies were identified and 138 were read. There are no randomized trials and evidence ranges in quality, but evidence for the embryo formation and loss in 4.5 percent of IUD users exists in good-quality research. Further research is needed to compare embryo loss in IUD users to loss in controls.