The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. (2016) [6], the OR had declined to less than half this at 1.44 [6]. As a library, NLM provides access to scientific literature. Cause of infertility maybe be a potential confounding factor. No studies were excluded from the analysis based on poor quality. 3a). Low-end normal TSH is 0.4 mIU per L. 2, 5 - 7 The upper-end normal range is from 4.0 to 4.5 mIU per L. 2, 5 - 7 FT 4 level is used to distinguish. Seminal plasma and IVF outcomes Thyroid Antibody-free preparation of spermatozoa and IVF outcomes Vasodilators Tacrolimus and IVF outcomes Uterine relaxants Patients on immunomodulation therapy for known autoimmune It therefore remains possible that some important data were omitted that may have influenced the results. Table6 It has been suggested that anti thyroid antibodies may bind antigens in the zona pellucida, thereby disrupting its function [39], and that ICSI may be able to overcome this effect. Even when thyroid function remains normal, TAI has been associated with adverse pregnancy outcomes including spontaneous miscarriage and preterm birth [1, 4, 5]. N Engl J Med. Female Infertility Related to Thyroid Autoimmunity: The Ovarian Follicle Hypothesis. 2016;23(4):51523. The Medline search utilised a combination of text and medical subject headings (MeSH): (Thyroid Gland[Mesh] AND Autoimmunity[Mesh]) OR thyroid autoimmunity OR thyroid autoantibody OR thyroid autoantibodies OR antithyroid peroxidase OR antithyroglobulin antibody, Fertilization in Vitro[Mesh] OR IVF OR invitro fertilization OR in vitro fertilization OR in-vitro fertilization OR invitro fertilization OR invitro fertilisation OR in vitro fertilisation OR in-vitro fertilisation OR invitro fertilisation OR Sperm Injections, Intracytoplasmic[Mesh] OR intracytoplasmic sperm injection OR ICSI OR ART [tiab] OR reproductive techniques, assisted[MeSH Terms] OR assisted reproductive technology. J Clin Diagnostic Res. Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence. TAI+, thyroid autoimmune; TAI-, not thyroid autoimmune; OR, odds ratio; CI, confidence interval. Results showed no significant difference in likelihood of live birth per clinical pregnancy between TAI+ and TAI- women overall (OR 0.67; 95%CI [0.28, 1.60]; P=0.37; 4 studies; I2=69%). Linear regression model was performed to analyze the association between the number of oocytes retrieved and relevant factors. b Association between thyroid autoimmunity and mean number of embryos transferred in euthyroid women. HH conceived and designed the project, assisted with data interpretation, manuscript drafting, manuscript revision and critical discussion. PubMed Zhong YP, Ying Y, Wu HT, Zhou CQ, Xu YW, Wang Q, et al. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment. (2016) [6], along with a more recent paper [23] which we included in our study. 2017 guidelines of the American Thyroid Association for the diagnosis and Management of Thyroid Disease during Pregnancy and the postpartum. Studies such as Chai et al. Importantly, we found that both groups were comparably aged thereby unequivocally ruling out the possibility of an age effect. Decrease of Free Thyroxine Levels After Controlled Ovarian Hyperstimulation, Thyroid Peroxidase Identified in Human Granulosa Cells: Another Piece to the Thyroid-Ovary Puzzle. Up to two day-3 embryos or blastocysts were transferred 3 or 5 days after oocyte retrieval. After downregulation was achieved, recombinant gonadotropins were administered for ovarian stimulation. Secondary outcomes such as overall MR (including all definitions of MR: BPR+CMR+CMR alone), maternal age, number of oocytes retrieved (NOR), and numbers of embryos transferred (ET) were also recorded. 2011;66(2):10814. The I2 statistic was used as a measure of heterogeneity between studies. The full text versions of relevant studies were retrieved and assessed for eligibility by the same author. Fourthly, half of the 12 studies included in Busnelli et al. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. J Obstet Gynaecol. Effect of levothyroxine on miscarriage among women with Normal thyroid function and thyroid autoimmunity undergoing in vitro fertilization and embryo transfer: a randomized clinical trial. Pregnancy outcomes in the TAI and control groups. It is worth noting that a number of studies included in previous analyses that were not included in the present study did not report serum TSH levels, making it possible that the relationship between TAI and adverse pregnancy outcomes may have been due to thyroid dysfunction. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Article We were also strict in analysing like-for-like outcomes (e.g. Autoimmune thyroid disease was defined by positive TPO and/or thyroglobulin antibodies and the primary outcome examined was live births in women who received the infertility treatments of IVF or ICSI. Kilic S, Tasdemir N, Yilmaz N, Yuksel B, Gul A, Batioglu S. The effect of anti-thyroid antibodies on endometrial volume, embryo grade and IVF outcome. of good-quality embryos per cycle, median (IQR). For instance, some papers considered miscarriage to include both clinical and biochemical pregnancy losses (BPL) (e.g. CAS Based on TGAb titers, patients with isolated positive for TGAb were divided into the high (TGAb 133.2 IU/ml) and low (TGAb < 133.2 IU/ml) titer groups. 2012;9(2):1215. Analysis of the 13 remaining studies revealed no significant differences in patient age between all TAI+ and TAI- women (SMD 0.12; 95%CI [0.04, 0.28]; P=0.15; 13 studies; I2=76%) (Fig. Figure1 CRD42019120947). In a recent study, Monteleone etal. It is hotly debated whether TAI adversely affects IVF/ICSI outcomes. No significant difference was observed in CMR between TAI+ and TAI- women (OR 1.18; 95%CI [0.52, 2.64]; P=0.69; 7 studies; I2=54%) (Fig. It is clear that treating overt hypothyroidism (high TSH and low T4) improves the success of pregnancies achieved through ART and decreases the miscarriage rate. JBRA Assist Reprod. Patients were excluded from the study if they had a history of other reproductive diseases, such as polycystic ovarian syndrome and endometriosis; a history of other thyroid diseases, such as hyperthyroidism or thyroid cancer; abnormal results on parental karyotyping; other endocrinological diseases, such as hyperprolactinemia and diabetes; or positive tests for the antinuclear antibody or lupus anticoagulants. In addition, in a meta-analysis, including 12 studies, Andrea etal. 2017;318(22):21908. Helps you get and maintain an erection when you need it. Newer studies may therefore include women with more intact thyroid function whereas older studies may have included patients with more severe thyroid imbalances, which may have increased the tendency to adverse outcomes in earlier meta-analyses. 2019;322(7):63241. Subgroup analysis for pregnancy outcomes according to isolated TGAb tertiles. Clin Endocrinol. Second, TAI is an immune disorder, and thyroid antibodies with different titers indicates an immune imbalance that impairs the establishment of immune tolerance during pregnancy. Leiva P, Schwarze JE, Vasquez P, Ortega C, Villa S, Crosby J, et al. Eggers weighted regression test was used to assess publication bias where more than 10 studies were included in the analysis. Lastly, our study did not investigate the use of levothyroxine because of the retrospective design; however, our previous study has shown that the use of levothyroxine did not affect IVF/ICSI outcomes (32). 8600 Rockville Pike Busnelli et al. Continuous data are shown as mean (standard deviation [SD]) for normally distributed data and median (interquartile range) for non-normally distributed data. a Overall association between thyroid autoimmunity and TSH levels. Reprod Sci. Given the powerful influence of female age on pregnancy outcome through effects on oocyte quality [20], a critically important strength of our study was to restrict analyses to papers that reported female age. Based on TPOAb titers, patients with isolated positive for TPOAb were divided into the high (TPOAb 165) and low (TPOAb < 165) titer groups. CMR and LBR per cycle) rather than combining variously defined outcomes into a single analysis. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Romitti M, Fabris VC, Ziegelmann PK, Maia AL, Spritzer PM. Toulis et al. It is hotly debated whether TAI adversely affects IVF/ICSI outcomes. Adjuvant immunotherapy treatments in in vitro fertilization (IVF) aim to improve the outcome of assisted reproductive technology . b Association between thyroid autoimmunity and likelihood of clinical pregnancy in euthyroid women. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Poppe K, Autin C, Veltri F, Kleynen P, Grabczan L, Rozenberg S, et al. FSH, follicle stimulating hormone; LH, luteinizing hormone; E2, estradiol; AMH, Anti-Mullerian hormone; FT4, free thyroxine; IQR, interquartile range; SD, standard deviation; TAI, thyroid autoimmunity; TSH, thyroid-stimulating hormone. Was 21.99. Likewise, Leiva et al. Methods The review was registered with PROSPERO: CRD42019120947. Revelli A, Casano S, Piane LD, Grassi G, Gennarelli G, Guidetti D, et al. (2018) [38] are due to the inclusion of more recent studies and stricter inclusion criteria. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. J Clin Endocrinol Metab. Negro R, Mangieri T, Coppola L, Presicce G, Casavola EC, Gismondi R, et al.. Levothyroxine Treatment in Thyroid Peroxidase Antibody-Positive Women Undergoing Assisted Reproduction Technologies: A Prospective Study. Effects of thyroid-stimulating hormone and thyroid autoantibodies on pregnancy outcome after in vitro fertilization and embryo transfer. There were no significant differences between the two groups in the rates of clinical pregnancy, miscarriage, live birth, and preterm delivery or birth weight in singleton or twin pregnancy ( 2015;38(12):133543. The .gov means its official. Although we considered this potential confounder, and analysis of the five studies that reported embryo numbers transferred showed no difference in relation to TAI status (Fig. Google Scholar. Several studies have demonstrated a significant association between reproductive factors and the risk of thyroid cancer (TC), and a higher prevalence of TC has been observed in women with infertility than in those without infertility [1,2,3].For women with TC complicated by infertility, a careful balance between TC and assisted reproductive treatment is required. Furthermore, by considering maternal TSH levels, the present study accounted for potential confounding effects due to substantial thyroid dysfunction. 2009;7:137. Canipari R, Mangialardo C, Di Paolo V, Alfei F, Ucci S, Russi V, et al.. Thyroid Hormones Act as Mitogenic and Pro Survival Factors in Rat Ovarian Follicles. Chai J, Yeung WT, Lee CV, Li HR, Ho P, Ng HE. However, it decreased the number of oocytes retrieved and birth weight in twin pregnancy. 4 UNI | 4.95 per 1UNI. There is no association between the presence of anti-thyroid antibodies and increased reproductive loss in pregnant women after ART: a systematic review and meta-analysis. Subgroup analysis for pregnancy outcomes according to isolated TPOAb tertiles. Muller AF, Verhoeff A, Mantel MJ, De Jong FH, Berghout A. On the other hand, our findings are consistent with those of He et al. First, the presence of TAI triggers a subtle deficiency of thyroid reserve and consequently, leading to a reduced capacity of the thyroid gland to adapt to the augmented demand in the process of COS and early pregnancy. Muller AF, Verhoeff A, Mantel MJ, Berghout A. Thyroid Autoimmunity and Abortion: A Prospective Study in Women Undergoing. Jin L, Wang M, Yue J, Zhu G-J, Zhang B. ukaszuk K, Kunicki M, Kulwikowska P, Liss J, Pastuszek E, Jaszczot M, et al. Endocr Connect. The AMH and E2 levels were significantly higher in patients with TAI than in age-matched controls, indicating a higher ovarian reserve in patients with TAI. 10a). Busnelli A, Paffoni A, Fedele L, Somigliana E. The impact of thyroid autoimmunity on IVF/ICSI outcome: a systematic review and meta-analysis. The below article by Dr. Lowe speaks volumes. J Reprod Med. Primary outcomes were clinical pregnancy rate, clinical miscarriage rate, biochemical pregnancy loss, livebirth rate per-cycle and live birth rate per clinical pregnancy (CP). Curr Opin Obstet Gynecol. Global infertility prevalence rates among couples are difficult to determine but are generally believed to range between 10 and 15% [Citation 1] and has not changed significantly despite of the evolution of assisted reproduction technologies (ART).In recent years, the relationship between reproductive failure and autoimmune conditions, including thyroid disorders, becomes . This systematic review and meta-analysis evaluated the relationship between thyroid autoimmunity (TAI) and IVF/ICSI outcomes, both overall and amongst euthyroid . Thyroid autoimmunity (TAI), diagnosed as the presence of thyroid antibody, is the most common autoimmune disorder among women of childbearing age. One theory: the reproductive tissue is similar to thyroid tissue and the thyroid antibodies also damage the tissue on the ovaries and uterus. Poppe K, Glinoer D, Tournaye H, Schiettecatte J, Devroey P, van Steirteghem A, et al.. Impact of Ovarian Hyperstimulation on Thyroid Function in Women With and Without Thyroid Autoimmunity. 2019;25(3):34461. Extracted data was compared to ensure accuracy, and discrepancies were corrected upon referral back to the original paper. 8b). TAI+, thyroid autoimmune; TAI-, not thyroid autoimmune; OR, odds ratio; CI, confidence interval, Association between thyroid autoimmunity and likelihood of live birth per cycle. Thyroid autoimmunity (TAI) is defined as the presence of antithyroid antibodies anti-thyroid peroxidase (TPO-Ab) and/or anti-thyroglobulin (TG-Ab) antibodies and is the most common autoimmune condition in women of reproductive age, with a prevalence of 814% [1, 2]. Wells GA, Shea, B., OConnell, D., Peterson, J., Welch, V., Tugwell, P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in metaanalyses.3rd Symposium on Systematic Reviews: Beyond the Basics 2000 [http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.]. The https:// ensures that you are connecting to the Overall CMR was reported by 8 studies. (2019) [22], Chen et al. A significant difference was observed in thyroid function between the TAI and control group. There were also limited details on individual patients such as stimulation protocols used, which could theoretically affect results given that antagonist and agonist protocols could have different effects on thyroid function [44]. A comparison of biochemical pregnancy rates between women who underwent IVF and fertile controls who conceived spontaneously. Systematic searches of the PubMed, Embase, Web of Science and Cochrane Library databases identified 491 citations, with 332 of these being non-duplicates (Fig. aClinical pregnancy was defined as at least one gestational sac in the uterus at 35 days after embryo transfer as identified on ultrasonography. There was no significant difference in biochemical pregnancy loss (OR 1.14; 95%CI [0.48, 2.72]; P=0.769; 4 studies; I2=0.0%), live birth rate per cycle (OR 0.84; 95%CI [0.67, 1.06]; P=0.145; I2=1.7%), live birth rate per clinical pregnancy (OR 0.67; 95%CI [0.28, 1.60]; P=0.369; I2=69.2%), both overall and in euthyroid women as all studies included consisted of euthyroid women only. The individualized dose of gonadotropins was decided based on the patients age, body mass index (BMI), and anti-Mllerian hormone (AMH) levels. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. However, we could not detect the difference in thyroid function between the two groups during COS due to the studys retrospective design. (2016) [10] and Leiva et al. In contrast, in the most recent meta-analysis, one quarter of included studies had not reported age and analysis of ages amongst those that did, found that TAI+ women were significantly older than TAI- women [6]. The lack of a detrimental effect of TAI on pregnancy outcomes that we find here is consistent with two recent large RCTs. Your US state privacy rights, b) Association between thyroid autoimmunity and likelihood of miscarriage according to all definitions in euthyroid women. Is there an effect of thyroid autoimmunity on the outcomes of assisted reproduction? 11b). Literature searches were conducted via MEDLINE, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), and Web of Science (Science and Social Science Citation Index) from inception to April 2019. Pooled effect sizes were estimated by applying random effects meta-analysis. Google Scholar. Individual studies assessed different antibodies (TPO-Ab and/or TG-Ab) and used different assays as well as different cut-off values for defining TAI positivity (Table 1), which could potentially affect outcomes. (2018) [38] found no difference in MR when analyses were strictly restricted to CPs, entirely in keeping with our findings. No use, distribution or reproduction is permitted which does not comply with these terms. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. TAI+, thyroid autoimmune; TAI-, not thyroid autoimmune; OR, odds ratio; CI, confidence interval, Association between thyroid autoimmunity and likelihood of biochemical pregnancy loss. It is therefore possible that previous negative effects on pregnancy outcomes in TAI+ women may have been due to SCH, rather than TAI itself. Adequate TH availability during pregnancy is crucial for fetal growth and development. Indeed, the study was powered against a predicted CMR of 30% for TAI+ women but unexpectedly, the actual MR in their untreated TAI+ arm was only 10.6%, which was no higher, and indeed, somewhat lower than the background rate of ~15% for women of a similar age [18, 19]. Statistical significance was defined as two-sided P value < 0.05. Studies were excluded if: (i) women had overt thyroid dysfunction, (ii) maternal age was not reported, (iii) women were being treated with levothyroxine, (iv) ART techniques aside from IVF/ICSI were used. 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