Impact of Local Biopsy to the Endometrium Prior to Controlled Ovarian Stimulation on Clinical Pregnancy (NIDABRECHE)

Influence of Local Biopsy of the Endometrium Prior to Controlled Ovarian Stimulation for IVF or ICSI Procedure on the Rates of Embryo Implantation, Clinical Pregnancy and Live Birth in ART

In vitro fertilization (IVF) is the only available solution for many couples with various forms of infertility. The embryo implantation step in the IVF procedure is a complex multistage process and represents the majority of the causes of the IVF failure. Several approaches have been evaluated to improve implantation rates but none has demonstrated its superiority. However, endometrial receptivity is important for pregnancy and several studies suggest that local injury to the endometrium of IVF patients improves the rates of embryo implantation, clinical pregnancy and live birth.

Study Overview

• Status: Completed
• Conditions: Primary or Secondary Infertility
• Intervention / Treatment: Procedure: biopsy; Procedure: IVF

Detailed Description

They are possible mechanisms by which endometrial sampling may increase receptivity and improve clinical pregnancy rate of IVF-ET. First, local injury to proliferative phase endometrium might induce the decidualization of the endometrium, and increase its implantation rate. Second, local injury to the endometrium might provoke the wound healing, involving a mass secretion of different cytokines and growth factor, which are beneficial for embryo implantation. Last, the injury might make the endometrium maturation.

This study proposes to evaluate the efficiency of an endometrial injury in the first controlled ovarian hyperstimulation cycle on the rate of clinical pregnancy, in assisted reproductive technologies. This study will compare 2 groups of patients. The first group will undergo biopsy of the endometrium before the IVF; the second will undergo the IVF alone. Inclusions will be conducted on 33 months; the patients will be in the study for a period of 36 weeks. The total duration of the study is 39 months

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33075
    • CHU de Bordeaux, Hôpital Saint André, service de chirurgie gynécologie et médecine de la reproduction
  • Pessac, France, 33600
    • Cabinet Médical de gynécologie
  • Toulouse, France, 31059
    • CHU de Toulouse, service de médecine et biologie de la reproduction

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• primary or secondary infertility
• first or second IVF attempt
• aged ≥18 and ≤38 years
• regular menstrual cycles
• FSH≤ 12IU/L
• Informed consent signed

Exclusion Criteria:

• ovocyte donor
• pathology of the uterus or annexes
• Body mass index (BMI)> 35
• ongoing vaginal infection
• undetermined vaginal bleeding
• contraindication to the Cornier pipette or to these treatments : Gonal F®, Puregon®, Ovitrelle®, Utrogestan®,
• women included in another study on medically assisted procreation
• any administrative or legal supervision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: group 1 : IVF with biopsy; fresh IVF-embryo transfer treated with long protocol or antagonist protocol for the controlled ovarian hyperstimulation plus local injury to the endometrium of patients one menstrual cycle before the IVF	Procedure: biopsy; The endometrium biopsy will be done as the same time as the GnRH treatment. The biopsy is realised with a Pipette de Cornier® (CDD international, PROMIDED France) following the laboratory protocol: Apply antiseptic solution (povidone-iodine, Dakin®) on the cervix and vagina. In most cases, using Pozzi forceps is not necessary.; Insert carefully the pipelle de Cornier® in the uterus through the cervix.; Withdraw the piston to create a negative pression; Move the pipelle de cornier® in and out while twisting. Take care to no remove the pipelle form the uterus (suction lost). Twist the pipelle de Cornier® to cover an angle of 360°. Make several "in and out" cycle in order to collect a complete sample of the endometrium.; Withdraw the pipelle de Cornier® when filled with tissue; Reinsert internal piston to deposit sample in cup filled with a fixative.
Active Comparator: group 2; fresh IVF-embryo transfer treated with long protocol or antagonist protocol for the controlled ovarian hyperstimulation alone	Procedure: IVF; fresh IVF-embryo transfer treated with long protocol for the controlled ovarian hyperstimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of clinical pregnancy	5 weeks after the embryo implantation in an IVF procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of clinical pregnancy	3 months after the IVF implantation
Rate of embryo implantation	5 weeks after the embryo implantation
Rate of miscarriage/extra-uterine pregnancy/multiple pregnancy	first trimester after the IVF
Adverse effects during the local injury (biopsy) to the endometrium	during the biopsy
Evaluation of the patients pain intensity and type from the biopsy.	during and after the biopsy

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Study Chair: Antoine Benard, Doctor, University Hospital Bordeaux, France; Principal Investigator: Sandrine Blancpain, Doctor, University Hospital Bordeaux, France

Publications and helpful links

General Publications

• Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril. 2003 Jun;79(6):1317-22. doi: 10.1016/s0015-0282(03)00345-5.
• Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003 Nov-Dec;9(6):515-22. doi: 10.1093/humupd/dmg045.
• Richter KS, Bugge KR, Bromer JG, Levy MJ. Relationship between endometrial thickness and embryo implantation, based on 1,294 cycles of in vitro fertilization with transfer of two blastocyst-stage embryos. Fertil Steril. 2007 Jan;87(1):53-9. doi: 10.1016/j.fertnstert.2006.05.064. Epub 2006 Nov 1.
• Raziel A, Schachter M, Strassburger D, Bern O, Ron-El R, Friedler S. Favorable influence of local injury to the endometrium in intracytoplasmic sperm injection patients with high-order implantation failure. Fertil Steril. 2007 Jan;87(1):198-201. doi: 10.1016/j.fertnstert.2006.05.062.
• Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002 Sep;17(9):2287-99. doi: 10.1093/humrep/17.9.2287.
• Revelli A, Dolfin E, Gennarelli G, Lantieri T, Massobrio M, Holte JG, Tur-Kaspa I. Low-dose acetylsalicylic acid plus prednisolone as an adjuvant treatment in IVF: a prospective, randomized study. Fertil Steril. 2008 Nov;90(5):1685-91. doi: 10.1016/j.fertnstert.2007.08.037. Epub 2007 Dec 11.
• Khairy M, Banerjee K, El-Toukhy T, Coomarasamy A, Khalaf Y. Aspirin in women undergoing in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2007 Oct;88(4):822-31. doi: 10.1016/j.fertnstert.2006.12.080. Epub 2007 May 16.
• Silver MM, Miles P, Rosa C. Comparison of Novak and Pipelle endometrial biopsy instruments. Obstet Gynecol. 1991 Nov;78(5 Pt 1):828-30.
• Gellersen B, Brosens IA, Brosens JJ. Decidualization of the human endometrium: mechanisms, functions, and clinical perspectives. Semin Reprod Med. 2007 Nov;25(6):445-53. doi: 10.1055/s-2007-991042.
• Lindhard A, Ravn V, Bentin-Ley U, Horn T, Bangsboell S, Rex S, Toft B, Soerensen S. Ultrasound characteristics and histological dating of the endometrium in a natural cycle in infertile women compared with fertile controls. Fertil Steril. 2006 Nov;86(5):1344-55. doi: 10.1016/j.fertnstert.2006.03.052. Epub 2006 Sep 14.
• Homburg R, Pap H, Brandes M, Huirne J, Hompes P, Lambalk CB. Endometrial biopsy during induction of ovulation with clomiphene citrate in polycystic ovary syndrome. Gynecol Endocrinol. 2006 Sep;22(9):506-10. doi: 10.1080/09513590600921366.
• Sulewski JM, Ward SP, McGaffic W. Endometrial biopsy during a cycle of conception. Fertil Steril. 1980 Dec;34(6):548-51. doi: 10.1016/s0015-0282(16)45193-9.
• Wentz AC, Herbert CM 3rd, Maxson WS, Hill GA, Pittaway DE. Cycle of conception endometrial biopsy. Fertil Steril. 1986 Aug;46(2):196-9. doi: 10.1016/s0015-0282(16)49510-5.
• Balasch J, Vanrell JA, Marquez M, Gonzalez-Merlo J. Endometrial biopsy inadvertently taken in the cycle of conception. Int J Gynaecol Obstet. 1984 Apr;22(2):95-9. doi: 10.1016/0020-7292(84)90020-1.
• Giorgetti C, Terriou P, Auquier P, Hans E, Spach JL, Salzmann J, Roulier R. Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers. Hum Reprod. 1995 Sep;10(9):2427-31. doi: 10.1093/oxfordjournals.humrep.a136312.
• Abramov Y, Elchalal U, Schenker JG. Severe OHSS: An 'epidemic' of severe OHSS: a price we have to pay? Hum Reprod. 1999 Sep;14(9):2181-3. doi: 10.1093/humrep/14.9.2181. No abstract available.
• Balasch J, Fabregues F, Arroyo V. Peripheral arterial vasodilation hypothesis: a new insight into the pathogenesis of ovarian hyperstimulation syndrome. Hum Reprod. 1998 Oct;13(1O):2718-30. doi: 10.1093/humrep/13.10.2718.
• Govaerts I, Devreker F, Delbaere A, Revelard P, Englert Y. Short-term medical complications of 1500 oocyte retrievals for in vitro fertilization and embryo transfer. Eur J Obstet Gynecol Reprod Biol. 1998 Apr;77(2):239-43. doi: 10.1016/s0301-2115(97)00263-7.
• Perrier D'hauterive S, Charlet-Renard C, Goffin F, Foidart M, Geenen V. [The implantation window]. J Gynecol Obstet Biol Reprod (Paris). 2002 Sep;31(5):440-55. French.
• Bourgain C. [Endometrial biopsy in the evaluation of endometrial receptivity]. J Gynecol Obstet Biol Reprod (Paris). 2004 Feb;33(1 Pt 2):S13-7. doi: 10.1016/s0368-2315(04)96397-1. French.
• Zhou L, Li R, Wang R, Huang HX, Zhong K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil Steril. 2008 May;89(5):1166-1176. doi: 10.1016/j.fertnstert.2007.05.064. Epub 2007 Aug 6.
• Cornier E. The Pipelle: a disposable device for endometrial biopsy. Am J Obstet Gynecol. 1984 Jan 1;148(1):109-10. doi: 10.1016/s0002-9378(84)80043-5. No abstract available.
• Check JH, Chase JS, Nowroozi K, Wu CH, Chern R. Clinical evaluation of the Pipelle endometrial suction curette for timed endometrial biopsies. J Reprod Med. 1989 Mar;34(3):218-20.
• Henig I, Chan P, Tredway DR, Maw GM, Gullett AJ, Cheatwood M. Evaluation of the Pipelle curette for endometrial biopsy. J Reprod Med. 1989 Oct;34(10):786-9.
• Machado F, Moreno J, Carazo M, Leon J, Fiol G, Serna R. Accuracy of endometrial biopsy with the Cornier pipelle for diagnosis of endometrial cancer and atypical hyperplasia. Eur J Gynaecol Oncol. 2003;24(3-4):279-81.
• Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv. 1989 Jun;44(6):430-40. doi: 10.1097/00006254-198906000-00004. No abstract available.
• Frantz S, Parinaud J, Kret M, Rocher-Escriva G, Papaxanthos-Roche A, Creux H, Chansel-Debordeaux L, Benard A, Hocke C. Decrease in pregnancy rate after endometrial scratch in women undergoing a first or second in vitro fertilization. A multicenter randomized controlled trial. Hum Reprod. 2019 Jan 1;34(1):92-99. doi: 10.1093/humrep/dey334.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 5, 2010
• First Posted (Estimate): February 8, 2010

Study Record Updates

• Last Update Posted (Estimate): April 8, 2015
• Last Update Submitted That Met QC Criteria: April 7, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: In Vitro Fertilization; pregnancy; Implantation; biopsy; Embryo; first or second IVF tentative
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: CHUBX 2009/12