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Sierra S, Min J, Saumet J, Shapiro H, Sylvestre C, Roberts J, Liu K, Buckett W, Velez MP, Mahutte N. The investigation and management of recurrent early pregnancy loss: a Canadian Fertility and Andrology Society clinical practice guideline. Reprod Biomed Online 2025; 50:104456. [PMID: 40015079 DOI: 10.1016/j.rbmo.2024.104456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 09/24/2024] [Indexed: 03/01/2025]
Abstract
This guideline defines recurrent early pregnancy loss (REPL) as two or more losses that occur before 10 weeks gestational age and includes non-consecutive and biochemical losses. Investigations should be considered on an individual basis and may include an evaluation of genetic, anatomical, endocrinological, structural and male-associated factors. Based on the findings and available resources, options for management may include preimplantation genetic testing (PGT) for aneuploidies or PGT for chromosomal structural rearrangements, progesterone supplementation and supportive care. This guideline emphasizes a personalized approach to the problem of REPL, recognizing an overall promising prognosis for this patient population and the avoidance of treatment options that have not been shown to be of benefit.
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Affiliation(s)
- Sony Sierra
- IVIRMA Global Research Alliance, TRIO Fertility, Toronto, Ontario, Canada; Women's College Hospital, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Toronto, Toronto, Ontario, Canada.
| | - Jason Min
- The Regional Fertility Centre, Calgary, Alberta, Canada; Department of Obstetrics and Gynecology, University of Calgary, Alberta, Canada
| | - Julio Saumet
- Miacleo Fertility, Montreal, Quebec, Canada; Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, University of Montreal, Montréal, Québec, Canada
| | - Heather Shapiro
- Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Toronto, Toronto, Ontario, Canada; Mount Sinai Fertility, Sinai Health System, Toronto, Ontario, Canada
| | - Camille Sylvestre
- Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, University of Montreal, Montréal, Québec, Canada; CHU Ste-Justine, Montreal, Quebec, Canada; Clinique OVO Fertilité, Montreal, Quebec, Canada
| | - Jeff Roberts
- Pacific Centre for Reproductive Medicine, Vancouver, British Columbia, Canada; Faculty of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of British Columbia, Vancouver, British Columbia, Canada
| | - Kimberly Liu
- Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Toronto, Toronto, Ontario, Canada; Mount Sinai Fertility, Sinai Health System, Toronto, Ontario, Canada
| | - William Buckett
- Department of Obstetrics and Gynecology, McGill University, Quebec, Canada
| | - Maria P Velez
- Department of Obstetrics and Gynecology, Queen's University, Ontario, Canada
| | - Neal Mahutte
- The Montréal Fertility Centre, Montréal, Quebec, Canada
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Patel MM, Patel DK, Patel LB, Dharaiya CB, Patel DM, Vasani RM, Patel MV. Macro-Thyrotropin Syndrome: Prevalence and Clinical Profile of an Under-Recognised Rare Entity in Thyroidology. Indian J Endocrinol Metab 2025; 29:95-100. [PMID: 40181858 PMCID: PMC11964358 DOI: 10.4103/ijem.ijem_256_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 11/21/2024] [Accepted: 12/02/2024] [Indexed: 04/05/2025] Open
Abstract
Introduction Macro-thyrotropin syndrome (macro-TSH) is a rare condition characterised by the formation of a complex between thyroid-stimulating hormone (TSH) and an unknown component, resulting in elevated TSH levels that do not accurately reflect thyroid status. This study aimed to investigate the prevalence and clinical profile of macro-TSH among patients with subclinical hypothyroidism (SCH). Methods A total of 1500 patients were evaluated, with 135 exhibiting elevated TSH levels (>10 IU/mL) and normal free-thyroxine levels. Macro-TSH was diagnosed based on persistent elevated TSH levels despite serial dilutions and confirmed by less than 60% TSH recovery following polyethylene glycol (PEG) precipitation. Results Finally, 115 were diagnosed with SCH, 15 with macro-TSH, and 1245 were categorised into non-thyroid groups. The prevalence of macro-TSH, SCH, and heterophilic antibodies interfering with immunoassay was 1.09%, 8.36%, and 0.36%, respectively. Among macro-TSH patients, 13.33% exhibited classical hypothyroid features, contrasting with the 52.0% observed in SCH patients. Female gender and a family history of hypothyroidism were associated with higher odds of having macro-TSH. Diabetes mellitus, clinical symptoms of hypothyroidism (except lethargy), higher TSH level, and post-PEG TSH recovery were significantly associated with SCH compared to macro-TSH. The mean TSH level was five times higher in macro-TSH compared to SCH. Conclusion Macro-TSH syndrome represents a distinct clinical entity within the spectrum of SCH, characterised by disproportionately high TSH levels. Recognising macro-TSH is crucial for accurate diagnosis and appropriate management of SCH.
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Affiliation(s)
- Maitri M. Patel
- Department of Paediatrics, Smt. NHLM Medical College Gujarat University, Ahmedabad, Gujarat, India
| | - Dhara K. Patel
- Department of Pathology, GCS Medical College and Research Centre, Gujarat Cancer and Research Society, Ahmedabad, Gujarat, India
| | - Lalitkumar B. Patel
- Department of Pulmonary Medicine, Narendra Modi Medical College, Gujarat University, Ahmedabad, Gujarat, India
| | - Chetan B. Dharaiya
- Department of Pathology, BJ. Medical College, Gujarat University, Ahmedabad, Gujarat, India
| | - Dhruvkumar M. Patel
- Department of Internal Medicine, Louisiana State University Health Science Center, Shreveport, LA, USA
| | - Ravi M. Vasani
- Department of Laboratory Health Care Pathology and Endocrine Laboratory, Maninagar, Ahmedabad, Gujarat, India
| | - Mukundkumar V. Patel
- Department of Medicine, Annaya College of Medicine and Research, Gujarat University, Ahmedabad, Gujarat, India
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Carafone L, Knutson AJ, Gigliotti BJ. A Review of Autoimmune Thyroid Diseases and Their Complex Interplay with Female Fertility. Semin Reprod Med 2024; 42:178-192. [PMID: 39667368 DOI: 10.1055/s-0044-1795160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
Hashimoto thyroiditis and Graves' disease are autoimmune thyroid disorders that are common in women of reproductive age and have a complex relationship with female fertility and health of the maternal-fetal dyad. Both hyperthyroidism and hypothyroidism, whether subclinical or overt in severity, directly or indirectly affect nearly every level of the hypothalamic-pituitary-ovary axis, uterine and ovarian function, as well as fetal development from implantation through delivery. Autoimmunity itself also appears to negatively impact both spontaneous and assisted fertility, as well as miscarriage risk, although the mechanism remains unclear, and the presence and magnitude of risk is variable in published literature. While treatment of overt hyperthyroidism and hypothyroidism is unequivocally recommended by professional societies, the impact of treatment on fertility outcomes, and the role of treatment in subclinical thyroid disease is more controversial. Unfortunately, levothyroxine has not been shown to abrogate the risk of subfertility and miscarriage observed in euthyroid thyroid autoantibody positive women.
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Affiliation(s)
- Lindsay Carafone
- Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, New York
| | - Alex J Knutson
- Department of Obstetrics & Gynecology, University of Rochester Medical Center, Rochester, New York
| | - Benjamin J Gigliotti
- Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, New York
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Giralt M, Díaz-Troyano N, Comas I, Blanco A, Conesa L, Mendoza M, Zafon C, Goya M, Ferrer R. Reference ranges of thyroid hormones during the first trimester in Catalan women using the Atellica ® IM Solution Immunoassay Analyzer. Ann Clin Biochem 2024; 61:284-290. [PMID: 37996255 DOI: 10.1177/00045632231219387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2023]
Abstract
BACKGROUND Gestational hypothyroidism has been shown to be associated with adverse pregnancy outcomes as well as adverse outcomes for the child. Thyroid hormones concentrations change in gestation, especially within the first trimester, so the results of thyroid function test often are outside non-pregnant reference ranges. The objective of this study was to establish the first trimester reference ranges for thyroid stimulating hormone (TSH) and free thyroxine (FT4) for pregnant women in Barcelona (Spain). METHODS It was a prospective study in which 673 women were recruited during their first trimester of gestation (8-13 weeks). Serum TSH, FT4 and antithyroid peroxidase antibodies (TPOAb) were measured with Atellica® IM 1600 (Siemens Healthineers). After excluding 418 women, the reference ranges for TSH and FT4 were calculated by the 2.5th and 97.5th percentiles. Potential variables examined in this study were age, body mass index (BMI), ethnicity, iodine supplementation and smoking habit. RESULTS The reference ranges established on the Atellica® IM 1600 for the first trimester pregnancy in our population were 0.111 to 4.291 mIU/L for TSH and 11.45 to 17.76 pmol/L for FT4. No significant differences were found in thyroid hormones concentrations regarding maternal age (≤30 years vs >30 years) (p = .117), iodine supplementation (p = .683) and smoking habit (p = .363). The prevalence of TPOAb was estimated at 10.0%. CONCLUSIONS We found that in our local population, the optimal TSH upper reference limit in the first trimester of gestation was 4.3 mIU/L, similar to that proposed by de ATA-2017 guideline (4.0 mIU/L).
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Affiliation(s)
- Marina Giralt
- Department of Biochemistry, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Noelia Díaz-Troyano
- Department of Biochemistry, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Immaculada Comas
- Department of Biochemistry, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Albert Blanco
- Department of Biochemistry, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Laura Conesa
- Department of Biochemistry, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Manel Mendoza
- Department of Obstetrics and Reproductive Medicine, Maternal-Fetal Medicine Unit, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Carles Zafon
- Diabetes and Metabolism Research Unit (VHIR) and Department of Endocrinology, University Hospital Vall d'Hebron, Barcelona, Spain
| | - María Goya
- Department of Obstetrics and Reproductive Medicine, Maternal-Fetal Medicine Unit, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Roser Ferrer
- Department of Biochemistry, Vall d'Hebron University Hospital, Barcelona, Spain
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Cai L, Wang P, Xue C, Chen J, Zhang Y. Clinical Characteristics and Risk Factors Associated With Adverse Pregnancy Outcomes in Patients With Gestational Hypothyroidism: A Case-Control Study. Endocr Pract 2024; 30:101-106. [PMID: 37913924 DOI: 10.1016/j.eprac.2023.10.135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 10/18/2023] [Accepted: 10/27/2023] [Indexed: 11/03/2023]
Abstract
OBJECTIVE To synthesize evidence, summarize the clinical features of patients diagnosed with gestational hypothyroidism (GH), and analyze the risk factors associated with adverse pregnancy outcomes. METHODS From February 2021 to March 2023, a case-control study was conducted on 298 hospitalized patients with GH and 312 pregnant women without GH who underwent physical examinations. The 312 pregnant women without GH were randomly selected during the same time period. They were allocated into the study and control groups for further comparison of clinical characteristics and pregnancy outcomes. RESULTS The parameters, including age, gestational diabetes, gestational hypertension, gravidity, parity, spontaneous abortion, history of gestation, thyroid-stimulating hormone, free triiodothyronine, thyroid peroxidase antibody (TPO-Ab), and free thyroxine were significantly different between the 2 groups (P <.05). Moreover, significant differences were found between the 2 groups in terms of preterm delivery, preeclampsia, premature rupture of membranes, placental abruption, and postpartum hemorrhage (P <.05). The multivariate logistic regression analysis revealed that the influencing factors of pregnancy outcome in patients with GH were age (≥30 years), gestational diabetes, gestational hypertension, gravidity (≥3 times), spontaneous abortion, parity, history of gestation (multiparity), and TPO-Ab (positive). CONCLUSION Our study revealed that the clinical features of patients with GH were age, gestational diabetes, gestational hypertension, gravidity, parity, spontaneous abortion, history of gestation, thyroid-stimulating hormone, free triiodothyronine, TPO-Ab, and free thyroxine.
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Affiliation(s)
- Lenan Cai
- Department of Hemodialysis, Dingzhou People's Hospital, Dingzhou, China
| | - Pan Wang
- Department of Radiotherapy, Dingzhou People's Hospital, Dingzhou, China.
| | - Caili Xue
- Department of Nursing, Dingzhou People's Hospital, Dingzhou, China
| | - Jie Chen
- Department of Nursing, Dingzhou People's Hospital, Dingzhou, China
| | - Yu Zhang
- Department of Pediatrics, Dingzhou People's Hospital, Dingzhou, China
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Abstract
In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C].
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Concepción-Zavaleta MJ, Coronado-Arroyo JC, Quiroz-Aldave JE, Concepción-Urteaga LA, Paz-Ibarra J. Thyroid dysfunction and female infertility. A comprehensive review. Diabetes Metab Syndr 2023; 17:102876. [PMID: 37866272 DOI: 10.1016/j.dsx.2023.102876] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 10/01/2023] [Accepted: 10/03/2023] [Indexed: 10/24/2023]
Abstract
INTRODUCTION Female infertility is defined as the inability to achieve pregnancy following one year of consistent, unprotected sexual intercourse. Among the various endocrine factors contributing to this complex issue, thyroid dysfunction assumes a pivotal and noteworthy role. METHODS A narrative review, encompassing 134 articles up to 2023, was conducted utilizing the PubMed/Medline, EMBASE, and Scielo databases. The primary focus of this review was to investigate the effects of thyroid dysfunction on female infertility. RESULTS Thyroid disorders exert a significant influence on folliculogenesis, fertilization, and implantation processes. Thyroid autoimmunity, although associated with diminished ovarian reserve, does not typically necessitate levothyroxine therapy. On the other hand, both subclinical and overt hypothyroidism often require levothyroxine treatment to enhance fertility and optimize obstetric outcomes. Hyperthyroidism warrants prompt intervention due to its heightened risk of miscarriage. Furthermore, thyroid dysfunction exerts notable effects on assisted reproductive technologies, underscoring the importance of achieving euthyroidism prior to ovarian stimulation. CONCLUSION Women presenting with thyroid dysfunction must undergo meticulous and individualized assessments since fertility outcomes, whether achieved through natural conception or assisted reproductive technologies, can be significantly influenced by thyroid-related factors.
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Affiliation(s)
| | | | - Juan Eduardo Quiroz-Aldave
- Division of Non-communicable diseases, Endocrinology research line, Hospital de Apoyo Chepén, Chepén, Perú
| | | | - José Paz-Ibarra
- Department of Medicine, School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
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Tena Vivó G, Parellada Esquius N, Cunillera Puértolas O, Albareda Riera M, Isidro Albaladejo M, Vila Ballester L. Description of thyroid disorders the year before conception: a population-based study. Front Endocrinol (Lausanne) 2023; 14:1236505. [PMID: 37818089 PMCID: PMC10561644 DOI: 10.3389/fendo.2023.1236505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 08/14/2023] [Indexed: 10/12/2023] Open
Abstract
Objective This study aimed to monitoring the prevalence of previously identified thyroid disorders and hypothyroidism monitoring before pregnancy. Material and methods A retrospective cross-sectional study of women whose pregnancies occurred between 2014 and 2016 was conducted, including 120,763 pregnancies in Catalonia (Spain). The presence of thyroid disorders in women was based on disease diagnostic codes and/or prescription of levothyroxine or antithyroid drugs. To evaluate the thyroid disorder diagnosis and monitoring, thyrotropin (TSH), free T4 (FT4), antiperoxidase antibody (TPOAb), and anti-TSH receptor antibody (TRAb) records were gathered and categorised according to the reference values of each laboratory. Results The prevalence of recorded thyroid disorders before the last menstrual period was 5.09% for hypothyroidism and 0.64% for hyperthyroidism,showing a significant increase with age. A thyroid monitoring test was not performed in the year before the last menstrual period in approximately 40% of women with a known thyroid disorder. Amongst the women with hypothyroidism who underwent a TSH test, 31.75% showed an above-normal result. Amongst women previously unknown to have thyroid disorders, 3.12% had elevated TSH levels and 0.73% had low TSH levels. Conclusion A high percentage of Catalan women with a known thyroid disorder were not properly monitored during the year before pregnancy. Amongst those monitored, more than one-third had TSH values outside the reference range. Therefore, it is important to evaluate women with thyroid disorders during pre-pregnancy visits.
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Affiliation(s)
- Glòria Tena Vivó
- Hospital de Viladecans, Obstetrics & Gynecology Viladecans, Barcelona, Spain
| | - Neus Parellada Esquius
- Institut Català de la Salut Gerència Territorial Metropolitana Sud, Epidemiology and Research, L'Hospitalet de Llobregat, Catalunya, Spain
| | - Oriol Cunillera Puértolas
- Unitat de Suport a la Recerca Metropolitana Sud, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina, l'Hospitalet de Llobregat, Catalunya, Spain
| | - Mercè Albareda Riera
- Endocrinology and Nutrition Division, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain
| | - Mónica Isidro Albaladejo
- Institut Catalá de la Salut (ICS), Sexual and Reproductive Primary Health Care, Sant Boi de Llobregat, Spain
| | - Lluís Vila Ballester
- Endocrinology and Nutrition Division, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Spain
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Şenocak Taşçı E, Yıldız İ, Erdamar S, Özer L. Discrepancy among microsatellite instability detection methodologies in non-colorectal cancer: Report of 3 cases. World J Clin Cases 2023; 11:3105-3113. [PMID: 37215411 PMCID: PMC10198076 DOI: 10.12998/wjcc.v11.i13.3105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/16/2023] [Accepted: 04/04/2023] [Indexed: 04/25/2023] Open
Abstract
BACKGROUND Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy. The tumor-agnostic nature of MSI makes it a denominator for immunotherapy in several solid tumors. It can be assessed using next-generation sequencing (NGS), fluorescent multiplex PCR, and immunohistochemistry (IHC). CASE SUMMARY Here, we report 3 cases with discordant MSI results detected using different methods. A cholangiocellular carcinoma case revealed proficient mismatch repair (MMR) by IHC but high MSI (MSI-H) by liquid NGS. A cervical cancer case revealed deficient MMR by IHC, microsatellite stable by PCR, and MSI-H by NGS. Lastly, an endometrial cancer case revealed proficient MMR by IHC but MSI-H by NGS. CONCLUSION IHC for MMR status is the first choice due to several advantages. However, in cases of indeterminate IHC results, molecular testing by MSI-PCR is preferred. Recently, NGS-based MSI assays are being widely used to detect MSI-H tumors. All three methods have high accuracy; however, the inconsistencies between them may lead to misdiagnosis.
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Affiliation(s)
- Elif Şenocak Taşçı
- Department of Medical Oncology, Acıbadem MAA University, Istanbul 12345, Turkey
| | - İbrahim Yıldız
- Department of Medical Oncology, Acıbadem MAA University, Istanbul 12345, Turkey
| | - Sibel Erdamar
- Department of Pathology, Acıbadem MAA University, Istanbul 12345, Turkey
| | - Leyla Özer
- Department of Medical Oncology, Acıbadem MAA University, Istanbul 12345, Turkey
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Ortiz MI, Carrizo C, Russo Picasso MF, Otaño L, Knoblovits P. Impact of preconception thyrotrophin on obstetric outcomes in the fertile population. ENDOCRINOLOGÍA, DIABETES Y NUTRICIÓN (ENGLISH ED.) 2023; 70:262-269. [PMID: 37024331 DOI: 10.1016/j.endien.2023.03.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 12/07/2022] [Indexed: 04/07/2023]
Abstract
INTRODUCTION There is evidence that subclinical hypothyroidism is associated with infertility, miscarriage and obstetric complications. However, there is controversy regarding the optimal TSH value in women seeking pregnancy. Current guidelines recommend that hypothyroid women with levothyroxine replacement who are planning pregnancy should optimise the dose of levothyroxine to achieve thyrotrophin (TSH) levels <2.5 mU/l, since these requirements increase in pregnancy, thus reducing the risk of TSH elevation during the first trimester. In women with infertility, who undergo highly complex treatments and have positive thyroid autoimmunity, values of TSH <2.5 mU/l prior to fertility treatment are suggested. Although this is a different population, these «optimal» TSH levels were also extended to euthyroid women without evidence of infertility, who are seeking pregnancy. OBJECTIVES Determine whether preconception TSH levels between 2.5 and 4.64 mIU/l are associated with adverse obstetric outcomes in euthyroid women. MATERIALS AND METHODS Retrospective cohort study. We evaluated 3265 medical records of pregnant women aged 18-40 years, euthyroid (TSH 0.5-4.64 mU/ml), with TSH measurement at least one year before gestation. 1779 met inclusion criteria. The population was divided according to categories: TSH 0.5-2.4 mU/l (optimal) and TSH 2.5-4.6 mU/l (suboptimal). Information on maternal and fetal obstetric outcomes was collected from each group. RESULTS We found no statistical difference in the occurrence of adverse obstetric events between the two groups. There was also no difference when adjusting for thyroid autoimmunity, age, body mass index, previous diabetes and previous arterial hypertension. CONCLUSION Our results suggest that the reference range of TSH used in the general population could be used in women seeking pregnancy, even in the presence of thyroid autoimmunity. Treatment with levothyroxine should be considered only in patients with special situations.
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Rahmati M, Nazarpour S, Minooee S, Behboudi-Gandevani S, Azizi F, Tehrani FR. A Bayesian model to estimate the cutoff value of TSH for management of preterm birth. PLoS One 2023; 18:e0283503. [PMID: 36989309 PMCID: PMC10058148 DOI: 10.1371/journal.pone.0283503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 03/06/2023] [Indexed: 03/30/2023] Open
Abstract
BACKGROUND Determining a thyroid hormone cutoff value in pregnancy is challenging issue and several approaches have been introduced to optimize a utility function. We aimed to estimate the cutoff value of TSH using Bayesian method for prediction of preterm-birth. METHODS This study was a secondary-analysis of the population-based data collected prospectively within the framework of the Tehran Thyroid and Pregnancy Study. A total of 1,538 pregnant women attending prenatal clinics. RESULTS Using Bayesian method resulted a TSH-cutoff of (3.97mIU/L,95%CI:3.95-4.00) for distinguishing pregnant women at risk of preterm-birth. The cutoff was associated with acceptable positive predictive and negative predictive values (0.84,95% CI:0.80-0.88) and 0.92 (95%CI: 0.91-0.94), respectively). In women who were negative for thyroid peroxides antibody (TPOAb) with sufficient urinary iodine concentration (UIC), the TSH cutoff of 3.92 mIU/L(95%CI:3.70-4) had the highest predictive value; whereas in TPOAb positive women with insufficient UIC, the cutoff of 4.0 mIU/L(95%:CI 3.94-4) could better predict preterm birth. Cutoffs estimated in this study are close to the revised TSH value of 4.0mIU/L which is currently recommended by the American Thyroid Association. CONCLUSION Regardless of TPOAb status or iodine insufficiency, risk of preterm labor is increased in pregnant women with TSH value of > 3.92 mIU/L; these women may benefit from Levothyroxine (LT4) therapy for preventing preterm birth.
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Affiliation(s)
- Maryam Rahmati
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sima Nazarpour
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Midwifery, Varamin-Pishva Branch, Islamic Azad University, Tehran, Iran
| | - Sonia Minooee
- Centre for Midwifery, Child and Family Health, Faculty of Health, University of Technology Sydney, Sydney, NSW, Australia
| | | | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Preconception Counseling in Patients with Hypothyroidism and/or Thyroid Autoimmunity. Medicina (B Aires) 2022; 58:medicina58081122. [PMID: 36013589 PMCID: PMC9415345 DOI: 10.3390/medicina58081122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/09/2022] [Accepted: 08/16/2022] [Indexed: 12/03/2022] Open
Abstract
Preconception counseling is an essential tool for preventing adverse pregnancy outcomes associated with thyroid dysfunction. The high prevalence of thyroid disease among women of reproductive age, and the increased risk of adverse pregnancy outcomes associated with thyroid dysfunction, emphasize the necessity for well-established screening and treatment criteria in the preconception period. We therefore conducted a literature review for relevant information on the screening, diagnosis and treatment of subclinical and overt hypothyroidism in women seeking pregnancy. While screening for thyroid disease is recommended only in the presence of risk factors, iodine supplementation should be recommended in most regions, with higher doses in areas with severe deficiency. Known hypothyroid women should be counseled about increasing their levothyroxine dose by 20–30% in the case of suspected or confirmed pregnancy (missed menstrual cycle or positive pregnancy test). Treating subclinical hypothyroidism appears to be beneficial, especially in the presence of autoimmunity or in patients undergoing artificial reproductive techniques. Regarding the management of TPOAb negative SCH women or euthyroid women with positive TPOAb, further research is necessary in order to make evidence-based recommendations.
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Adverse Effects of Hypothyroidism on Fertility and Pregnancy: A Mini Review. MEDICAL LABORATORY JOURNAL 2022. [DOI: 10.52547/mlj.16.4.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
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Kardalas E, Sakkas E, Ruchala M, Macut D, Mastorakos G. The role of transforming growth factor beta in thyroid autoimmunity: current knowledge and future perspectives. Rev Endocr Metab Disord 2022; 23:431-447. [PMID: 34529221 DOI: 10.1007/s11154-021-09685-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/30/2021] [Indexed: 12/17/2022]
Abstract
The complex mechanisms, which are related to the pathophysiology and the development of autoimmune thyroid diseases, involve transforming growth factor beta (TGF-β) and its interplay with the immune system. The aim of this review is to examine the role of TGF-β regarding thyroid autoimmunity and explore the potent role of this molecule either as a diagnostic or prognostic marker or a therapeutic target regarding autoimmune thyroid diseases. TGF-β is clearly a master regulator of the immune response, exerting either inhibitory or facilitatory effects on cells of the immune system. Thus, this molecule is involved in the pathogenesis and development of autoimmune thyroid diseases. Recent research has revealed the involvement of TGF-β in the pathophysiology of autoimmune thyroid diseases. The role of TGF-β in the development of autoimmune thyroid diseases varies, depending on its concentrations, the type of the activated TGF-β signalling pathway, the genetic predisposition of the patient and the pathophysiologic stage of the disease. TGF-β could emerge as a useful diagnostic or prognostic marker for the evolution of thyroid autoimmunity. Promising perspectives for the effective therapeutic use of TGF-β regarding thyroid autoimmunity exist. The main treatment approaches incorporate either enhancement of the immunosuppressive role of TGF-β or inhibition of its facilitatory role in the autoimmune thyroid diseases. Further research towards deeper understanding of TGF-β physiology and clinical application of its possible therapeutic role regarding thyroid autoimmunity is needed.
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Affiliation(s)
- Efstratios Kardalas
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, 'Aretaieion' Hospital, Medical School, National and Kapodistrian University of Athens, Vassilissis Sofias Str. 76, Athens, 11528, Greece
| | - Evangelos Sakkas
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, 'Aretaieion' Hospital, Medical School, National and Kapodistrian University of Athens, Vassilissis Sofias Str. 76, Athens, 11528, Greece
- Obstetrics and Gynecology Private Practice, Michalakopoulou Str. 169, Athens, 11527, Greece
| | - Marek Ruchala
- Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Przybyszewskiego 49, Poznan, 60-355, Poland
| | - Djuro Macut
- Clinic for Endocrinology, Diabetes and Diseases of Metabolism, Univercity Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotića Street 8, Belgrade, 11000, Serbia
| | - George Mastorakos
- Unit of Endocrinology, Diabetes Mellitus and Metabolism, 'Aretaieion' Hospital, Medical School, National and Kapodistrian University of Athens, Vassilissis Sofias Str. 76, Athens, 11528, Greece.
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Rao M, Wang L, Yan G, Chen M, Tang L, Zhao S. Normal-Range Paternal Serum-Free Thyroxine Concentrations and Outcomes of Assisted Reproductive Technologies. Thyroid 2022; 32:705-713. [PMID: 35286181 DOI: 10.1089/thy.2022.0049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background: A recent study showed that paternal subclinical hypothyroidism adversely affects the clinical outcomes of assisted reproductive technologies (ARTs). The aim of this study was to determine whether paternal serum-free thyroxine (fT4) concentrations within the reference range are associated with ART outcomes. Methods: This retrospective cohort study included 4066 couples who received 4894 ART treatment cycles in our clinic between April 1, 2016 and August 31, 2021. The differences in sperm parameters and ART outcomes across the paternal fT4 concentration tertiles were compared by using generalized linear models or generalized estimation equation models. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR) per oocyte retrieval after the first embryo transfer cycle. Results: The mean ages of the males and their female partners were 32.8 (standard deviation, 5.0) and 30.7 (standard deviation, 4.1) years, respectively. No significant differences were observed in the sperm parameters or ART outcomes between the paternal fT4 concentration tertiles of the overall population. However, a stratified analysis of men aged ≥35 showed an adjusted CPR of 0.36 [confidence interval, CI: 0.27-0.45] for the lower paternal fT4 concentration tertile relative to the middle (adjusted rate: 0.45, CI: 0.38-0.53) and upper (adjusted rate: 0.43, CI: 0.36-0.51) tertiles (p for trend >0.05). The adjusted LBRs were 0.21 [CI: 0.15-0.30] for men aged ≥35 in the lower fT4 concentration tertile (p = 0.024, with reference to the upper tertile), 0.27 [CI: 0.21-0.35] for those in the middle tertile, and 0.30 [CI: 0.23-0.38] for those in the upper tertile. No differences in these outcomes were observed in men aged <35. The nonlinear smoothing curve obtained by using fT4 concentration as a continuous variable further supported these findings. Conclusions: Men of older reproductive age (≥35 years old) with low-normal fT4 concentrations within the reference range are associated with a decreased LBR. Future prospective studies are warranted to confirm the detrimental effects of low-normal paternal fT4 concentrations on ART outcomes.
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Affiliation(s)
- Meng Rao
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Longda Wang
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Gaofeng Yan
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Mengxiang Chen
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Li Tang
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shuhua Zhao
- Department of Reproduction and Genetics, The First Affiliated Hospital of Kunming Medical University, Kunming, China
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Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome. Int J Mol Sci 2022; 23:ijms23084248. [PMID: 35457066 PMCID: PMC9029102 DOI: 10.3390/ijms23084248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/31/2022] [Accepted: 04/07/2022] [Indexed: 02/05/2023] Open
Abstract
Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites’ composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation.
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d’Assunção VRN, Montagna E, d’Assunção LEN, Caldas MMP, Christofolini DM, Barbosa CP, Negreiros RAM, Laganà AS, de Oliveira R, Bianco B. Effect of thyroid function on assisted reproduction outcomes in euthyroid infertile women: A single center retrospective data analysis and a systematic review and meta-analysis. Front Endocrinol (Lausanne) 2022; 13:1023635. [PMID: 36299456 PMCID: PMC9589421 DOI: 10.3389/fendo.2022.1023635] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 09/23/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The influence of thyroid-stimulating hormone (TSH) on gestational outcomes have been studied and checked whether differing TSH levels are relevant on human reproduction outcomes. International guidelines recommend TSH values <2.5 mIU/L in women trying to conceive, since values above this level are related to a higher frequency of adverse reproductive outcomes. This study aimed to evaluate whether TSH values correlate with different gestational outcomes in euthyroid infertile women without autoimmune thyroid disease. METHODS A retrospective cohort study was conducted involving 256 women who underwent in vitro fertilization (IVF) treatment. The participants were divided into two groups: TSH 0.5-2.49 mIU/L (n=211) and TSH 2.5-4.5 mIU/L (n=45). The clinical data, hormonal profiles and reproductive outcomes were compared between groups. Additionally, a systematic review with meta-analysis following the PRISMA protocol was carried out in PubMed/MEDLINE, EMBASE, and SciELO, with no time or language restrictions, for articles comparing TSH groups named "low TSH" (<2,5 mIU/L) and "high TSH" (≥2.5 mIU/L). A meta-analysis of proportions was performed with pooled estimates expressed as relative risk (RR) of events and a random effects model. RESULTS Age, BMI, free thyroxine levels (FT4) hormonal profile and IVF outcomes were not different between groups, neither gestational outcomes (p=0.982). Also, no difference was observed when the TSH and FT4 levels were compared between patients with positive or negative gestational outcomes (p=0.27 and p=0.376). Regarding the systematic review with meta-analysis, 17 studies from 2006 to 2022 were included, and added by this original retrospective research comprising 13.247 women undergoing IVF. When comparing the proportions of clinical pregnancy between the TSH groups, no significant difference was found (RR 0.93, 95% CI 0.80-1.08), with high between studies heterogeneity (I²: 87%; τ2: 0.0544; p<0.01). The number of deliveries was not significantly different between groups, despite a trend towards higher frequency in the high-TSH group (RR 0.96, 95% CI 0.90-1.02). CONCLUSION Variation in TSH levels within the normal range was not associated with pregnancy and delivery rates in women, without autoimmune thyroid disease, who underwent IVF treatment. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier CRD 42022306967.
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Affiliation(s)
| | - Erik Montagna
- Postgraduation Program in Health Sciences, Faculdade de Medicina do ABC, Santo André, Brazil
| | | | | | - Denise Maria Christofolini
- Discipline of Sexual and Reproductive Health, and Populational Genetics, Department of Collective Health, Faculdade de Medicina do ABC, Santo André, Brazil
| | - Caio Parente Barbosa
- Discipline of Sexual and Reproductive Health, and Populational Genetics, Department of Collective Health, Faculdade de Medicina do ABC, Santo André, Brazil
| | | | - Antonio Simone Laganà
- Unit of Gynecologic Oncology, Azienda di Rilievo Nazionale ed Alta Specializzazione Ospedali Civico Di Cristina Benfratelli (ARNAS) “Civico – Di Cristina – Benfratelli”, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Renato de Oliveira
- Discipline of Sexual and Reproductive Health, and Populational Genetics, Department of Collective Health, Faculdade de Medicina do ABC, Santo André, Brazil
| | - Bianca Bianco
- Discipline of Sexual and Reproductive Health, and Populational Genetics, Department of Collective Health, Faculdade de Medicina do ABC, Santo André, Brazil
- Department of Urology, Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, Brazil
- *Correspondence: Bianca Bianco,
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Prunella vulgaris can improve the pregnancy outcomes of experimental autoimmune thyroiditis rats by inhibiting Th1/Th17 immune responses. J Reprod Immunol 2021; 149:103469. [PMID: 34979369 DOI: 10.1016/j.jri.2021.103469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 12/07/2021] [Accepted: 12/23/2021] [Indexed: 12/18/2022]
Abstract
Autoimmune thyroiditis (AIT), one of the most common autoimmune diseases among women of reproductive age, is closely associated with reproductive failure and other obstetric complications. However, effective clinical strategies for the management of pregnant women with AIT are limited. It has been shown that Prunella vulgaris (PV), a traditional herbal medicine, can ameliorate AIT and other common thyroid disorders. Therefore, using an experimental autoimmune thyroiditis (EAT) rat model, we investigated the potential effects of PV on AIT-related pregnancy outcomes. According to the administered dose of PV, EAT rats were randomly divided into the untreated EAT and PV-treated EAT groups. We found that thyroid peroxidase antibody and thyroglobulin antibody serum levels and the inflammatory infiltration of the thyroid were reduced in all PV-treated groups. Increased splenic Tgfb1 mRNA levels and Treg cell proportions were associated with decreased Th1/Th17 cell proportions, and Ifng mRNA levels were reduced in rats that received low and medium doses of PV. Moreover, in the low-dose PV group, fetal development retardation and placental injuries were reversed. Overall, our findings indicated that PV could alleviate AIT and improve pregnancy outcomes in EAT rats by downregulating Th1/Th17 immune responses and inducing Treg cell proliferation.
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Repelaer van Driel-Delprat C, van Dam E, van de Ven P, Aissa K, Ter Haar M, Feenstra Y, de Roos A, Beelen G, Schats R, Lambalk C. More Live Births in Primary Subfertile Intracytoplasmic Sperm Injection-Treated Women with High Normal TSH Levels. Gynecol Obstet Invest 2021; 86:398-407. [PMID: 34515132 DOI: 10.1159/000518083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 06/07/2021] [Indexed: 11/19/2022]
Abstract
OBJECTIVES The aim of this study was to analyze the fertility outcome in intracytoplasmic sperm injection (ICSI)-treated women across normal range thyroid-stimulating hormone (TSH) levels. Published results are inconclusive about optimal TSH levels and fertility. DESIGN This is a retrospective cohort study in 752 ICSI-treated women with predominantly severe male factor subfertility, starting treatment between the first of January 2008 and the first of March 2012 with a follow-up until 2014. Participants/Materials, Setting, Methods: Women aged 22-45 years with TSH 0.3-4.5 mIU/L without thyroid hormone substitution were included in Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands, an iodine-sufficient area. Demographic and baseline characteristics were compared between groups of patients based on TSH, using one-way ANOVA, Kruskal-Wallis ANOVA, and χ2 test. The patient was the unit of analysis: all cumulative cycles per patient were analyzed up to and including the first ongoing pregnancy. The primary outcome was a cumulative live birth rate. Clinical pregnancy rate, pregnancy loss, and ongoing pregnancy rate were secondary outcomes. The χ2 test and logistic regression were used to compare interquartile groups while adjusting for confounders. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Primary and secondary subfertile women were analyzed separately. RESULTS Analysis of the total cohort (n = 752) showed no difference in fertility outcomes across the normal TSH range. The cumulative live birth rate for the 4 groups of primary subfertile women (n = 455) was 76% in the upper TSH quartile compared to 56%, 60%, and 59% in the lower TSH quartiles. LIMITATIONS Levels of thyroxine and presence of thyroid autoimmunity were not measured in this retrospective cohort study. CONCLUSIONS The observation that a higher live birth rate was found in primary subfertile ICSI-treated women with high but allegedly normal TSH levels contributes to the hypothesis that in certain subfertile women in addition to a male factor, female factors such as subtle hypothyroidism and/or thyroid autoimmunity may play a role in keeping them from conception, which can be overcome by the process of ICSI.
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Affiliation(s)
- Constance Repelaer van Driel-Delprat
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Eveline van Dam
- Department of Internal Medicine, Division of Endocrinology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Peter van de Ven
- Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Khadija Aissa
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Melanie Ter Haar
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Yikke Feenstra
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Aletta de Roos
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Gaby Beelen
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Roel Schats
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Cornelis Lambalk
- Department of Obstetrics, Gynaecology and Reproductive Medicine, Division of Reproductive Medicine, Amsterdam Reproduction & Development, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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Effect of the Cut-Off Level for Thyroid-Stimulating Hormone on the Prevalence of Subclinical Hypothyroidism among Infertile Mexican Women. Diagnostics (Basel) 2021; 11:diagnostics11030417. [PMID: 33804476 PMCID: PMC8001256 DOI: 10.3390/diagnostics11030417] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 02/24/2021] [Accepted: 02/25/2021] [Indexed: 01/21/2023] Open
Abstract
The primary aim of this study was to compare the prevalence of subclinical hypothyroidism (SCH) using two different cut-off levels for TSH values (≥2.5 mIU/L versus ≥4.1 mIU/L). The secondary objective was to analyze the clinical-biochemical characteristics in women with and without SCH. This was a retrospective cross-sectional study. In total, 1496 Mexican women with infertility were included: Group 1, women with TSH levels ranging between 0.3 and 2.49 mIU/L, n = 886; Group 2, women with TSH between 2.5 and 4.09 mIU/L, n = 390; and Group 3, women with TSH ≥4.1 mIU/L n = 220. SCH prevalence was 40.7% (CI 95%: 38.3-43.3%) with TSH cut-off ≥ 2.5 mIU/L, and 14.7% (CI 95%: 12.7-16.5%) with TSH cut-off ≥ 4.1 mIU/L, (p = 0.0001). The prevalence of overweight was higher in Group 2 than in Groups 1 and 3. Thyroid autoimmunity, obesity and insulin resistance were higher in Group 3 than in Group 1 (p < 0.05). No other differences were observed between groups. Conclusions: The prevalence of SCH in our selected patients increased almost three times using a TSH cut-off ≥ 2.5 mIU/L compared with a TSH cut-off ≥ 4.1 mIU/L. Women with TSH ≥4.1 mIU/L compared with TSH cut-off ≤ 2.5 mIU/L more often presented with obesity, thyroid autoimmunity and insulin resistance.
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Wadhwa L, Marghret KM, Arora S. Evaluation of Reproductive Outcome in Infertile Hypothyroid Women on Thyroxine Therapy. J Hum Reprod Sci 2021; 13:272-276. [PMID: 33627975 PMCID: PMC7879836 DOI: 10.4103/jhrs.jhrs_14_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 06/04/2020] [Accepted: 09/13/2020] [Indexed: 11/04/2022] Open
Abstract
Introduction Thyroid dysfunction is associated with increased risk of infertility. Serum thyroid stimulating hormone (TSH) screening in all women seeking infertility care is recommended and hypothyroid infertile women should be treated with thyroxine until the preconception serum TSH level is <2.5 mU/l.[1] However, insufficient evidence exist to determine if thyroxine therapy improves fertility in subclinical hypothyroid women who are trying to conceive naturally. Objectives The objective is to study the effect of thyroxine therapy on reproductive outcome in infertile women with clinical and subclinical hypothyroidism (SCH). Materials and Methods The study is a descriptive cohort study with 72 subjects. Women between 20 and 40 years of age with primary or secondary infertility with hypothyroidism were studied and thyroid profile including free T3, T4, TSH, and thyroid antibodies were done. Thyroxine was given to clinical, subclinical hypothyroid subjects depending on TSH levels such that serum TSH levels are maintained < 2.5 mU/L. Serial thyroid function test was done every 6 weeks until the optimal levels were reached. Once normal TSH levels were reached subjects were followed up for 6 months. Reproductive outcome was analyzed in two groups. Group A included hypothyroid infertile women who conceived and Group B included those who did not conceive following thyroxine therapy. Results Thirty-eight out of 72 subjects (54%) conceived during thyroxine treatment (Group A) of which 4 cases had miscarriage. Maximum infertile women in Group A (20/38) conceived between 6 and 12 months (52.6%) of thyroxine therapy. Significant decrease was observed in mean TSH levels over a period of 6 months (P < 0.001). The infertility period until pregnancy in Group A reduced significantly from 5.2 ± 1.8 years to 0.5 ± 0.8 years after thyroxine treatment (P = 0.001). Conclusion Thyroxine therapy enhances fertility in infertile women with clinical and SCH.
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Affiliation(s)
- Leena Wadhwa
- IVF & Fertility Research Centre, Department of Obstetrics and Gynecology, ESI-PGIMSR, Basaidarapur, Delhi, India
| | - K Monica Marghret
- IVF & Fertility Research Centre, Department of Obstetrics and Gynecology, ESI-PGIMSR, Basaidarapur, Delhi, India
| | - Sarika Arora
- IVF & Fertility Research Centre, Department of Biochemistry, ESI-PGIMSR, Basaidarapur, Delhi, India
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Chung CW, Mo EY, Jung GS, Kim YH, Cho SW, Park DJ, Bae JM, Park YJ. Decreased Expression of Ileal Thyroid Hormone Transporters in a Hypothyroid Patient: A Case Report. Front Endocrinol (Lausanne) 2021; 12:664839. [PMID: 34122338 PMCID: PMC8187942 DOI: 10.3389/fendo.2021.664839] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 03/30/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Malabsorption of levothyroxine (LT4) is a common problem faced in clinical practice. It is usually solved, if there are no complexities including gastrointestinal absorption disorder, by taking medicines on an empty stomach and avoiding foods interfering with LT4. Herein we present a rare case of a patient exhibiting malabsorption of LT4 with decreased membranous expression of ileal transporters. CASE The 22-Year-old female presented with sustained hypothyroid status despite medication of 7.8 μg/kg LT4. Medical history and LT4 absorption test (the absorption rate 8.4%) excluded pseudomalabsorption. No organic gastrointestinal disorder was found in the patient by blood chemistry, endoscopies, and abdominal computed tomography scan. The immunohistochemical analysis showed decreased membranous expression of LAT1 and LAT2 in distal ileum and ascending colon in the patient compared to 20 controls who have no thyroid disease. The expression of MCT8 in colon appeared at both nucleus and brush border in the patient, while it was limited to brush border in controls. The expression of other transporters was similar between the patient and controls. CONCLUSION The changes of the expression of LAT1 and LAT2 in this patient showing LT4 malabsorption might help to understand the role of intestinal transporters in the absorption of LT4 in humans. The functional relevance of the decrement of LAT1 and LAT2 in this patient remains to be elucidated.
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Affiliation(s)
- Chae Won Chung
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Eun Young Mo
- Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, South Korea
| | - Gyung Seo Jung
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Yoo Hyung Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Sun Wook Cho
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Do Joon Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeong Mo Bae
- Department of Pathology, Seoul National University Hospital, Seoul, South Korea
- *Correspondence: Young Joo Park, ; Jeong Mo Bae,
| | - Young Joo Park
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea
- *Correspondence: Young Joo Park, ; Jeong Mo Bae,
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Runkle I, de Miguel MP, Barabash A, Cuesta M, Diaz Á, Duran A, Familiar C, de la Torre NG, Herraiz MÁ, Izquierdo N, Diaz Á, Marcuello C, Matia P, Melero V, Montañez C, Moraga I, Perez-Ferre N, Perez N, Assaf-Balut C, Rubio MÁ, Ruiz-Sanchez JG, Sanabria C, Torrejon MJ, Valerio J, Del Valle L, Calle-Pascual A. Early Levothyroxine Treatment for Subclinical Hypothyroidism or Hypothyroxinemia in Pregnancy: The St Carlos Gestational and Thyroid Protocol. Front Endocrinol (Lausanne) 2021; 12:743057. [PMID: 34737722 PMCID: PMC8560890 DOI: 10.3389/fendo.2021.743057] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 09/22/2021] [Indexed: 11/17/2022] Open
Abstract
UNLABELLED The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact. OBJECTIVE To define the TSH/FT4 percentiles corresponding with 2.5 µIU/mL and 7.5 pg/mL levels, respectively, at GW8 (Study 1), and evaluate the effects of protocol-based LT before GW9 on gestation evolution, in women with TSH ≥2.5 µIU/mL and/or FT4≤ 7.5 pg/mL (study 2). SUBJECTS 2768 consecutive pregnant women attending the first gestational visit from 2013-2014 and 3026 from 2015-2016 were eligible for Study I and 2 respectively. A final 2043 (study 1) and 2069 (study 2) women were assessed in these studies. RESULTS Study 1: The FT4 level of 7.5 pg/mL corresponds with the 17.9th percentile, a TSH level of 2.5 µIU/mL with the 75.8th. Women with TSH ≥2.5 µIU/mL had a history of fetal losses more frequently than those <2.5 (OR 2.33 (95%CI): 1.58-3.12), as did those with FT4 ≤7.5 pg/ml compared to those >7.5 (OR 4.81; 3.25-8.89). Study 2: A total of 1259 women had optimal TSH/FT4 levels (Group 1), 672 (32.4%, Group 2) had suboptimal TSH or T4l, and 138 (6.7%, Group 3) had suboptimal values of both. 393 (58.5%) in Group 2 and 88 (63.8%) in Group 3 started LT before GW9. Mean (SD) GW24 levels were TSH: 1.96 ± 1.22 µIU/mL and FT4: 7.07 ± 1.25 pg/mL. The highest FT4 value was 12.84 pg/mL. The adjusted risk for an adverse event if LT was started early was 0.71 (0.43-0.91) for Group 2 and 0.80 (0.66-0.94) for Group 3. CONCLUSIONS Early LT in women with suboptimum levels of TSH/FT4 (≥2.5µIU/mL/≤7.5 pg/ml) at or before GW9 is safe and improves gestation progression. These data support the recommendation to adopt these cut-off points for LT initiation, which should be started as early as possible.
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Affiliation(s)
- Isabelle Runkle
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - María Paz de Miguel
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Ana Barabash
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
| | - Martin Cuesta
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
| | - Ángel Diaz
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Alejandra Duran
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Cristina Familiar
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Nuria García de la Torre
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
| | - Miguel Ángel Herraiz
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
- Gynecology and Obstetrics Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Nuria Izquierdo
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
- Gynecology and Obstetrics Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Ángel Diaz
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Clara Marcuello
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Pilar Matia
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Verónica Melero
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Carmen Montañez
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Inmaculada Moraga
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Natalia Perez-Ferre
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Noelia Perez
- Gynecology and Obstetrics Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Carla Assaf-Balut
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Miguel Ángel Rubio
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
| | - Jorge Gabriel Ruiz-Sanchez
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Concepción Sanabria
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - María José Torrejon
- Clinical Laboratory Department Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Johanna Valerio
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Laura Del Valle
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | - Alfonso Calle-Pascual
- Endocrinology and Nutrition Department, Hospital Clínico Universitario San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
- Medicina II Department, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
- Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
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Kamrul-Hasan ABM, Aalpona FTZ, Selim S. Impact of Subclinical Hypothyroidism on Reproductive and Metabolic Parameters in Polycystic Ovary Syndrome - A Cross-sectional Study from Bangladesh. EUROPEAN ENDOCRINOLOGY 2020; 16:156-160. [PMID: 33117449 PMCID: PMC7572170 DOI: 10.17925/ee.2020.16.2.156] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 03/09/2020] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Separately, polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) exert adverse effects on several reproductive and metabolic parameters; however, in conjunction, their effects are unclear. This study evaluated the impact of SCH on reproductive and metabolic parameters in women with PCOS. METHODS In this cross-sectional study, women with newly diagnosed PCOS were evaluated. Data on their clinical presentation and anthropometric measurements were recorded, in addition to oral glucose tolerance test, fasting lipid profile, serum thyroid-stimulating hormone (TSH), free thyroxine (FT4) and anti-thyroid peroxidase (anti-TPO). RESULTS Four hundred and sixty-five women, aged 12-40 years, with PCOS were included in this study; 10.8% of them had SCH and 18.3% were positive for anti-TPO. All participants had statistically similar mean age, body mass index (BMI), waist circumference, systolic blood pressure (BP) and diastolic BP. A similar number of participants in both the euthyroid PCOS and PCOS-SCH groups had menstrual irregularity, acne, subfertility, a first-degree family member with thyroid dysfunction, acanthosis nigricans and elevated BP. Participants with SCH-PCOS had a lower modified Ferriman-Gallwey score and hirsutism frequency, though serum total testosterone levels were similar in the two groups. More subjects in the SCH group were overweight/obese, and had central obesity and goiter compared to the euthyroid group. Blood glucose, lipids and prolactin levels were similar between the two groups; the frequencies of dysglycaemia and dyslipidaemia were also similar. A higher frequency of metabolic syndrome was observed in the SCH group, though the difference was not statistically significant (p=0.098). CONCLUSION In women with PCOS, the presence of SCH does not amplify the risk of metabolic and reproductive dysfunctions.
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Affiliation(s)
- ABM Kamrul-Hasan
- Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
| | - Fatema Tuz Zahura Aalpona
- Outpatient Department, Gynaecology and Obstetrics, Mymensingh Medical College Hospital, Mymensingh, Bangladesh
| | - Shahjada Selim
- Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
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Pilz S, Theiler-Schwetz V, Malle O, Steinberger E, Pandis M, Lerchbaum E, Trummer C. Schilddrüse: Fertilität, Schwangerschaft und Laktation. JOURNAL FÜR KLINISCHE ENDOKRINOLOGIE UND STOFFWECHSEL 2020; 13:106-114. [DOI: 10.1007/s41969-020-00107-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
ZusammenfassungSchilddrüsenhormone und Schilddrüsenerkrankungen spielen eine wichtige Rolle bei Fertilität, Schwangerschaft und Laktation. Die diversen Richtlinien und Expertenempfehlungen zur Diagnostik und Therapie von Schilddrüsenerkrankungen bei Kinderwunsch und Schwangerschaft sind teils heterogen und oftmals ohne klare Handlungsanweisung für oder gegen eine bestimmte Maßnahme, was eine gewisse Verunsicherung hervorruft. In diesem Übersichtsartikel möchten wir daher die derzeitige Evidenz auf diesem Gebiet in Bezug auf praktische Handlungsanweisungen darlegen, um dem Leser für die Praxis eine nützliche Entscheidungshilfe an die Hand zu geben. Wir werden besonders auf die aktuelle Evidenzlage bzgl. der Behandlung der latenten Hypothyreose präkonzeptionell, bei Infertilität und in der Schwangerschaft eingehen, sowie auf die Wichtigkeit der Beratung und gemeinsamen Therapieentscheidung bei Hyperthyreose und Kinderwunsch bzw. Schwangerschaft. Wir möchten auch besonders betonen, dass diverse wichtige Studien erst nach Publikation der aktuellen Richtlinien auf diesem Gebiet veröffentlicht wurden, was in der Routinebehandlung unserer Patientinnen natürlich berücksichtigt werden sollte. Da manifeste Schilddrüsenerkrankungen präkonzeptionell und in der Schwangerschaft häufig und in der Regel therapiebedürftig sind, plädieren wir für ein generelles Screening auf Schilddrüsenfunktionsstörungen bei allen Frauen mit Kinderwunsch sowie bei allen mit positivem Schwangerschaftstest.
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Kakita-Kobayashi M, Murata H, Nishigaki A, Hashimoto Y, Komiya S, Tsubokura H, Kido T, Kida N, Tsuzuki-Nakao T, Matsuo Y, Bono H, Hirota K, Okada H. Thyroid Hormone Facilitates in vitro Decidualization of Human Endometrial Stromal Cells via Thyroid Hormone Receptors. Endocrinology 2020; 161:5815305. [PMID: 32242219 DOI: 10.1210/endocr/bqaa049] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2019] [Accepted: 04/02/2020] [Indexed: 02/07/2023]
Abstract
Endometrial stromal cells differentiate into decidual cells through the process of decidualization. This differentiation is critical for embryo implantation and the successful establishment of pregnancy. Recent epidemiological studies have suggested that thyroid hormone is important in the endometrium during implantation, and it is commonly believed that thyroid hormone is essential for proper development, differentiation, growth, and metabolism. This study aimed to investigate the impact of thyroid hormone on decidualization in human endometrial stromal cells (hESCs) and define its physiological roles in vitro by gene targeting. To identify the expression patterns of thyroid hormone, we performed gene expression profiling of hESCs during decidualization after treating them with the thyroid hormone levothyroxine (LT4). A major increase in decidual response was observed after combined treatment with ovarian steroid hormones and thyroid hormone. Moreover, LT4 treatment also affected the regulation of many transcription factors important for decidualization. We found that type 3 deiodinase, which is particularly important in fetal and placental tissues, was upregulated during decidualization in the presence of thyroid hormone. Further, it was observed that progesterone receptor, an ovarian steroid hormone receptor, was involved in thyroid hormone-induced decidualization. In the absence of thyroid hormone receptor (TR), due to the simultaneous silencing of TRα and TRβ, thyroid hormone expression was unchanged during decidualization. In summary, we demonstrated that thyroid hormone is essential for decidualization in the endometrium. This is the first in vitro study to find impaired decidualization as a possible cause of infertility in subclinical hypothyroidism (SCH) patients.
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Affiliation(s)
| | - Hiromi Murata
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Akemi Nishigaki
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Yoshiko Hashimoto
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Shinnosuke Komiya
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Hiroaki Tsubokura
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Takeharu Kido
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Naoko Kida
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Tomoko Tsuzuki-Nakao
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
| | - Yoshiyuki Matsuo
- Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata, Japan
| | - Hidemasa Bono
- Database Center for Life Science (DBCLS), Research Organization of Information and Systems (ROIS), Mishima, Japan
| | - Kiichi Hirota
- Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata, Japan
| | - Hidetaka Okada
- Department of Obstetrics and Gynecology, Kansai Medical University, Hirakata, Japan
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Risk factors and maternal outcomes following preterm premature rupture of membrane in the second trimester of gestation. Arch Gynecol Obstet 2020; 301:1207-1212. [PMID: 32274636 DOI: 10.1007/s00404-020-05533-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 03/28/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE To characterize the population of women who underwent mid-trimester preterm premature rupture of membrane (PPROM) in a country where mid-trimester abortions are legal and available. METHODS A retrospective cross-sectional cohort study was conducted at a tertiary referral hospital, during 2013-2016. Mid-trimester defined as gestational age 13 + 0 to 23 + 6 weeks. Rupture of membrane was defined by documentation of fluid passing through the cervix on sterile speculum examination, and a positive Nitrazine (Bristol-Myers Squibb, Princeton, NJ) or erning test. All records were evaluated for medical history, laboratory data, postnatal examination, and autopsy findings, and a database was constructed. RESULTS A total of 61 women were hospitalized for mid-trimester PPROM during the study period. Mean maternal age was 32 ± 5.98, range 20-45 years old. The majority (50, 82%) of patients decided to terminate their pregnancy before reaching the limit of viability at 24 weeks gestation. The overall prognosis of pregnancies reaching term was better than expected, with six (9.8%) patients delivering live babies and four of them born at term (36 ± 5 to 40 ± 6 weeks gestation), all after PPROM following amniocentesis or selective fetal reduction. A total of 60% of women with hypothyroidism had unbalanced TSH levels above 4.0 mIU/L prior to their pregnancy. A notable number of women (15, 24.6%) had PPROM following a pregnancy achieved by assisted reproductive technology (ART). CONCLUSIONS Most women with diagnosed mid-trimester PPROM opted for pregnancy termination before the limit of viability when granted the choice. Possible risk factors for early PPROM are unbalanced hypothyroidism and ART. PPROM following amniocentesis can in some cases reseal and reach term, suggesting conservative treatment is a reasonable management for those cases.
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Fallatah AM, Hasanain A, Babatin H, Nassibi KM, Thigah S, Abduljabbar HS. Pregnancy Outcomes among Obese Pregnant Women with Hypothyroidism: Medical Record Review of a Single Tertiary Center in Saudi Arabia. Cureus 2020; 12:e6938. [PMID: 32190490 PMCID: PMC7067361 DOI: 10.7759/cureus.6938] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background Thyroid disorder is common among pregnant women. Hashimoto thyroiditis is the most common etiology of hypothyroidism among pregnant women. Many studies showed that hypothyroidism during pregnancy has been associated with negative outcomes for the mother and for child as well including miscarriage, intrauterine growth retardation, preterm delivery and cognitive impairment in the offspring. Objectives To assess the adverse maternal and neonatal outcome among hypothyroidism obese pregnant women. Methods This is a retrospective study conducted among obese pregnant women diagnosed with hypothyroidism attending King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia between January 1, 2013, and December 31, 2018. For analysis, we used (1) descriptive statistics, (2) Chi-square test, Pearson correlation, independent t-test, and one-way ANOVA to test the difference in thyroid stimulating hormone (TSH) levels and adverse pregnancy outcomes. A p-value of <0.05 is used to calculate statistical significance. Results A total of 9095 pregnant women had delivered in the last five years, 65 of these pregnant women had been diagnosed with hypothyroidism and 57 were enrolled in our study. Out of 65, 44 (77.2%) were Saudi, and 13 (22.8%) non-Saudis. Mean age at the time of delivery was 32.9 ± 5.6 years, while BMI means were 35.7 ± 4.6. A total of 35 (61.4%) were from class 1, 14 (26.2%) were from class 2 and eight (12.3%) were from class 3. Out of 57, 16 (28.1%) developed undesired antepartum outcomes, while 14 (21.5%) had postpartum outcomes. Preterm labor, gestational diabetes mellitus, and urinary tract infections were significantly associated with abnormal TSH levels (P < 0.05). Conclusion As demonstrated earlier, hypothyroidism during pregnancy leads to unfavorable outcomes. Therefore, screening for thyroid function tests in prenatal and antenatal periods is vital to avoid potential adverse outcomes.
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Khadilkar S. Thyroid-Stimulating Hormone Values in Pregnancy: Cutoff Controversy Continues? J Obstet Gynaecol India 2019; 69:389-394. [PMID: 31598039 DOI: 10.1007/s13224-019-01272-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Accepted: 08/23/2019] [Indexed: 12/14/2022] Open
Abstract
Thyroid disorders in pregnancy are important causes of adverse pregnancy outcome. So it is very pertinent that thyroid function is maintained in normal range during pregnancy. Serum thyroid-stimulating hormone (TSH) value is the best indicator for assessing and monitoring thyroid function. The increasing metabolic demands of pregnancy alter the thyroid physiology in early pregnancy; hence, it becomes necessary to define trimester-specific reference range. Several reports and guidelines have been published recommending varied TSH cutoffs in different studies. The most significant guidelines which created controversy about TSH cutoffs was that of American Thyroid Association (ATA) (Stagnaro-Green et al. in Thyroid 21:1081-1125, 2011) followed by Endocrine Society clinical practice guideline (De Groot et al. in J Clin Endocrinol 97:2543-2565, 2012). Both these gave stricter TSH cutoffs as .1 to 2.5 mIU/L in first trimester, .2 to 3.0 mIU/L in second trimester and .3 to 3 mIU/L in third trimester. Subsequently many reports, meta-analysis and systematic reviews were published which recommended higher cutoffs. With due consideration, ATA revised the guidelines in 2017, recommending the upper cutoff limit .5 mIU/L less than the preconception TSH value or as 4.0 mIU/L when local population-specific reference range is not available (Alexander et al. Thyroid 27(3):315-389, 2017). The controversy is not yet completely resolved specially regarding management of subclinical hypothyroidism. This editorial addresses this ongoing controversy.
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Wu MQ, Liu J, Wang YQ, Yang Y, Yan CH, Hua J. The Impact of Subclinical Hypothyroidism on Adverse Perinatal Outcomes and the Role of Thyroid Screening in Pregnancy. Front Endocrinol (Lausanne) 2019; 10:522. [PMID: 31447778 PMCID: PMC6691141 DOI: 10.3389/fendo.2019.00522] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 07/16/2019] [Indexed: 12/12/2022] Open
Abstract
Subclinical hypothyroidism (SCH) is a mild form of hypothyroidism that is common among women of childbearing age. The impact of SCH on adverse perinatal outcomes is unclear and universal screening for thyroid function before or during pregnancy is also much debated. In the present retrospective cohort study on 7,587 women from Shanghai, we assessed whether SCH was associated with adverse perinatal outcomes. The relationship between the risks of adverse outcomes and the time of screening and LT4 treatment status for SCH were also evaluated. SCH was associated with hypertensive disorders of pregnancy (HDP) [odds ratio (OR): 4.04; 95% confidence interval (CI): 1.85-8.84; P = 0.000]. After classification into four different groups based on the time of screening for thyroid function, the increased likelihood of HDP persisted in those diagnosed with SCH in the first and second trimesters (OR: 9.69; 95% CI: 1.73-54.48; P = 0.01 and OR: 3.66; 95% CI: 1.07-12.57, P = 0.03, respectively). The diagnosis of SCH in the preconception period and the third trimester was not significantly associated with HDP and other adverse perinatal outcomes. Five out of 120 (5/120) treated women (4.17%) vs. 4/45 untreated women (8.89%) developed HDP, 4/5 were treated after conception. The results indicate that during pregnancy, SCH conferred an increased risk of HDP, particularly in women diagnosed with the disorder in the first and second trimesters.
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Affiliation(s)
- Mei-Qin Wu
- MOE, Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jin Liu
- Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
| | - Ya-Qian Wang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Yang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chong-Huai Yan
- MOE, Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Chong-Huai Yan
| | - Jing Hua
- The Women and Children's Health Care Department, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
- Jing Hua
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Homer HA. Modern management of recurrent miscarriage. Aust N Z J Obstet Gynaecol 2018; 59:36-44. [DOI: 10.1111/ajo.12920] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 09/23/2018] [Indexed: 02/06/2023]
Affiliation(s)
- Hayden Anthony Homer
- Christopher Chen Oocyte Biology Research Laboratory, UQ Centre for Clinical Research; The University of Queensland; Brisbane Queensland Australia
- Reproductive Endocrinology & Infertility Clinic; Royal Brisbane & Women's Hospital; Brisbane Queensland Australia
- Queensland Fertility Group and Eve Health; Brisbane Queensland Australia
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