Corifollitropin Alfa Followed by Menotropin for Poor Ovarian Responders Trial

Infertility Clinical Trial

— COMPORT  

Official title:

Corifollitropin Alfa Followed by Hp-HMG Versus Recombinant FSH in Young Poor Ovarian Responders. A Multicentre Randomized Controlled Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01816321
• Other study ID #: 143201316398
• Secondary ID: 2013-000583-29
• Status: Completed
• Phase: Phase 3
• First received: March 16, 2013
• Last updated: June 21, 2016
• Start date: March 2013
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: Universitair Ziekenhuis Brussel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

In combination with the existing literature, previous work indicates that 1) women with poor ovarian response fulfilling the "Bologna criteria" have very low pregnancy rates, irrespective of age 2) current treatment protocols demonstrate ongoing pregnancy rates that do not exceed 8.5% and 3) corifollitropin alfa followed by hpHMG might increase ongoing pregnancy rates in young patients (<40years old) fulfilling the criteria. These findings provide a strong rationale for a definitive large RCT. The COMPORT study will provide conclusive evidence regarding the superiority or not of this novel protocol with corifollitropin alfa followed by hpHMG for the treatment of young poor ovarian responders fulfilling the Bologna criteria.

Description:

Recently, the European Society of Human Reproduction and Embryology developed a new definition in order to select patients suitable for inclusion in future clinical trials as poor ovarian responders, the so-called "Bologna criteria". However, a limited number of studies has been published to date including patients with poor ovarian response according to the "Bologna criteria", whereas no randomized trial is published or ongoing for this population.

Preliminary reports in "Bologna poor responders" highlight the limited prospects for these women. Natural cycle IVF has been shown to result in disappointingly low live birth rates, regardless of patients' age and ovarian stimulation with widely accepted treatment modalities, e.g. short agonist protocol, did not appear demonstrate substantial benefits.

Nonetheless, despite the disappointing results from the vast majority of the preliminary studies in this population, a recent pilot study by our group has shown that a specific protocol may indeed be a promising option for women of younger age fulfilling the "Bologna criteria". Corifollitropin alfa followed by highly purified hMG in an antagonist protocol demonstrated an ongoing pregnancy rate of 28% in women <40years, strongly suggesting the conduction of a future randomized trial testing this novel treatment protocol

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 39 Years

Eligibility

Inclusion Criteria:

• Age less than 40 years

• Fulfillment of the "Bologna criteria" for poor ovarian response.

Based on inclusion criteria two patients' categories are eligible:

1. Women < 40 years old AND =3 oocytes in one of the previous cycles AND (Antral follicle count <7 or antimullerian hormone serum values <1.1 ng/ml)

2. Women <40 years old and =3 oocytes in two the previous cycles with maximum ovarian stimulation

In addition women less than 40 years old will be considered eligible if they had undergone previous ovarian surgery or chemotherapy (risk factors for poor ovarian response) and have an AMH<1.1ng/ml or an AFC<7, as suggested by the Bologna criteria

Exclusion Criteria:

• Uterine abnormalities

• Recent history of any current untreated endocrine abnormality

• Unilateral or bilateral hydrosalpinx (visible on transvaginal ultrasound, unless clipped)

• Contraindications for the use of gonadotropins

• Recent history of severe disease requiring regular treatment

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Infertility
• Poor Ovarian Response

Intervention

Drug:
• Corifollitropin alfa
Corifollitropin alfa 150µg on day 2 of the menstrual cycle (stimulation day 1)
• recombinant FSH
recombinant FSH 300IU/daily from day 2 of the cycle (stimulation day 8)until day of ovulation triggering
• Ganirelix
Ganirelix 0.25mg/daily from day 7 of the cycle(stimulation day 6) until day of ovulation triggering
• hp HMG
hp HMG 300IU/daily from day 9 of the cycle (stimulation day 8)until day of ovulation triggering

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Brussel	Brussels
Vietnam	University of Medicine and Pharmacy of Ho Chi Minh City	Ho Chi Minh City

Sponsors (2)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel	Ho Chi Minh City University of Medicine and Pharmacy

Countries where clinical trial is conducted

Belgium,  Vietnam, 

References & Publications (5)

Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19. — View Citation

Polyzos NP, Blockeel C, Verpoest W, De Vos M, Stoop D, Vloeberghs V, Camus M, Devroey P, Tournaye H. Live birth rates following natural cycle IVF in women with poor ovarian response according to the Bologna criteria. Hum Reprod. 2012 Dec;27(12):3481-6. doi: 10.1093/humrep/des318. Epub 2012 Aug 30. — View Citation

Polyzos NP, De Vos M, Corona R, Vloeberghs V, Ortega-Hrepich C, Stoop D, Tournaye H. Addition of highly purified HMG after corifollitropin alfa in antagonist-treated poor ovarian responders: a pilot study. Hum Reprod. 2013 May;28(5):1254-60. doi: 10.1093/humrep/det045. Epub 2013 Feb 26. — View Citation

Polyzos NP, Devos M, Humaidan P, Stoop D, Ortega-Hrepich C, Devroey P, Tournaye H. Corifollitropin alfa followed by rFSH in a GnRH antagonist protocol for poor ovarian responder patients: an observational pilot study. Fertil Steril. 2013 Feb;99(2):422-6. doi: 10.1016/j.fertnstert.2012.09.043. Epub 2012 Oct 16. — View Citation

Polyzos NP, Devroey P. A systematic review of randomized trials for the treatment of poor ovarian responders: is there any light at the end of the tunnel? Fertil Steril. 2011 Nov;96(5):1058-61.e7. doi: 10.1016/j.fertnstert.2011.09.048. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cycle cancellation due to poor ovarian response	Number of cycles cancelled due to monofollicular or no follicular development	Day 8-10 of ovarian stimulation	No
Other	Number of cycles reaching the stage of embryo transfer	The outcome will be evaluated 3 days after oocyte retrieval	9 -20 days from initiation of ovarian stimulation	No
Other	Number and quality of embryos	3 days after oocyte retrieval	Day of embryo transfer	No
Other	Number of cycles with frozen supernumerary embryos	The outcome will be evaluated 5 days after oocyte retrieval or 2-3 days after embryo transfer in case of an embryo transfer	9 -20 days from initiation of ovarian stimulation	No
Other	Endocrine parameters (LH,FSH, E2, Progesterone) during ovarian stimulation		Days 1,6,8,10 of stimulation and day of ovulation triggering	No
Other	Cycle cancellation due to serious adverse effects of medication	20-25 days after the initiation of ovarian stimulation all patients (cycles) will be monitored for the occurence of any adverse effect and cycle cancellation(during ovarian stimulation) due to a serious adverse effect from medication	20-25 days after initiation of stimulation	Yes
Primary	Ongoing pregnancy	The presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation.	9-10 weeks of gestation	No
Secondary	Clinical pregnancy	The presence of intrauterine gestational sac at 7 weeks of gestation	7 weeks of gestation	No
Secondary	Biochemical pregnancy	Positive pregnancy test 2 weeks after embryo transfer	2 weeks after embryo transfer	No
Secondary	Number of oocytes retrieved	The outcome will be evaluated on the day of oocyte retrieval	9 -20 days from initiation of ovarian stimulation	No