Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey

Christianson, Mindy S.; Wu, Harold; Zhao, Yulian; Yemini, Matan; Leong, Milton; Shoham, Zeev

doi:10.1007/s10815-014-0414-x

Cited by 14 publications

(13 citation statements)

References 26 publications

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“…christianson, a.P. cheng [27,28] в своих исследованиях отмечают, что применение метформина при индукции овуляции снижает суммарную дозу гонадотропинов и повышает частоту наступления беременности. Большей части пациенток (42) была проведена контролируемая стимуляция суперовуляции рекомбинантным фолликулостимулирующим гормоном в программе ЭКО и ЭКО/иКси в протоколе с применением антагонистов гонадотропин-рилизинг-гормона.…”

Section: Retrospective Analysis Of Pregnancies Resulted From Assistedunclassified

Retrospective analysis of pregnancies resulted from assisted reproductive technology in women with type 2 diabetes mellitus

et al. 2019

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Hypothesis/aims of study. Type 2 diabetes mellitus (T2D) is one of the most widespread diseases in the world. The etiology of this disease is associated with genetic, age and ethnic factors. It is generally accepted that a sedentary lifestyle and obesity can cause T2D. This illness has serious complications that affect the women’s health and quality of life. It is well known that obesity and T2D are a common cause of anovulatory infertility in women of reproductive age. The number of T2D patients who are planning pregnancy by assisted reproductive technology (ART) has increased over the past 10 years. This study was aimed at investigating the effect of carbohydrate metabolism compensation in the preconception period on the outcomes of pregnancies resulted from in vitro fertilization (IVF) in T2DM women. Study design, materials, and methods. 51 T2D pregnancies after ART and their outcomes were analyzed retrospectively. Results. The age of the patients who applied to ART departments ranged from 27 to 46 years. The mean body mass index was 33.9 ± 6.5 kg/m2. The duration of infertility varied from 3 to 18 years. Infertility was caused by tubal occlusion in 17 cases, by anovulation in 16 cases, by male factor in 9 cases, by genital endometriosis in 7 cases, and by hypergonadotropic hypogonadism in 2 cases. One of the patients underwent IVF procedure twice in 4 years. All T2D patients received prepregnancy care including weight loss, diabetes compensation, diabetes complications treatment, and, if necessary, a transfer to insulin therapy and insulin treatment education for 1–2 months before entering into the IVF protocol. Angiotensin-converting enzyme inhibitors and statins should be stopped if they were prescribed in case of hypertension or dyslipidemia and other medications allowed during pregnancy should be started. 26 women (51%) did not take periconceptional multivitamin supplementation before IVF procedure. The level of glycated hemoglobin (HbA1c) in this group was 6.4 ± 0.5%. 25 patients (49%) underwent incomplete preparation for pregnancy before entering into the IVF protocol but not in full. An important stage of prepregnancy care was weight loss in women with overweight and obesity. The duration of a prepregnancy care program varied from 2 to 6 months and on average was 3.8 ± 1.7 months. The mean HbA1c level in this group was 5.8 ± 0.4%. All cases of IVF pregnancies in women with T2D resulted with live birth. The incidence of preeclampsia, cesarean section delivery, and preterm labor was lower in the group of women who had been given prepregnancy care. Conclusion. Proper prepregnancy care including weight loss, diabetes compensation, early start of insulin therapy, and diabetes complications treatment before conception is an effective method of preventing perinatal complications in women with T2D.

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Section: Retrospective Analysis Of Pregnancies Resulted From Assistedunclassified

Retrospective analysis of pregnancies resulted from assisted reproductive technology in women with type 2 diabetes mellitus

et al. 2019

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“…In the IVF setting, metformin has a beneficial effect by increasing pregnancy rates and decreasing miscarriages [71]. We have discussed the concept before that augmenting energy production might be better than inhibiting it with drugs that act as inhibitors on mitochondrial function such as the biguanidine metformin.…”

Section: What Should Be Done Next?mentioning

confidence: 99%

Why AMPK agonists not known to be stressors may surprisingly contribute to miscarriage or hinder IVF/ART

Puscheck

Bolnick

Awonuga

et al. 2018

J Assist Reprod Genet

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Here we examine recent evidence suggesting that many drugs and diet supplements (DS), experimental AMP-activated protein kinase (AMPK) agonists as well as energy-depleting stress, lead to decreases in anabolism, growth or proliferation, and potency of cultured oocytes, embryos, and stem cells in an AMPK-dependent manner. Surprising data for DS and drugs that have some activity as AMPK agonists in in vitro experiments show possible toxicity. This needs to be balanced against a preponderance of evidence in vivo that these drugs and DS are beneficial for reproduction. We here discuss and analyze data that leads to two possible conclusions: First, although DS and drugs that have some of their therapeutic mechanisms mediated by AMPK activity associated with low ATP levels, some of the associated health problems in vivo and in vitro fertilization/assisted reproductive technologies (IVF/ART) may be better-treated by increasing ATP production using CoQ10 (Ben-Meir et al., Aging Cell 14:887-895, 2015). This enables high developmental trajectories simultaneous with solving stress by energy-requiring responses. In IVF/ART, it is ultimately best to maintain handling and culture of gametes and embryos in the quietest state with low metabolic activity (Leese et al., Mol Hum Reprod 14:667-672, 2008; Leese, Bioessays 24 (9):845-849, 2002) using back-to-nature or simplex algorithms to identify optima (Biggers, Reprod Biomed Online 4 Suppl 1:30-38, 2002). Stress markers, such as checkpoint proteins like TRP53 (aka p53) (Ganeshan et al., Exp Cell Res 358:227-233, 2017); Ganeshan et al., Biol Reprod 83:958-964, 2010) and a small set of kinases from the protein kinome that mediate enzymatic stress responses, can also be used to define optima. But, some gametes or embryos may have been stressed in vivo prior to IVF/ART or IVF/ART optimized for one outcome may be suboptimal for another. Increasing nutrition or adding CoQ10 to increase ATP production (Yang et al., Stem Cell Rev 13:454-464, 2017), managing stress enzyme levels with inhibitors (Xie et al., Mol Hum Reprod 12:217-224, 2006), or adding growth factors such as GM-CSF (Robertson et al., J Reprod Immunol 125:80-88, 2018); Chin et al., Hum Reprod 24:2997-3009, 2009) may increase survival and health of cultured embryos during different stress exposure contexts (Puscheck et al., Adv Exp Med Biol 843:77-128, 2015). We define "stress" as negative stimuli which decrease normal magnitude and speed of development, and these can be stress hormones, reactive oxygen species, inflammatory cytokines, or physical stimuli such as hypoxia. AMPK is normally activated by high AMP, commensurate with low ATP, but it was recently shown that if glucose is present inside the cell, AMPK activation by low ATP/high AMP is suppressed (Zhang et al., Nature 548:112-116, 2017). As we discuss in more detail below, this may also lead to greater AMPK agonist toxicity observed in two-cell embryos that do not import glucose. Stress in embryos and stem cells increases AMPK in large stimulation indexes but also dir...

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“…Weltweit wird Metformin als Begleitmedikament bei der ART-Behandlung erfolgreich eingesetzt, um die Schwangerschaftsraten zu steigern, das Risiko für Aborte zu senken und somit die Lebendgeburtenrate zu erhöhen [9,30] [29]. Ab der dritten SSW überweisen wir bei auffälliger GDM-Testung im Sinne eines GDM oder eines manifesten DM in der Schwangerschaft entsprechend Leitlinie tagesgleich oder am folgenden Werktag an eine DSP zu einem Notfalltermin.…”

Section: Stoffwechselkontrolle Im Art-zyklusunclassified

Glukosestoffwechsel und assistierte Reproduktion

Bals‐Pratsch

Malfertheiner

2017

Gynäkologische Endokrinologie

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Metformin use in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey

Abstract: While metformin is used worldwide as an adjunct to standard IVF protocols, there is much variation in its use and the majority of centers report lack of evidence supporting its use.

Cited by 14 publications

References 26 publications

Retrospective analysis of pregnancies resulted from assisted reproductive technology in women with type 2 diabetes mellitus

Retrospective analysis of pregnancies resulted from assisted reproductive technology in women with type 2 diabetes mellitus

Why AMPK agonists not known to be stressors may surprisingly contribute to miscarriage or hinder IVF/ART

Glukosestoffwechsel und assistierte Reproduktion

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