On the path to motherhood through assisted reproduction, success does not depend solely on embryo quality. A recent study, led by the IVI RMA Global Foundation, has shed light on one piece of the puzzle: the genetic profile of the endometrium.

Thanks to the use of artificial intelligence algorithms and big data analysis, researchers have been able to identify why, even with top-quality embryos, some pregnancies do not reach term.

IVI’s presence at the 73^rd Annual Scientific Meeting of the Society for Reproductive Investigation (SRI), held from 24–28 March in Puerto Rico, was marked by this study led by the IVI Foundation and IVI RMA Global. The paper, Genistein and Pioglitazone as Promising Repurposed Drugs to Treat Endometrial Failure Independent of Endometrial Timing, received the President’s Plenary Award for this oral presentation.

The research used systems pharmacology techniques to find solutions among existing drugs. The result was the identification of two unexpected allies:

• Genistein: A natural phytoestrogen (found in soy) with potent antioxidant and anti-inflammatory properties.
• Pioglitazone: A drug commonly used for type 2 diabetes that improves insulin sensitivity.

Why is this a milestone? Both compounds have been shown to improve decidualisation. This is the critical biological process in which the endometrium prepares to receive and nourish the embryo. Since these are already marketed and safe drugs, their clinical implementation could be much faster than that of a new medication.

Personalisation: The Key to Optimising Each Embryo

A healthy endometrium is crucial for the success of fertility treatments. Endometrial failure is a highly studied issue in reproductive medicine. The lack of effective treatments has led researchers to focus on artificial intelligence and pharmacology to identify approved drugs capable of correcting endometrial alterations that prevent pregnancy.

Dr Patricia Díaz Gimeno, principal investigator, emphasises that this advance allows for preventive action. Instead of waiting for an implantation failure to occur, AI helps identify molecular risk profiles before the embryo transfer.

“On average, three to five attempts are required to reach a cumulative pregnancy probability of over 95–98% with high-quality embryos. The first attempt is around 65%, leading to the loss of embryos along the way. Now, we can try to improve these rates by identifying these profiles preventively and treating them before performing the embryo transfer,” explains Dr Patricia Díaz Gimeno, the study’s lead researcher.

Dr Díaz Gimeno adds that these drugs were discovered to molecularly reverse a previously “unknown” cause of infertility. “To discover them, a sophisticated big data analysis approach, pioneering in the field of human reproduction, was used. Namely, systems pharmacology and signature matching (carried out by the first author of the study, Antonio Párraga Leo, following a stay at UCSF, University of San Francisco, CA)”.

The Metabolic Factor: How Does BMI Influence Risk?

A second study presented at the SRI Congress analysed the effect of Body Mass Index (BMI) on the risk of pregnancy loss. The data are clear: obesity not only makes conception more difficult but also increases the risk of gestational loss.

IVI RMA Global presented the study The Weight of Loss: Obese Patients Have a Higher Risk of Pregnancy Loss after Euploid Frozen Embryo Transfer. It included a sample of 16,000 patients, showing that those with obesity had a lower likelihood of live birth compared to non-obese patients, a risk that progressively increases with higher BMI.

The study observed that:

• Women with obesity have an 18% higher risk of miscarriage.
• The probability of live birth decreases progressively as BMI increases, even when transferred embryos are chromosomally normal.

“These findings underscore the importance of fully personalising reproductive treatments to achieve high success rates, taking into account the patient’s medical history, lifestyle, and particularly her body weight. It is essential to counsel patients on the impact of female obesity on gestational complications, such as miscarriage. This will be more frequent even when the embryos transferred to the uterus show no chromosomal abnormalities,” explains Dr José Bellver, gynaecologist at IVI Valencia.

Towards a Comprehensive Reproductive Health Model

This dual approach (advanced pharmacology + lifestyle management) redefines what precision medicine means in fertility. Dr Bellver emphasises that lifestyle counselling is not an “extra”. It is a fundamental part of medical treatment.

In addition to counselling,maintaining healthy lifestyle habits can be very beneficial for patients undergoing assisted reproduction. These include:

• A balanced diet
• Adequate hydration
• Avoiding alcohol and tobacco
• Regular exercise, adapted to each woman’s needs