Hormone Evaluation in Artificial Reproductive Technology
Condition: Female Infertility
MeSH terms: Infertility; Infertility, Female
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Follitropin alpha; Menotropin
Intervention type(s): Drug; Drug
Intervention description(s): The objective is to measure the effect of the drug according to gonadotropin receptor genotype.; The objective is to measure the effect of the drug according to gonadotropin receptor genotype.
Other intervention name(s): Gonal F; Puregon; Urofollitropin; Menopur
Intervention MeSH terms: Menotropins; Follicle Stimulating Hormone
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Women undergoing in vitro fertilization are randomized 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.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: gonadotropin; receptor; assisted reproduction