|Year : 2016 | Volume
| Issue : 2 | Page : 79-83
Endocrine dysfunction and recurrent spontaneous abortion: An overview
Ramandeep Kaur1, Kapil Gupta2
1 Centre for Interdisciplinary Biomedical Research, Adesh University, Bathinda, Punjab, India
2 Department of Biochemistry, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab, India
|Date of Submission||01-Sep-2015|
|Date of Acceptance||15-Jan-2016|
|Date of Web Publication||21-Mar-2016|
Department of Biochemistry, Adesh Institute of Medical Sciences and Research, Bathinda, Punjab
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15–20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20th week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus.
Keywords: Hyperandrogenism, hyperprolactinemia, luteal phase defect, polycystic ovarian disease, recurrent spontaneous abortion, thyroid dysfunction
|How to cite this article:|
Kaur R, Gupta K. Endocrine dysfunction and recurrent spontaneous abortion: An overview. Int J App Basic Med Res 2016;6:79-83
|How to cite this URL:|
Kaur R, Gupta K. Endocrine dysfunction and recurrent spontaneous abortion: An overview. Int J App Basic Med Res [serial online] 2016 [cited 2020 Sep 20];6:79-83. Available from: http://www.ijabmr.org/text.asp?2016/6/2/79/179024
| Introduction|| |
Miscarriage or spontaneous abortion is defined as expulsion or extraction of the embryo or fetus weighing <500 g, which is equivalent to approximately 20–22 weeks of gestation. It is the most common complication of early pregnancy. Recurrent spontaneous abortion (RSA) or habitual abortion means three or more clinically recognized pregnancy loses before 20th week of gestational age affecting about 2–4% of reproductive age couples. A pregnancy loss that occurs after a positive human chorionic gonadotropin (hCG) or a raised serum β-hCG, but before ultrasound or histological verification is defined as a biochemical loss occurring before 6 weeks of gestation, whereas the clinical miscarriage is the loss of positive ultrasound examination or histological evidence for intrauterine pregnancy. The rate of pregnancy loss among clinically diagnosed pregnancies is 8–15%. The 80% of miscarriages occur before 12 weeks of gestation, with miscarriage rates decreasing sharply after the first trimester.
RSA is a multifactorial disorder resulting from genetic factors, anatomic factors, autoimmune disorders, endocrine dysfunction, thrombophilia, life style factors, and maternal infections. However, the underlying cause remains undetermined in up to 50% of cases.,
The endocrinology of human pregnancy involves endocrine and metabolic changes that result from physiological alterations at the boundary between mother and fetus; which results in growth and development of the fetus. Although vast majority of pregnant women have no preexisting endocrine abnormalities, a small percentage of women (8–12%) may develop endocrine alterations that could potentially lead to sporadic or recurrent miscarriage.
Literature search was performed using electronic databases, Google scholarly articles, and PubMed (1990–2013). We have included all studies in English found in literature focusing on endocrine abnormalities and its association with spontaneous abortion and RSA. We have used different key words such as endocrine abnormalities, polycystic ovary disease, obesity, hyperinsulinemia, hyperandrogenism, thyroid dysfunction, hyperprolactinemia, luteal phase defect, and these words were combined with spontaneous abortion, miscarriage, recurrent miscarriage, or RSA to generate a set of results. These search results were combined to generate most relevant results for critical appraisal.
The major endocrinal causes of recurrent abortions are polycystic ovarian syndrome (PCOS), obesity, hyperinsulinemia, and insulin resistance (IR) among others [Table 1].
| Polycystic Ovarian Syndrome|| |
PCOS is the most common cause of anovulatory infertility in the developed countries  and most commonly identified abnormality among women with recurrent miscarriage. Spontaneous loss of fetus occurs in 40% women with PCOS  and the underlying cause may include obesity, hyperinsulinemia, IR, hyperandrogenemia, hyperhomocysteinemia, high levels of plasminogen activator inhibitor-1 factor, poor endometrial receptivity, and elevated levels of luteinizing hormone (LH).
| Obesity|| |
Obesity is believed to act on female reproductive function through hyperinsulinemia and on the production of androgen. Maternal obesity has been reported as an independent risk factor for miscarriage, leading to sudden and unexplained intrauterine death  with increased risk in PCOS women receiving infertility treatment. IR may play a key role in explaining the association among obesity, PCOS, and recurrent miscarriages.
| Hyperinsulinemia and Insulin Resistance|| |
Pregestational diabetes, including Type 1 and Type 2 diabetes, complicate up to 1% of all pregnancies. It increases the risk of spontaneous abortion, preterm labor, hypertensive disorders, and operative deliveries. The main underlying cause is lethal embryonic malformations, the prevalence of which increases in the case of poorly controlled diabetes during the periconceptional period.
Women with idiopathic RSA have high fasting insulin and IR. IR is known to play a critical role in the ovarian androgen excess and might promote miscarriage by increasing circulating testosterone concentration, hyperhomocysteinemia, and the increased risk of PCOS. Hyperhomocysteinemia interferes with endometrial blood flow and vascular integrity  resulting in increased oxidative stress in vascular endothelium and so early pregnancy loss. The well-controlled diabetes mellitus is not a risk factor for RSA and attention should first be given to optimal metabolic control of diabetic women during the preconceptional period. Treatment of PCOS patients with metformin decreases IR, thus helps in improving ovulation cycles and therefore conception rates in infertile women. Metformin is also helpful in reducing the risk of miscarriage in women with a history of RSA and abnormal results of glucose tolerance test. Whether metformin is helpful in reducing the risk of miscarriage in PCOS women is yet unclear.
| Hypersecretion of Luteinizing Hormone|| |
It has been reported that hypersecretion of basal LH with or without polycystic ovaries is a risk factor for miscarriage. Raised follicular phase serum LH levels increase the risk of miscarriage following either spontaneous conception  or assisted conception. Elevated urinary LH excretion has been reported in 57% of women with recurrent miscarriage. Deleterious effects of high LH can be reversed by LH suppression using gonadotropin-releasing hormone analogs.
| Hyperandrogenism|| |
Elevated androgens levels are associated with the retardation of endometrial development in luteal phase. An elevated free androgen index (FAI) appears to be a prognostic factor for miscarriage in women with earlier miscarriage and risk increases significantly (FAI >5) during follicular phase, indicating the sensitivity of assessment in this phase.
| Hyperprolactinemia|| |
Prolactin is essential for female reproduction and commonly measured in women with RSA, as elevated prolactin levels are associated with ovulatory dysfunction. Past in vitro studies have shown that prolactin plays a critical role in corpus luteum maintenance and progesterone production in rodents, but not in humans. Moreover, progesterone secretion by cultured granulose cells obtained from human ovarian follicles is almost completely inhibited by high prolactin concentrations (100 ng/ml), but not by lower concentrations (10–20 ng/ml). These observations suggest that high prolactin in early follicular growth may inhibit progesterone secretion, which results in luteal phase defects. Some recent researches on rodents have revealed that prolactin receptors are involved not only in generating, but also in maintaining pregnancy. It has been reported that hyperprolactinemia may occur in a transient manner, around the preovulatory phase. A rise of 200% greater than mid follicular baseline levels at the time of peak follicular maturity indicated transient hyperprolactinemia, associated with unexplained infertility and repeated miscarriages. On the other hand, one study revealed that lower basal serum prolactin concentration is associated with an increased risk of miscarriage in a subsequent pregnancy in women with unexplained recurrent miscarriage. Rate of successful pregnancy is higher in hyperprolactinemic women with RSA who are treated with bromocriptine during randomized control trial (4.6–15.5 ng/ml, P < 0.01 or P < 0.05).
| Luteal Phase Defect|| |
Decreased levels of progesterone are found in women with recurrent pregnancy loss. Progesterone production triggers morphological and physiological changes in the endometrium creating a suitable environment for the embryo during the implantation window. Progesterone also helps in maintaining early pregnancy. It affects proliferation and differentiation of stromal cells, augments uterine receptivity through the modulation of locally acting growth factors, and regulation of cytokine production in maternal fetal interface. Studies on humans and animals suggest that progesterone maintains pregnancy by down regulation of Th1 cytokines and stimulation of Th2 cytokines as Th2 cytokines favor normal pregnancy, while excess of Th1 cytokines leads to termination of pregnancy. In the presence of progesterone, lymphocytes of pregnant women release a 35 kDa protein known as progesterone-induced blocking factor, which in turn alters the profile of cytokine secretion of activated lymphocytes and shift the balance toward Th2 dominance., All these changes fail to occur if progesterone production is lower than the normal minimum. In early pregnancy, the corpus luteum continuously produces progesterone until the luteal placental shift. Luteal phase defect is originally thought to derive from inadequate production of progesterone by the corpus luteum and subsequent inadequate endometrial maturation to allow proper placentation. Abnormalities of the luteal phase defect have been historically reported to occur in up to 35% of women with recurrent pregnancy loss. Serum progesterone levels >10 ng/ml in the mid luteal phase are rarely associated with an abnormal luteal phase, whereas the levels below 12 ng/ml have been associated with an increased risk of miscarriage.
| Thyroid Dysfunction|| |
Thyroid hormones are vital for the development of the brain both during fetal and early postnatal life. Impaired maternal thyroid hormone availability may induce irreversible brain damage with consequent neurological abnormalities. Thyroid hormones also have an impact on oocytes at the level of the granulosa and luteal cells that interfere with normal ovulation.
| Hyperthyroidism|| |
It occurs in approximately 0.1–0.4% of pregnancies. Pregnant women with untreated excess hyperthyroidism are at an increased risk for spontaneous miscarriage, congestive heart failure, thyroid storm, preterm delivery, preeclampsia, fetal growth restriction, and increased perinatal morbidity or mortality. Improved pregnancy outcome has been reported in patients who are treated for overt Graves' hyperthyroidism. However, hyperthyroidism has not commonly been reported as an independent cause of RSA, although one study found that excess exogenous thyroid hormone is associated with an elevated rate of fetal loss.
| Hypothyroidism|| |
In contrast to hyperthyroidism, hypothyroidism is common in pregnancy. It is more prevalent (7%) during pregnancy and there is a statistical significant relationship of hypothyroidism with recurrent pregnancy loss in < 20 weeks of gestation. The most prevalent cause of hypothyroidism in pregnant women, affecting approximately 0.5% of patients is chronic autoimmune thyroiditis. The TSH levels above 6 mIU/ml are significantly associated with higher frequency of still birth  and risk increases by 15% for each 1 mIU/ml elevation. Other causes include endemic iodine deficiency, prior radioactive iodine therapy, and thyroidectomy. Untreated hypothyroidism in pregnancy is associated with an increased risk for adverse pregnancy complications, detrimental effects on fetal neurocognitive development, and decreased fertility. Both overt hypothyroidism and subclinical thyroid dysfunction can have adverse effects on fetal and maternal outcome, but in women with subclinical hypothyroidism, gestational age is low at the time of abortion.
| Thyroid Autoimmunity|| |
Autoimmune thyroid disease is the most frequent cause of hypothyroidism in women of reproductive age, with an overall prevalence of 10–15%. There has been found an association between thyroid autoimmunity (TA) and recurrent abortions, as women with TA has higher prevalence of recurrent miscarriage. Therefore, it has been suggested that thyroid auto antibodies may be employed as a marker for at-risk pregnancies. TA has a positive association with preterm delivery and neonatal respiratory distress syndrome in euthyroid women. Although the mechanism is not completely understood, it is postulated that TA results in early pregnancy loss because of activation of immune system  or act as an infertility factor and results in delayed conception.
| Low Serum Human Chorionic Gonadotropin Levels|| |
hCG is a glycoprotein produced primarily by placenta and peaks at the end of the first trimester of pregnancy. hCG can stimulate the thyroid gland by binding with thyrotropin (TSH) receptor of the thyroid cell membrane during pregnancy due to its structural similarity to TSH, resulting in increased secretion of T4 and T3 and partial suppression of serum TSH. The higher serum hCG concentration is seen in multiple gestation pregnancies and associated with an even greater decrease in TSH. hCG levels are used as a marker for miscarriage; women with low hCG levels are at much higher risk of child loss. On contrary, one study reported that there is no correlation between TSH and hCG levels.
| Conclusion|| |
Factors responsible for recurrent pregnancy loss are multiple, and endocrine dysfunction is one of them. Altered endocrine profile results in loss of pregnancy, especially in the early stages of gestation. There is need of the hour that women expecting a pregnancy must be screened to assess the endocrine profile even before conception to avoid loss of otherwise wanted pregnancy and to improve the health and social well-being of the females.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Baek KH, Lee EJ, Kim YS. Recurrent pregnancy loss: The key potential mechanisms. Trends Mol Med 2007;13:310-7.
Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol 2007;50:132-45.
Jauniaux E, Farquharson RG, Christiansen OB, Exalto N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod 2006;21:2216-22.
Chen BA, Creinin MD. Contemporary management of early pregnancy failure. Clin Obstet Gynecol 2007;50:67-88.
Wang X, Chen C, Wang L, Chen D, Guang W, French J. Conception, early pregnancy loss, and time to clinical pregnancy: A population-based prospective study. Fertil Steril 2003;79:577-84.
Ford HB, Schust DJ. Recurrent pregnancy loss: Etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009;2:76-83.
Feldt-Rasmussen U, Mathiesen ER. Endocrine disorders in pregnancy: Physiological and hormonal aspects of pregnancy. Best Pract Res Clin Endocrinol Metab 2011;25:875-84.
Smith ML, Schust DJ. Endocrinology and recurrent early pregnancy loss. Semin Reprod Med 2011;29:482-90.
Arredondo F, Noble LS. Endocrinology of recurrent pregnancy loss. Semin Reprod Med 2006;24:33-9.
Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000;85:2434-8.
Clifford K, Rai R, Watson H, Regan L. An informative protocol for the investigation of recurrent miscarriage: Preliminary experience of 500 consecutive cases. Hum Reprod 1994;9:1328-32.
Rai R, Backos M, Rushworth F, Regan L. Polycystic ovaries and recurrent miscarriage – A reappraisal. Hum Reprod 2000;15:612-5.
Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin. Hum Reprod 2002;17:2858-64.
Bellver J, Rossal LP, Bosch E, Zúñiga A, Corona JT, Meléndez F, et al.
Obesity and the risk of spontaneous abortion after oocyte donation. Fertil Steril 2003;79:1136-40.
Frøen JF, Arnestad M, Frey K, Vege A, Saugstad OD, Stray-Pedersen B. Risk factors for sudden intrauterine unexplained death: Epidemiologic characteristics of singleton cases in Oslo, Norway, 1986-1995. Am J Obstet Gynecol 2001;184:694-702.
Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: Retrospective study. BMJ 2000;321:1320-1.
Tian L, Shen H, Lu Q, Norman RJ, Wang J. Insulin resistance increases the risk of spontaneous abortion after assisted reproduction technology treatment. J Clin Endocrinol Metab 2007;92:1430-3.
Gabbe SG, Graves CR. Management of diabetes mellitus complicating pregnancy. Obstet Gynecol 2003;102:857-68.
Melamed N, Hod M. Perinatal mortality in pregestational diabetes. Int J Gynaecol Obstet 2009;104 Suppl 1:S20-4.
Gutaj P, Zawiejska A, Wender-Ozegowska E, Brazert J. Maternal factors predictive of first-trimester pregnancy loss in women with pregestational diabetes. Pol Arch Med Wewn 2013;123:21-8.
Ispasoiu CA, Chicea R, Stamatian FV, Ispasoiu F. High fasting insulin levels and insulin resistance may be linked to idiopathic recurrent pregnancy loss: A case-control study. Int J Endocrinol 2013;2013:576926.
Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod 2003;18:721-7.
Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, Rifai N, et al.
Fasting plasma homocysteine levels in the insulin resistance syndrome: The Framingham offspring study. Diabetes Care 2001;24:1403-10.
Quéré I, Mercier E, Bellet H, Janbon C, Marès P, Gris JC. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001;75:823-5.
Nicholson W, Baptiste-Roberts K. Oral hypoglycaemic agents during pregnancy: The evidence for effectiveness and safety. Best Pract Res Clin Obstet Gynaecol 2011;25:51-63.
Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2012;5:CD003053.
Zolghadri J, Tavana Z, Kazerooni T, Soveid M, Taghieh M. Relationship between abnormal glucose tolerance test and history of previous recurrent miscarriages and beneficial effects of metformin in these patients: A prospective clinical study. Fertil Steril 2008;90:727-30.
Regan L, Owen EJ, Jacobs HS. Hypersecretion of luteinising hormone, infertility, and miscarriage. Lancet 1990;336:1141-4.
Homburg R, Armar NA, Eshel A, Adams J, Jacobs HS. Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome. BMJ 1988;297:1024-6.
Madani T, Ashrafi M, Yeganeh LM. Comparison of different stimulation protocols efficacy in poor responders undergoing IVF: A retrospective study. Gynecol Endocrinol 2012;28:102-5.
Okon MA, Laird SM, Tuckerman EM, Li TC. Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function. Fertil Steril 1998;69:682-90.
Cocksedge KA, Saravelos SH, Wang Q, Tuckerman E, Laird SM, Li TC. Does free androgen index predict subsequent pregnancy outcome in women with recurrent miscarriage? Hum Reprod 2008;23:797-802.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7.
Frasor J, Park K, Byers M, Telleria C, Kitamura T, Yu-Lee LY, et al.
Differential roles for signal transducers and activators of transcription 5a and 5b in PRL stimulation of ERalpha and ERbeta transcription. Mol Endocrinol 2001;15:2172-81.
Porter MB, Brumsted JR, Sites CK. Effect of prolactin on follicle-stimulating hormone receptor binding and progesterone production in cultured porcine granulosa cells. Fertil Steril 2000;73:99-105.
Bussen S, Sütterlin M, Steck T. Endocrine abnormalities during the follicular phase in women with recurrent spontaneous abortion. Hum Reprod 1999;14:18-20.
Li W, Ma N, Laird SM, Ledger WL, Li TC. The relationship between serum prolactin concentration and pregnancy outcome in women with unexplained recurrent miscarriage. J Obstet Gynaecol 2013;33:285-8.
Hirahara F, Andoh N, Sawai K, Hirabuki T, Uemura T, Minaguchi H. Hyperprolactinemic recurrent miscarriage and results of randomized bromocriptine treatment trials. Fertil Steril 1998;70:246-52.
Dante G, Vaccaro V, Facchinetti F. Use of progestagens during early pregnancy. Facts Views Vis Obgyn 2013;5:66-71.
Graham JD, Clarke CL. Physiological action of progesterone in target tissues. Endocr Rev 1997;18:502-19.
Kalinka J, Szekeres-Bartho J. The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion. Am J Reprod Immunol 2005;53:166-71.
Szekeres-Bartho J, Balasch J. Progestagen therapy for recurrent miscarriage. Hum Reprod Update 2008;14:27-35.
Arck PC, Rücke M, Rose M, Szekeres-Bartho J, Douglas AJ, Pritsch M, et al.
Early risk factors for miscarriage: A prospective cohort study in pregnant women. Reprod Biomed Online 2008;17:101-13.
Glinoer D. The regulation of thyroid function during normal pregnancy: Importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab 2004;18:133-52.
Wakim AN, Polizotto SL, Buffo MJ, Marrero MA, Burholt DR. Thyroid hormones in human follicular fluid and thyroid hormone receptors in human granulosa cells. Fertil Steril 1993;59:1187-90.
Glinoer D. Thyroid hyperfunction during pregnancy. Thyroid 1998;8:859-64.
Millar LK, Wing DA, Leung AS, Koonings PP, Montoro MN, Mestman JH. Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism. Obstet Gynecol 1994;84:946-9.
Anselmo J, Cao D, Karrison T, Weiss RE, Refetoff S. Fetal loss associated with excess thyroid hormone exposure. JAMA 2004;292:691-5.
Masand D, Patel J. Prevalence of hypothyroidism in unexplained recurrent miscarriages. J Evol Med Dent Sci 2014;3:767-77.
Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ, et al.
Maternal thyroid deficiency and pregnancy complications: Implications for population screening. J Med Screen 2000;7:127-30.
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. J Clin Endocrinol Metab 2010;95:E44-8.
Wasserstrum N, Anania CA. Perinatal consequences of maternal hypothyroidism in early pregnancy and inadequate replacement. Clin Endocrinol (Oxf) 1995;42:353-8.
De Vivo A, Mancuso A, Giacobbe A, Moleti M, Maggio Savasta L, De Dominici R, et al.
Thyroid function in women found to have early pregnancy loss. Thyroid 2010;20:633-7.
Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol (Oxf) 2007;66:309-21.
Lata K, Dutta P, Sridhar S, Rohilla M, Srinivasan A, Prashad GR, et al.
Thyroid autoimmunity and obstetric outcomes in women with recurrent miscarriage: A case-control study. Endocr Connect 2013;2:118-24.
Marai I, Carp H, Shai S, Shabo R, Fishman G, Shoenfeld Y. Autoantibody panel screening in recurrent miscarriages. Am J Reprod Immunol 2004;51:235-40.
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Thyroid antibody positivity in the first trimester of pregnancy is associated with negative pregnancy outcomes. J Clin Endocrinol Metab 2011;96:E920-4.
Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990;264:1422-5.
Lejeune B, Grun JP, de Nayer P, Servais G, Glinoer D. Antithyroid antibodies underlying thyroid abnormalities and miscarriage or pregnancy induced hypertension. Br J Obstet Gynaecol 1993;100:669-72.
Fantz CR, Dagogo-Jack S, Ladenson JH, Gronowski AM. Thyroid function during pregnancy. Clin Chem 1999;45:2250-8.
Glinoer D, De Nayer P, Robyn C, Lejeune B, Kinthaert J, Meuris S. Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy. J Endocrinol Invest 1993;16:881-8.
la Marca A, Morgante G, De Leo V. Human chorionic gonadotropin, thyroid function, and immunological indices in threatened abortion. Obstet Gynecol 1998;92:206-11.
|This article has been cited by|
||Maternal Testosterone Excess Contributes to Reproductive System Dysfunction of Female Offspring Mice
| ||Yu Zhou,Anhong Zhang,Min Gong,Yingfei Lu,Chengcheng Zhao,Xia Shen,Xiaomei Zhang,Lin Wang,Jianquan Chen,Rong Ju |
| ||Endocrinology. 2020; 161(5) |
|[Pubmed] | [DOI]|
||Association of IL-1ß, IL-6, TNF-a, and TGFß1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome
| ||Afrah F. Alkhuriji,Suliman Y. Al Omar,Zainb A. Babay,Manal F. El-khadragy,Lamjed A. Mansour,Wazirah G. Alharbi,Mahmoud I. Khalil |
| ||Disease Markers. 2020; 2020: 1 |
|[Pubmed] | [DOI]|
||Relationship between gestational risk and type of delivery in high risk pregnancy
| ||Marcos Benatti Antunes,Robson Marcelo Rossi,Sandra Marisa Pelloso |
| ||Revista da Escola de Enfermagem da USP. 2020; 54 |
|[Pubmed] | [DOI]|
||LncRNA HULC Polymorphism Is Associated With Recurrent Spontaneous Abortion Susceptibility in the Southern Chinese Population
| ||Zhenzhen Fang,Yanfang Yang,Yufen Xu,Hanran Mai,Wanqi Zheng,Lei Pi,Lanyan Fu,Huazhong Zhou,Yaqian Tan,Di Che,Xiaoqiong Gu |
| ||Frontiers in Genetics. 2019; 10 |
|[Pubmed] | [DOI]|
||CRY2 suppresses trophoblast migration and invasion in recurrent spontaneous abortion
| ||Lianzhi Wu,Biheng Cheng,Qian Liu,Ping Jiang,Jing Yang |
| ||The Journal of Biochemistry. 2019; |
|[Pubmed] | [DOI]|
||Obesity and reproductive function of women: epigenetic and somato-psychological features.
| ||Elena Nikolaevna Andreeva,Yulia Sergeevna Absatarova,Ekaterina Viktorovna Sheremetyeva,Valentina Alekseevna Fursenko |
| ||Obesity and metabolism. 2019; |
|[Pubmed] | [DOI]|
||The lncRNA MALAT1 rs619586 G Variant Confers Decreased Susceptibility to Recurrent Miscarriage
| ||Di Che,Yanfang Yang,Yufen Xu,Zhenzhen Fang,Lei Pi,LanYan Fu,Huazhong Zhou,Yaqian Tan,Zhaoliang Lu,Li Li,Qihua Liang,Qingshan Xuan,Xiaoqiong Gu |
| ||Frontiers in Physiology. 2019; 10 |
|[Pubmed] | [DOI]|
||Early miscarriage rate in lean polycystic ovary syndrome women after euploid embryo transfer – a matched-pair study
| ||Lu Luo,Fang Gu,Huying Jie,Chenhui Ding,Qiang Zhao,Qiong Wang,Canquan Zhou |
| ||Reproductive BioMedicine Online. 2017; |
|[Pubmed] | [DOI]|
||Cell cycle and histone modification genes were decreased in placenta tissue from unexplained early miscarriage
| ||Yuanchang Zhu,Bing Li,Tonghua Wu,Lijun Ye,Yong Zeng,Yaou Zhang |
| ||Gene. 2017; 636: 17 |
|[Pubmed] | [DOI]|
||Is the incidence of recurrent pregnancy loss increasing? A retrospective register-based study in Sweden
| ||Emma Rasmark Roepke,Leif Matthiesen,Rebecca Rylance,Ole Bjarne Christiansen |
| ||Acta Obstetricia et Gynecologica Scandinavica. 2017; |
|[Pubmed] | [DOI]|
||Insulin resistance in patients with recurrent pregnancy loss is associated with lymphocyte population aberration
| ||Yan Yan,Shihua Bao,Shile Sheng,Liuliu Wang,Weiyan Tu |
| ||Systems Biology in Reproductive Medicine. 2017; : 1 |
|[Pubmed] | [DOI]|
||Genetic variation in the progesterone receptor gene and susceptibility to recurrent pregnancy loss: a case-control study
| ||W Bahia,RR Finan,M Al-Mutawa,A Haddad,A Soua,F Janhani,T Mahjoub,WY Almawi |
| ||BJOG: An International Journal of Obstetrics & Gynaecology. 2017; |
|[Pubmed] | [DOI]|
||Maternal genetic polymorphisms and unexplained recurrent miscarriage: a systematic review and meta-analysis
| ||X. Shi,X. Xie,Y. Jia,S. Li |
| ||Clinical Genetics. 2016; |
|[Pubmed] | [DOI]|
||Reproductive dysfunctions in viral hepatitis
| ||A. M. Kurmanova,G. M. Kurmanova,V. N. Lokshin |
| ||Gynecological Endocrinology. 2016; 32(sup2): 37 |
|[Pubmed] | [DOI]|