Predicting Ovarian Response in Artificial Insemination With Low Stimulation

NCT01662180 | Unknown

• 1 other identifier: PRORAILS trial
• Study Type: observational
• Target: 510
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Subfertility

Keywords

subfertility, IUI, rec FSH, FSH, E2, AMH

Outcome Measures

Primary Outcomes (1)

• 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

  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

  one menstrual cycle, one month

• Pregnancy rate per started cycle.

  three months

• Multiple pregnancy rate per started cycle.

  three months

• Miscarriage rate per started cycle.

  five months

• Cancellation rate per stimulated cycle

  one menstrual cycle, one month

Study Arms (1)

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.

Drug: Follicle Stimulating Hormone

Interventions

Follicle Stimulating Hormone DRUG

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.

Also known as: Puregon [Merck Sharp & Dohme bv], Gonal -F [Serono Benelux bv]

Subfertile couples

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Isala: lead
• Merck Serono International SA: collaborator

Study Sites (7)

OLVG

Amsterdam, Po 95500, 1090 HM, Netherlands

NOT YET RECRUITING

Isala Klinieken

Zwolle, PO Box 10400, 8000 GK, Netherlands

RECRUITING

Catharina Ziekenhuis

Eindhoven, PO Box 1350, 5602 ZA, Netherlands

NOT YET RECRUITING

AMC

Amsterdam, PO Box 22660, 1100 DD, Netherlands

NOT YET RECRUITING

VUMC

Amsterdam, PO Box 7057, 1007 MB, Netherlands

NOT YET RECRUITING

UMC Utrecht

Utrecht, PO Box 85500, 3508 GA, Netherlands

NOT YET RECRUITING

st Elizabeth Gasthuis

Tilburg, PO Box 90151, 5000 LC, Netherlands

NOT YET RECRUITING

Related Publications (10)

• 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.

  PMID: 17943739 BACKGROUND

• 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.

  PMID: 17054143 BACKGROUND

• 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.

  PMID: 9207576 BACKGROUND

• 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.

  PMID: 18983747 BACKGROUND

• 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.

  PMID: 19602518 BACKGROUND

• 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.

  PMID: 20303323 BACKGROUND

• 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.

  PMID: 19934213 BACKGROUND

• 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.

  PMID: 19793843 BACKGROUND

• 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.

  PMID: 22238112 BACKGROUND

• 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.

  PMID: 35460412 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood sample tested for FSH, E2 and AMH

MeSH Terms

Conditions

Infertility

Interventions

Follicle Stimulating Hormone; follitropin beta; Glycoprotein Hormones, alpha Subunit

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropins, Pituitary; Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Peptides; Amino Acids, Peptides, and Proteins; Chorionic Gonadotropin; Luteinizing Hormone; Thyrotropin; Placental Hormones

Study Officials

• Ben Cohlen, dr.

  Isala

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maaike M Bloemendal, Drs.

CONTACT

0031384247506; m.m.bloemendal@isala.nl

Ben Cohlen, Dr.

CONTACT

0031384247570; b.cohlen@isala.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: drs.

Study Record Dates

• First Submitted: July 26, 2012
• First Posted: August 10, 2012
• Study Start: December 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: March 1, 2015
• Last Updated: December 13, 2012

Record last verified: 2012-12

Locations

NL (7)