Female InfertilityHEARTNCT03737253
Hormone Evaluation in Artificial Reproductive Technology
A study testing Follitropin alpha and Menotropin in people with Female Infertility, run by Lund University at 2 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 25 to 40 years, women only
- Conditions the study is for
- Female Infertility
- What is being tested?
- Follitropin alpha and Menotropin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 810 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2016to 2 Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: 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.
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.
Read the 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.
- Conditions
- Female Infertility
- Being tested
- Follitropin alpha, Menotropin
- Keywords
- gonadotropin, receptor, assisted reproduction
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Follitropin alphaDrug
Also called Gonal F, Puregon, Urofollitropin
The objective is to measure the effect of the drug according to gonadotropin receptor genotype.
MenotropinDrug
Also called Menopur
The objective is to measure the effect of the drug according to gonadotropin receptor genotype.
| Study group | Role | What they receive |
|---|---|---|
| Follitropin alpha | Active comparator | Follitropin alpha (GONAL-f, Merck-Serono, Darmstadt, Germany), injections, dosage varying 1500-2500 IU, duration 2-5 days. Receives: Drug: Follitropin alpha; Drug: Menotropin |
| Menotropin | Active comparator | Menotropin (Menopur, Ferring GmbH, Kiel, Germany), injections, dosage varying 1500-2500 IU, duration 2-5 days. Receives: Drug: Follitropin alpha; Drug: Menotropin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pregnancy
Association between pregnancy rate and genotype is evaluated
Measured: up to 12 months after treatment
Secondary outcomes (2)
Number of oocytes
Number of eggs developed in response to drug according to genotype is measured
Measured: up to 6 months after treatment
live birth
Live birth rate according to genotype is analyzed
Measured: up to 12 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2018
- Study startSep 2016
- Primary completion31 Dec 2021
- Study completion2 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Female InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 810 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lund University
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Yvonne Lundberg Giwercman, PhD, Principal investigator, Lund University, Lund, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03737253
- Sponsor's protocol ID
- 2016_467
- Acronym
- HEART
- Status last verified
- Mar 2025
- First submitted
- 23 Oct 2018
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT03737253
- Acronym / sponsor ID
- HEART / 2016_467
- Conditions
- Female Infertility
- Keywords
- gonadotropin, receptor, assisted reproduction
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 810 participants (actual)
- Lead sponsor
- Lund UniversityUniversity, hospital or other
- Collaborators
- European Commission
- Study start
- Sep 2016 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 2 Oct 2024 (actual)
- First posted
- 9 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Follitropin alpha | Active comparator | Drug: Follitropin alpha, Drug: MenotropinFollitropin alpha (GONAL-f, Merck-Serono, Darmstadt, Germany), injections, dosage varying 1500-2500 IU, duration 2-5 days. |
| Menotropin | Active comparator | Drug: Follitropin alpha, Drug: MenotropinMenotropin (Menopur, Ferring GmbH, Kiel, Germany), injections, dosage varying 1500-2500 IU, duration 2-5 days. |
Who may qualify
- Ages
- 25 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- Anti Müllerian Hormone <5pmol or cycle day 2-3 FSH >12
- Endometriosis
- polycystic ovarian syndrome
- pre ovarian failure
- smoking
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Follitropin alphaAlso: Gonal F, Puregon, UrofollitropinThe objective is to measure the effect of the drug according to gonadotropin receptor genotype. | Drug | Follitropin alpha, Menotropin |
| MenotropinAlso: MenopurThe objective is to measure the effect of the drug according to gonadotropin receptor genotype. | Drug | Follitropin alpha, Menotropin |
Primary outcome
Pregnancy
Time frame: up to 12 months after treatment
Association between pregnancy rate and genotype is evaluated
2 secondary outcomes
Number of oocytes
Time frame: up to 6 months after treatment
live birth
Time frame: up to 12 months after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yvonne Lundberg Giwercman, PhD principal investigator
Lund University, Lund, Sweden
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Follitropin alpha and Menotropin in people with Female Infertility, run by Lund University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Poland, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pregnancy (time frame: up to 12 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.