Current partner codePEPTIDESDE
NCT02118051·Phase 3·INTERVENTIONAL

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

Status

Completed

Phase

Phase 3

Enrollment

234

Locations

1

Results

Not posted

Publications

12

Study summary

What the protocol is testing.

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

Full detailed 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.

Interventions

Treatment arms and agents.

DRUG

Ganirelix 0.25 mg.

Ganirelix 0.25 mg. Route of administration: Subcutaneous use. Dose: 250μg/24h since the day observe a follicle\> 14mm.

DRUG

Recombinant choriogonadotropin alfa

Recombinant choriogonadotropin alfa. Route of administration: Subcutaneous use. Dose: 6,500 IU, pods, when follicles\> 17 mm are observed

DRUG

Micronized natural progesterone.

Micronized natural progesterone. Route of administration: vaginal . Dose: 400mg/24, from embryo transfer until the day of b-hCG.

Timeline

From registration to results.

  1. First posted

    Apr 21, 2014

  2. Study start

    Sep 2013

  3. Primary completion

    Jun 2017

  4. Study completion

    Jun 2017

  5. Results posted

    Not reported

  6. Registry updated

    Jun 12, 2017

Outcomes

What the study measures.

Primary outcomes

Rate of evolutionary gestation in each cycle

Time frame · 20 week of gestation

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

oocytes (MII) rate by patient

Time frame · participants will be followed for the duration of the cycle,an expected average of 8-16 days.

When follicular puncture occurs, we value the number of punctured follicles, total oocytes and MII oocytes

Secondary outcomes

Number of Participants with Adverse Events

Time frame · participants will be followed for the duration of the cycle,an expected average of 16 days.

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
40 Years
Sex
FEMALE
Healthy volunteers
No

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

Study locations

1 registered sites.

Spain. Showing up to 24 locations stored in the fast local snapshot.

Human Reproduction Unit of the La Fe University and Politechnic Hospital

Valencia, Spain

Publications

Results and literature.

PMID 17241818Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol. 2007 Apr;21(2):293-308. doi: 10.1016/j.bpobgyn.2006.12.003. Epub 2007 Jan 22.PMID 19684043Devroey 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.PMID 15126522Devroey 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. doi: 10.1210/jc.2003-031766.PMID 21505041Ferraretti 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.PMID 9166190Keay 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. doi: 10.1111/j.1471-0528.1997.tb11525.x. No abstract available.PMID 19523618Kim 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.PMID 25492411Kolibianakis EM, Venetis CA, Bosdou JK, Zepiridis L, Chatzimeletiou K, Makedos A, Masouridou S, Triantafillidis S, Mitsoli A, Tarlatzis BC. Corifollitropin alfa compared with follitropin beta in poor responders undergoing ICSI: a randomized controlled trial. Hum Reprod. 2015 Feb;30(2):432-40. doi: 10.1093/humrep/deu301. Epub 2014 Dec 9.PMID 18639875Kyrou 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.PMID 22277766Mahmoud 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.PMID 20091563Pandian 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;2010(1):CD004379. doi: 10.1002/14651858.CD004379.pub3.PMID 3106105Pellicer 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. doi: 10.1016/s0015-0282(16)59170-5.PMID 9797096Pellicer A, Ardiles G, Neuspiller F, Remohi J, Simon 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. doi: 10.1016/s0015-0282(98)00268-4.

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