SubfertilityNCT01662180

Predicting Ovarian Response in Artificial Insemination With Low Stimulation

An observational study of Subfertility, run by Isala at 7 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Trial summary

This large prospective multi-center cohort study aims to identify patient's characteristics that significantly influence ovarian response to mild stimulation with a fixed dose of 75 IU recombinant FSH. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Subfertility
What is being tested?: Follicle Stimulating Hormone
Type of treatment: Injection or infusion
How many people: 510 participants
Where: 7 sitesNetherlands
Study dates: Dec 2012to Mar 2015
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 45 years
All sexes
Healthy volunteers accepted
Adult

Study population: Subfertile couples presenting at fertility clinics with an indication for IUI in stimulated cycles

Who may be able to join

couples with unexplained or mild male subfertility (1-3) and a spontaneous chance of conception below 40% (Hunault score).
Unexplained subfertility including minimal to mild endometriosis (AFS grade 1 or 2) is defined as the failure to conceive after at least one year of unprotected intercourse whereas the standard fertility work-up was unable to detect any factors that might influence fertility negatively.
semen analysis should be normal according to the WHO guidelines (8),
ovulation should be documented (by BBT charts, ovulation detection by ultrasound or normal luteal progesterone values),
tubal patency should be confirmed (HSG, laparoscopy or fertiloscopy) and when a postcoital test was performed a cervical factor should have been excluded.
Mild male subfertility is defined as abnormal semen parameters according to the WHO (8) but an average total motile sperm account before processing of at least 10 million.

Who cannot join

Hunault score ≥ 40%
Endometriosis AFS grade 3 or 4
Contra-indications for the use of gonadotrophins (cysts larger than 2 cm, allergy for gonadotrophins)
Total motile sperm count after sperm processing below 1 million
Women aged younger than eighteen years or older than 45 years.
Previous treatment with COH/IUI for treating current subfertility
Unable to speak or read the Dutch language

Trial locations and contacts

7 sites in 1 country.

Maaike M Bloemendal, Drs. contact

0031384247506

m.m.bloemendal@isala.nl

Ben Cohlen, Dr. contact

0031384247570

b.cohlen@isala.nl

City, postcode or hospital

Sites recruiting now only

7 sites in 1 country

Netherlands7 sites, 7 recruiting

OLVG
Amsterdam, Po 95500, 1090 HM
Eugenie Kaaijk, dr., 0031205993481, e.m.kaaijk@olvg.nl
Sabine Logtenberg, 003120-5999111, s.l.m.logtenberg@olvg.nl
Not yet recruiting
AMC
Amsterdam, PO Box 22660, 1100 DD
Fulco van der Veen, prof. dr., 003120 - 566 4287, f.vanderveen@amc.uva.nl
Tessa de Vries, 00316 - 23799274, t.s.devries@amc.uva.nl
Not yet recruiting
VUMC
Amsterdam, PO Box 7057, 1007 MB
Cornelis Lambalk, prof. dr., 0031204444444, cb.lambalk@vumc.nl
Angelique de Vos-Brouwer, 003120-4442180, m.devos-brouwer@vumc.nl
Not yet recruiting
Catharina Ziekenhuis
Eindhoven, PO Box 1350, 5602 ZA
Minouche van Rumste, dr., 003140 239 71 00, minouche.v.rumste@catharinaziekenhuis.nl
Milou Peters, 00316-5102 8887, milou.peters@catharinaziekenhuis.nl
Not yet recruiting
st Elizabeth Gasthuis
Tilburg, PO Box 90151, 5000 LC
Jesper Smeenk, dr., 0031013539 30 06, j.smeenk@elizabeth.nl
Jesper Smeenk, dr.
Not yet recruiting
UMC Utrecht
Utrecht, PO Box 85500, 3508 GA
Frank Broekmans, prof. dr., 088-7551041, f.broekmans@umcutrecht.nl
Marian Kosterman, 088-7555555, M.J.T.Kosterman@umcutrecht.nl
Not yet recruiting
Isala Klinieken
Zwolle, PO Box 10400, 8000 GK
Maaike Bloemendal, Drs., 0031384247506, m.m.bloemendal@isala.nl
Henriette Hulsebos, 0031384247783, h.j.m.hulsebos@isala.nl
Recruiting

Other trials in Netherlands

About this study

Read the detailed description

A multi-center, open-label, prospective cohorts study. Patients with a regular indication for COH/IUI (controlled ovarian stimulation/ intra uterine insemination) will be asked to participate. Patient's characteristics will be documented including age, weight, BMI, smoking status, cycle day 2 3 or 4 FSH /Estradiol levels, antral follicle count, and AMH. AMH and FSH/Estradiol will be determined centrally after completion of inclusion of all patients in the study. All patients will receive a fixed 75 IU recFSH per day conform normal stimulation protocol starting from cycle day 3, 4 or 5 after exclusion of ovarian cysts by ultrasound. Ovarian response will be documented by ultrasound only. Once the dominant follicle(s) reach a mean diameter of 16-18 mm, hCG (5000IU or 250 mcg) will be applied and insemination will be scheduled 36-42 hours later. Cancellation criteria will be defined according to the national guidelines provided by the NVOG (7).

Conditions: Subfertility
Being tested: Follicle Stimulating Hormone
Keywords: subfertility, IUI, rec FSH, FSH, E2, AMH
Medical subject headings: Infertility

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Follicle Stimulating HormoneDrug
Also called Puregon [Merck Sharp & Dohme bv], Gonal -F [Serono Benelux bv]
All patients will receive a fixed 75 IU rec follicle stimulating hormone per day subcutaneous injection stimulation protocol starting from cycle day 3, 4 or 5. The intervention done in this study is conform normal stimulation protocol and is not the target of this study.

Study groups in NCT01662180
Study group	Role	What they receive
Subfertile couples		Subfertile couples presenting at fertility clinics with an indication for IUI in stimulated cycles All patients will receive a fixed 75 IU recombinant follicle stimulating hormone per day conform normal stimulation protocol starting from cycle day 3, 4 or 5. Once the dominant follicle(s) reach a mean diameter of 16-18 mm, hCG (5000IU or 250 mcg) will be applied and insemination will be scheduled 36-42 hours later. Patients will be followed for the time of one menstrual cycle. Receives: Drug: Follicle Stimulating Hormone

What is being measured

The primary outcome is the main question the study is designed to answer.

To assess the relationship between AMH serum levels and ovarian response
(defined by the number of dominant follicles >15mm) in IUI cycles stimulated with a fixed dose of 75 IU recFSH. All follicles > 11 mm will be documented
Measured: one menstrual cycle, one month

Secondary outcomes (5)

To assess the relationship between age, weight, BMI, smoking, AFC, FSH/E2 on CD3 and ovarian response
(defined by the number of dominant follicles >15mm) in IUI cycles stimulated with a fixed dose of 75 IU recFSH.
Measured: one menstrual cycle, one month
Pregnancy rate per started cycle.
From start of the menstrual cycle until a positive heartbeat registered at 12 weeks of gestation.
Measured: three months
Multiple pregnancy rate per started cycle.
From start of the menstrual cycle until positive heartbeats registered at 12 weeks of gestation.
Measured: three months
Miscarriage rate per started cycle.
miscarriage up to 16 weeks of gestation
Measured: five months
Cancellation rate per stimulated cycle
Measured: one menstrual cycle, one month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2012Mar 2015

First posted10 Aug 2012 (estimated)
Study startDec 2012
Primary completionSep 2014 (estimated)
Study completionMar 2015 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (10)Papers the sponsor has linked to this study.
Other trials for SubfertilityStudies 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: Cohort
Time perspective: Prospective
Enrolment: 510 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01662180
Sponsor's protocol ID: PRORAILS trial
Status last verified: Dec 2012
First submitted: 26 Jul 2012
Last updated: 13 Dec 2012
Results posted: No
Data monitoring committee: No

Publications

Bensdorp AJ, Cohlen BJ, Heineman MJ, Vandekerckhove P. Intra-uterine insemination for male subfertility. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000360. doi: 10.1002/14651858.CD000360.pub4.
PubMed 17943739
Verhulst SM, Cohlen BJ, Hughes E, Te Velde E, Heineman MJ. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001838. doi: 10.1002/14651858.CD001838.pub3.
PubMed 17054143
Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril. 1997 Jul;68(1):8-12. doi: 10.1016/s0015-0282(97)81467-7.
PubMed 9207576
Freiesleben NL, Lossl K, Bogstad J, Bredkjaer HE, Toft B, Loft A, Bangsboll S, Pinborg A, Budtz-Jorgensen E, Andersen AN. Predictors of ovarian response in intrauterine insemination patients and development of a dosage nomogram. Reprod Biomed Online. 2008 Nov;17(5):632-41. doi: 10.1016/s1472-6483(10)60310-0.
PubMed 18983747
la Cour Freiesleben N, Lossl K, Bogstad J, Bredkjaer HE, Toft B, Rosendahl M, Loft A, Bangsboll S, Pinborg A, Nyboe Andersen A. Individual versus standard dose of rFSH in a mild stimulation protocol for intrauterine insemination: a randomized study. Hum Reprod. 2009 Oct;24(10):2523-30. doi: 10.1093/humrep/dep239. Epub 2009 Jul 14.
PubMed 19602518
Freiesleben Nl, Rosendahl M, Johannsen TH, Lossl K, Loft A, Bangsboll S, Friis-Hansen L, Pinborg A, Andersen AN. Prospective investigation of serum anti-Mullerian hormone concentration in ovulatory intrauterine insemination patients: a preliminary study. Reprod Biomed Online. 2010 May;20(5):582-7. doi: 10.1016/j.rbmo.2010.02.007. Epub 2010 Feb 12.
PubMed 20303323
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun;16(3):231-45. doi: 10.1093/humupd/dmp048. Epub 2009 Nov 24.
PubMed 19934213
La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010 Mar-Apr;16(2):113-30. doi: 10.1093/humupd/dmp036. Epub 2009 Sep 30.
PubMed 19793843
Nelson SM, Anderson RA, Broekmans FJ, Raine-Fenning N, Fleming R, La Marca A. Anti-Mullerian hormone: clairvoyance or crystal clear? Hum Reprod. 2012 Mar;27(3):631-6. doi: 10.1093/humrep/der446. Epub 2012 Jan 11.
PubMed 22238112
Rutten A, van Ballegooijen H, Broekmans F, Cohlen B; PRORAILS study group. Insights into ovarian response with a fixed low dose FSH stimulation in an IUI programme: the PRORAILS study. Hum Reprod. 2022 Jun 30;37(7):1440-1450. doi: 10.1093/humrep/deac076.
PubMed 35460412

Want to know more?

Maaike M Bloemendal, Drs.

0031384247506

m.m.bloemendal@isala.nl

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The FLORA-project: in Search for the Microbial Cause of Chronic Endometritis and the Most Appropriate Treatment to Obtain a Successful Pregnancy IVF/ICSI
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All Subfertility trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Predicting Ovarian Response in Artificial Insemination With Low Stimulation
ClinicalTrials.gov ID: NCT01662180
Acronym / sponsor ID: PRORAILS trial
Conditions: Subfertility
Keywords: subfertility, IUI, rec FSH, FSH, E2, AMH
Study type: Observational
Recruitment status: Unknown status
Enrolment: 510 participants (estimated)
Lead sponsor: IsalaUniversity, hospital or other
Collaborators: Merck Serono International SA
Study start: Dec 2012
Primary completion: Sep 2014 (estimated)
Study completion: Mar 2015 (estimated)
First posted: 10 Aug 2012 (estimated)
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.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Subfertile couples	–	Drug: Follicle Stimulating HormoneSubfertile couples presenting at fertility clinics with an indication for IUI in stimulated cycles All patients will receive a fixed 75 IU recombinant follicle stimulating hormone per day conform normal stimulation protocol starting from cycle day 3, 4 or 5. Once the dominant follicle(s) reach a mean diameter of 16-18 mm, hCG (5000IU or 250 mcg) will be applied and insemination will be scheduled 36-42 hours later. Patients will be followed for the time of one menstrual cycle.

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult
Study population: Subfertile couples presenting at fertility clinics with an indication for IUI in stimulated cycles

Key inclusion criteria (6 listed)

couples with unexplained or mild male subfertility (1-3) and a spontaneous chance of conception below 40% (Hunault score).
Unexplained subfertility including minimal to mild endometriosis (AFS grade 1 or 2) is defined as the failure to conceive after at least one year of unprotected intercourse whereas the standard fertility work-up was unable to detect any factors that might influence fertility negatively.
semen analysis should be normal according to the WHO guidelines (8),
ovulation should be documented (by BBT charts, ovulation detection by ultrasound or normal luteal progesterone values),
tubal patency should be confirmed (HSG, laparoscopy or fertiloscopy) and when a postcoital test was performed a cervical factor should have been excluded.

Key exclusion criteria (7 listed)

Hunault score ≥ 40%
Endometriosis AFS grade 3 or 4
Contra-indications for the use of gonadotrophins (cysts larger than 2 cm, allergy for gonadotrophins)
Total motile sperm count after sperm processing below 1 million
Women aged younger than eighteen years or older than 45 years.

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
Follicle Stimulating HormoneAlso: Puregon [Merck Sharp & Dohme bv], Gonal -F [Serono Benelux bv]All patients will receive a fixed 75 IU rec follicle stimulating hormone per day subcutaneous injection stimulation protocol starting from cycle day 3, 4 or 5. The intervention done in this study is conform normal stimulation protocol and is not the target of this study.	Drug	Subfertile couples

Primary outcome

To assess the relationship between AMH serum levels and ovarian response
Time frame: one menstrual cycle, one month
(defined by the number of dominant follicles >15mm) in IUI cycles stimulated with a fixed dose of 75 IU recFSH. All follicles > 11 mm will be documented

5 secondary outcomes

To assess the relationship between age, weight, BMI, smoking, AFC, FSH/E2 on CD3 and ovarian response
Time frame: one menstrual cycle, one month
Pregnancy rate per started cycle.
Time frame: three months
Multiple pregnancy rate per started cycle.
Time frame: three months
Miscarriage rate per started cycle.
Time frame: five months
Cancellation rate per stimulated cycle
Time frame: one menstrual cycle, one month

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2012.
Background: PubMed 17943739Bensdorp AJ, Cohlen BJ, Heineman MJ, Vandekerckhove P. Intra-uterine insemination for male subfertility. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000360. doi: 10.1002/14651858.CD000360.pub4.
Background: PubMed 17054143Verhulst SM, Cohlen BJ, Hughes E, Te Velde E, Heineman MJ. Intra-uterine insemination for unexplained subfertility. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD001838. doi: 10.1002/14651858.CD001838.pub3.
Background: PubMed 9207576Tummon IS, Asher LJ, Martin JS, Tulandi T. Randomized controlled trial of superovulation and insemination for infertility associated with minimal or mild endometriosis. Fertil Steril. 1997 Jul;68(1):8-12. doi: 10.1016/s0015-0282(97)81467-7.
Background: PubMed 18983747Freiesleben NL, Lossl K, Bogstad J, Bredkjaer HE, Toft B, Loft A, Bangsboll S, Pinborg A, Budtz-Jorgensen E, Andersen AN. Predictors of ovarian response in intrauterine insemination patients and development of a dosage nomogram. Reprod Biomed Online. 2008 Nov;17(5):632-41. doi: 10.1016/s1472-6483(10)60310-0.
Background: PubMed 19602518la Cour Freiesleben N, Lossl K, Bogstad J, Bredkjaer HE, Toft B, Rosendahl M, Loft A, Bangsboll S, Pinborg A, Nyboe Andersen A. Individual versus standard dose of rFSH in a mild stimulation protocol for intrauterine insemination: a randomized study. Hum Reprod. 2009 Oct;24(10):2523-30. doi: 10.1093/humrep/dep239. Epub 2009 Jul 14.
Background: PubMed 20303323Freiesleben Nl, Rosendahl M, Johannsen TH, Lossl K, Loft A, Bangsboll S, Friis-Hansen L, Pinborg A, Andersen AN. Prospective investigation of serum anti-Mullerian hormone concentration in ovulatory intrauterine insemination patients: a preliminary study. Reprod Biomed Online. 2010 May;20(5):582-7. doi: 10.1016/j.rbmo.2010.02.007. Epub 2010 Feb 12.
Background: PubMed 19934213Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun;16(3):231-45. doi: 10.1093/humupd/dmp048. Epub 2009 Nov 24.
Background: PubMed 19793843La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010 Mar-Apr;16(2):113-30. doi: 10.1093/humupd/dmp036. Epub 2009 Sep 30.
Background: PubMed 22238112Nelson SM, Anderson RA, Broekmans FJ, Raine-Fenning N, Fleming R, La Marca A. Anti-Mullerian hormone: clairvoyance or crystal clear? Hum Reprod. 2012 Mar;27(3):631-6. doi: 10.1093/humrep/der446. Epub 2012 Jan 11.
Derived from this study: PubMed 35460412Rutten A, van Ballegooijen H, Broekmans F, Cohlen B; PRORAILS study group. Insights into ovarian response with a fixed low dose FSH stimulation in an IUI programme: the PRORAILS study. Hum Reprod. 2022 Jun 30;37(7):1440-1450. doi: 10.1093/humrep/deac076.

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Association of Ultrasound Features of the Myometrium Suggestive of Adenomyosis and Clinical Symptoms
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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.

Maaike M Bloemendal, Drs. contact

0031384247506

m.m.bloemendal@isala.nl

Ben Cohlen, Dr. contact

0031384247570

b.cohlen@isala.nl

Ben Cohlen, dr. principal investigator

Isala

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Subfertility, run by Isala at 7 sites in Netherlands.

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 6 inclusion and 7 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 13 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Netherlands. 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 Maaike M Bloemendal, Drs. (0031384247506, m.m.bloemendal@isala.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To assess the relationship between AMH serum levels and ovarian response (time frame: one menstrual cycle, one month). 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 NCT01662180, which also lists 10 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 13 Dec 2012.