Effect of Treatment With Corifollitropin Alpha in Vitro Fertilization in Patients With Poor Ovarian Response.

Infertility Clinical Trial

Official title:

Prospective Randomized Study for the Evaluation of Controlled Ovarian Stimulation With Corifollitropin Alpha in Patients With Expected or Poor Ovarian Response in IVF Cycles

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02118051
• Other study ID #: POR-ELONVA
• Secondary ID: 2013-002027-42
• Status: Completed
• Phase: Phase 3
• First received: April 14, 2014
• Last updated: June 9, 2017
• Start date: September 2013
• Est. completion date: June 2017

Study information

• Verified date: September 2016
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients who have had or are expected to have a poor ovarian response (POR), because they meet any of the criteria of Bologna, can benefit from ovarian stimulation with 150 mg of alpha Corifollitropin (CFA) (Elonva ®) as single dose for a week, in the cycles of in vitro fertilization (IVF).

In this study aims to demonstrate non-inferiority of the Corifollitropin Alpha (CFA ) versus daily administration of Human Menopausal Gonadotropin (hMG) (Menopur ®) during the first seven days of ovarian stimulation, in a protocol with gonadotropin-releasing hormone ( GnRH) antagonists

Description:

One of the most significant problems in fertilization treatments is Controlled Ovarian Stimulation low responsiveness . The incidence of low ovarian response is estimated at around 10-25%.The wide range of prevalence reported in the literature can be explained by the lack of consensus existed as to the criteria for the low response.

The ovarian response to gonadotropin stimulation is crucial for successful assisted reproduction techniques .Cycles with low rates response was obtained and increased cancellation rate and worst pregnancy rates .

Different criteria for the definition of low response, different tests to assess ovarian reserve and different threshold values for each has been used.

In 2010 a group of experts from the ESHRE ,achieved consensus on the criteria for low ovarian response to homogenize the study groups and reach meaningful conclusions, are known as "The Bologna criteria" ,they defined the "Poor Ovarian Response" (POR).

There is not sufficient to recommend most of the proposed treatments to improve pregnancy rates in poor responders evidence.

Taking into account the profile of equivalence and safety of CFA (Corifollitropin Alpha , active of ELONVA ® ) , different studies had been concluded that CFA can be an alternative to daily injections of recombinant follicle stimulating hormone ( rFSH) in normal responders patients in vitro fertilization cycle with ovarian stimulation.But more research is needed to determine whether long-acting recombinant follicle stimulating hormone ( rFSH) is safe and effective for use in women with low and high response.

The ovarian controlled stimulation with Alpha Corifollitropin produces significantly more oocytes compared to recombinant follicle stimulating hormone (r FSH ) administrated daily in normal responders patients, For this reason , the use of Alpha Corifollitropin may be beneficial in patients with poor response which the number of oocytes retrieved is crucial for successful treatment

There have been two studies in which the results are compared after ovarian stimulation with daily rFSH vs CFA . In both shows , retrospectively and prospectively , the CFA seems to be at least as effective as hMG recombinant follicle stimulating hormone ( rFSH) daily.

There are scientific publications showing that the association of luteinizing hormone ( LH) to recombinant follicle stimulating hormone ( rFSH) can improve embryos quality and achieved better pregnancy rate . The pregnancy rate was not statistically significant , in normal responders patients.

Recently reported the beneficial effect in POR patients treated with CFA and hMG.

The IVF treatment is known to affects the physical and mental condition in patients with infertility , being the excess emotional stress one of the most important reasons for discontinuation of treatment.

The ovarian stimulation with CFA simplifies treatment , reducing the administration of multiple daily injections ,and may reduce the emotional burden on patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 234
• Est. completion date: June 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. - Age = 18 years old.

2. - Signed informed consent to perform IVF and participation in this study.

3. - Due to characteristics of our center not perform treatments in patients

• 40 years old ,and being one of the Bologna criteria that we will not be able to consider ,we decided to include patients affected subsidiary infertility treatment by IVF or intracytoplasmatic sperm injection (ICSI), present one of the following factors

1. Have a history of surgical or medical treatment as a risk factor for POR.

2. Patients witch had have a poor ovarian response in response to the ovarian controlled stimulation (previous cycle after conventional stimulation with = 3 oocytes)

3. Patients with ovarian reserve test anti-mullerian hormone(AMH ) <1.1 ng / ml (<8 pM) or antral follicle count (AFC)<7

Exclusion Criteria:

1. -Anovulation.

2. -Patient with tubal factor, untreated

3. -Patient with uterine pathology untreated

4. - Couples with severe male factor, fresh count <5 million / ml, and azoospermia in which the patient's sperm, epididymal or testicular is used

Related Conditions & MeSH terms

• Infertility

Intervention

Drug:
• Ganirelix 0.25 mg.
Ganirelix 0.25 mg. Route of administration: Subcutaneous use. Dose: 250µg/24h since the day observe a follicle> 14mm.
• Recombinant choriogonadotropin alfa
Recombinant choriogonadotropin alfa. Route of administration: Subcutaneous use. Dose: 6,500 IU, pods, when follicles> 17 mm are observed
• Micronized natural progesterone.
Micronized natural progesterone. Route of administration: vaginal . Dose: 400mg/24, from embryo transfer until the day of b-hCG.

Locations

Country	Name	City	State
Spain	Human Reproduction Unit of the La Fe University and Politechnic Hospital	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (17)

Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol. 2007 Apr;21(2):293-308. Epub 2007 Jan 22. Review. — View Citation

Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC; ENGAGE Investigators.. A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod. 2009 Dec;24(12):3063-72. doi: 10.1093/humrep/dep291. Epub 2009 Aug 14. Erratum in: Hum Reprod. 2014 May;29(5):1116-20. — View Citation

Devroey P, Fauser BC, Platteau P, Beckers NG, Dhont M, Mannaerts BM. Induction of multiple follicular development by a single dose of long-acting recombinant follicle-Stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization. J Clin Endocrinol Metab. 2004 May;89(5):2062-70. — View Citation

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

Keay SD, Liversedge NH, Mathur RS, Jenkins JM. Assisted conception following poor ovarian response to gonadotrophin stimulation. Br J Obstet Gynaecol. 1997 May;104(5):521-7. Review. — View Citation

Kim CH, Jeon GH, Cheon YP, Jeon I, Kim SH, Chae HD, Kang BM. Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection. Fertil Steril. 2009 Nov;92(5):1758-60. doi: 10.1016/j.fertnstert.2009.05.013. Epub 2009 Jun 12. — View Citation

Kyrou D, Kolibianakis EM, Venetis CA, Papanikolaou EG, Bontis J, Tarlatzis BC. How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis. Fertil Steril. 2009 Mar;91(3):749-66. doi: 10.1016/j.fertnstert.2007.12.077. Epub 2008 Jul 21. Review. — View Citation

Kyrou Kolibianakis EM, Masouridou S, Chatzimeletiou K, Mitsoli A, Tarlatzis BC. Is corifollitropin alfa beneficial in poor responders undergoing IVF?. O-285. Congreso ESHRE 2012.

Mahmoud Youssef MA, van Wely M, Aboulfoutouh I, El-Khyat W, van der Veen F, Al-Inany H. Is there a place for corifollitropin alfa in IVF/ICSI cycles? A systematic review and meta-analysis. Fertil Steril. 2012 Apr;97(4):876-85. doi: 10.1016/j.fertnstert.2012.01.092. Epub 2012 Jan 23. Review. Erratum in: Fertil Steril. 2012 Jun;97(6):1479. — View Citation

Pandian Z, McTavish AR, Aucott L, Hamilton MP, Bhattacharya S. Interventions for 'poor responders' to controlled ovarian hyper stimulation (COH) in in-vitro fertilisation (IVF). Cochrane Database Syst Rev. 2010 Jan 20;(1):CD004379. doi: 10.1002/14651858.CD004379.pub3. Review. — View Citation

Pellicer A, Ardiles G, Neuspiller F, Remohí J, Simón C, Bonilla-Musoles F. Evaluation of the ovarian reserve in young low responders with normal basal levels of follicle-stimulating hormone using three-dimensional ultrasonography. Fertil Steril. 1998 Oct;70(4):671-5. — View Citation

Pellicer A, Lightman A, Diamond MP, Russell JB, DeCherney AH. Outcome of in vitro fertilization in women with low response to ovarian stimulation. Fertil Steril. 1987 May;47(5):812-5. — 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

Pouwer AW, Farquhar C, Kremer JA. Long-acting FSH versus daily FSH for women undergoing assisted reproduction. Cochrane Database Syst Rev. 2012 Jun 13;(6):CD009577. doi: 10.1002/14651858.CD009577.pub2. Review. Update in: Cochrane Database Syst Rev. 2015;(7):CD009577. — View Citation

Requena A, Landeras JL, Martínez-Navarro L, Calatayud C, Sánchez F, Maldonado V, Muñoz M, Fernández M, González A, López S, López R, Pacheco A, Calderón G, Martínez V. Could the addition of hp-hMG and GnRH antagonists modulate the response in IVF-ICSI cycles? Hum Fertil (Camb). 2010 Mar;13(1):41-9. doi: 10.3109/14647270903586356. — View Citation

Tarlatzis BC, Zepiridis L, Grimbizis G, Bontis J. Clinical management of low ovarian response to stimulation for IVF: a systematic review. Hum Reprod Update. 2003 Jan-Feb;9(1):61-76. Review. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of evolutionary gestation in each cycle	Evolutionary pregnancy has been defined as gestation of at least 1 fetus reaches 20 weeks of gestation diagnosed by normal ultrasound or confirmed by live birth	20 week of gestation
Primary	oocytes (MII) rate by patient	When follicular puncture occurs, we value the number of punctured follicles, total oocytes and MII oocytes	participants will be followed for the duration of the cycle,an expected average of 8-16 days.
Secondary	Number of Participants with Adverse Events		participants will be followed for the duration of the cycle,an expected average of 16 days.