inSIGHT: SIGnificance of Routine Hysteroscopy Prior to a First 'in Vitro Fertilization'(IVF) Treatment Cycle

Sponsor

UMC Utrecht (Other)

Overall Status

Completed

CT.gov ID

NCT01242852

Collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other), Erasmus Medical Center (Other), Maastricht University Medical Center (Other), Maxima Medical Center (Other)

750

Enrollment

Location

Arms

Duration (Months)

16.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

BACKGROUND: Despite the numerous advances in the field of in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI), there still exists a maximum implantation rate per embryo transferred of about 30%. Next to the physiological and physic burden that comes with every IVF treatment cycle, implantation failure also adds up to the considerable costs associated with ART. Studies have shown, that minor intrauterine abnormalities can be found in 11-40% of the infertile women with a normal transvaginal sonography. Detection and treatment of these abnormalities by office hysteroscopy have led to a 9-13% increase in pregnancy rate. Therefore, it is increasingly advocated to screen all infertile women on intracavitary pathology prior to the start of IVF/ICSI.

OBJECTIVE: The aim of the proposed study is to assess whether diagnosing and treating unsuspected intrauterine abnormalities by saline infusion sonography and/or routine office hysteroscopy prior to a first IVF/ICSI treatment cycle improves the cost-effectiveness of the fertility treatment.

STUDY DESIGN: Multicenter randomized intervention study. POPULATION: Asymptomatic women, indicated for a first IVF/ICSI treatment cycle and a normal transvaginal ultrasonography.

INTERVENTION: Participants will be randomized for a (SIS and) hysteroscopy with treatment-on-the spot of predefined intrauterine abnormalities versus no diagnostic work-up. In both groups standard IVF/ICSI treatment will be initiated.

PRIMARY OUTCOME MEASURE:

Cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomization (obtained in both treatment cycles with fresh embryos, as well as in subsequent cryo/thaw cycles)

SECONDARY OUTCOME MEASURE:

Cumulative implantation rate achieved within 18 months of IVF/ICSI treatment after randomization (obtained in both treatment cycles with fresh embryos, as well as in subsequent cryo/thaw cycles)
Cumulative miscarry rate within 18 months of IVF/ICSI treatment after randomization (obtained in both treatment cycles with fresh embryos, as well as in subsequent cryo/thaw cycles)
Cost calculations of, SIS, hysteroscopy procedures and the IVF treatment
Patient preference and tolerance of a SIS and diagnostic/therapeutic hysteroscopy procedure
Prevalence of unexpected intrauterine abnormalities
Diagnostic accuracy of SIS in diagnosing intrauterine abnormalities

Condition or Disease	Intervention/Treatment	Phase
Intrauterine Abnormalities in Infertility	Procedure: Office hysteroscopy (in combination with a 'Saline Infusion Sonography'(SIS))	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

750 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Care Provider)

Primary Purpose:

Diagnostic

Official Title:

SIGnificance of Routine Hysteroscopy Prior to a First 'in Vitro Fertilization'(IVF) Treatment Cycle

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Additional diagnostic tests Participants in the experimental arm will undergo standard hysteroscopy with treatment-on-the spot of predefined intrauterine abnormalities. In two of the participating clinics, also a 'Saline Infusion Sonography' (SIS) will be performed, 1 week before the hysteroscopy. After the additional diagnostic test(s), standard IVF/ICSI treatment will be initiated.	Procedure: Office hysteroscopy (in combination with a 'Saline Infusion Sonography'(SIS)) Routine fertility work-up, added up with diagnostic tests. In 5 research centers the extra tests consist of SIS & hysteroscopy (HY). In the other research hospitals it consists of only a HY. The HY examination will be scheduled on Day 3-12 of a cycle. It will be performed in an outpatient setting with a vaginoscopic approach. A 5-mm diameter continuous flow hysteroscope and a 30º direction of view will be used. The uterus will be inspected methodically a endometrial biopsy obtained and the findings recorded into a standardized form. Intrauterine pathology is defined as septum, endometrial polyp, submucous myoma, adhesions & endometritis. These will be treated, using scissors, Versapoint, grasping forceps, polyp snare or antibiotics. In 5 of the research hospitals, 1 week prior to the HY, also a SIS will be performed. Via a catheter saline solution will be infused into the uterine cavity as distention media. The findings at the following sonography will be standardized recorded. Other Names: Hysteroscopy
No Intervention: Routine fertility workup Patients allocated to the conventional strategy will be scheduled for IVF and undergo standard treatment, without SIS or hysteroscopy.

Arm

Intervention/Treatment

Experimental: Additional diagnostic tests

Participants in the experimental arm will undergo standard hysteroscopy with treatment-on-the spot of predefined intrauterine abnormalities. In two of the participating clinics, also a 'Saline Infusion Sonography' (SIS) will be performed, 1 week before the hysteroscopy. After the additional diagnostic test(s), standard IVF/ICSI treatment will be initiated.

Procedure: Office hysteroscopy (in combination with a 'Saline Infusion Sonography'(SIS))

Routine fertility work-up, added up with diagnostic tests. In 5 research centers the extra tests consist of SIS & hysteroscopy (HY). In the other research hospitals it consists of only a HY. The HY examination will be scheduled on Day 3-12 of a cycle. It will be performed in an outpatient setting with a vaginoscopic approach. A 5-mm diameter continuous flow hysteroscope and a 30º direction of view will be used. The uterus will be inspected methodically a endometrial biopsy obtained and the findings recorded into a standardized form. Intrauterine pathology is defined as septum, endometrial polyp, submucous myoma, adhesions & endometritis. These will be treated, using scissors, Versapoint, grasping forceps, polyp snare or antibiotics. In 5 of the research hospitals, 1 week prior to the HY, also a SIS will be performed. Via a catheter saline solution will be infused into the uterine cavity as distention media. The findings at the following sonography will be standardized recorded.

Other Names:

Hysteroscopy

No Intervention: Routine fertility workup

Patients allocated to the conventional strategy will be scheduled for IVF and undergo standard treatment, without SIS or hysteroscopy.

Outcome Measures

Primary Outcome Measures

Ongoing pregnancy [18 months]
Cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation (obtained in both treatment cycles with fresh embryos, as well as in subsequent cryo/thaw cycles)

Secondary Outcome Measures

Implantation rate [18 months]
Cumulative implantation rate achieved within 18 months of IVF/ICSI treatment after randomisation (obtained in both treatment cycles with fresh embryos, as well as in subsequent cryo/thaw cycles)
Miscarry rate [18 months]
Cumulative miscarry rate within 18 months of IVF/ICSI treatment after randomisation (obtained in both treatment cycles with fresh embryos, as well as in subsequent cryo/thaw cycles)
Costs [24 months]
Cost calculations of, SIS, hysteroscopy procedures and the IVF treatment
Patient tolerance [24 months]
Patient tolerance of a SIS and diagnostic/therapeutic hysteroscopy procedure
Prevalence of unexpected intrauterine abnormalities [3 months]
Diagnostic accuracy of SIS [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Women indicated for a first IVF/ICSI treatment
Primary or secondary infertility
Normal Transvaginal Ultrasound, performed in the follicular phase of the menstrual cycle