A multi-centre randomised controlled study of pre-IVF outpatient hysteroscopy in women with recurrent IVF implantation failure: Trial of Outpatient Hysteroscopy - [TROPHY] in IVF

Abstract

BackgroundThe success rate of IVF treatment is low. A recent systematic review and meta-analysis found that the outcome of IVF treatment could be improved in patients who have experienced recurrent implantation failure if an outpatient hysteroscopy (OH) is performed before starting the new treatment cycle. However, the trials were of variable quality, leading to a call for a large and high-quality randomised trial. This protocol describes a multi-centre randomised controlled trial to test the hypothesis that performing an OH prior to starting an IVF cycle improves the live birth rate of the subsequent IVF cycle in women who have experienced two to four failed IVF cycles.Methods and designEligible and consenting women will be randomised to either OH or no OH using an internet based trial management programme that ensures allocation concealment and employs minimisation for important stratification variables including age, body mass index, basal follicle stimulating hormone level and number of previous failed IVF cycles. The primary outcome is live birth rate per IVF cycle started. Other outcomes include implantation, clinical pregnancy and miscarriage rates.The sample size for this study has been estimated as 758 participants with 379 participants in each arm. Interim analysis will be conducted by an independent Data Monitoring Committee (DMC), and final analysis will be by intention to treat. A favourable ethical opinion has been obtained (REC reference: 09/H0804/32).Trail RegistrationThe trial has been assigned the following ISRCTN number: ISRCTN35859078

The Value of Routine Hysteroscopy before the First Intracytoplasmic Sperm Injection Treatment Cycle

“…In our series, no complications were reported and the procedure was well tolerated by all women. The vaginoscopic approach without using speculum and tenaculum is helpful in improving patients' tolerance [15] . Minor abnormalities have successfully been treated in the same setting.…”

“…Currently, hysteroscopy is conventional intra uterine investigation of women with repeated implantation failure [9,10,14,15] . However, in the medical literature, there is no adequate evidence concerning routine hysteroscopy before starting the first IVF treatment.…”

Effect of hysteroscopic examination on the outcome of in vitro fertilization

“…Nije utvrđeno postojanje značajne razlike u uspešnosti ishoda IVF postupka kod bolesnica sa normalnim histeroskopskim nalazom i onih sa detektovanom patologijom kavuma. Metaanaliza je pokazala da se izvođe-njem histeroskopije pre planiranog IVF ciklusa stopa trudnoće duplira, mada su rezultati velikog multicentarskog ispitivanja, koje je u toku, neophodni za uspostavljanje protokola procedura i utvrđivanja definitivnog učinka histeroskopije na ishod IVF ciklusa 18 . Ovi rezultati slažu se sa našim i konačno se potvrđuje da otkrivanje urednog nalaza histeroskopije daje dvostuko veću stopu trudnoće i porođaja.…”

Endometrial inflammation and effect on implantation improvement and pregnancy outcome

“…Still, there is no consensus protocol regarding the optimal number and timing of the biopsies that are needed for achieving the improvement in implantation and a large-scale prospective randomized trial is required in order to elucidate this issue. Along this line, other forms of mechanical manipulation in human, such as curettage and hysteroscopy (Friedler et al 1993, Mooney & Milki 2003, Rama Raju et al 2006, El-Toukhy et al 2009, Bosteels et al 2010, also generate a favorable effect on the pregnancy outcome in IVF patients. Taken together, these findings suggest that the success of implantation in all these cases is apparently attributed to an injury-induced inflammatory reaction that leads to the development of an adequate decidua supporting implantation.…”