Effects of in Vitro Fertilization (IVF) Therapies on Metabolic, Endocrine and Inflammatory Status in IVF-Conceived Pregnancy

Ayla Coussa; Hayder A. Hasan; Thomas M. Barber

Disclosures

Clin Endocrinol. 2020;93(6):705-712. 

In This Article

Abstract and Introduction

Abstract

Rationale: In vitro fertilization (IVF) is a common treatment for infertility. In mice, IVF is associated with development of glucose intolerance. However, human data are limited regarding the metabolic, endocrine and inflammatory effects of IVF therapy in IVF-conceived pregnancies.

Objective: To explore effects of IVF therapies on metabolic, endocrine and inflammatory parameters in IVF-conceived pregnancy.

Methodology: Twelve-week prospective observational study of adult normoglycaemic women, BMI 18.5–38 kg/m2 and ≤ 39 years awaiting IVF therapy. Fasting blood samples were collected at baseline and 12 weeks, and serum analysed for reproductive hormones, glucose, lipids, insulin sensitivity, thyroid status, adiponectin inflammatory marker and lipopolysaccharide-binding protein (LBP).

Results: Two hundred and seventy-five women were analysed: 158 IVF-conceived pregnant women and 117 with failed IVF. Compared with baseline, nonpregnant women had significant (P < .001) increases in 12-week glucose (86.04–87.62 mg/dL), insulin (8.72–9.37 μIU/mL), HOMA-IR (1.9–2.1), T-Chol (169.5–174.9 mg/dL), TG (71.0–83.7 mg/dL) and HDL-C (52.0–54.11 mg/dL) levels. At 12 weeks, pregnant women also had (P < .001) increases in T-Chol (177.5–199.5 mg/dL), TG (73.5–126.78 mg/dL) and HDL-C (55.3–65.1 mg/dL), while a significant reduction in glucose (86.15–82.19 mg/dL), HbA1c (5.3–5.08%) and TSH (1.71–1.36 μIU/mL) levels from baseline. Adiponectin and LBP levels remained the same in either group.

Conclusion: In vitro fertilization hormonal therapy impairs glucose and insulin levels; these effects are masked in early pregnancy. Changes in lipid profile occur following IVF therapies regardless of pregnancy outcome. Neither adiponectin nor LBP is affected by IVF therapies and during early IVF-conceived pregnancy.

Introduction

Infertility is a growing health concern and affects 20% of couples of reproductive age.[1] Accordingly, assisted reproductive technologies have emerged as important therapeutic options for the management of infertility, primarily in vitro fertilization (IVF).[2] Similar in composition to IVF, long-term usage of oral contraceptive hormones (based on oestrogen and progesterone) associates with adverse effects on metabolic, endocrine and inflammatory status, changes in gut microflora and gastrointestinal side effects.[3] However, IVF therapies constitute much higher doses but shorter exposure duration to these hormones and their safety on both maternal and foetal outcomes remains incompletely understood.[4,5]

Pregnancy is characterized by hormonal-driven changes with consequences on metabolic, endocrine and inflammatory status and possibly on gut microflora. Insulin sensitivity deteriorates starting from the second trimester and subsequent hyperinsulinemia.[6] Metabolic response to oral contraceptive therapies bear similarities to those that occur during the second trimester of pregnancy.[7,8] Furthermore, in mice IVF therapy is associated with development of glucose intolerance.[9] Reproductive hormonal therapies also alter thyroid function with increased serum thyroxine-binding globulin and total serum thyroxine levels; a comparable effect is seen during pregnancy.[10,11] Additionally, increase in lipid profile occurs normally mid-pregnancy[12] and with contraceptives use.[7]

Physiological changes of pregnancy may also induce micro-inflammation and synthesis of inflammatory markers;[13] a similar effect was observed in obese women on oral contraceptive therapies.[14] Inflammation (as a stressor) increases permeability of the gut lining;[15] a surrogate marker of gut endotoxemia is lipopolysaccharide-binding protein (LBP). LBP binds bacterial compounds, including lipopolysaccharides (LPS; outer membrane component of gram-negative bacteria of the gut). Similarly, long-term use of oral contraceptives impairs gut permeability, with enhanced levels of LBP and LPS signalling and associated cytokine-mediated inflammatory diseases.[16] Adiponectin is another anti-inflammatory and insulin sensitizer marker, which gradually declines in pregnancy.[17]

Given the high doses of IVF hormones combined with gestational hormones, physiological changes may hence be manifested earlier in IVF-conceived pregnancies. The aim of this study was to assess metabolic, endocrine and inflammatory effects of IVF hormonal therapies within 12 weeks following its administration in the two groups: women with successful IVF-conceived pregnancy and women with failed IVF.

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