In Vitro Fertilisation Versus Intracytoplasmic Sperm Injection in Patients Without Severe Male Factor Infertility

NCT04128904 | Active Not Recruiting DMC

• 1 other identifier: INVICSI2019
• Study Type: interventional
• Target: 824
• Locations: 1 country
• Sites: 6

Brief Summary

Over recent decades, the use of intracytoplasmic sperm injection (ICSI) has increased, even among patients without severe male factor infertility. Despite the increasing use, there is no evidence to support that ICSI results in a higher live birth rate compared to conventional in vitro fertilisation (IVF) in cases without severe male factor infertility. The primary objective of this trial is to determine whether ICSI is superior to standard IVF in patients without severe male factor infertility. The primary outcome measure is live birth rate. A total of 824 participants with infertility without severe male factor will be included in the study and allocated randomly into two groups (IVF or ICSI). The main inclusion criteria for the women are age 18-42 years, normal to slightly decreased male partner sperm/ use of donor sperm and no prior fertility treatment. In addition to live birth rate, outcome measures include fertilisation rate, total fertilisation failure, embryo quality, clinical pregnancy, miscarriage rate, preterm delivery, birth weight and congenital anomalies of the child. The study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committee of the Capital Region of Denmark and the Knowledge Centre on Data Protection Compliance. Study findings will be presented in international conferences and submitted for publication in peer-reviewed journals.

Conditions

Infertility

Keywords

Infertility; Non-male factor infertility; In vitro fertilisation (IVF); Intracytoplasmic sperm injection (ICSI); Assisted reproductive technologies (ART); Live birth rate; Reproductive outcome

Outcome Measures

Primary Outcomes (1)

• Cumulative live birth rate from first live birth episode of a study cycle

  The cumulative first live birth from the oocyte collection. Includes transfer of fresh embryos and frozen-thawed embryos.

  Minimum follow-up time is one year after inclusion

Secondary Outcomes (19)

• Fertilisation rate

  16-20 hours after IVF/ICSI

• Total fertilisation failure

  16-20 hours after IVF/ICSI

• Embryo quality

  Up to six days after oocyte pick-up

• Time-lapse kinetics

  Minimum follow-up time is one year after inclusion

• Embryo utilisation rate

  Up to six days after oocyte pick-up

Study Arms (2)

Standard in vitro fertilisation (IVF)

ACTIVE COMPARATOR

Oocytes are fertilised with standard IVF. For details please see "Project Description".

Procedure: IVF

Intracytoplasmic sperm injection (ICSI)

ACTIVE COMPARATOR

Oocytes are fertilised with ICSI. For details please see "Project Description".

Procedure: ICSI

Interventions

IVF PROCEDURE

Fertilisation with standard in vitro fertilisation (IVF). For details please see "Project Description".

Standard in vitro fertilisation (IVF)

ICSI PROCEDURE

Fertilisation with intracytoplasmic sperm injection (ICSI). For details please see "Project Description".

Intracytoplasmic sperm injection (ICSI)

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women 18-42 years of age (both included) at the beginning of the ovarian stimulation
• BMI 18-35 kg/m2
• Indication for IVF due to tubal factor infertility, unexplained infertility, PCOS or light to moderate decreased semen quality
• Women treated with gonadotrophin in a standard short or long protocol and receiving ovulation trigger for oocyte pick up
• First treatment cycle for the couple
• Male partner with normal or non-severely decreased sperm parameters, where the sperm sample (purified) on the day of oocyte pick up is expected to contain a minimum of 2 million/mL progressive motile spermatozoa. Alternatively use of donorsperm.
• Willing to sign the informed consent

You may not qualify if:

• Ovarian cysts \>4 cm
• Known liver or kidney disease
• Previous IVF or ICSI treatment with current partner
• Use of donor oocytes or frozen oocytes
• Unregulated thyroid disease
• Endometriosis stage 3-4
• Hypogonadotropic hypogonadism
• Severe comorbidity (e.g. diabetes or cardiovascular disease)
• Not speaking / understanding Danish or English language
• Not willing to sign the informed consent

Sponsors & Collaborators

• Copenhagen University Hospital, Hvidovre: lead

Study Sites (6)

The Fertility Clinic, Rigshospitalet, Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

The Fertility Clinic, Herlev Hospital, Copenhagen University Hospital

Herlev, 2730, Denmark

Location

The Fertility Clinic, Nordsjællands Hospital, Hillerød

Hillerød, 3400, Denmark

Location

The Fertility Clinic, the Reginal Hospital Horsens

Horsens, Denmark

Location

The Fertility Clinic, Hvidovre Hospital, Copenhagen University Hospital

Hvidovre, 2650, Denmark

Location

The Fertility Clinic, Zealand University Hospital

Køge, Denmark

Location

Related Publications (12)

• Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992 Jul 4;340(8810):17-8. doi: 10.1016/0140-6736(92)92425-f.

  PMID: 1351601 BACKGROUND

• Dyer S, Chambers GM, de Mouzon J, Nygren KG, Zegers-Hochschild F, Mansour R, Ishihara O, Banker M, Adamson GD. International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010. Hum Reprod. 2016 Jul;31(7):1588-609. doi: 10.1093/humrep/dew082. Epub 2016 May 20.

  PMID: 27207175 BACKGROUND

• European IVF-monitoring Consortium (EIM); European Society of Human Reproduction and Embryology (ESHRE); Calhaz-Jorge C, De Geyter C, Kupka MS, de Mouzon J, Erb K, Mocanu E, Motrenko T, Scaravelli G, Wyns C, Goossens V. Assisted reproductive technology in Europe, 2013: results generated from European registers by ESHRE. Hum Reprod. 2017 Oct 1;32(10):1957-1973. doi: 10.1093/humrep/dex264.

  PMID: 29117383 BACKGROUND

• Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015 Jan 20;313(3):255-63. doi: 10.1001/jama.2014.17985.

  PMID: 25602996 BACKGROUND

• van Rumste MM, Evers JL, Farquhar CM. Intra-cytoplasmic sperm injection versus conventional techniques for oocyte insemination during in vitro fertilisation in patients with non-male subfertility. Cochrane Database Syst Rev. 2003;(2):CD001301. doi: 10.1002/14651858.CD001301.

  PMID: 12804403 BACKGROUND

• Bhattacharya S, Hamilton MP, Shaaban M, Khalaf Y, Seddler M, Ghobara T, Braude P, Kennedy R, Rutherford A, Hartshorne G, Templeton A. Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Lancet. 2001 Jun 30;357(9274):2075-9. doi: 10.1016/s0140-6736(00)05179-5.

  PMID: 11445099 BACKGROUND

• Khamsi F, Yavas Y, Roberge S, Wong JC, Lacanna IC, Endman M. Intracytoplasmic sperm injection increased fertilization and good-quality embryo formation in patients with non-male factor indications for in vitro fertilization: a prospective randomized study. Fertil Steril. 2001 Feb;75(2):342-7. doi: 10.1016/s0015-0282(00)01674-5.

  PMID: 11172837 BACKGROUND

• Tannus S, Son WY, Gilman A, Younes G, Shavit T, Dahan MH. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod. 2017 Jan;32(1):119-124. doi: 10.1093/humrep/dew298. Epub 2016 Nov 16.

  PMID: 27852688 BACKGROUND

• Sfontouris IA, Kolibianakis EM, Lainas GT, Navaratnarajah R, Tarlatzis BC, Lainas TG. Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved. J Assist Reprod Genet. 2015 May;32(5):691-7. doi: 10.1007/s10815-015-0459-5. Epub 2015 Mar 11.

  PMID: 25758990 BACKGROUND

• Berntsen S, Zedeler A, Grondahl ML, Gabrielsen AV, Petersen MR, Skipper DF, Nohr B, Englund AL, Lokkegaard E, Praetorius L, Westergaard D, Pinborg A, Nielsen HS, la Cour Freiesleben N. Early embryo developmental kinetics following IVF versus ICSI in patients without severe male factor infertility: a secondary analysis of a multicentre, randomized controlled trial (INVICSI). Hum Reprod. 2025 Oct 1;40(10):1877-1885. doi: 10.1093/humrep/deaf157.

  PMID: 40796141 DERIVED

• Berntsen S, Zedeler A, Nohr B, Ronn Petersen M, Grondahl ML, Andersen LF, Lossl K, Lokkegaard E, Englund AL, Vestergaard Gabrielsen A, Praetorius L, Behrendt-Moller I, Langhoff Thuesen L, Vomstein K, Petri Lauritsen M, Ivanoska Trajcevski A, Froding Skipper D, Westergaard D, Pinborg A, Svarre Nielsen H, la Cour Freiesleben N. IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial. Nat Med. 2025 Jun;31(6):1939-1948. doi: 10.1038/s41591-025-03621-x. Epub 2025 Apr 11.

  PMID: 40217077 DERIVED

• Berntsen S, Nohr B, Grondahl ML, Petersen MR, Andersen LF, Englund AL, Knudsen UB, Praetorius L, Zedeler A, Nielsen HS, Pinborg A, Freiesleben NC. In vitro fertilisation (IVF) versus intracytoplasmic sperm injection (ICSI) in patients without severe male factor infertility: study protocol for the randomised, controlled, multicentre trial INVICSI. BMJ Open. 2021 Jun 24;11(6):e051058. doi: 10.1136/bmjopen-2021-051058.

  PMID: 34168037 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Sperm Injections, Intracytoplasmic

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Fertilization in Vitro; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques

Study Officials

• Nina la Cour Freiesleben, ph.d.

  The Fertility Clinic, Hvidovre Hospital, Copenhagen University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Consultant, Ph.D., Clinical Associate Professor

Study Record Dates

• First Submitted: October 7, 2019
• First Posted: October 16, 2019
• Study Start: November 29, 2019
• Primary Completion: December 14, 2023
• Study Completion (Estimated): December 14, 2027
• Last Updated: February 11, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available from 3 months following first publication and ending 5 years after the study has been concluded.
• Access Criteria: Individual participant data will be shared with researches who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee.

Locations

DK (6)