M3: Stratified treatment in ovarian hyper stimulation

Women undergoing in vitro fertilization receive high doses of the gonadotropins follicle stimulating hormone (FSH) and human chorionic gonadotropin (hCG), which is acting as luteinizing hormone (LH) for stimulation of the ovaries to obtain a high number of eggs. There are marked individual differences in the hormonal response, ranging from lack of increased egg maturation to hyper stimulation. The hypothesis is that genetic variants in the gonadotropin receptors (LH and FSH receptors), are influencing the outcome. This assumption is supported by a recent study on more than 600 women undergoing in vitro fertilization, in which it was demonstrated that only 10% of women with asparagine in both genes (FSHR N680S and LHR N312S) became pregnant, compared to 40% success rate of those with serine.

This project has a retrospective and a prospective clinical arm.

The retrospective part is based on biomaterial from two Danish IVF cohorts at Rigshospitalet and Herlev Hospital. All the women were stimulated with either of the two compounds. The clinical outcome is well defined. Only genotyping the biological material in the biobanks is needed. The different genotypes define subgroups of women. The groups are compared with type of stimulation and success rates. The aim is to include more than 850 women in this part.

The prospective part is done together with fertility clinics in Malmø and in Poznan, Poland.

In total 890 women, 445 in Poznan and 445 in Malmö with a male or tubal factor indication for IVF/ICSI treatment or unexplained infertility, will be invited to participate in the study. Two blood samples are drawn and stored at -20°C; one for subsequent genotyping and one for AMH measurement. The treatment is according to normal procedures at respective clinic. If genetic variants in strategic genes are recognized as biomarkers for chance of pregnancy or risk of ovarian hyper stimulation syndrome, more individualised therapy and efficient treatment modalities can be developed. Moreover, risk groups for overstimulation can be defined.

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