Placental passage of metformin in women with polycystic ovary syndrome

Vanky, Eszter; Zahlsen, Kolbjørn; Spigset, Olav; Carlsen, Sven Magnus

doi:10.1016/j.fertnstert.2004.11.051

Cited by 211 publications

(149 citation statements)

References 11 publications

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“…Recent studies have shown that Met is significantly higher in umbilical arterial and venous plasma than in maternal plasma [92], suggesting that Met crosses the placenta and accesses the embryo and its stem cells after implantation. The earliest postimplantation human embryo in the trophoblast plate stage and lacunar stage has direct access to maternal capillary plasma, which surrounds the embryo [93,94].…”

Section: Discussionmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

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Purpose The purpose of the present study is to test whether metformin, aspirin, or diet supplement (DS) BioResponse-3, 3′-Diindolylmethane (BR-DIM) can induce AMP-activated protein kinase (AMPK)-dependent potency loss in cultured embryos and whether metformin (Met) + Aspirin (Asa) or BR-DIM causes an AMPK-dependent decrease in embryonic development. Methods The methods used were as follows: culture post-thaw mouse zygotes to the two-cell embryo stage and test effects after 1-h AMPK agonists' (e.g., Met, Asa, BR-DIM, control hyperosmotic stress) exposure on AMPK-dependent loss of Oct4 and/or Rex1 nuclear potency factors, confirm AMPK dependence by reversing potency loss in two-cell-stage embryos with AMPK inhibitor compound C (CC), test whether Met + Asa (i.e., co-added) or DS BR-DIM decreases development of two-cell to blastocyst stage in an AMPK-dependent (CCsensitive) manner, and evaluate the level of Rex1 and Oct4 nuclear fluorescence in two-cell-stage embryos and rate of two-cell-stage embryo development to blastocysts. Result(s) Met, Asa, BR-DIM, or hyperosmotic sorbitol stress induces rapid~50-85 % Rex1 and/or Oct4 protein loss in twocell embryos. This loss is~60-90 % reversible by co-culture with AMPK inhibitor CC. Embryo development from twocell to blastocyst stage is decreased in culture with either Met + Asa or BR-DIM, and this is either >90 or~60 % reversible with CC, respectively. Conclusion These experimental designs here showed that Met-, Asa-, BR-DIM-, or sorbitol stress-induced rapid potency loss in two-cell embryos is AMPK dependent as suggested by inhibition of Rex1 and/or Oct4 protein loss with an AMPK inhibitor. The DS BR-DIM or fertility drugs (e.g., Met + Asa)Capsule Drugs metformin and aspirin and diet supplement BR-DIM cause AMPK-dependent potency loss and decrease embryonic development from two-cell to blastocyst stage. Reprod Genet (2016) 33:1027-1039 DOI 10.1007 that are used to enhance maternal metabolism to support fertility can also chronically slow embryo growth and block development in an AMPK-dependent manner.

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Section: Discussionmentioning

confidence: 99%

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Bolnick

Abdulhasan

Kilburn

et al. 2016

J Assist Reprod Genet

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“…metformin seems to pass the placental barrier and was found to be present in the fetal circulation. However, androgen and estrogen levels did not seem to be influenced and remained within normal range , whereas elevated SHBG levels have been reported in newborns after intrauterine metformin exposure (Vanky et al, 2005). The clinical relevance of these findings remains unclear.…”

Section: Metformin As a Pcos-specific Therapymentioning

confidence: 76%

The Impact of Polycystic Ovarian Syndrome on Gestational Diabetes

Aust¹,

Ott²

2011

Gestational Diabetes

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“…We have previously reported that metformin passes the placental barrier and is present in the fetal circulation in therapeutic concentrations (11). If metformin affects glucose homeostasis in the fetus, we would expect lower umbilical insulin concentrations in the metformin group.…”

Section: :5mentioning

confidence: 81%

“…Metformin passes the placenta and is present in the fetal circulation at therapeutic concentrations (11). Despite no difference in birth weight, 1-year-old children exposed to metformin in utero weighed on average 0.5 kg more than children exposed to placebo (12).…”

Section: Introductionmentioning

confidence: 99%

Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin

Helseth

Stridsklev

Vogt

et al. 2014

European Journal of Endocrinology

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Context: Metformin is suggested to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS). Metformin crosses the placenta and therapeutic concentrations are measured in the fetal circulation. Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified. Objectives: To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations. Design: Post-hoc analysis of a subgroup of PCOS women participating in a double-blind randomized controlled trial. Setting: University hospital setting. Participants: Women with PCOS (nZ118), aged 19-39 years. Main outcome measures: Maternal and umbilical cord insulin concentrations immediately after birth. Results: At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259G209 vs 361G261 pmol/l; PZ0.020). No difference was found in insulin concentrations in umbilical venous (PZ0.95) and arterial (PZ0.39) blood between the metformin and placebo groups. The arteriovenous difference was also equal between the groups (PZ0.38). Insulin concentrations were higher in the umbilical vein than in the umbilical artery independent of randomization (70G51 vs 45G48 pmol/l; P!0.0005). Conclusions: In PCOS, metformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery. Metformin treatment did not affect fetal insulin concentrations. Higher insulin concentrations in the umbilical vein indicate that the placenta somehow secretes insulin to the fetus. The possibility of placental insulin secretion to the fetus deserves further investigations.

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Placental passage of metformin in women with polycystic ovary syndrome

Cited by 211 publications

References 11 publications

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos

The Impact of Polycystic Ovarian Syndrome on Gestational Diabetes

Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin

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