HYALOBARRIER® GEL ENDO Versus no HYALOBARRIER® GEL ENDO Following Operative Hysteroscopy for Improving Reproductive Outcome in Women With Intrauterine Pathology Wishing to Become Pregnant

Infertility Clinical Trial

— AGNOHSTIC  

Official title:

The Cost-effectiveness of Anti-adhesion Treatment With HYALOBARRIER® GEL ENDO Versus no Gel Following the Removal by Hysteroscopy of Endometrial Polyps, Fibroids With Uterine Cavity Deformation, Uterine Septa, Intrauterine Adhesions or Retained Products of Conception for Improving Reproductive Outcome in Women Wishing to Become Pregnant: a Multi-centre, Parallel Group, Superiority, Double-blind, Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03880435
• Other study ID #: AGNOHSTIC
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 1, 2019
• Est. completion date: May 31, 2025

Study information

• Verified date: January 2024
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the costs and effects of HYALOBARRIER® GEL ENDO versus no HYALOBARRIER® GEL ENDO for increasing the chance of conception leading to live birth measured at 30 weeks after randomization in women wishing to become pregnant after surgical removal of intrauterine pathology (endometrial polyps, fibroids with uterine cavity deformation, uterine septa, IUAs or RPOC after miscarriage) by hysteroscopy as an outpatient or in hospital treatment.

Description:

Design: Multi-centre, parallel group, superiority, double-blind, randomized controlled trial. Post market study of a Medical Device class III. Participant: Women aged 18 to 47 years attending Belgian gynaecological departments, scheduled for operative hysteroscopy for endometrial polyps, fibroids with uterine cavity deformation, uterine septa, intrauterine adhesions (IUAs) or retained products of conception, and wishing to conceive spontaneously or before fertility treatment with ovulation induction (OI), controlled ovarian stimulation (COS), intrauterine insemination (IUI) or IVF/ICSI. Treatment: Application of Hyalobarrier® gel endo at time of surgery Control: No application of Hyalobarrier® gel endo Follow up: short term follow-up: 30 weeks after receiving the treatment allocation long term follow-up: 66 weeks after receiving the treatment allocation To blind all trial participants, fertility physicians and gynaecologists doing second- or third-look hysteroscopy, 10 ml of a sterile ultrasound gel will be applied into the vagina at the end of the procedure in all women regardless of their treatment allocation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 419
• Est. completion date: May 31, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 47 Years

Eligibility

Inclusion Criteria:

Women aged 18 to 47 years attending Belgian fertility clinics, scheduled for operative hysteroscopy for endometrial polyps, fibroids with uterine cavity deformation, uterine septa, intrauterine adhesions (IUAs) and retained products of conception, and wishing to conceive spontaneously or before fertility treatment with ovulation induction (OI), controlled ovarian stimulation (COS), intrauterine insemination (IUI) or IVF/ICSI.

Exclusion Criteria:

• Women younger than 18 years
• Women 48 years of age or older
• Women with a known allergy to HYALOBARRIER® GEL ENDO
• Women with an active infection of the genital tract proven by genital swabs for PCR (Chlamydia, gonococci) or endometrial biopsy (endometritis), not treated at the time of the pre- screening visit. Women adequately treated with proven cure (negative swabs or normal endometrial biopsy) can be included
• Subserosal fibroids (FIGO or PALM-COEIN classification type 6, 7) - leiomyomas that originate from the myometrium at the serosa of the uterus or intramural fibroids without uterine cavity deformation as documented by ultrasound, hysterography or hysteroscopy - as the sole uterine cavity abnormality identified in the screening phase.
• Women with fibroids, polyps, uterine septa or IUAs suffering from other symptoms, for instance abnormal uterine bleeding, but not wishing to conceive from 6 weeks following surgery
• Women with other Müllerian tract anomalies other than a uterine septum as the sole uterine cavity abnormality identified in the screening phase
• Women who participated in the trial but failed to conceive and who present with a recurrence of polyps, fibroids with cavity deformation, uterine septum or IUAs
• Women who refuse to give written informed consent.

Related Conditions & MeSH terms

• Adhesion
• Hysteroscopy
• Infertility
• Leiomyoma
• Myoma;Uterus
• Polyp Uterus
• Polyps
• Retained Products of Conception
• Septate Uterus
• Tissue Adhesions
• Uterine Septum

Intervention

Device:
• Hyalobarrier® gel endo
Intra-uterine application of 10ml sterile gel containing 30mg APC. It will be administered once, peroperatively immediate after the complete hysteroscopic removal of the polyp, myoma, adhesion, uterine septum or retained products of conception

Locations

Country	Name	City	State
Belgium	University hospital Ghent	Ghent	East-Flanders

Sponsors (9)

Lead Sponsor	Collaborator
University Hospital, Ghent	Belgium Health Care Knowledge Centre, Health, Innovation and Research Institute (HIRUZ) UZ Ghent, Jessa hospital, Hasselt, Nordic Pharma SAS, UCL Bruxelles, Universitair Ziekenhuis Brussel, Universitaire Ziekenhuizen KU Leuven, University of Liege

Country where clinical trial is conducted

Belgium, 

References & Publications (12)

Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, Cirillo D, Taylor A, Nappi C. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. Hum Reprod. 2003 Sep;18(9):1918-21. doi: 10.1093/humrep/deg368. — View Citation

Bosteels J, Weyers S, Kasius J, Broekmans FJ, Mol BW, D'Hooghe TM. Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility. Cochrane Database Syst Rev. 2015 Nov 9;(11):CD011110. doi: 10.1002/14651858.CD011110.pub2. — View Citation

Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on fertility. Gynecol Endocrinol. 2006 Feb;22(2):106-9. doi: 10.1080/09513590600604673. — View Citation

Di Spiezio Sardo A, Spinelli M, Bramante S, Scognamiglio M, Greco E, Guida M, Cela V, Nappi C. Efficacy of a polyethylene oxide-sodium carboxymethylcellulose gel in prevention of intrauterine adhesions after hysteroscopic surgery. J Minim Invasive Gynecol. 2011 Jul-Aug;18(4):462-9. doi: 10.1016/j.jmig.2011.04.007. — View Citation

Farhi J, Orvieto R. Cumulative clinical pregnancy rates after COH and IUI in subfertile couples. Gynecol Endocrinol. 2010 Jul;26(7):500-4. doi: 10.3109/09513590903367036. — View Citation

Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P. Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD001122. doi: 10.1002/14651858.CD001122.pub3. — View Citation

Gnoth C, Godehardt D, Godehardt E, Frank-Herrmann P, Freundl G. Time to pregnancy: results of the German prospective study and impact on the management of infertility. Hum Reprod. 2003 Sep;18(9):1959-66. doi: 10.1093/humrep/deg366. — View Citation

Guida M, Acunzo G, Di Spiezio Sardo A, Bifulco G, Piccoli R, Pellicano M, Cerrota G, Cirillo D, Nappi C. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. Hum Reprod. 2004 Jun;19(6):1461-4. doi: 10.1093/humrep/deh238. Epub 2004 Apr 22. — View Citation

Jansen FW, Vredevoogd CB, van Ulzen K, Hermans J, Trimbos JB, Trimbos-Kemper TC. Complications of hysteroscopy: a prospective, multicenter study. Obstet Gynecol. 2000 Aug;96(2):266-70. doi: 10.1016/s0029-7844(00)00865-6. — View Citation

Kasius JC, Broekmans FJ, Veersema S, Eijkemans MJ, van Santbrink EJ, Devroey P, Fauser BC, Fatemi HM. Observer agreement in the evaluation of the uterine cavity by hysteroscopy prior to in vitro fertilization. Hum Reprod. 2011 Apr;26(4):801-7. doi: 10.1093/humrep/der003. Epub 2011 Feb 9. — View Citation

McLernon DJ, Maheshwari A, Lee AJ, Bhattacharya S. Cumulative live birth rates after one or more complete cycles of IVF: a population-based study of linked cycle data from 178,898 women. Hum Reprod. 2016 Mar;31(3):572-81. doi: 10.1093/humrep/dev336. Epub 2016 Jan 18. — View Citation

Perez-Medina T, Bajo-Arenas J, Salazar F, Redondo T, Sanfrutos L, Alvarez P, Engels V. Endometrial polyps and their implication in the pregnancy rates of patients undergoing intrauterine insemination: a prospective, randomized study. Hum Reprod. 2005 Jun;20(6):1632-5. doi: 10.1093/humrep/deh822. Epub 2005 Mar 10. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Conception leading to live birth	the amount of clinical pregnancies at 30 weeks after randomisation, leading to live birth (at least one live foetus after 20 weeks of gestation, that resulted in at least one live baby (the investigators counted the delivery of singleton, twin or multiple pregnancies as one live birth)	> 30 weeks after randomisation
Secondary	Time to conception	the time from receiving the allocated treatment to the date of conception	< 30 weeks after receiving treatment allocation
Secondary	Clinical pregnancy	An ultrasound visible gestational sac	< 30 weeks after receiving treatment allocation
Secondary	Miscarriage	a spontaneous loss of pregnancy before 20 completed weeks of gestational age, or if gestational age is unknown, the loss of an embryo/fetus of less than 400 grams	< 30 weeks after receiving treatment allocation
Secondary	Ectopic pregnancy	a pregnancy in which implantation takes place outside the uterine cavity	< 30 weeks after receiving treatment allocation
Secondary	Adhesions	The severity will be scored according to the revised American Fertility Society (AFS) scoring system	> 30w after receiving treatment allocation (in women who failed to conceive)
Secondary	Pre-eclampsia	Pre-eclampsia in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation	> 30 weeks after receiving treatment allocation
Secondary	Preterm birth	Preterm birth in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation	> 30 weeks after receiving treatment allocation
Secondary	Stilbirth	Stillbirth in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation	> 30 weeks after receiving treatment allocation
Secondary	Low/very low birth weight (gram)	low/very low birth weight (gram) in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation	> 30 weeks after receiving treatment allocation
Secondary	Caesarean section rates	caesarean section rates in women who conceived during the study period, leading to an ongoing pregnancy beyond 20 weeks of gestation	> 30 weeks after receiving treatment allocation
Secondary	Neonatal complications	Neonatal complications in women who conceived during the study period,	> 30 weeks after receiving treatment allocation
Secondary	The total hospital bill	Direct health-related costs	measured at the time of diagnosis of an ongoing pregnancy by the detection at 12 weeks in a clinical pregnancy of a positive heart beat on ultrasound examination