Inflammatory Changes after Medical Suppression of Suspected Endometriosis for Implantation Failure: Preliminary Results.

Unexplained euploid embryo transfer failure (UEETF) is a frustrating and unanswered conundrum accounting for 30 to 50% of failures in in vitro fertilization using preimplantation genetic testing for aneuploidy (PGT-A). Endometriosis is thought by many to account for most of such losses and menstrual suppression or surgery prior to the next transfer has been reported to be beneficial. In this study, we performed endometrial biopsy in a subset of women with UEETF, testing for the oncogene BCL6 and the histone deacetylase SIRT1. We compared 205 PGT-A cycles outcomes and provide those results following treatment with GnRH agonist versus controls (no treatment). Based on these and previous promising results, we next performed a pilot randomized controlled trial comparing the orally active GnRH antagonist, elagolix, to oral contraceptive pill (OCP) suppression for 2 months before the next euploid embryo transfer, and monitored inflammation and miRNA expression in blood, before and after treatment. These studies support a role for endometriosis in UEETF and suggest that medical suppression of suspected disease with GnRH antagonist prior to the next transfer could improve success rates and address underlying inflammatory and epigenetic changes associated with UEETF.

The Need for Dynamic Clinical Guidelines: A Systematic Review of New Research Published After Release of the 2017 ATA Guidelines on Thyroid Disease During Pregnancy and the Postpartum.

Background: The American Thyroid Association Guidelines on Thyroid Disease During Pregnancy and the Postpartum (ATA Guidelines) were published in 2017, with an update not expected for another 5 years. Since release of the 2017 ATA Guidelines, greater than 500 articles have been published in the field. Furthermore, there are presently 14 prospective, interventional trials in progress registered at Clinicaltrials.gov Static guidelines updated every 5-7 years fail to provide timely evidence-based guidance to practicing clinicians. Consequently, guideline development should move toward the creation of dynamic documents. The present article reviews the literature published since the 2017 ATA Guidelines, both to benefit clinicians in practice and to make the case for Dynamic ATA Guidelines. Methods: Using the search terms "thyroid" and "pregnancy," a systematic review of literature published in Pubmed from 3/1/2017 to 12/31/2018 was conducted. The titles and/or abstracts of all articles were reviewed. All articles were classified by subject headings used in the 2017 ATA Guidelines. English-text articles classified under "hypothyroidism" or "thyroid autoimmunity" were examined in full-text. Using the questions and recommendations put forth by the previous ATA Guidelines, relevant articles were selected for discussion in this review. Results: At the time of the search, 659 unique articles on "thyroid and pregnancy" were identified, including 66 original studies on hypothyroidism and 26 on thyroid autoimmunity. Of these, 26 studies on hypothyroidism and 18 studies on thyroid autoimmunity were selected for inclusion in this review based on specific questions in the 2017 ATA Guidelines. Based on these 44 articles, we propose two specific changes to the 2017 ATA Guidelines. Conclusion: Based on new research, we recommend the 2017 ATA Guidelines be updated to recommend against treating thyroid antibody-negative women diagnosed with subclinical hypothyroidism in the second trimester or later; to reflect new, moderate-quality evidence supporting the treatment of thyroid peroxidase antibody-negative women with elevated thyroid stimulating hormone levels in the first trimester or earlier; and to recommend against treatment of euthyroid, thyroid peroxidase antibody-positive women undergoing assisted reproductive technology. Transitioning to a Dynamic ATA Guidelines would allow for these and future recommendations to be implemented in real time.

Subclinical hypothyroidism and thyroid autoimmunity in recurrent pregnancy loss: a systematic review and meta-analysis.

OBJECTIVE: To determine whether overt/subclinical hypothyroidism and/or thyroid autoimmunity is associated with recurrent pregnancy loss (RPL) and whether treatment improves outcomes. DESIGN: Systematic review and meta-analysis. SETTING: University obstetrics and gynecology departments. PATIENT(S): Women with RPL and overt/subclinical hypothyroidism, and/or thyroid autoimmunity. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Associations between RPL and overt/subclinical hypothyroidism and/or thyroid autoimmunity and any effects of treatment. RESULT(S): After our review of articles from PubMed, EMBASE, Web of Science, and CENTRAL, we found two interventional studies in which levothyroxine did not improve the subsequent live-birth rate in women with subclinical hypothyroidism with or without thyroid antibodies. A meta-analysis of five studies revealed the prevalence of subclinical hypothyroidism in RPL to be 12.9% (95% confidence interval [CI], 0%-35.2%). A meta-analysis of 17 studies revealed a statistically significant association between RPL and thyroid autoimmunity (odds ratio 1.94; 95% CI, 1.43-2.64). However, a randomized study suggested that levothyroxine does not benefit euthyroid women with thyroid autoimmunity. CONCLUSION(S): Based on the limited observational studies available, no association exists between RPL and subclinical hypothyroidism, nor does levothyroxine improve subsequent pregnancy outcomes. An association exists between RPL and thyroid autoimmunity, but levothyroxine does not improve subsequent pregnancy outcomes. Women with RPL should be screened/treated for overt thyroid disease but not thyroid autoimmunity. Thyroid antibody screening is not supported by the published studies, and further randomized studies are needed. No recommendation regarding the treatment of subclinical hypothyroidism can be made at this time; prospective and randomized studies are urgently needed.

Universal screening for thyroid disease during pregnancy should be performed.

Thyroid disease can significantly impact the pregnant woman and her child. Human and animal studies have firmly linked overt hypothyroidism and overt hyperthyroidism to miscarriage, preterm delivery and other adverse pregnancy outcomes. Overt hypothyroidism and overt hyperthyroidism affect 1% of all pregnancies. Treatment is widely available, and if detected early, results in decreased rates of adverse outcomes. Universal screening for thyroid disease in pregnancy can identify patients with thyroid disease requiring treatment, and ultimately decrease rates of complications. Universal screening is cost-effective compared to the currently accepted practice of targeted screening and may even be cost-saving in some healthcare systems. Targeted screening, which is recommended by most professional associations, fails to detect a large proportion of pregnant women with thyroid disease. In fact, an increasing number of providers are performing universal screening for thyroid disease in pregnancy, contrary to society guidelines. Limited evidence concerning the impact of untreated and treated subclinical disease and thyroid autoimmunity has distracted from the core rationale for universal screening - the beneficial impact of detecting and treating overt thyroid disease. Evidence supporting universal screening for overt disease stands independently from that of subclinical and autoimmune disease. The time to initiate universal screening is now.

Steroid reservoir loss during removal of perforated Levonorgestrel 52 mg intrauterine device.

A 22-year-old G1P1 Caucasian female had hysteroscopic removal of a perforated intrauterine device during which the steroid reservoir of the intrauterine device was lost. Isolated steroid reservoirs are radiolucent on plain film radiography. We located the reservoir in the peritoneal cavity with magnetic resonance imaging and removed it via laparoscopy.

Differences in Diagnostic Criteria Mask the True Prevalence of Thyroid Disease in Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: The reported prevalence of thyroid disease in pregnancy varies widely through the published literature. These discrepancies are due to differences in criteria for euthyroidism, nationality, iodine status, and gestational age at screening. As a result, currently, an accepted rate of prevalence does not exist for the various thyroid diseases in pregnancy. Understanding the true prevalence rates of these disorders has important implications for clinical management and the ongoing discussion regarding universal screening. The aims of this study were to assess (i) the true prevalence of thyroid disorders in pregnancy and (ii) the impact of diagnostic methodology on these rates. METHODS: A systematic review was conducted of the existing literature, including the Pubmed database and references from relevant review articles. Sixty-three studies reporting prevalence of overt hypothyroidism, subclinical hypothyroidism, isolated hypothyroxinemia, subclinical hyperthyroidism, and overt hyperthyroidism in pregnant women were included. Studies were further classified by thyrotropin (TSH) cutoff for diagnosis in hypothyroid disease and timing of screening for hyperthyroid disease. Meta-analysis yielded pooled prevalence rates, with subgroup analyses for TSH cutoff and timing of screening. Analysis of studies using the 97.5th percentile TSH cutoff was assessed to yield the most accurate prevalence rates for hypothyroidism. RESULTS: Pooled prevalence rates for hypothyroidism calculated from studies using the 97.5th percentile as an upper limit for TSH were 0.50% for overt hypothyroidism, 3.47% for subclinical hypothyroidism, and 2.05% for isolated hypothyroxinemia. Pooled prevalence rates in the first and second trimesters for hyperthyroidism were 0.91% and 0.65%, respectively, for overt hyperthyroidism and 2.18% and 0.98%, respectively, for subclinical hyperthyroidism. CONCLUSION: Population-based, trimester-specific TSH cutoffs for diagnosis of hypothyroid disease in pregnancy result in more accurate diagnosis and better estimates for prevalence of disease. Prevalence of hyperthyroidism in pregnancy varies depending on timing of screening. The prevalence rates reported in this study represent the best estimate to date of the true rates of thyroid disease in pregnancy.