From successful conception to a healthy family – Belgian research raises the bar for IVF

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Belgium is one of the top countries in the world for in vitro fertilization (IVF). Despite the high cumulative success rates of these interventions, disproportionally little attention has been given to the health of both mother and child during and after pregnancy. With the HEART (High risk for pre-Eclampsia after Assisted Reproductive Technology) project, Belgian researchers strive to understand why some women have an increased risk for pre-eclampsia after IVF and whether biomarkers can be identified to estimate these risks early in pregnancy or even before conception. They aim to raise the standard from successful conception to improved child and maternal health.

Conception is just the beginning

Belgium is a pioneer in in vitro fertilization (IVF), with the first Belgian IVF baby born in 1983. The Belgian Register for Assisted Procreation reports over 42,000 treatment cycles in 2021, of which 27% were performed at Brussels IVF, UZ Brussel. “More than 48,000 babies have been born following in vitro treatment at our center,” says Shari Mackens, Medical Director and fertility specialist at Brussels IVF, and clinical professor at UZ Brussel and VUB. “By using cutting-edge technologies and combining individualized clinical care with pioneering scientific research, we achieve very high success rates.” Brussels IVF indeed ranks among the top performers in IVF globally.

However, the success of an IVF cycle entails more than just achieving conception or even childbirth. “Research shows that some women who get pregnant using IVF treatment are at higher risk of pre-eclampsia, a condition that can have serious consequences for maternal and child health,” explains Mackens. Pre-eclampsia is typically diagnosed during the second half of pregnancy, when symptoms such as high blood pressure and presence of protein in the urine are observed. Although the exact cause is still unclear and might differ depending on the patient, it is suspected that the blood vessel network responsible for supplying oxygen and nutrients to the placenta did not establish properly, leading to dysfunctional placental development. Pre-eclampsia can lead to fetal growth restriction, preterm birth, or organ damage in mother and baby. If left untreated, the condition can be life-threatening for both. In the long term, women who experienced pre-eclampsia during pregnancy carry a lifelong increased risk to develop cardiovascular conditions.

“Research shows that some women who get pregnant using IVF treatment are at higher risk of pre-eclampsia, a condition that can have serious consequences for maternal and child health.” – Shari Mackens, Brussels IVF

Early diagnosis is essential in mitigation of the complications associated with pre-eclampsia. First trimester screening methods to identify patients at risk are gaining ground. Using an ultrasound scan to determine the blood flow to the uterus and a number of other clinical and biochemical maternal parameters, a potent algorithm, developed by the Fetal Medicine Foundation (FMF), can estimate the risk to develop pre-eclampsia later in pregnancy. “Our clinic’s preliminary data show that in some women conceiving after IVF, we detect an elevated risk for pre-eclampsia,” says Mackens. “However, estimation of this risk does not seem to be as accurate as in the population conceiving spontaneously. We are trying to optimize the predictive algorithm taking into account specific IVF characteristics.” In the general population, an increased risk for pre-eclampsia can be mitigated by prescribing aspirin. Mackens’ team is also studying whether aspirin prophylaxis has the same beneficial effect on risk mitigation in the setting of IVF, as the pathophysiology leading to pre-eclampsia probably differs between natural and assisted reproduction.

At the HEART of the solution

With the HEART project – an acronym for ‘High risk for pre-Eclampsia after Assisted Reproductive Technology’ – an interdisciplinary team of expert clinicians specialized in fertility, prenatal development, cardiology, nutrition, pediatrics, and genetics, aims to elucidate the differences in pathophysiology among women who underwent IVF for different indications. “It is our goal to find early biomarkers that are associated with a higher risk of pre-eclampsia, and use those to optimize preconceptional, prenatal, as well as post-natal care,” says Mackens, who is leading the pioneering project. The project focuses on two groups of patients – women undergoing IVF following a diagnosis of polycystic ovary syndrome (PCOS), one of the most common endocrine conditions associated with reduced fertility, and women receiving oocytes (eggs) from a donor.

“It is our goal to find early biomarkers that are associated with a higher risk of pre-eclampsia, and use those to optimize preconceptional, prenatal, as well as post-natal care.” – Shari Mackens, Brussels IVF

“Although the risk of pre-eclampsia is increased in the two patient groups, the cause is likely different for both,” states Mackens. The consortium aims to include a total of 1000 women in the study, an ambitious yet crucial objective. “In order to identify markers that can accurately predict the risk in our IVF patients, we need a large sample size,” Mackens says. “The first patients enrolled in the project have recently given birth,” she states. “Both suffered from pre-eclampsia during their pregnancy, indicating again the high incidence of the condition in these specific populations.”

The HEART Project. ©The Bonnie Collection

One of the interesting aspects of this groundbreaking study is the opportunity to include and monitor women at a very early stage, even before conception. “To a certain extent, we can already predict which women are at risk to develop pre-eclampsia, even before conception. By monitoring and sampling the women and linking those data to later occurrence of the condition, we can extract valuable insights and identify potential biomarkers.” Data and samples collected preconceptionally include serum biomarkers, cardiac and metabolism measurements, endometrium biopsies, and extended questionnaires reviewing dietary and other habits. During pregnancy, cardiac function and blood samples are assessed together with regular ultrasound scans to follow up on the baby and placenta. “We are looking forward to the moment when all data comes together and patterns can be identified,” says Mackens. “With that information, we will be able to approach fertility in a more holistic manner, emphasizing the importance of a healthy lifestyle before entering an IVF trajectory.”

Communication is key

The impact of the research project extends beyond the fertility aspect. Women experiencing pre-eclampsia have an increased risk of chronic, mainly cardiovascular diseases later in life compared to healthy individuals. Development of pre-eclampsia can be viewed as a warning signal after a ‘stress-test’ which is in this case the state of pregnancy. “With this project, we aim to emphasize the need to counsel these women, both before and after pregnancy,” says Mackens. “Through regular screening and advising a healthy lifestyle, including physical activity and a balanced diet, the risk of future cardiovascular complications can be effectively reduced. Women should be made aware of this and guided throughout their entire lifespan.” Many women are still unaware of the symptoms and risks of pre-eclampsia, even though the condition is a major cause of morbidity in western societies, and leading cause of pregnancy-related mortality in developing countries. “Communication and sensitization are essential and should be key priorities of healthcare systems.”

“With this project, we aim to emphasize the need to counsel these women, both before and after pregnancy.” – Shari Mackens, Brussels IVF

The HEART Project. ©The Bonnie Collection

Mackens calls for more considerate and scientifically sound communication towards women and couples going through IVF. Patients undergoing such emotionally challenging journeys often exhibit high receptivity to various recommendations, including scientifically understudied or even inaccurate information circulating on social or other media. “Women suffering from repeated implantation failures following IVF or recurrent early pregnancy losses are particularly vulnerable. Desperate to conceive, they are willing to follow any kind of advice or invest time and money in non-evidence-based approaches. It is our responsibility to provide these patients with correct information and offer them the support of a multidisciplinary team of specialists, including physicians and psychologists.”

In addition to communication directed towards patients and the general public, there is also a need for more communication among specialists. “Especially in complex cases, it is vital that healthcare professionals communicate with each other and exchange information. At the moment, there is too little interaction between experts such as fertility specialists and prenatal gynecologists,” Mackens states. “Although both are gynecologists by training, their specialized focus often impairs them from seeing the bigger picture and linking aspects of both disciplines.”

With the HEART project, Mackens and her team hope to improve the outcomes for patients going through IVF. The goal is to raise the bar from achieving successful conception to ensuring the present and future health of both babies and mothers. Through their communication efforts, they want to lead by example and impact the way we look at reproductive and, more generally, women’s health. In her newly appointed role as member of the Young Academy – an independent, interdisciplinary forum for young top scientists and artists – Mackens aims to further amplify her reach and put women’s health and gender equality in science and medicine on the national agenda.