Hormone Evaluation in Artificial Reproductive Technology

Female Infertility Clinical Trial

— HEART  

Official title:

Prospective Randomised Clinical Study on Pharmacogenetics of Gonadotropin Receptors in Relation to Pregnancy and Life Birth Rate as Well as Unwanted Side Effects Such as Ovarian Hyper Stimulation Syndrome During Assisted Reproduction.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03737253
• Other study ID #: 2016_467
• Status: Completed
• Phase: Phase 4
• Start date: September 1, 2016
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2022
• Source: Lund University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 796
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female

Intervention

Drug:
• Follitropin alpha
The objective is to measure the effect of the drug according to gonadotropin receptor genotype.
• Menotropin
The objective is to measure the effect of the drug according to gonadotropin receptor genotype.

Locations

Country	Name	City	State
Poland	Poznan University of Medical Sciences	Poznan
Sweden	Reproductive Medicine Center	Malmö

Sponsors (2)

Lead Sponsor	Collaborator
Lund University	Ferring Pharmaceuticals

Countries where clinical trial is conducted

Poland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ovarian hyper stimulation syndrome	Association between overreaction to hormonal stimulation and genotype is analysed	Up to 6 months after treatment
Other	Poor response	No or poor development of eggs in response to drug is analysed, genotype taken into account	Up to 6 months after treatment
Primary	Pregnancy	Association between pregnancy rate and genotype is evaluated	up to 12 months after treatment
Secondary	Number of oocytes	Number of eggs developed in response to drug according to genotype is measured	up to 6 months after treatment
Secondary	live birth	Live birth rate according to genotype is analyzed	up to 12 months after treatment