Impact of contraception and IVF hormones on metabolic, endocrine, and inflammatory status

Ayla Coussa, Hayder A Hasan, Thomas M Barber, Ayla Coussa, Hayder A Hasan, Thomas M Barber

Abstract

Assisted reproductive technologies (ART) represent commonly utilized management strategies for infertility with multifactorial causes (including genetically predisposed diseases). Amongst ART, in vitro fertilization (IVF) is the most popular. IVF treatment may predispose the mother to increased risks and complications during pregnancy, and there may be adverse fetal outcomes. Hormonal therapies, including oral contraceptives, may impair glucose and lipid metabolism, and promote insulin resistance and inflammation. IVF treatment involves administration of reproductive hormones, similar in composition but in much higher doses than those used for oral contraception. The provision of IVF reproductive hormones to mice associates with glucose intolerance. In addition, the physiological and hormonal changes of pregnancy can trigger an inflammatory response, and metabolic and endocrine changes. There is controversy regarding the potential effects of IVF hormonal therapies in the promotion of diabetogenic and inflammatory states, additional to those that occur during pregnancy, and which may therefore predispose women with IVF-conceived pregnancies to adverse obstetric outcomes compared with women with spontaneously conceived pregnancies. This review summarizes the limited published evidence regarding the effect of IVF-based fertility therapies on glucose homeostasis, insulin resistance, cardio-metabolic profile, and markers of inflammation.

Keywords: Assisted reproduction; Gestational diabetes; IVF; Infertility; Pregnancy.

Conflict of interest statement

The authors declare that they have no conflict of interest.

References

    1. American Society For Reproductive Medicine (ASRM). Infertility: an overview; a guide for patients. Birmingham, Alabama (US); 2012 [cited 2017 Nov 10]. pp 1–20. Available from:
    1. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13(1):1–9.
    1. American Society for Reproductive Medicine (ASRM). Assisted reproductive technology: a guide for patients. 2015 [cited 2018 Oct 28]. pp 3–32. Available from:
    1. Balen AH, Morley LC, Misso M, Franks S, Legro RS, Wijeyaratne CN, Stener-Victorin E, Fauser BC, Norman RJ, Teede H. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22(6):687–708.
    1. Rothberg A, Lanham M, Randolph J, Fowler C, Miller N, Smith Y. Feasibility of a brief, intensive weight loss intervention to improve reproductive outcomes in obese, subfertile women: a pilot study. Fertil Steril Ò. 2016;106(5):1212–1232.
    1. Poppe K, Velkeniers B. Female infertility and the thyroid. Best Pract Res Clin Endocrinol Metab. 2004;18(2):153–165.
    1. Pfeifer S, Butts S, Fossum G, Gracia C, La Barbera A, Mersereau J, et al. Optimizing natural fertility: a committee opinion. Fertil Steril. 2017;107(1):52–58.
    1. Källén B, Finnström O, Nygren KG, Otterblad Olausson P, Wennerholm UB. In vitro fertilisation in Sweden: obstetric characteristics, maternal morbidity and mortality. BJOG Int J Obstet Gynaecol. 2005;112(11):1529–1535.
    1. Wright VC, Schieve LA, Reynolds MA, Jeng G. Assisted reproductive technology surveillance—United States, 2002. Morb Mortal Wkly Rep Surveill Summ. 2005;54(2):1–24.
    1. Kozinszky Z, Zádori J, Orvos H, Katona M, Pál A, Kovács L. Obstetric and neonatal risk of pregnancies after assisted reproductive technology: a matched control study. Acta Obstet Gynecol Scand. 2003;82(9):850–856.
    1. Long L, Liren HE, Chuan YE, Yuyan LI, Wei HE. Maternal and neonatal perinatal outcomes in pregnancies after in vitro fertilization and natural pregnancy: a systematic: a meta analysis. Chongqing Med. 2017;46(16):2228–2232.
    1. Ramsay M, Parameshwaran S. Maternal medical complications in pregnancy following assisted reproductive technology. Clin Manag Pregnancies Follow ART. 2017:157–72.
    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(4):1430–1433.
    1. Kathpalia SK, Kapoor K, Sharma A. Complications in pregnancies after in vitro fertilization and embryo transfer. Med J Armed Forces India. 2016;72(3):211–214.
    1. Zhu L, Zhang Y, Liu Y, Zhang R, Wu Y, Huang Y, Zhu Y. Maternal and live-birth outcomes of pregnancies following assisted reproductive technology: a retrospective cohort study. Sci Rep. 2016;6(35141):1–11.
    1. Ensing S, Abu-Hanna A, Roseboom TJ, Repping S, Van Der Veen F, Mol BWJ, et al. Risk of poor neonatal outcome at term after medically assisted reproduction: a propensity score-matched study. Fertil Steril. 2015;104(2):1–8.
    1. Ombelet W, Martens G, Bruckers L. Pregnant after assisted reproduction: a risk pregnancy is born! 18-years perinatal outcome results from a population-based registry in Flanders, Belgium. Facts Views Vis ObGyn. 2016;8(4):1–19.
    1. Dayan N, Fell DB, Guo Y, Wang H, Velez MP, Spitzer K. Laskin CA. Severe maternal morbidity in women with high BMI in IVF and unassisted singleton pregnancies. Hum Reprod. 2018;33(8):1548–1556.
    1. Kessous R, Davidson E, Meirovitz M, Sergienko R, Sheiner E. The risk of female malignancies after fertility treatments: a cohort study with 25-year follow-up. J Cancer Res Clin Oncol. 2016;142(1):287–293.
    1. Shevell T, Malone FD, Vidaver J, Porter TF, Luthy DA, Comstock CH, et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol. 2005;106(5):1039–1045.
    1. Schieve LA, Cohen B, Nannini A, Ferre C, Reynolds MA, Zhang Z, Jeng G, Macaluso M, Wright VC, Massachusetts Consortium for Assisted Reproductive Technology Epidemiologic Research (MCARTER) A population-based study of maternal and perinatal outcomes associated with assisted reproductive technology in Massachusetts. Matern Child Health J. 2007;11(6):517–525.
    1. Ochsenkühn R, Strowitzki T, Gurtner M, Strauss A, Schulze A, Hepp H, Hillemanns P. Pregnancy complications, obstetric risks, and neonatal outcome in singleton and twin pregnancies after GIFT and IVF. Arch Gynecol Obstet. 2003;268(4):256–261.
    1. Setti P, Moioli M, Smeraldi A, Cesaratto E, Menduni F, Livio S, et al. Obstetric outcome and incidence of congenital anomalies in 2351 IVF/ICSI babies. J Assist Reprod Genet. 2016;33(6):711–717.
    1. Chen M, Norman RJ, Heilbronn LK. Does in vitro fertilisation increase type 2 diabetes and cardiovascular risk? Curr Diabetes Rev. 2011;7(6):426–432.
    1. Sonagra AD, Biradar SM, Dattatreya K, DS JM. Normal pregnancy-a state of insulin resistance. J Clin Diagn Res. 2014;8(11):1–3.
    1. Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr. 2000;71(5):1256S–1261S.
    1. Di Cianni G, Miccoli R, Volpe L, Lencioni C, Del Prato S. Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev. 2003;19(4):259–270.
    1. McLachlan KA, O’Neal D, Jenkins A, Alford FP. Do adiponectin, TNFα, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with or without gestational diabetes, during and after pregnancy. Diabetes Metab Res Rev. 2006;22(23):131–138.
    1. Diamanti-Kandarakis E, Baillargeon JP, Iuorno MJ, Jakubowicz DJ, Nestler JE. A modern medical quandary: polycystic ovary syndrome, insulin resistance, and oral contraceptive pills. J Clin Endocrinol Metab. 2003;88(5):1927–1932.
    1. Adeniji AA, Essah PA, Nestler JE, Cheang KI. Metabolic effects of a commonly used combined hormonal oral contraceptive in women with and without polycystic ovary syndrome. J Women’s Health. 2016;25(6):638–645.
    1. Espeland MA, Hogan PE, Fineberg SE, Howard G, Schrott H, Waclawiw MA. Effect of postmenopausal hormone therapy on glucose and insulin concentrations. Diabetes Care. 1998;21(10):1589–1595.
    1. Melhado-Kimura V, Alegre SM, Pavin EJ, Dos Santos PDNS, Bahamondes L, Fernandes A. High prevalence of insulin resistance assessed by the glucose clamp technique in hormonal and non-hormonal contraceptive users. Eur J Contracept Reprod Health Care. 2015;20(2):110–118.
    1. Simbulan RK, Liu X, Feuer SK, Maltepe E, Donjacour A, Rinaudo P. Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue. J Dev Orig Health Dis. 2016;7(1):73–82.
    1. Robinson S, Pemberton P, Laing I, Nardo LG. Low grade inflammation, as evidenced by basal high sensitivity CRP, is not correlated to outcome measures in IVF. J Assist Reprod Genet. 2008;25(8):383–388.
    1. Christiansen OB, Nielsen HS, Kolte AM. Inflammation and miscarriage. Semin Fetal Neonatal Med. 2006;11(5):302–308.
    1. Van Rooijen M, Hansson LO, Frostegård J, Silveira A, Hamsten A, Bremme K. Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response. J Thromb Haemost. 2006;4(1):77–82.
    1. Williams MJA, Williams SM, Milne BJ, Hancox RJ, Poulton R. Association between C-reactive protein, metabolic cardiovascular risk factors, obesity and oral contraceptive use in young adults. Int J Obes. 2004;28(8):998–1003.
    1. Sahu S, Abraham REBECCA, Vedavalli R, Daniel MARY. Study of lipid profile, lipid peroxidation and vitamin E in pregnancy induced hypertension. Indian J Physiol Pharmacol. 2009;53(4):365–369.
    1. Vrijkotte TG, Krukziener N, Hutten BA, Vollebregt KC, Van Eijsden M, Twickler MB. Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study. J Clin Endocrinol Metab. 2012;97(11):3917–3925.
    1. De J, Mukhopadhyay A, Saha PK. Study of serum lipid profile in pregnancy induced hypertension. Indian J Clin Biochem. 2006;21(2):165–168.
    1. Lippi G, Albiero A, Montagnana M, Salvagno GL, Scevarolli S, Franchi M, Guidi GC. Lipid and lipoprotein profile in physiological pregnancy. Clin Lab. 2007;53(3–4):173–178.
    1. Kowalska K, Ściskalska M, Bizoń A, Śliwińska-Mossoń M, Milnerowicz H. Influence of oral contraceptives on lipid profile and paraoxonase and commonly hepatic enzymes activities. J Clin Lab Anal. 2018;32(1):1–7.
    1. Oubeid WS, Salih HH, Hadry DH, Jasim NA. Effect of using combined oral contraceptive on thyroid hormones and lipid profile in female. Tikrit J Pharm Sci. 2017;12(2):2017.
    1. Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med. 2016;8(1):1–12.
    1. Utzschneider KM, Kratz M, Damman CJ, Hullarg M. Mechanisms linking the gut microbiome and glucose metabolism. J Clin Endocrinol Metab. 2016;101(4):1445–1454.
    1. Liang H, Hussey SE, Sanchez-Avila A, Tantiwong P, Musi N. Effect of lipopolysaccharide on inflammation and insulin action in human muscle. PLoS One. 2013;8(5):1–7.
    1. Mokkala K, Pellonperä O, Röytiö H, Pussinen P, Rönnemaa T, Laitinen K. Increased intestinal permeability, measured by serum zonulin, is associated with metabolic risk markers in overweight pregnant women. Metabolism. 2017;69:43–50.
    1. De Punder K, Pruimboom L. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability. Front Immunol. 2015;6(223):1–12.
    1. Vieira AT, Castelo PM, Ribeiro DA, Ferreira CM. Influence of oral and gut microbiota in the health of menopausal women. Front Microbiol. 2017;8(1884):1–7.
    1. Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Bäckhed HK, Gonzalez A, Werner JJ, Angenent LT, Knight R, Bäckhed F, Isolauri E, Salminen S, Ley RE. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. 2012;150(3):470–480.
    1. Cornish JA, Tan E, Simillis C, Clark SK, Teare J, Tekkis PP. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis magnets for surgery view project optical biopsy view project. Am J Gastroenterol. 2008;103(9):1–7.
    1. Kim JJ, Sears DD. TLR4 and insulin resistance. Gastroenterol Res Pract. 2010;2010:1–11.
    1. Khalili H. Risk of inflammatory bowel disease with oral contraceptives and menopausal hormone therapy: current evidence and future directions. Drug Saf. 2016;39(3):193–197.
    1. Aghahosseini M, Asgharifard H, Aleyasin A, Banihashemi AT. Effects of thyroid stimulating hormone (TSH) level on clinical pregnancy rate via in vitro fertilization (IVF) procedure. Med J Islam Repub Iran. 2014;28(46).
    1. Glinoer D. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev. 1997;18(3):404–433.
    1. Santin AP, Furlanetto TW. Role of estrogen in thyroid function and growth regulation. J Thyroid Res. 2011;2011:1–7.
    1. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017;27(3):315–389.
    1. Lazarus JH. Thyroid function in pregnancy. Br Med Bull. 2010;97(1):137–148.
    1. Ryan EA, Ennis L. Role of gestational hormones in the induction of insulin resistance. J Clin Endocrinol Metab. 1988;67(2):341–347.
    1. Gizzo S, Noventa M, Quaranta M, Vitagliano A, Esposito F, Andrisani A, Venturella R, Alviggi C, Plebani M, Gangemi M, Nardelli GB, D’Antona D. The potential role of GnRH agonists and antagonists in inducing thyroid physiopathological changes during IVF. Reprod Sci. 2016;23(4):515–523.

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