Metformin Improves Reproductive Outcomes in Patients with Insulin Resistance

• Insulin resistance may be related to recurrent miscarriages, a condition affecting approximately 2-5% of women of reproductive age
• Another study evaluates the presence of a family of proteins that protect telomeres, preventing their shortening and, consequently, premature aging. These findings could help define treatments to prevent or even reverse ovarian aging

 VANCOUVER, MARCH 15, 2024

As every year, researchers from around the world gather these days at the Society for Reproductive Investigation (SRI) Congress, held this year in Vancouver, Canada, to present the latest advances in research that will help improve the reproductive outcomes of women and couples requiring assisted reproduction to fulfill their gestational desires.

Among them is the study titled “Metformin treatment decreases clinical miscarriage and improves live birth rates in infertile patients with insulin resistance,” which demonstrates how treatment with metformin reduces rates of clinical abortion and improves birth rates in women undergoing assisted reproduction with insulin resistance.

“The imbalance of insulin resistance during embryo implantation and pregnancy leads to elevated levels of glucose in maternal and fetal blood, resulting in complications that may lead to spontaneous abortion. The use of metformin has been described as a treatment that leads to a decrease in blood glucose levels without associated risks, in addition to improving endometrial function, positioning it as a possible treatment for women in whom insulin resistance is an important factor that may be related to worse reproductive outcomes. In this regard, we evaluated the effect of metformin on the reproductive outcomes of these women”, explains Dr. Hortensia Ferrero, researcher at the IVI Foundation and author of this study.

Recurrent pregnancy loss affects approximately 2-5% of women of reproductive age. Although other disorders have been described, such as chromosomal and uterine anomalies, endocrine imbalances, autoimmune factors, obstetric complications, and metabolic anomalies as possible causes of pregnancy loss, previous studies have shown that insulin resistance may play an important role in female reproductive dysfunction.

“We have observed an increase in rates of spontaneous clinical abortion in women with insulin resistance. Probably because there is a deterioration in cellular glucose uptake due to insulin resistance, which leads to inadequate embryonic nutrition and energy deficiency culminating in pregnancy loss. This increased rate of clinical abortion in women with insulin resistance was significantly reduced in those treated with metformin compared to those who did not receive the treatment. Additionally, we have found an increase in the rate of babies born to these patients with insulin resistance and metformin treatment compared to those who did not take it, even when compared among patients without insulin resistance,” Dr. Ferrero points out.

Reversing Ovarian Aging by Studying Telomeres and Their Length

Although it cannot prevent aging, science advances in ways to prevent and even reverse it. This is the focus of the study titled “Telomere protection is impaired in the ovary of SAMP8 mouse model with reproductive senescence,” which points to telomere shortening as a sign of ovarian aging.

“Telomeres are a great marker to assess aging. In this sense, we have seen that there is a family of proteins – the shelterins – that protect and ‘take care of’ these telomeres. Specifically, TRF1 is one of the most relevant. Thus, we have studied whether these protective proteins are altered in the ovaries of a mouse model that ages prematurely (SAMP8), confirming that mice that age prematurely have less TRF1 in their ovaries, and specifically, in their follicles. This can cause telomeres to shorten prematurely and consequently age earlier”, says Dr. Juan Antonio García Velasco, scientific director of IVI, co-director of IVI Madrid, and author of this study..

This potential alteration can generate inadequate telomere protection, so understanding the mechanisms that produce it can help define treatments that prevent or even reverse reproductive aging.

In total, IVI has presented nearly twenty papers at this scientific meeting, addressing topics of great scientific interest such as endocrine disruptors and their effect on fertility, polycystic ovaries or stem cells, in addition to those already mentioned.