Predicting Ovarian Response in Artificial Insemination With Low Stimulation

Subfertility Clinical Trial

Official title:

Predicting Ovarian Response in Artificial Insemination With Low Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01662180
• Other study ID #: PRORAILS trial
• Status: Recruiting
• Phase: N/A
• First received: July 26, 2012
• Last updated: December 12, 2012
• Start date: December 2012
• Est. completion date: March 2015

Study information

• Verified date: December 2012
• Source: Isala
• Contact: Maaike M Bloemendal, Drs.
• Phone: 0031384247506
• Email: m.m.bloemendal[@]isala.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 510
• Est. completion date: March 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Subfertility

Intervention

Drug:
• Follicle Stimulating Hormone
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.

Locations

Country	Name	City	State
Netherlands	AMC	Amsterdam	PO box 22660
Netherlands	OLVG	Amsterdam	Po 95500
Netherlands	VUMC	Amsterdam	PO box 7057
Netherlands	Catharina Ziekenhuis	Eindhoven	PO box 1350
Netherlands	st Elizabeth Gasthuis	Tilburg	PO box 90151
Netherlands	UMC Utrecht	Utrecht	PO box 85500
Netherlands	Isala Klinieken	Zwolle	PO Box 10400

Sponsors (2)

Lead Sponsor	Collaborator
Isala	Merck Serono International SA

Country where clinical trial is conducted

Netherlands, 

References & Publications (9)

Bensdorp AJ, Cohlen BJ, Heineman MJ, Vandekerckhove P. Intra-uterine insemination for male subfertility. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD000360. Review. Update in: Cochrane Database Syst Rev. 2016;2:CD000360. — View Citation

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. Review. — View Citation

Freiesleben NL, Lossl K, Bogstad J, Bredkjaer HE, Toft B, Loft A, Bangsboll S, Pinborg A, Budtz-Jørgensen 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. — View Citation

Freiesleben Nl, Rosendahl M, Johannsen TH, Løssl K, Loft A, Bangsbøll S, Friis-Hansen L, Pinborg A, Andersen AN. Prospective investigation of serum anti-Müllerian 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. — View Citation

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. — View Citation

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. Review. — View Citation

Nelson SM, Anderson RA, Broekmans FJ, Raine-Fenning N, Fleming R, La Marca A. Anti-Müllerian hormone: clairvoyance or crystal clear? Hum Reprod. 2012 Mar;27(3):631-6. doi: 10.1093/humrep/der446. Epub 2012 Jan 11. — View Citation

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. — View Citation

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. Review. Update in: Cochrane Database Syst Rev. 2012;9:CD001838. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	one menstrual cycle, one month	No
Secondary	Pregnancy rate per started cycle.	From start of the menstrual cycle until a positive heartbeat registered at 12 weeks of gestation.	three months	No
Secondary	Multiple pregnancy rate per started cycle.	From start of the menstrual cycle until positive heartbeats registered at 12 weeks of gestation.	three months	No
Secondary	Miscarriage rate per started cycle.	miscarriage up to 16 weeks of gestation	five months	No
Secondary	Cancellation rate per stimulated cycle		one menstrual cycle, one month	No

External Links

•   PRORAILS website