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.

Introduction: Over the last decades, the use of intracytoplasmic sperm injection (ICSI) has increased, even among patients without male factor infertility. The increase has happened even though there is no evidence to support that ICSI results in higher live birth rates compared with conventional in vitro fertilisation (IVF) in cases with nonmale factor infertility. The lack of robust evidence on an advantage of using ICSI over conventional IVF in these patients is problematic since ICSI is more invasive, complex and requires additional resources, time and effort. Therefore, the primary objective of the IVF versus ICSI (INVICSI) study is to determine whether ICSI is superior to standard IVF in patients without severe male factor infertility. The primary outcome measure is first live birth from fresh and frozen-thawed transfers after one stimulated cycle. Secondary outcomes include fertilisation rate, ongoing pregnancy rate, birth weight and congenital anomalies.
Methods and Analysis: This is a two-armed, multicentre, randomised, controlled trial. In total, 824 couples/women with infertility without severe male factor will be recruited and allocated randomly into two groups (IVF or ICSI) in a 1:1 ratio. Participants will be randomised in variable block sizes and stratified by trial site and age. The main inclusion criteria are (1) no prior IVF/ICSI treatment, (2) male partner sperm with an expected count of minimum 2 million progressive motile spermatozoa following density gradient purification on the day of oocyte pick up and (3) age of the woman between 18 and 42 years.
Ethics and Dissemination: 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. Study findings will be presented, irrespectively of results at international conferences and submitted for publication in peer-reviewed journals.
Trial Registration Number: NCT04128904. Pre-results.
Competing Interests: Competing interests: SB and NLCF received a research grant from the Capital Region of Denmark and two unrestricted grants from Gedeon Richter to support the INVICSI study as mentioned under ‘Funding’. Outside the submitted work authors have received grants/fees/funding or declare relationships with the following third parties: SB: Gedeon Richter, the Capital Region of Denmark. NLCF: Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, Head of the steering committee for the Danish Fertility Guidelines made by members of the Danish Fertility Society (no payment), Guerbet, Advisory Board (personal fee). AP: Gedeon Richter, Ferring Pharmaceuticals, Merck A/S, Theramex. UBK: IBSA, Ferring Pharmaceuticals, Merck A/S. LFA: Gedeon Richter. BN: Gedeon Richter, IBSA, Merck A/S. HSN: Ferring Pharmaceuticals, Merck A/S, AstraZeneca, Cook Medical, Freya Biosciences ApS, Ferring Pharmaceuticals, BioInnovation Institute, Danish Ministry of Education. MLG: Gedeon Richter, Merck A/S. LP: Gedeon Richter, Merck A/S.
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