Impact of Local Biopsy to the Endometrium Prior to Controlled Ovarian Stimulation on Clinical Pregnancy - Full Text View

Purpose

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.

Condition	Intervention	Phase
Primary or Secondary Infertility	Procedure: biopsy Procedure: IVF	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Health Services Research
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Infertility

U.S. FDA Resources

Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:

Rate of clinical pregnancy [ Time Frame: 5 weeks after the embryo implantation in an IVF procedure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of clinical pregnancy [ Time Frame: 3 months after the IVF implantation ] [ Designated as safety issue: No ]
Rate of embryo implantation [ Time Frame: 5 weeks after the embryo implantation ] [ Designated as safety issue: No ]
Rate of miscarriage/extra-uterine pregnancy/multiple pregnancy [ Time Frame: first trimester after the IVF ] [ Designated as safety issue: Yes ]
Adverse effects during the local injury (biopsy) to the endometrium [ Time Frame: during the biopsy ] [ Designated as safety issue: Yes ]
Evaluation of the patients pain intensity and type from the biopsy. [ Time Frame: during and after the biopsy ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	358
Study Start Date:	February 2010
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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

Eligibility

Ages Eligible for Study:	18 Years to 38 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064193

Contacts

Contact: Sandrine Blancpain, Doctor	05 56 79 58 35	sandrine.blancpain@chu-bordeaux.fr
Contact: Claude Hocke, Professor	05 56 79 58 35	claude.hocke@chu-bordeaux.fr

Locations

France
CHU de Bordeaux, Hôpital Saint André, service de chirurgie gynécologie et médecine de la reproduction	Recruiting
Bordeaux, France, 33075
Contact: Sandrine Blancpain, Doctor 05 56 79 58 35 sandrine.blancpain@chu-bordeaux.fr
Principal Investigator: Sandrine Blancpain, Doctor
Cabinet Médical de gynécologie	Recruiting
Pessac, France, 33600
Contact: Gaëlle Rocher-Escriva
Principal Investigator: Gaëlle Rocher-Escriva, Dr
CHU de Toulouse, service de médecine et biologie de la reproduction	Recruiting
Toulouse, France, 31059
Contact: Jean Parinaud, Professeur 05 67 77 10 07 parinaud.j@chu-toulouse.fr
Principal Investigator: Jean Parinaud, Professor

Sponsors and Collaborators

University Hospital, Bordeaux

Investigators

Study Chair:	Antoine Benard, Doctor	University Hospital Bordeaux, France
Principal Investigator:	Sandrine Blancpain, Doctor	University Hospital Bordeaux, France

More Information

Publications:

Bourgain C, Devroey P. The endometrium in stimulated cycles for IVF. Hum Reprod Update. 2003 Nov-Dec;9(6):515-22. Review.

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. Epub 2006 Nov 1.

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.

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.

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. Review.

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. 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. Epub 2007 May 16. Review.

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. Review.

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. 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.

Sulewski JM, Ward SP, McGaffic W. Endometrial biopsy during a cycle of conception. Fertil Steril. 1980 Dec;34(6):548-51.

Wentz AC, Herbert CM 3rd, Maxson WS, Hill GA, Pittaway DE. Cycle of conception endometrial biopsy. Fertil Steril. 1986 Aug;46(2):196-9.

Balasch J, Vanrell JA, Márquez M, González-Merlo J. Endometrial biopsy inadvertently taken in the cycle of conception. Int J Gynaecol Obstet. 1984 Apr;22(2):95-9.

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.

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. Review. No abstract available.

Balasch J, Fábregues 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. Review.

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.

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. Review. 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. Review. 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):1166-76. 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. 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, León 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. Review. No abstract available.

Responsible Party:	University Hospital, Bordeaux
ClinicalTrials.gov Identifier:	NCT01064193 History of Changes
Other Study ID Numbers:	CHUBX 2009/12
Study First Received:	February 5, 2010
Last Updated:	January 17, 2013
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:

In Vitro Fertilization
biopsy
pregnancy

Implantation
Embryo
first or second IVF tentative

Additional relevant MeSH terms:

Infertility
Genital Diseases, Male
Genital Diseases, Female

ClinicalTrials.gov processed this record on June 18, 2013

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