Cara Buskmiller, Harrison, D., Ruppersberger, L. A., & Yeung PP Jr (2020). Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices. The Linacre Quarterly, 87(1), 60-77. https://doi.org/10.1177/0024363919854289
Cara Buskmiller, Harrison D, Ruppersberger LA, Yeung PP Jr. Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices. Linacre Q. 2020;87(1):60-77. doi:10.1177/0024363919854289
Cara Buskmiller, et al. "Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices." The Linacre Quarterly, vol. 87, no. 1, 2020, pp. 60-77.
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. The review found no randomized studies.
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 review pools older studies that measured pregnancy markers in IUD users. Quality varied widely. The authors describe the overall evidence as moderate to low, and rate several β-hCG studies good quality. The review found no randomized trials and cannot compare embryo loss between IUD users and nonusers or assess whether IUDs cause the losses. Levonorgestrel IUDs were studied far less often than copper IUDs. The markers are indirect signs of an embryo, and the authors say late luteal β-hCG in normal IUD users can reasonably be considered trophoblastic in origin.
RRM Context
Restorative reproductive medicine counts accurate facts about how a method works as part of informed consent for both partners. The authors say hiding relevant facts from patients violates informed consent. They call for prospective trials with control groups.
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.
Yeung P, 2025·J Restorative Reprod Med·Free to read
Restorative reproductive surgery has emerged to become an exciting and promising field of surgery that can transform the way that we treat patients, especially regarding fertility. As a prime example of this type of surgery, restorative reproductive surgery for endometriosis, a common and debilitating disease that can lead to infertility and pelvic pain, offers a root cause treatment to remove the actual disease and to optimize the reproductive anatomy, for best patient outcomes. Optimal excision of endometriosis and prevention of pelvic adhesions has been shown to lead to reduce symptoms, to lead to high natural fertility rates, and to lead to very low rates of the need for repeat surgery. Patients have improved symptoms and quality of life, in addition to improved fertility chances for one and subsequent pregnancies (if desired), demonstrating the link between wellness and fertility.
There is an urgent need for more resources, training, advocacy, research and publication for this exciting area of restorative reproductive surgery. Its time has come.
Yeung P et al., 2025·Acta Scientific Women's Health·Free to read
The primary purpose of this prospective cohort study was to determine if treating endometriosis with optimal excision surgery leads to lower rates of repeat surgery as compared to historical rates of repeat surgery by ablation. A secondary outcome was to examine whether the use of hormonal suppression differed before surgery, depending on the stage of endometriosis found at surgery. Optimal excision was defined as completely excising all areas of abnormal peritoneum, wherever found in the pelvis, having looked systematically with near contact laparoscopy. All surgeries were performed by a single surgeon specializing in optimal excision at a tertiary referral center. The rate of repeat surgery after optimal excision surgery for endometriosis was remarkably low (2.5%, 15/620) as compared to historical rates of repeat surgery by ablation. Additionally, the lack of significant evidence between hormonal suppression use and progression of stage of endometriosis provides implicit evidence that hormonal suppression does not prevent progression of the disease. Further controlled studies are needed to verify these findings.
Fetal Lower Urinary Tract Obstruction (LUTO) is associated with oligohydramnios and significant fetal morbidity, resulting in poor lung development and perinatal death. However, oligohydramnios may develop at different gestational periods, and the impact of timing on fetal outcomes remains unknown. Our objective was to characterize the impact onset of oligohydramnios had on prenatal outcomes. This study is a retrospective cohort study of all patients with a prenatal diagnosis of LUTO at our tertiary referral center from 2014 to 2023. All patients underwent detailed ultrasonography and interdisciplinary counseling and were subsequently delivered at our institution. Data were obtained from electronic medical records and complete extraction was required for final inclusion. During the study time period, 93 patients met inclusion criteria of which 68 (73.1%) developed oligohydramnios during their pregnancy. 63 (93%) of these pregnancies resulted in livebirths with 28 (41.1%) perinatal deaths. Onset of oligohydramnios was earlier in pregnancies with perinatal death (23 vs. 28 weeks, p = 0.004) and associated with pulmonary hypoplasia. Our data show the impact of oligohydramnios timing in pregnancy on pulmonary hypoplasia and ultimately perinatal death. This allows for detailed patient counseling on the impact oligohydramnios may have on pregnancies by the gestational age of onset.
There are many potential mechanisms of action for the intrauterine device (IUD), which vary by type of IUD (inert, copper, or hormonal). This paper reviews the evidence for each potential mechanism of action. On the basis of available data for fertilization rates and clinical pregnancy rates, the relative contribution of mechanisms acting before or after fertilization were quantitatively estimated. These estimates indicate that, although prefertilization effects are more prominent for the copper IUD, both prefertilization and postfertilization mechanisms of action contribute significantly to the effectiveness of all types of intrauterine devices.
The mechanism of action of contraceptive drugs and devices forms an essential part of informed consent for patients considering various methods of family planning. Currently the literature is confusing at best, in part due to non-uniform definitions of basic terms, as well as the misinterpretation of endpoints of current. AAPLOG members take different positions on the issue of contraception per se. The purpose of this document is to investigate and summarize the current evidence-based concerns regarding potential embryocidal mechanisms of action of modern contraceptive drugs and devices.
There are three reasons for concern about embryos conceived during the use of a particular contraceptive drug or device:
1. 1) All contraceptive drugs and devices “fail” at a certain rate. As noted in a recent paper, “Unintended pregnancies occur with all contraceptive methods, including IUDs. This provides incontrovertible evidence that fertilization and implantation can occur, albeit rarely, with modern methods of contraception.”1
2. 2) Since pregnancies can and do occur during the use of all contraceptive drugs and devices, then we know by definition that fertilization, which marks the beginning of an embryonic human organism, can and does happen with all contraceptive drugs and devices since by definition, an embryo must be created for pregnancy to occur. That means embryos are created at a certain rate with all contraceptive drugs or devices.
3. 3) The contraceptive drug or device will create a certain environment for the embryos created during their use. This environment may adversely affect embryo survival up to the point of yielding a positive pregnancy test at the end of the cycle (the contraceptive efficacy end point).
The remainder of this article will try to summarize what is known in the published medical literature about the environment facing an embryo who has been created during the use of various kinds of contraceptive drugs or devices.
Dinehart E et al., 2020·Journal of assisted reproduction and genetics·Free full text on PubMed Central
Intrauterine devices (IUDs) are effective and safe long-acting reversible contraceptive methods for preventing unplanned pregnancies. While extensive studies were conducted to evaluate return to fertility after removal of IUDs, majority of them were focused on multiparous women using copper IUDs. Current trends indicate increased use of levonorgestrel (LNG) IUDs in nulliparous women for very long periods of time, with both nulliparity and long duration of LNG-IUD use being potentially associated with trends towards longer time to conception post removal. Understanding the effects that LNG-IUDs may have on endometrial morphology and gene expression has important implications to further understanding their mechanism of action. Studies examining endometrial gene expression show persistent changes in receptivity markers up to 1 year after removal of an inert IUD, and no similar studies have been performed after removal of LNG-IUDs. Given the current gap in the literature and trends in LNG-IUD use in nulliparous young women, studies are needed that specifically look at the interaction of nulliparity, long-term use of LNG-IUD, and return to normal fertility. Herein, we review the available literature on the mechanism of action of IUDs with a specific focus on the effect on endometrial gene expression profile changes associated with IUDs.
Harrison D et al., 2018·Linacre Q·Free full text on PubMed Central
The purpose of this review was to determine whether there is evidence that ovulation can occur in women using hormonal contraceptives and whether these drugs might inhibit implantation. We performed a systematic review of the published English-language literature from 1990 to the present which included studies on the hormonal milieu following egg release in women using any hormonal contraceptive method. High circulating estrogens and progestins in the follicular phase appear to induce dysfunctional ovulation, where follicular rupture occurs but is followed by low or absent corpus luteum production of progesterone. Hoogland scoring of ovulatory activity may inadvertently obscure the reality of ovum release by limiting the term "ovulation" to those instances where follicular rupture is followed by production of a threshold level of luteal progesterone, sufficient to sustain fertilization, implantation, and the end point of a positive β-human chorionic gonadotropin. However, follicular ruptures and egg release with subsequent low progesterone output have been documented in women using hormonal contraception. In the absence of specific ovulation and fertilization markers, follicular rupture should be considered the best marker for egg release and potential fertilization. Women using hormonal contraceptives may produce more eggs than previously described by established criteria; moreover, suboptimal luteal progesterone production may be more likely than previously acknowledged, which may contribute to embryo loss. This information should be included in informed consent for women who are considering the use of hormonal contraception. For this study, the authors looked at English-language research articles that focused on how hormonal birth control, such as the birth control pill, may affect very early human embryos. The authors found that abnormal ovulation, or release of an egg followed by abnormal hormone levels, may often occur in women using hormonal birth control. This may increase the number of very early human embryos who are lost before a pregnancy test becomes positive. For women who are thinking about using hormonal birth control, this is important information to consider.
Contraception › Long Acting Methods › Intrauterine Devices · Research Methods › Evidence Synthesis › Systematic Reviews
Patrick Yeung, Cara Buskmiller, Donna Harrison, Lester Ruppersberger
Pat Yeung, P Yeung, C Buskmiller, D Harrison, L Ruppersberger
PMID 32431449 32431449 DOI 10.1177/0024363919854289 10.1177/0024363919854289 Buskmiller et al. 2020, Buskmiller 2020
Cite this article
Cara Buskmiller, Harrison, D., Ruppersberger, L. A., & Yeung PP Jr (2020). Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices. The Linacre Quarterly, 87(1), 60-77. https://doi.org/10.1177/0024363919854289
Cara Buskmiller, Harrison D, Ruppersberger LA, Yeung PP Jr. Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices. Linacre Q. 2020;87(1):60-77. doi:10.1177/0024363919854289
Cara Buskmiller, et al. "Systematic Review of Postfertilization Effects and Potential for Embryo Formation and Loss during the Use of Intrauterine Devices." The Linacre Quarterly, vol. 87, no. 1, 2020, pp. 60-77.
Keywords
Abortifacient, Contraceptive, Early Pregnancy Factor, Embryo, Human Chorionic Gonadotropin, Intrauterine Device, Postfertilization, Pregnancy-specific Binding Globulin
