Female Infertility
Conditions
Keywords
gonadotropin, receptor, assisted reproduction
Brief summary
The aim is to be able to predict the hormonal response according to gonadotropin receptor genotype and hormone type used for treatment of women undergoing in vitro fertilization or egg donation. Outcome will be measured as pregnancy success, live born babies and unwanted side effects.
Detailed description
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 in order to obtain a high number of eggs. There are however 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, demonstrating that whereas only 10% of women with asparagine in both genes (FSHR N680S and LHR N312S) became pregnant, 40% of those with serine did (Lindgren I et al. Hum Repr 2016; 3:672-83). Most (90%) of the women were treated with rFSH (recombinant). However, of the 10% asparagine carriers who actually became pregnant, most if not all, were treated with menotropin - a urine derivated compound (Menopur, Ferring), which contains both LH and FSH. This finding was not stressed in the manuscript as it could have been due to chance because of the small number of women treated with menotropin. The objective is therefore to perform a prospective randomized study regarding efficacy of treatment in the first and second in vitro fertilization trial with rFSH and menotropin, respectively, genotype taken into account. In total 890 women, 445 in Poznan, Poland and 445 in Malmö, Sweden, with unexplained infertility or a male or tubal factor indication for treatment will be invited to participate in the study. At first appointment, information is provided and informed consent retrieved. Two blood samples are drawn and stored at -20°C; one for subsequent genotyping and one for anti mullerian hormone measurement. The succeeding treatment is according to normal procedures at respective clinic.
Interventions
The objective is to measure the effect of the drug according to gonadotropin receptor genotype.
DRUGMenotropin
The objective is to measure the effect of the drug according to gonadotropin receptor genotype.
Sponsors
European Commission
Lund University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Patients and care providers need to know the type of hormone provided in order to be able to instruct and treat the patient. However, all roles are masked regarding the genotype.
Intervention model description
Women undergoing in vitro fertilization are allocated to either menotropin (urin derivate) or recombinant follicle stimulating hormone. Inclusion criteria are: * younger than 40 years of age * more than 12 months of unprotected intercourse * normal ovulatory cycles 26-32 days * first or second IVF treatment * indication for IVF is male factor * tubal factor or unexplained infertility. Exclusion criteria are: * Anti müllerian hormone less than 5pmol or FSH more than 12 cycle day 2-3 * Endometriosis * polycystic ovarian syndrome * pre ovarian failure * smoking * male age more than 56. The succeeding treatment is according to normal procedures at respective clinic. End points are: total hormonal dosage, number of retrieved oocytes, fertilization rate, rate of blastocyst transfer, pregnancy rate, live birth rate. Adverse effects e.g overstimulation is recorded.
Eligibility
Sex/Gender
FEMALE
Age
25 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Normal ovulatory cycles 26-32 days * First and second IVF treatment * Indication for IVF is male factor, tubal factor or unexplained infertility * Medical indication for IVF; \>12 months unprotected intercourse
Exclusion criteria
* Anti Müllerian Hormone \<5pmol or cycle day 2-3 FSH \>12 * Endometriosis * polycystic ovarian syndrome * pre ovarian failure * smoking * male age more than 56.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pregnancy | up to 12 months after treatment | Association between pregnancy rate and genotype is evaluated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of oocytes | up to 6 months after treatment | Number of eggs developed in response to drug according to genotype is measured |
| live birth | up to 12 months after treatment | Live birth rate according to genotype is analyzed |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ovarian hyper stimulation syndrome | Up to 6 months after treatment | Association between overreaction to hormonal stimulation and genotype is analysed |
| Poor response | Up to 6 months after treatment | No or poor development of eggs in response to drug is analysed, genotype taken into account |
Countries
Poland, Sweden
Outcome results
None listed