Short summary

DNA fragmentation in spermatozoa of fertility patients is an elusive area within the field of fertility treatment due to patents, lack of uniformity in testing and accessibility. The aim of this project is to validate a more accessible method for the measurement of DNA fragmentation in spermatozoa and to investigate the implications for the chance of pregnancy after fertility treatment. Lastly, it will be examined whether a supplement of an oral antioxidant can decrease the amount of DNA fragmentation and increase the pregnancy rate at couples receiving fertility treatment. 

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Rationale

Every seventh couple will experience a period of infertility. Fifteen percent of these will go undiagnosed. It is therefore important to illuminate some of the underlying factors behind the infertility.

Previous studies have estimated that 10-20% of all male fertility patients are affected by additional parameters besides reduced number or movement of spermatozoa. It is believed that the internal quality of the spermatozoa is also of great importance. If these patients can be properly diagnosed, a more precise fertility treatment course can be established with a decrease in time-to-pregnancy. Novel therapeutic possibilities are expected to reduce the number of couples needing invasive fertility treatment and to reduce societal as well as personal costs of infertility.

This industrial PhD project is carried out by AAGAARD Gynækologisk Klinik in collaboration with the fertility clinic at the Odense University Hospital. A comparison study is carried out in collaboration with Reproductive Medicine Centre in Malmö. The present project focuses on andrology - a specialized function at the Odense University Hospital. 

The aim is to investigate the significance of the quality of the DNA in the male fertility patient's spermatozoa. Male fertility testing has traditionally focused on the concentration and total number of spermatozoa in the ejaculate, and the focus of the treatment has been shifted to the female if the quality of the ejaculate and the male anamnesis were normal. However, up to 15% of fertility couples receive a diagnosis of unexplained infertility.

Extant research shows a connection between subfertility and increased DNA fragmentation (DNA fragmentation index, DFI) in the spermatozoa; yet, the clinical and therapeutic significance of this observation remain obscure. Moreover, DNA fragmentation has so far been difficult to measure. However, a novel method in the diagnosis of male fertility, DNA fragmentation assessment of spermatozoa by flow cytometry may change this situation.

The aims of the present project are to:

• determine if a novel software for analysis of DFI is comparable to "the golden standard".
• investigate a possible connection between increased DFI and the pregnancy rate after intrauterine insemination.
• establish the stability of the analysis through a treatment period.
• investigate if a reverse correlation between the total antioxidant capacity in the seminal fluids and DFI can be established.
• investigate whether intake of antioxidants can reduce DFI and increase the pregnancy rate after intra uterine insemination.  

If data allow us to conclude that it is possible to reduce the amount of DNA fragmentation in males with increased DNA fragmentation by administrating an oral antioxidant, it is possible to reduce the extent of the fertility treatment needed for these patients.
If DFI is increased, the chance of pregnancy after the first line of treatment, intrauterine insemination, is greatly reduced. The subsequent line of treatment is in vitro fertilization (IVF) or Intra Cytoplasmic Sperm Injection (ICSI). IVF and ICSI procedures both require hormone stimulation and an invasive oocyte retrieval from the female.
Previous studies have estimated that 10-20% of all male fertility patients are affected by increased DFI. If these patients can be properly diagnosed, a more precise fertility treatment course can be established with a decrease in time-to-pregnancy. Novel therapeutic possibilities are expected to reduce the number of couples needing invasive fertility treatment and to reduce the economical as well as personal costs of infertility.

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Description of the cohort

Participants are primarily fertility patients recruited from AAGAARD Gynækologisk Klinik and the fertilityclinic Dep. D at Odense University Hospital.
For a minor part of the study, sperm samples from donors from Skejby CryoBank  is used. 

Data and biological material

Data will primarily be retracted from a DNA fragmentation analysis on sperm samples. Furthermore, information of pregnancy after fertility treatment will be registered.   

Collaborating researchers and departments

Department of Gynaecology and Obstetrics, Odense University Hospital

• PhD-student Anne Sofie Rex
• Professor Jens Fedder

AAGAARD Klinik

• Jørn Aagaard, MD

Reproductive Medicine Centre, Malmö

• Head of department Mona Bungum