Research team
Expertise
Tailored management of subfertile patients will lead to an increased number of couples fulfilling their wish to have a child. Background Infertility is defined as the failure to become pregnant during a twelve months period of regular unprotected sexual intercourse. Infertility and subfertility are affecting 9% of the couples with a desire to have a child. Apart from the obvious reasons for non-conception such as a bilateral tubal block, anovulation, extremely low sperm count or absence of sperm in the ejaculate, severe endometriosis and premature ovarian insufficiency, most couples are suffering from subfertility and this is by far the majority. Subfertile couples have one or more aspects that are under the norm after fertility investigation and these are usually combined with factors such as increasing older age of the women (men), lower sexual intercourse frequency, busy jobs, more planning and lack of time. Although these patients are often categorized as having mild to moderate endometriosis, mild male subfertility or having no obvious reasons for not conceiving (unexplained or idiopathic infertility), this in itself is usually not the explanation for their involuntary childlessness. This subfertility is explained by the fact that reproduction is a matter of chance depending on the subtle balance between success and failure of complex and mostly poorly understood sequential processes that may lead to a pregnancy such as spermatogenesis, oogenesis, ovulation, sexual intercourse, transport of gametes, fertilization, embryogenesis and last but not least implantation. Besides the patient population with a clear indication for treatment all other couples (the majority) are facing subfertility rather than infertility. This poses a tremendous challenge to the treating physician to balance his or her advice between expectant management or active treatment such as intra-uterine insemination (IUI) or IVF/ICSI. The decision for one or the other depends on numerous factors whereby scientific information and patient preferences should lead to the best option for the couple. What we have been underestimating is that in our continuous strive to increase the quality of our treatment, patients may experience the biggest difficulty in “holding on” to the therapy and discontinuation or dropout from fertility treatment is underestimated. Discontinuation is to a large extent explained by the burden of the treatment, both physically as psychological. Objectives The research I want to continue focusses on both improvement of efficacy and safety but also be patient centered by taking into account patient’s preferences to keep our patients “on board”. As part of the research project “How does detection of DNA damage in sperm influence the patient’s chance of conception? “we will investigate the role of sperm DNA fragmentation as a sperm function test with the potential to discriminate and select couples with optimal chances for intra-uterine insemination. A Belgian multicenter study will be started and coordinated by myself to investigate the dropout rate and reasons for drop-out in case of the availability of cryopreserved embryos in a large Belgian ART population. We are conducting a study where we investigate whether a digital pre-conceptional lifestyle assistant in fertility treatment can be a trustworthy toolbox in assisting patients during their treatment and increasing cumulative ongoing pregnancy rates. I am the chief-investigator in an investigator- led KCE sponsored trial in 12 Belgian fertility centers to investigate whether the addition of Lipiodol during tubal patency testing (Hyfosy) will lead to a higher chance of conception which will lead to fewer patients that have to undergo more invasive fertility treatments subsequently
OOMITOCARE: Strategic mitochondrial interventions in the oocyte as preconception care in conditions of maternal metabolic stress.
Abstract
Obesity is a global threat that not only affects women's fertility but also endangers the health of the offspring. The developmental capacity of oocytes under metabolic stress, associated with obesity, is decreased due to higher levels of oxidative stress (OS) and mitochondrial (MT) dysfunction. Inheritance of such defective oocyte mitochondria compromises epigenetic programming, development and postnatal health. Early embryos cannot activate the processes of mitophagy (removal of dysfunctional mitochondria) and mitogenesis (synthesis of new mitochondria), which are crucial for rejuvenating mitochondrial functions and supporting embryo survival. While current clinical preconception care interventions, such as diet normalization, improve systemic metabolic health, mitochondrial abnormalities in the oocyte persist. MT-targeted antioxidants and mitophagy-inducing substances are proven to be effective in enhancing somatic cell mitochondrial function and metabolic health. However, the potential of these compounds in oocyte-targeted preconception care strategies has never been explored. Using an outbred mouse model, this project will specifically focus on oocyte mitochondria as the key to improve female gamete quality under maternal metabolic stress conditions. The research will combine functional and molecular assessments to generate a clear understanding of the effects of MitoQ, Liraglutide and Rapamycin on oocyte and embryo quality, epigenetic programming and offspring health.Researcher(s)
- Promoter: Leroy Jo
- Co-promoter: De Neubourg Diane
- Co-promoter: Marei Waleed
- Co-promoter: Martinet Wim
- Fellow: Loier Lien
Research team(s)
Project type(s)
- Research Project
UZA-Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, pragmatic trial in infertile women with at least one patent tube at Hysterosalpingo-foam sonography (HYFOIL).
Abstract
Live birth after additional tubal flushing with oil-based contrast versus no additional flushing: a randomised, multicentre, parallel group pragmatic trial in infertile women with at least one patent tube at Hysterosalpingo-foam sonography (HYFOIL study). Ten to 15 percent of couples in their reproductive lifetime face fertility problems which is defined by WHO as the absence of pregnancy after minimal 12 months of unprotected sexual intercourse. The three most frequent causes of subfertility are: sperm defects, ovulation disorders and tubal pathology. In order to exclude tubal pathology, tubal patency tests are performed under ultrasound guidance with foam (hysterosalpingo-foam sonography (Hyfosy)) or with contrast/water (hysterosalpingo-contrast sonography (Hycosy)). This trial will investigate whether tubal flushing with an oil-soluble contrast medium (OSCM) can increase the likelihood of a spontaneous conception after tubal patency testing with Hyfosy under ultrasound guidance compared to no additional flushing in a population of infertile women between 18 and 40 years of age with absence of pregnancy after 12 months of unprotected sexual intercourse or who have three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy. The use of Lipiodol Ultra Fluide® is off-label in Hyfosy. This multicenter, randomised, open-label, comparative and pragmatic trial compares 2 arms which will be randomised 1:1: - Intervention group: Tubal flush with 5-10mL oil-soluble contrast medium (Lipiodol Ultra Fluide®, Guerbet, France) immediately after Hyfosy - Control group: No additional intervention after Hyfosy The study comprises a screening period of maximum 8 weeks (w-8 to d1), randomisation (w-8 to d1), a start study visit at which the Hyfosy is performed (d1) and a fertility treatment period of 6 months (d1-w26). If the woman is not pregnant at 6 months after Hyfosy, the follow-up will last till 12 months (w52). If the participant is pregnant at 6 months after Hyfosy, the follow-up will last till maximal 4 months after live birth or miscarriage. The primary endpoint is the occurrence of live birth, with the first day of the last menstrual cycle in which the patient conceives within 6 months after Hyfosy. Secondary endpoints consist of reproductive outcomes, gestational age at delivery, birth weight, neonatal mortality, major congenital anomaly, neonatal outcomes and thyroid function, pregnancy complications, number of complications during or immediately after the intervention, pain score of the Hyfosy and additional flush, thyroid function of the mother, general and disease-specific quality of life.Researcher(s)
- Promoter: De Neubourg Diane
Research team(s)
Project type(s)
- Research Project
Fundamental understanding and development of preconception care strategies to improve maternal fertility and to protect offspring's health in obese individuals
Abstract
Obesity is becoming a global threat, reducing mother's health and reproductive capacities and affecting the offspring's health. Clear preconception care guidelines for obese future mothers are lacking. Clinical studies are flawed and fundamental studies in basic animal models are scarce. The importance of preconception weight loss on reproduction and baby's health is heavily debated and has never been investigated in detail. This project aims to uncover the role and the importance of clinically relevant preconception care advices to obese women planning for pregnancy. To do so, we propose strategically designed fundamental obese mouse models to assess the impact of preconception weight loss, diet normalization, increased physical activity, omega-3 rich diet or the combination thereof. We will focus on four distinct major research challenges: 1) can we find improvements of mother's metabolic profile before conception in relation to the observed weight loss; 2) does the mother's own fertility success increase; 3) can we improve the postnatal health of the offspring and 4) can we safeguard the offspring's reproductive physiology. Physiological and in depth molecular outcome parameters will be combined to generate a clear and integrated view on the effects of preconception care lifestyle interventions. If successful, these novel insights will be the basis for developing future awareness and education programs aiming at improved human maternal health at the time of conception.Researcher(s)
- Promoter: Leroy Jo
- Co-promoter: Bols Peter
- Co-promoter: De Neubourg Diane
- Co-promoter: Marei Waleed
Research team(s)
Project type(s)
- Research Project
Development of strategic preconception care to improve maternal fertility and protect offspring's health in obese individuals: steps towards evidence based clinical advice.
Abstract
Obesity is becoming a global threat, reducing mother's health and reproductive capacities and affecting the offspring's health. Clear preconception care guidelines for obese future mothers are completely lacking. Clinical studies are flawed and more fundamental studies in basic animal models are very scarce. The importance of preconception weight loss on reproduction and baby's health is heavily debated and never been investigated in detail. This research project aims to propose strategically designed animal research models to provide relevant scientific evidence for effective and sustainable preconception care advices to obese women planning for pregnancy. To do so, we will assess the impact of preconception weight loss, diet normalization, increased physical activity, omega-3 rich diet or the combination thereof in obese outbred mother mice on four distinct major outcome parameters: 1) improvement of mother's metabolic profile before conception in relation to the observed weight loss; 2) mother's own fertility success; 3) postnatal health of the offspring and 4) offspring's reproductive physiology. Effective guidelines for preconception care lifestyle interventions in obese patients will drastically lower the (public) health care cost associated with assisted reproduction and should maximally safeguard the health of the baby. The data generated will be the basis for awareness and education programs aiming at improved maternal health at the time of conception.Researcher(s)
- Promoter: Leroy Jo
- Co-promoter: De Neubourg Diane
- Fellow: Smits Anouk
Research team(s)
Project type(s)
- Research Project
UZA-The digital Preconceptional lifestyle assistant in fertility treatment – a trustworthy toolbox. PRE-LIFE study.
Abstract
Fertility related problems occur in 9% of the Flemish population and cause considerate emotional and economic burden. Improving success and reducing the concomitant distress and discontinuation of fertility treatment is one of the most important research priorities in fertility care. Increasing evidence suggests that lifestyle factors (including mental well-being, physical activity and diet) are modifiable factors that contribute to improving the success rate and management of burden in fertility treatment. Nevertheless, no preconceptional lifestyle support intervention is routinely available in the fertility setting. Mobile health is a promising method as it is an effective method to promote healthy behaviour change, matches to the time demands of young couples and has the potential for broad dissemination. Therefore, the aim of this project is to evaluate if adding an application based preconceptional lifestyle intervention 'PRE-LIFE app' to standard care in couples undergoing assisted reproductive technology (ART) increases their cumulative ongoing pregnancy rate and decreases their ART discontinuation rate. In addition, we will evaluate if the 'PRE-LIFE app' affects lifestyle behaviour. The 'PRE-LIFE app' will include tailored advice, monitoring, interaction and feedback on mental wellbeing, physical activity and diet and will be provided in the blended format of a mobile application in combination with a 'just in time' coach. The 'PRE-LIFE app' is based on our previous research but will be tailored to the needs, perceptions and preferences of the target population by using the concepts of User Experience Research. The efficacy of the 'PRE-LIFE app' will be evaluated in a multicentre randomised controlled study in couples undergoing ART. We hypothesize that the intervention will induce a behavioural change, reduce ART discontinuation rate, and ultimately enhance the chance of a healthy pregnancy and live birth.Researcher(s)
- Promoter: De Neubourg Diane
Research team(s)
Project type(s)
- Research Project
UZA-How does detection of DNA damage in sperm influence the patient's chance of conception.
Abstract
Male subfertility diagnosis is hampered by two major hurdles: poor prognostic values of semen analysis and suboptimal treatment modalities applied. The main objective of this project is to develop and implement a new sperm function test (DNA fragmentation) towards diagnosis of male subfertility and application of optimally related medically assisted reproductive technologies. To bring the reality of sperm function testing closer to implementation into clinical pathways, the assay has to be robust, cost effective, easy to use and clinically useful using standardized procedures. Additionally, such robust sophisticated functional assays have to be placed in the patient's pathway to assist/change management decisions. Finally, the test has to be effective in increasing the chances of conception by choosing the right fertility treatment. Decreasing time to pregnancy should result in a positive economical and psychological benefit for the patient which is a positive 'medical impact'. In order to reach our objectives we need to implement a three step approach: In work package 1, we will analyse DNA fragmentation in subfertile males and correlate them with semen parameters. As a control group, DNA fragmentation levels will be determined in sperm donors, fertile men and in couples where natural conception occurs via cycle monitoring but with no intervention of the semen sample to obtain pregnancy. In work package 2, the cut-off values obtained on a healthy population (work package 1) will be implemented in a well designed group of patients entering an intra-uterine insemination (IUI) program (first-line treatment). DNA fragmentation will be tested before the start of the treatment and during every IUI cycle resulting in the validation of a sperm function test in the patients clinical pathway and in selecting the appropriate patients for IUI treatment. In work package 3, patients after 4 failed IUI cycles (work package 2) will be proceeded to an in vitro fertilization (IVF) program (second line treatment) to test the hypothesis that patients with a "poor prognosis to become pregnant with IUI" may be better off to skip IUI treatment and proceed to IVF even though standard WHO sperm analysis parameters would not suggest to go immediately for IVF and criteria for IUI were met for these patients. The major outcomes of this project aims to overcome these hurdles and includes a sperm function testing protocol (more informative both before and after sperm preparation) and a personalized clinical approach (IUI/IVF) with a positive medical impact (shorter time to pregnancy). As such, the results of this project will be immediately translated into clinical care and will have major advantages both for the patients and the clinicians. Based on the development of robust sperm DNA fragmentation testing in this project, we envision to reinforce male subfertilty diagnosis and appropriate treatment to this subgroup of patients. Conventional data combined with functional data generated at the molecular levels can be optimally integrated with the clinical expertise by providing a unique 'andrology service' that enables solutions tailored to the needs of the individual patient. Analysis of sperm DNA fragmentation testing at two levels will help develop specific guidelines in the diagnosis and treatment of male subfertility. Conventional semen parameters combined with sperm function testing will help identify the underlying causes of increased DNA damage. Together with the andrologists (gynecologists, urologists and endocrinologists) steps can be undertaken for clinical corrections wherever applicable. Analysis after sperm preparation will help identify the most healthy sperm population used for therapy. All this combined with the appropriate treatment modality (IUI/IVF) will help in obtaining our ultimate goal – increased healthy live births for our patients.Researcher(s)
- Promoter: De Neubourg Diane
Research team(s)
Project type(s)
- Research Project