Hormone Evaluation in Artificial Reproductive Technology (HEART)

Lund University

Status: Completed

Conditions: Female Infertility

Treatments: Drug: Menotropin; Drug: Follitropin alpha

Study type: Interventional

Funder types: Other

Identifiers

NCT03737253

2016_467

Details and patient eligibility

About

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.

Full 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.

Enrollment: 810 patients

Sex: Female

Ages: 25 to 40 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Health Services Research

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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810 participants in 2 patient groups

Follitropin alpha

Active Comparator group

Description:

Follitropin alpha (GONAL-f, Merck-Serono, Darmstadt, Germany), injections, dosage varying 1500-2500 IU, duration 2-5 days.

Treatment:

Drug: Follitropin alpha

Drug: Menotropin

Menotropin

Active Comparator group

Description:

Menotropin (Menopur, Ferring GmbH, Kiel, Germany), injections, dosage varying 1500-2500 IU, duration 2-5 days.

Treatment:

Drug: Follitropin alpha

Drug: Menotropin