In Vitro FertilizationNCT04122729
N680S Polymorphism of the FSHR Gene and Its Relationship With the Type of Gonadotropin Used in COS
An observational study of In Vitro Fertilization and Controlled Ovarian Stimulation, run by Angelini Farmacéutica at 12 sites in Spain.
Trial summary
This project wants to determinate whether there is a relationship between the N680S polymorphism genotype of the FSHR gene and the nature of the FSH used in controlled ovarian stimulation. Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- In Vitro Fertilization, Controlled Ovarian Stimulation
- How many people
- 300 participants
- Where
- 12 sitesSpain
- Study dates
- 25 Sep 2019to Jun 2020
- Phase
- Observational
- 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 18 to 37 years
- Women only
- No healthy volunteers
- Adult
Study population: Patients undergoing two cycles of IVF/ICSI who achieved a suboptimal response after the 1st cycle, did not become pregnant, and consequently underwent another cycle of COS in which the protocol was amended during the 2nd cycle to change the nature of the FSH used during the 1st cycle.
Who may be able to join
- Signature of Informed Consent
- Age ≤ 37 years
- BMI < 30 kg/m2
- Antral follicles count 1st cycle COS = 5-15
- Antimüllerian hormone basal 1st cycle COS > 1,1 ng/ml and < 3,1 ng/ml
- COS protocol: equal starting dose in the 2 cycles of COS (150-225 UI/day) with dose adjustment from the 5th day of COS; pituitary suppression protocol in the 2 cycles of COS with GnRH antagonist with onset when ≥ 1 follicle of ≥ 14 mm in diameter or E2 ≤ 600 pg/ml; and triggering with hCGr or GnRH agonist
Show all 9Show fewer
- Optional the use of oral contraceptives (OC) (however, same in the 2 cycles)
- 4-9 recovered oocytes in the 1st cycle of COS
- ≤ 6 months between the 2 cycles of COS
Who cannot join
- Use of the LH activity during the cycles of COS
- Presence of severe male factor
- Grade III-IV endometriosis
- Patients with polycystic ovary syndrome, a history of uterine or ovarian surgeries, hydrosalpinx visible by ultrasound, or uterine fibroids measuring > 30 mm
- Major systemic or uncontrolled endocrine-metabolic diseases affecting the pituitary gland, the thyroid gland, the adrenal glands, the pancreas, the liver, or the kidneys
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Spain12 sites, 12 recruiting
- Recruiting
Hospital Universitario Fundación Alcorcón
Alcorcón, Madrid
Berta Mª Martín, PhD
- Not yet recruiting
Hospital Clínic
Barcelona
Dolors Manau, PhD
- Not yet recruiting
Hospital Universitario Vall d'Hebron
Barcelona
Julio Herrero, PhD
- Not yet recruiting
Hospital Universitario Reina Sofía
Córdoba
Juan Lorente, PhD
- Not yet recruiting
Hospital Virgen de las Nieves
Granada
Luis Martínez, PhD
- Not yet recruiting
Hospital Clínico San Carlos
Madrid
Mª Isabel Calventus, PhD
- Recruiting
Hospital General Universitario Gregorio Marañon
Madrid
Miguel Caballero, PhD
- Recruiting
Hospital Universitario 12 de Octubre
Madrid
Laura de la Fuente, PhD, +34 917 452 520
- Recruiting
Hospital Universitario La Paz
Madrid
Sonia Lobo, PhD, +34 917 277 219
- Not yet recruiting
Hospital Universitario Príncipe de Asturias
Madrid
Irene Heras, PhD
- Not yet recruiting
Hospital Universitario y Politécnico La Fe
Valencia
José Mª Rubio, PhD
- Not yet recruiting
Hospital Clínico Universitario Valladolid
Valladolid
Ana Casas, PhD
About this study
Official title: Study of the N680S Polymorphism of the FSHR Gene and Its Relationship With the Type of Gonadotropin Used in Controlled Ovarian Stimulation
This project wants to determinate whether there is a relationship between the N680S polymorphism genotype of the FSHR gene and the nature of the FSH used in controlled ovarian stimulation.
It is a non-interventional, observational, cross-sectional and retrospective, national and multicenter study, in which a genetic test will be carried out to determine the genotype of the N680S polymorphism in samples of blood of patients who have undergone two cycles of controlled ovarian stimulation in the last 8 months.
Read the detailed description
The investigators want to investigate whether the N680S polymorphism of the FSRH gene could affects ovarian response with different nature of the FSH used (human FSH and recombinant FSH) in patients undergoing two consecutive cycles of IVF/ICSI with controlled ovarian stimulation.
All patients who agree to participate in the study will have a blood sample taken on the same day as a routine extraction performed for the 2nd cycle of the controlled ovarian stimulation in accordance with the standard clinical practice of each hospital. The sample will be sent to the central laboratory to determine the genotype of the afore mentioned polymorphism and correlate it with the clinical results obtained with the two cycles of controlled ovarian stimulation.
In order to avoid any bias, the study population will follow a crossover design with respect to the type of FSH used in the first and second cycles of the COS (i.e., half of the recruited patients must have undergone a first cycle of COS with recombinant FSH and a second cycle with human FSH; and, conversely, the other half must have undergone a first cycle with human FSH and a second cycle with recombinant FSH). In order to avoid potential modifications to the inclusion criteria, the time elapsed between the two cycles should not exceed 6 months.
- Keywords
- Highly purified human follicle stimulating hormone (HP-FSH), Recombinant follicle stimulating hormone (rFSH), FSH receptor (FSHR), Polymorphism N680S of the FSHR, Polymorphism N312S of the LHCGR, LHCG receptor (LHCGR), Polymorphism c.2039G>A, Polymorphism c.935A>G
What is being measured
The primary outcome is the main question the study is designed to answer.
Oocytes retrieved
Number of oocytes retrieved in each IVF/ICSI cycle with controlled ovarian stimulation used different nature of the FSH in each one (human FSH and recombinant FSH).
Measured: Through study completion, an average of 1 year
Genotype of the N680S polymorphism of the FSHR gene
Genotype of the N680S polymorphism of the FSHR gene will be tested on blood samples
Measured: Through study completion, an average of 1 year
Secondary outcomes (1)
Genotype of the N312S polymorphism of the LHCGR gene
Genotype of the N312S polymorphism of the LHCGR gene will be tested on blood samples
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start25 Sep 2019
- Primary completionApr 2020 (estimated)
- Study completionJun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for In Vitro FertilizationStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Angelini Farmacéutica
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sistemas Genómicos
- Responsible party
- Sponsor
- Investigators
- María Carrera, PhD, Study director, Hospital Universitario 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04122729
- Sponsor's protocol ID
- ANG-FOS-2019-01
- Status last verified
- Oct 2019
- First submitted
- 9 Oct 2019
- Last updated
- 10 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the controlled ovulatory cycle. Science. 1981 May 8;212(4495):681-2. doi: 10.1126/science.7221557.
PubMed 7221556Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.
PubMed 21558332Kligman I, Rosenwaks Z. Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders. Fertil Steril. 2001 Dec;76(6):1185-90. doi: 10.1016/s0015-0282(01)02893-x.
PubMed 11730748Freour T, Masson D, Mirallie S, Jean M, Bach K, Dejoie T, Barriere P. Active smoking compromises IVF outcome and affects ovarian reserve. Reprod Biomed Online. 2008 Jan;16(1):96-102. doi: 10.1016/s1472-6483(10)60561-5.
PubMed 18252054Coccia ME, Rizzello F. Ovarian reserve. Ann N Y Acad Sci. 2008 Apr;1127:27-30. doi: 10.1196/annals.1434.011.
PubMed 18443326Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006 Nov-Dec;12(6):685-718. doi: 10.1093/humupd/dml034. Epub 2006 Aug 4.
PubMed 16891297Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014 Sep-Oct;20(5):688-701. doi: 10.1093/humupd/dmu020. Epub 2014 May 12.
PubMed 24821925Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
PubMed 21505041Polyzos NP, Nwoye M, Corona R, Blockeel C, Stoop D, Haentjens P, Camus M, Tournaye H. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014 Apr;28(4):469-74. doi: 10.1016/j.rbmo.2013.11.010. Epub 2013 Dec 4.
PubMed 24581984Sunkara SK, Coomarasamy A, Faris R, Braude P, Khalaf Y. Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial. Fertil Steril. 2014 Jan;101(1):147-53. doi: 10.1016/j.fertnstert.2013.09.035. Epub 2013 Nov 1.
PubMed 24188873Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, Muasher SJ. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014 Apr;101(4):967-73. doi: 10.1016/j.fertnstert.2013.12.026. Epub 2014 Jan 23.
PubMed 24462057van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S, van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010 Nov-Dec;16(6):577-89. doi: 10.1093/humupd/dmq015. Epub 2010 Jun 25.
PubMed 20581128van der Gaast MH, Eijkemans MJ, van der Net JB, de Boer EJ, Burger CW, van Leeuwen FE, Fauser BC, Macklon NS. Optimum number of oocytes for a successful first IVF treatment cycle. Reprod Biomed Online. 2006 Oct;13(4):476-80. doi: 10.1016/s1472-6483(10)60633-5.
PubMed 17007663Verberg MF, Eijkemans MJ, Macklon NS, Heijnen EM, Baart EB, Hohmann FP, Fauser BC, Broekmans FJ. The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF: a meta-analysis. Hum Reprod Update. 2009 Jan-Feb;15(1):5-12. doi: 10.1093/humupd/dmn053.
PubMed 19091754Polyzos NP, Sunkara SK. Sub-optimal responders following controlled ovarian stimulation: an overlooked group? Hum Reprod. 2015 Sep;30(9):2005-8. doi: 10.1093/humrep/dev149. Epub 2015 Jul 21.
PubMed 26202582
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the N680S Polymorphism of the FSHR Gene and Its Relationship With the Type of Gonadotropin Used in Controlled Ovarian Stimulation
- ClinicalTrials.gov ID
- NCT04122729
- Acronym / sponsor ID
- ANG-FOS-2019-01
- Keywords
- Highly purified human follicle stimulating hormone (HP-FSH), Recombinant follicle stimulating hormone (rFSH), FSH receptor (FSHR), Polymorphism N680S of the FSHR, Polymorphism N312S of the LHCGR, LHCG receptor (LHCGR), Polymorphism c.2039G>A, Polymorphism c.935A>G
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Angelini FarmacéuticaIndustry (pharma, biotech, devices)
- Collaborators
- Sistemas Genómicos
- Study start
- 25 Sep 2019 (actual)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 10 Oct 2019 (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.
This project wants to determinate whether there is a relationship between the N680S polymorphism genotype of the FSHR gene and the nature of the FSH used in controlled ovarian stimulation.
It is a non-interventional, observational, cross-sectional and retrospective, national and multicenter study, in which a genetic test will be carried out to determine the genotype of the N680S polymorphism in samples of blood of patients who have undergone two cycles of controlled ovarian stimulation in the last 8 months.
Detailed description
The investigators want to investigate whether the N680S polymorphism of the FSRH gene could affects ovarian response with different nature of the FSH used (human FSH and recombinant FSH) in patients undergoing two consecutive cycles of IVF/ICSI with controlled ovarian stimulation.
All patients who agree to participate in the study will have a blood sample taken on the same day as a routine extraction performed for the 2nd cycle of the controlled ovarian stimulation in accordance with the standard clinical practice of each hospital. The sample will be sent to the central laboratory to determine the genotype of the afore mentioned polymorphism and correlate it with the clinical results obtained with the two cycles of controlled ovarian stimulation.
In order to avoid any bias, the study population will follow a crossover design with respect to the type of FSH used in the first and second cycles of the COS (i.e., half of the recruited patients must have undergone a first cycle of COS with recombinant FSH and a second cycle with human FSH; and, conversely, the other half must have undergone a first cycle with human FSH and a second cycle with recombinant FSH). In order to avoid potential modifications to the inclusion criteria, the time elapsed between the two cycles should not exceed 6 months.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Patients undergoing two cycles of IVF/ICSI who achieved a suboptimal response after the 1st cycle, did not become pregnant, and consequently underwent another cycle of COS in which the protocol was amended during the 2nd cycle to change the nature of the FSH used during the 1st cycle.
Key inclusion criteria (9 listed)
- Signature of Informed Consent
- Age ≤ 37 years
- BMI < 30 kg/m2
- Antral follicles count 1st cycle COS = 5-15
- Antimüllerian hormone basal 1st cycle COS > 1,1 ng/ml and < 3,1 ng/ml
Key exclusion criteria (5 listed)
- Use of the LH activity during the cycles of COS
- Presence of severe male factor
- Grade III-IV endometriosis
- Patients with polycystic ovary syndrome, a history of uterine or ovarian surgeries, hydrosalpinx visible by ultrasound, or uterine fibroids measuring > 30 mm
- Major systemic or uncontrolled endocrine-metabolic diseases affecting the pituitary gland, the thyroid gland, the adrenal glands, the pancreas, the liver, or the kidneys
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Oocytes retrieved
Time frame: Through study completion, an average of 1 year
Number of oocytes retrieved in each IVF/ICSI cycle with controlled ovarian stimulation used different nature of the FSH in each one (human FSH and recombinant FSH).
Genotype of the N680S polymorphism of the FSHR gene
Time frame: Through study completion, an average of 1 year
Genotype of the N680S polymorphism of the FSHR gene will be tested on blood samples
1 secondary outcome
Genotype of the N312S polymorphism of the LHCGR gene
Time frame: Through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2019.
- Background: PubMed 7221556Trounson AO, Leeton JF, Wood C, Webb J, Wood J. Pregnancies in humans by fertilization in vitro and embryo transfer in the controlled ovulatory cycle. Science. 1981 May 8;212(4495):681-2. doi: 10.1126/science.7221557.
- Background: PubMed 21558332Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011 Jul;26(7):1768-74. doi: 10.1093/humrep/der106. Epub 2011 May 10.
- Background: PubMed 11730748Kligman I, Rosenwaks Z. Differentiating clinical profiles: predicting good responders, poor responders, and hyperresponders. Fertil Steril. 2001 Dec;76(6):1185-90. doi: 10.1016/s0015-0282(01)02893-x.
- Background: PubMed 18252054Freour T, Masson D, Mirallie S, Jean M, Bach K, Dejoie T, Barriere P. Active smoking compromises IVF outcome and affects ovarian reserve. Reprod Biomed Online. 2008 Jan;16(1):96-102. doi: 10.1016/s1472-6483(10)60561-5.
- Background: PubMed 18443326Coccia ME, Rizzello F. Ovarian reserve. Ann N Y Acad Sci. 2008 Apr;1127:27-30. doi: 10.1196/annals.1434.011.
- Background: PubMed 16891297Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update. 2006 Nov-Dec;12(6):685-718. doi: 10.1093/humupd/dml034. Epub 2006 Aug 4.
- Background: PubMed 24821925Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014 Sep-Oct;20(5):688-701. doi: 10.1093/humupd/dmu020. Epub 2014 May 12.
- Background: PubMed 21505041Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
- Background: PubMed 24581984Polyzos NP, Nwoye M, Corona R, Blockeel C, Stoop D, Haentjens P, Camus M, Tournaye H. Live birth rates in Bologna poor responders treated with ovarian stimulation for IVF/ICSI. Reprod Biomed Online. 2014 Apr;28(4):469-74. doi: 10.1016/j.rbmo.2013.11.010. Epub 2013 Dec 4.
- Background: PubMed 24188873Sunkara SK, Coomarasamy A, Faris R, Braude P, Khalaf Y. Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial. Fertil Steril. 2014 Jan;101(1):147-53. doi: 10.1016/j.fertnstert.2013.09.035. Epub 2013 Nov 1.
- Background: PubMed 24462057Steward RG, Lan L, Shah AA, Yeh JS, Price TM, Goldfarb JM, Muasher SJ. Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil Steril. 2014 Apr;101(4):967-73. doi: 10.1016/j.fertnstert.2013.12.026. Epub 2014 Jan 23.
- Background: PubMed 20581128van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S, van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010 Nov-Dec;16(6):577-89. doi: 10.1093/humupd/dmq015. Epub 2010 Jun 25.
- Individual participant dataSharing planned: Undecided
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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.
María Carrera, PhD study director
Hospital Universitario 12 de Octubre
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of In Vitro Fertilization and Controlled Ovarian Stimulation, run by Angelini Farmacéutica at 12 sites in Spain.
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 9 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 10 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Spain. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cristina Macarrilla (+34 932 534 643, cristina.macarrilla@angelinipharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Oocytes retrieved (time frame: Through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04122729, which also lists 40 linked publications.
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 10 Oct 2019; AzTrials last refreshed its copy on 7 Nov 2026.