Corifollitropin Alfa and Embryo Morphokinetics

NCT ID: NCT04142190

Last Updated: 2019-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1351 participants

Study Classification

OBSERVATIONAL

Study Start Date

2013-01-31

Study Completion Date

2018-12-31

Brief Summary

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The study evaluates the influence of corifollitropin alfa (Elonva) on embryo morphokinetics and fertility treatment outcome in comparison to a control group stimulated with Follitropin beta (Puregon).

Detailed Description

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Morphokinetic parameters of embryo development have been intensively investigated. However, little attention has been paid to the influence of ovarian stimulation on morphokinetic parameters. Gryshenko et al. found a significant difference in the fourth cell division time (t5) of embryos obtained after controlled ovarian hyperstimulation in long GnRH agonists and GnRH antagonist protocols. Furthermore, higher gonadotropin doses were found to slow down the development of the embryos.

Hence, the aim of this study is to investigate the influence of corifollitropin alfa (Elonva) on embryo morphokinetics and fertility treatment outcome in comparison to a control group stimulated with Follitropin beta (Puregon). The investigators hypothesize that there are differences in morphokinetic behavior of embryos within the different stimulation protocols.

A total of 742 embryos from 215 different patients suffering from infertility undergoing ovarian stimulation with Elonva and a total of 5148 embryos from 1136 patients undergoing ovarian stimulation with Puregon will be retrospectively analyzed. To exclude environmental factors the evaluation will distinguish between embryos cultured under 21% oxygen and embryos with reduced oxygen conditions (5% oxygen) in the embryoscope. Groups will be age and BMI matched.

All women included in the study underwent GnRH (Gonadotropin-releasing hormone) antagonist protocol controlled ovarian hyperstimulation. Patients received recombinant human follicle-stimulating hormone (Elonva; MSD Sharp \&Dohme GMBH, Puregon; MSD Sharp \& Dohme GMBH). ELONVA was administered for 7 days with subsequent administration of Puregon (MSD Sharp \& Dohme GMBH) in case of further need of stimulation. Puregon was administered for 8-10 days with dosage adaption according to age, weight, serum anti-mullerian hormone (sAMH) concentration, and hormonal status. Trans-vaginal sonography was performed after 5 days of stimulation, followed by every second day until the day of oocyte retrieval. Ultrasonographical measurement was performed using a RIC 5-9-D 4D intravaginal probe of a GE Voluson E8 BT09 ultrasound machine (both from GE Healthcare Austria GmbH). GnRH antagonist (Cetrotide, Merck KGaA) was injected to avoid premature ovulation. Triggering was initiated 35 h before oocyte retrieval, administered with 5000-10,000 IU human chorionic gonadotropin (hCG) subcutaneously (Pregnyl, N.V. Organon), with dosage adaption according to body weight of the patient.

Follicles larger than 10 mm in diameter were aspirated under sedation (Propofol, Fresenius Kabi Austria GmbH; Rapifen, Janssen-Cilag Pharma GmbH) and transvaginal ultrasound guidance (GE Healthcare Austria GmbH). Follicular fluid (FF) were examined for oocytes under constant conditions of 37 °C in an IVF workstation L24E with heating stage (K-SYSTEMS Kivex Biotec A/S). Intracytoplasmic sperm injection (ICSI) was performed on all metaphase II (MII) oocytes 4-5h after oocyte retrieval according to our standard operating procedure in both groups of patients.

After oocyte retrieval and fertilization, oocytes were cultivated in universal culture medium (Gynemed Medizinprodukte GmbH \& Co. KG, Germany). After 14-16 h, fertilization check was performed. All normal fertilized embryos with two pronuclei (PN) were then cultured using Embryoslide dishes in Embryoscope® time-lapse incubator (both Vitrolife AB, Sweden). With the built-in camera and microscope, images of the developing embryo were taken every 15 min in seven different layers. Definition of morphokinetic parameters was performed according to the criteria proposed by Ciray et al. and was analyzed with software developed for time-lapse image analysis (Embryoviewer® software; Vitrolife AB, Sweden).

Conditions

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Infertility

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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ELONVA

Patients stimulated with Elonva

ELONVA

Intervention Type DRUG

Elonva is a solution for injection that contains the active substance corifollitropin alfa. It is available as a pre-filled syringe (100 and 150 micrograms).Elonva is used in women who are undergoing fertility treatment to stimulate the development of more than one mature egg at a time in the ovaries.

PUREGON

Patients stimulated with Puregon

PUREGON

Intervention Type DRUG

Puregon contains the active substance follitropin beta. fertilisation). Puregon is administered to stimulate the ovaries to produce more than one egg at a time

Interventions

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ELONVA

Elonva is a solution for injection that contains the active substance corifollitropin alfa. It is available as a pre-filled syringe (100 and 150 micrograms).Elonva is used in women who are undergoing fertility treatment to stimulate the development of more than one mature egg at a time in the ovaries.

Intervention Type DRUG

PUREGON

Puregon contains the active substance follitropin beta. fertilisation). Puregon is administered to stimulate the ovaries to produce more than one egg at a time

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age: 18-42
* BMI: 19-29.9
* Primary or secondary infertility
* Ovarian stimulation with Elonva/Puregon
* Embryos cultured in embryoscope

Exclusion Criteria

* unexpected low response
* genetic testing
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Kinderwunsch Institut GmbH

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Schenk, Dr.

Role: PRINCIPAL_INVESTIGATOR

Das Kinderwunsch Institut Schenkg GmbH

Locations

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Das Kinderwunsch Institut Schenk GmbH

Dobl, Styria, Austria

Site Status

Countries

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Austria

References

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Gryshchenko MG, Pravdyuk AI, Parashchyuk VY. Analysis of factors influencing morphokinetic characteristics of embryos in ART cycles. Gynecol Endocrinol. 2014 Oct;30 Suppl 1:6-8. doi: 10.3109/09513590.2014.945763.

Reference Type BACKGROUND
PMID: 25200818 (View on PubMed)

Wissing ML, Bjerge MR, Olesen AI, Hoest T, Mikkelsen AL. Impact of PCOS on early embryo cleavage kinetics. Reprod Biomed Online. 2014 Apr;28(4):508-14. doi: 10.1016/j.rbmo.2013.11.017. Epub 2013 Dec 17.

Reference Type BACKGROUND
PMID: 24581983 (View on PubMed)

Chawla M, Fakih M, Shunnar A, Bayram A, Hellani A, Perumal V, Divakaran J, Budak E. Morphokinetic analysis of cleavage stage embryos and its relationship to aneuploidy in a retrospective time-lapse imaging study. J Assist Reprod Genet. 2015 Jan;32(1):69-75. doi: 10.1007/s10815-014-0372-3. Epub 2014 Nov 14.

Reference Type BACKGROUND
PMID: 25395178 (View on PubMed)

Armstrong S, Vail A, Mastenbroek S, Jordan V, Farquhar C. Time-lapse in the IVF-lab: how should we assess potential benefit? Hum Reprod. 2015 Jan;30(1):3-8. doi: 10.1093/humrep/deu250. Epub 2014 Oct 14.

Reference Type BACKGROUND
PMID: 25316446 (View on PubMed)

Milewski R, Kuc P, Kuczynska A, Stankiewicz B, Lukaszuk K, Kuczynski W. A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development. J Assist Reprod Genet. 2015 Apr;32(4):571-9. doi: 10.1007/s10815-015-0440-3. Epub 2015 Feb 18.

Reference Type BACKGROUND
PMID: 25690157 (View on PubMed)

VerMilyea MD, Tan L, Anthony JT, Conaghan J, Ivani K, Gvakharia M, Boostanfar R, Baker VL, Suraj V, Chen AA, Mainigi M, Coutifaris C, Shen S. Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study. Reprod Biomed Online. 2014 Dec;29(6):729-36. doi: 10.1016/j.rbmo.2014.09.005. Epub 2014 Sep 21.

Reference Type BACKGROUND
PMID: 25444507 (View on PubMed)

Other Identifiers

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FRED001

Identifier Type: -

Identifier Source: org_study_id

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