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

Cara Buskmiller; Donna Harrison; Lester A Ruppersberger; Patrick P Yeung Jr

doi:10.1177/0024363919854289

Contraception Long Acting Methods

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

Buskmiller C, Harrison D, Ruppersberger LA, Yeung PP Jr

Published February 2020 The Linacre Quarterly, 87(1), 60-77

DOI 10.1177/0024363919854289 PMID 32431449 PMC PMC7016440

RRM Academy Synopsis

IUD users show pregnancy-marker evidence of embryo formation and loss

A systematic review of studies in women using IUDs found evidence of fertilization and pregnancy failure in 7.3 percent of users. In good-quality studies, 4.5 percent showed it.

Key Findings

The search identified 1,073 studies and 138 were read in detail. The review included 23 studies of β-hCG, 2 of pregnancy-specific binding globulin and 1 of heat-shock protein 10 (Hsp10).
Across studies of any quality, 124 of 1,699 IUD users (7.3 percent) had evidence of fertilization without clinical pregnancy. In good-quality studies, 10 of 220 (4.5 percent) did.
Late luteal β-hCG indicated probable trophoblastic activity in 62 of 996 copper IUD users (about 6.2 percent) and 3 of 124 levonorgestrel IUD users (2.4 percent).
One Hsp10 study found the marker in 6 of 23 IUD-user cycles and 0 of 13 control cycles. In Hsp10-positive cycles, no presumed embryo went on to make detectable β-hCG.
One tubal-flushing study found no normally developing embryos in the IUD group and ten in noncontracepting controls, on assumptions the reviewers criticize.

Interpretation

The pooled studies measured pregnancy markers in women using IUDs, drawing on β-hCG, pregnancy-specific binding globulin, and Hsp10 data. The authors note the overall evidence as moderate to low, with several β-hCG studies rated good quality. Late luteal β-hCG in IUD users can reasonably be considered trophoblastic in origin, the authors say. The findings support larger, prospective studies of post-fertilization loss in IUD users.

RRM Context

Restorative reproductive medicine treats accurate information about how a method works as part of informed consent for both partners. The authors say hiding relevant facts from patients violates informed consent.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objectives

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.

Methods

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.

Results

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.

Discussion

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.

Conclusion

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.

Topics

Contraception › Long Acting Methods › Intrauterine Devices · Research Methods › Evidence Synthesis › Systematic Reviews

Cara Buskmiller, Donna Harrison, Lester A Ruppersberger, Patrick P Yeung Jr

C Buskmiller, D Harrison, L Ruppersberger, Pat Yeung, P Yeung

PMID 32431449 32431449 DOI 10.1177/0024363919854289 10.1177/0024363919854289 Buskmiller et al. 2020, Buskmiller 2020

Keywords

Abortifacient, Contraceptive, Early Pregnancy Factor, Embryo, Human Chorionic Gonadotropin, Intrauterine Device, Postfertilization, Pregnancy-specific Binding Globulin

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

IUD users show pregnancy-marker evidence of embryo formation and loss

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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Keywords