Fertility

Research profile

Research

Research at the Fertility Clinic is focused on various areas with impact on improving fertility treatment.

 

Among the major subjects for our research are

-  Evaluation of new approaches to achieve improved embryo selection (time-lapse, NMR, gene expression)

-  Influence of life style factors on successful treatment by ART

-  Infertility and endometriosis

-  Assisted reproduction and child neurodevelopment

-  Follow-up of Danish children born after preimplantation genetic diagnosis (PGD)

-  Psychology and infertility treatment. Cause-effect and intervention

 

These lines of research are implemented through a rather extensive network of collaborating research groups and institutions.

 

Evaluation of new approaches to achieve improved embryo selection (time-lapse, NMR, gene expression)

In order to maintain or even improve pregnancy rates, selection of the most competent embryo for transfer is par excellence the challenge in assisted reproductive technology (ART). Embryo selection is currently based on morphology, and although assessment of morphological parameters at given, discrete inspection points correlated closely with the reproductive potential, the inability to accurately estimate embryo viability is considered a main reason for the relatively low pregnancy rate following ART. Several methods are now emerging and they provide the embryologist with new possibilities for assessing embryonic competence.

One of the new approaches is time-lapse evaluations of embryonic development

 

Time-lapse

One obvious advantage of time-lapse is the possibility of a flexible and dynamic evaluation of all the morphological parameters of which most are temporary conditions and for that reason easily overlooked in a static evaluation. Time-lapse monitoring allows, moreover, for the development of automated analyses by the use of computer-based algorithms. Also, time-lapse may morphokinetic differences between embryos derived from women with PCOS comared with endocrinologically normal women.

 

NMR

NMR is a powerful technique that can provide details on structural and dynamic information, making metabolite identification obtainable. The correlation of potentially minute changes in metabolic profile as seen in NMR spectra to known differences in embryonic development allows not only the development of models for predicting the embryonic potential, but also the identification of the key metabolites responsible for such differences.

A pilot study performed by our group indicates that NMR spectroscopy of media collected from a cohort of top quality embryos on day 3 after oocyte retrieval can be used to predict blastocyst development on day 5.

Using NMR spectroscopy we aim at investigating how the metabolic profile of spent culture media from human embryos correlates to developmental and reproductive potential. Furthermore the influence of external factors such as culture conditions, maternal health factors including ovarian reserve, and hormonal treatment are being studied. 

 

Gene expression

Gene expression profiling is a novel strategy with potential to identify the most viable embryo. Several publications suggest that differences in gene expression patterns are related to embryo potential and quality. A bovine study identified specific genes related to viability using microarray technology, proposing their use as markers of viability. A similar study has been performed on human embryos, identifying 7000 transcripts associated to successful IVF treatment.

In the ongoing studies, we have selected a subset of genes that in animal studies seems to predict implantation success. We will define the expression levels of human analogues of these genes in human trophectoderm biopsies. Further, New Generation Sequencing (NGS) is being performed  to characterize gene expression profiles in biopsies from embryos giving rise to an ongoing pregnancy and compared to embryos that did not so.

 

Contact persons:

Hans Jakob Ingerslev & Kirstine Kirkegaard

 

Influence of life style factors on successful treatment by ART

Life style factors are of importance for health in general, and also for reproductive health.

The literature on the influence of life style factors on success rates following treatment of infertility is generally of varying quality and the results are often not consistent from one study to another. Accordingly, there is still room for meticulous analysis of large datasets.

During nearly 15 years life style data have been recorded for patients and treatments by assisted reproductive techniques, enumerating a total of nearly 10.000 treatment cycles by IVF or ICSI.

 

Contact persons: Ulrik Kesmodel and Hans Jakob Ingerslev

 

Assisted reproduction and child neurodevelopment

Over the last few years, several studies have been published on potentially adverse pregnancy outcomes, however few studies have been performed on the neuropsychological development of these children. The infertility of the parents, the higher prevalence of chromosomal abnormalities in subfertile men and the possible increased risks of genomic imprinting disorders are among the biologically plausible reasons for increased vigilance. The objectives of the studies are to investigate the effect of ART on child IQ, attention, behavior and executive functions at age 5, and to investigate the effect of ART on the child risk of mental retardation.

 

Contact persons: Bjørn Bay Ulrik and Kesmodel

 

Follow-up of Danish children born after preimplantation genetic diagnosis (PGD)

In Denmark the first children following preimplantation genetic diagnosis (PGD) were born in 1999. Until now, no Danisgh follow-up studies have been performed, but several international. All together, there does not seem to be reasons to believe that biopsy of embryos at the 8-cell stage could have health related negative consequences for the children. However so far no Danish register-based study has been performed comparing PGD children with normal controls. Further, previous studies have focused on short follow-ups related to the neonatal period or the first six months. The current study shall elucidate growth, health and neupsychological development of children born following PGD in Denmark in the period of 1999-2012.

 
Contact persons: Bjørn Bay, Ulrik Kesmodel and Hans Jakob Ingerslev

 

Psychology and infertility treatment. Cause-effect, intervention and follow-up

It is well-known that infertility represents a chronic psycho-social strain. Several studies indicate that this may reduce chance of pregnancy. However, there are very few and often inconclusive controlled studies on interventional measures in this patient group. Expressive writing is presently being evaluated as a tool to improve satisfaction of life, emotional state and reactions, thoughts on childlessness and the treatment, results of ART and psychological adaption.

Long term persistent infertility is associated with grief, hopelessness, poor self esteem, maladaptive evasive coping strategies, sexual problems and increased risk of suicide. Presently a cohort of psychologically evaluated infertile couples are followed-up ten years after the primary evaluation. We are investigating long-term consequences both among those that achieved a child and among those that did not. The prospective design allows the evaluation of changes of baseline measures such as anxiety and depressive symptoms, allowing an evaluation of long term consequences of persistent infertility.

 

Contact persons: Hans Jakob Ingerslev, Ulrik Kesmodel, Signe Mathiesen, Yoon Frederiksen